The patient is returned to the Trendelenburgs position, and the small bowel is reflected cranially after the completion of full mobilisation of the left colon. The surgical team rearranges itself once again back to its original position. The grasper and previously inserted transabdominal sutures are used to elevate the rectosigmoid colon out of the pelvis and away from the retroperitoneum and sacral promontory, to enable entry into the presacral space. The posterior aspect of the mesorectum is easily identified and the mesorectal plane dissected with ultrasonic scissors or electrocautery-based, intruments preserving the hypogastric nerves. Dissection is continued down to the presacral space in this avascular plane toward the pelvic floor. Elevation of the upper rectum by transabdominal sutures facilitates further posterior dissection along the back of mesorectum to the pelvic floor. The anterior dissection between the rectum and the posterior vaginal wall (in females) and the seminal vesicles and prostate (in men) is performed by decreasing tension of the transabdominal sutures and retracting the peritoneal fold anterior to the rectum. Dissection is proceeded laterally on both sides of rectum until circumferential mobilisation of lower rectum is accomplished. Digital examination is performed to verify the distance between tumors inferior margin and the line of resection and the adequacy of distal margin is marked with a clip. One 5 mm port is now replaced with a 10 mm port. A blue EndoGIA roticulator stapler (Covidien Ltd., Norwalk, Conn. USA) 45-mm is fired twice from this port to divide the lower rectum safely. The abdomen is then deflated and a wound protector (Alexis O TM, Applied Medical Rancho Santo Margarita, CA) placed at the aperture of SILS port. The specimen is extracted through the SILS aperture and resected. Extracorporal preparation of the proximale colon is completed with placement of the anvil of a 29–mm circular stapler in position to perform a side-to-end or end-to-end colorectal anastomosis. After pneumoperitoneum reestablishment, a conventional intracorporeal colorectal anastomosis is made with transanal insertion of a circular stapler (Proximate ILS circular stapler, Ethicon, Endo-surgery, Puerto Rico USA) under direct vision. Testing for anastomosis is performed by insufflating air into the rectum while having the pelvic cavity filled with water. If there is a small leak it can be located by using methylene blue and eliminated by inserting a stitch that is tied intracorporally. This procedure often needs the insertion of an additional port. Drainage is not indicated routinely. As in open or CLS it is always imperative to check the resected tissue doughnuts to make sure they are complete. An incomplete doughnut should prompt a laparoscopic suture repair of the anastomosis. If the area of the defect is not recognised, the whole anastomosis should be revised and if necessary, interrupted sutures placed around the whole circumference. This is a challenging procedure with SILS technique at present. Therefore the procedure should be converted to either a CLS or an open operation. If the transumblical access is used, the fascia is closed with PDS sutures continuously and the skin is first trimmed to adapt the incision and is then closed with interrupted 3/0 nylon sutures (Fig. 9). In the cases needing a proximal diverting ileostomy, the diversion loop ilostomy is brought out through the SILS aperture approximately 20 cm proximate to the ileocoecal valve. The loop ileostomy is created using 3/0 vicryl sutures (Fig. 10). Intraabdominal smoke formation is drained via the insertion of a

### **6.2 Hartmann´s operation**

The procedure is similar to that of low anterior resection except that the splenic flexure need not be taken down routinely, there is no anastomosis and the mobilised colon is exteriorized

intravenous cannula working as a separate venting channel at the suprapubic site.

The patient is returned to the Trendelenburgs position, and the small bowel is reflected cranially after the completion of full mobilisation of the left colon. The surgical team rearranges itself once again back to its original position. The grasper and previously inserted transabdominal sutures are used to elevate the rectosigmoid colon out of the pelvis and away from the retroperitoneum and sacral promontory, to enable entry into the presacral space. The posterior aspect of the mesorectum is easily identified and the mesorectal plane dissected with ultrasonic scissors or electrocautery-based, intruments preserving the hypogastric nerves. Dissection is continued down to the presacral space in this avascular plane toward the pelvic floor. Elevation of the upper rectum by transabdominal sutures facilitates further posterior dissection along the back of mesorectum to the pelvic floor. The anterior dissection between the rectum and the posterior vaginal wall (in females) and the seminal vesicles and prostate (in men) is performed by decreasing tension of the transabdominal sutures and retracting the peritoneal fold anterior to the rectum. Dissection is proceeded laterally on both sides of rectum until circumferential mobilisation of lower rectum is accomplished. Digital examination is performed to verify the distance between tumors inferior margin and the line of resection and the adequacy of distal margin is marked with a clip. One 5 mm port is now replaced with a 10 mm port. A blue EndoGIA roticulator stapler (Covidien Ltd., Norwalk, Conn. USA) 45-mm is fired twice from this port to divide the lower rectum safely. The abdomen is then deflated and a wound protector (Alexis O TM, Applied Medical Rancho Santo Margarita, CA) placed at the aperture of SILS port. The specimen is extracted through the SILS aperture and resected. Extracorporal preparation of the proximale colon is completed with placement of the anvil of a 29–mm circular stapler in position to perform a side-to-end or end-to-end colorectal anastomosis. After pneumoperitoneum reestablishment, a conventional intracorporeal colorectal anastomosis is made with transanal insertion of a circular stapler (Proximate ILS circular stapler, Ethicon, Endo-surgery, Puerto Rico USA) under direct vision. Testing for anastomosis is performed by insufflating air into the rectum while having the pelvic cavity filled with water. If there is a small leak it can be located by using methylene blue and eliminated by inserting a stitch that is tied intracorporally. This procedure often needs the insertion of an additional port. Drainage is not indicated routinely. As in open or CLS it is always imperative to check the resected tissue doughnuts to make sure they are complete. An incomplete doughnut should prompt a laparoscopic suture repair of the anastomosis. If the area of the defect is not recognised, the whole anastomosis should be revised and if necessary, interrupted sutures placed around the whole circumference. This is a challenging procedure with SILS technique at present. Therefore the procedure should be converted to either a CLS or an open operation. If the transumblical access is used, the fascia is closed with PDS sutures continuously and the skin is first trimmed to adapt the incision and is then closed with interrupted 3/0 nylon sutures (Fig. 9). In the cases needing a proximal diverting ileostomy, the diversion loop ilostomy is brought out through the SILS aperture approximately 20 cm proximate to the ileocoecal valve. The loop ileostomy is created using 3/0 vicryl sutures (Fig. 10). Intraabdominal smoke formation is drained via the insertion of a

intravenous cannula working as a separate venting channel at the suprapubic site.

The procedure is similar to that of low anterior resection except that the splenic flexure need not be taken down routinely, there is no anastomosis and the mobilised colon is exteriorized

**6.2 Hartmann´s operation**

through the left premarked colostomy site which is used as the placement of a SILS port as well.

Fig. 9. Umblical wound after low anterior resection with transumblical access

Fig. 10. Appereance at six days following low anterior resection with protective ileostomy performed with SILS technique.

Single – Incision Laparoscopic Surgery for Rectal Cancer 149

The abdominal part of the procedure is similar to that of low anterior resection except that the splenic flexure need not be taken down routinely and no distal rectal transection is required. The left lower quadrant premarked colostomy site is used as the placement of SILS port. The patient and surgical team positions are similar to those in Hartmann´s operation. An incision of 2,5 cm located at the marked stoma site on the left side is used to access the abdomen and the SILS port is placed. The surgeon and the camera operator is located on the left side of the patient (Fig. 11). The patient is then placed in steep Trendelenburg position.

Fig. 11. Operative view of self-constructed port position at proposed left-sided colostomy

Mesocolic dissection and inferior mesenteric pedicle isolation is achieved with lateral approach by using 5 mm instruments and rectosigmoid colon is suspended towards the abdominal wall with transabdominal sutures**.** The superior rectal artery is divided just below the inferior mesenteric artery. The left ureter is then recognized and subsequently lateral-to-medial dissection is continued until the left colon is mobilised so that it may be brought up comfortably through the stoma site.Then, the posterior aspect of the mesorectum is easily identified and the mesorectal plane dissected with harmonic scalpel, preserving the pelvic nerves. The total mesorectal excision (TME) dissection is continued down to the presacral space in the avascular space towards the pelvic floor untill the level of os coccygis in the posterior level. At the anterior level the dissection is continued till the upper margin of the vagina. By decreasing tension of the transabdominal sutures to the sigmoid colon the anterior dissection can be performed. Lateral dissection is performed until circumferential mobilisation of the rectum is accomplished as mentioned the above. A 5 mm ports is replaced with a 10 mm port inside the device (SILS port). The sigmoid colon is

**6.3 Abdominoperineal resection 6.3.1 Abdominal approach**

site.

An incision of 2,5 cm located at the marked stoma site on the left side is used to access the abdomen and the SILS port is placed. A 5 mm straight laparoscope with a 30 degree optic is used to image abdominal cavity. The surgeon and the camera assistant is located on the left side of the patient (Fig. 4). The patient is then placed in steep Trendelenburg position. Transabdominal sutures are used and rectosigmoid colon is suspended towards the abdominal wall. Mesocolic dissection and inferior mesenteric pedicle isolation is achieved with lateral approach by using 5 mm instruments**.** The superior rectal artery is divided just below the inferior mesenteric artery after application of 5 mm clips or Endo-GIA (vascular cartridge). The left ureter is then recognized and subsequently lateral-to-medial dissection is continued until the left colon is mobilised so that it may be brought up comfortably through the stoma site. Then the posterior aspect of the mesorectum is easily identified and the mesorectal plane dissected, preserving the pelvic nerves. The total mesorectal excision (TME) dissection is continued down to the presacral space in the avascular space towards the pelvic floor untill the level of os coccygis in the posterior level. At the anterior level the dissection is continued till the upper margin of the vagina. By decreasing tension of the transabdominal sutures to the sigmoid colon the anterior dissection can be performed. Lateral dissection is performed until circumferential mobilisation of the rectum is accomplished. A 5 mm port is replaced with a 10 mm port inside the device (SILS port). Digital examination is performed to verify the distance between tumors inferior margin and the line of resection and the adequacy of distal margin is marked with a clip. A blue EndoGIA roticulator stapler (Covidien Ltd., Norwalk, Conn. USA) 45-mm is fired to divide the lower rectum safely. The abdomen is then deflated and a wound protector (Alexis O TM, Applied Medical Rancho Santo Margarita, CA) placed at the aperture of SILS port. The specimen is extracted through the SILS aperture and resected. The divided left colon is brought out to form a colostomy in the SILS aperture and then the colostomy is fashioned with interrupted 3/0 vicryl sutures and a colostomy bag is attached to the skin**.**

There are some potential technical difficulties with operating from the left side of the patient:

#### **6.3 Abdominoperineal resection 6.3.1 Abdominal approach**

148 Rectal Cancer – A Multidisciplinary Approach to Management

An incision of 2,5 cm located at the marked stoma site on the left side is used to access the abdomen and the SILS port is placed. A 5 mm straight laparoscope with a 30 degree optic is used to image abdominal cavity. The surgeon and the camera assistant is located on the left side of the patient (Fig. 4). The patient is then placed in steep Trendelenburg position. Transabdominal sutures are used and rectosigmoid colon is suspended towards the abdominal wall. Mesocolic dissection and inferior mesenteric pedicle isolation is achieved with lateral approach by using 5 mm instruments**.** The superior rectal artery is divided just below the inferior mesenteric artery after application of 5 mm clips or Endo-GIA (vascular cartridge). The left ureter is then recognized and subsequently lateral-to-medial dissection is continued until the left colon is mobilised so that it may be brought up comfortably through the stoma site. Then the posterior aspect of the mesorectum is easily identified and the mesorectal plane dissected, preserving the pelvic nerves. The total mesorectal excision (TME) dissection is continued down to the presacral space in the avascular space towards the pelvic floor untill the level of os coccygis in the posterior level. At the anterior level the dissection is continued till the upper margin of the vagina. By decreasing tension of the transabdominal sutures to the sigmoid colon the anterior dissection can be performed. Lateral dissection is performed until circumferential mobilisation of the rectum is accomplished. A 5 mm port is replaced with a 10 mm port inside the device (SILS port). Digital examination is performed to verify the distance between tumors inferior margin and the line of resection and the adequacy of distal margin is marked with a clip. A blue EndoGIA roticulator stapler (Covidien Ltd., Norwalk, Conn. USA) 45-mm is fired to divide the lower rectum safely. The abdomen is then deflated and a wound protector (Alexis O TM, Applied Medical Rancho Santo Margarita, CA) placed at the aperture of SILS port. The specimen is extracted through the SILS aperture and resected. The divided left colon is brought out to form a colostomy in the SILS aperture and then the colostomy is fashioned

with interrupted 3/0 vicryl sutures and a colostomy bag is attached to the skin**.**

patient:

surgeons to this approach.

mesenteric dissection.

There are some potential technical difficulties with operating from the left side of the

1. Most of the laparoscopic colorectal surgeons, have not been familiar with left side approach and exposure to abdominal cavity through a left-sided port, although we have previously used traditional approach of the lateral-to-medial dissection sequence from the right side of abdomen. There is an adaptation process for laparoscopic

2. The distance between left-sided single-port and anatomical landmarks as inferior mesenteric artery or left ureter are relatively short and this condition can limit the free manoeuvre possibilities of laparoscopic instruments and the facility of proper

3. In some rare conditions in which the tumor coexists with a colonic inflammatory process (e.g., diverticulitis), the initial divisions of the sigmoid lateral attachments may be difficult and dangereous because the lateral dissection plane is blurred. There is an

4. If there is a need of early division of the white line of Toldt before vessel ligation increases the sigmoid redundancy and sometimes hinders the upcoming procedures (e.g. dissection of inferior mesenteric artery) during the operation. On the other hand, tilting of the patient to the right side allows gravity to aid in the retraction of the colon

increased risk of inadvertent injury of left ureter and gonadal vessels.

and makes identification of the ureter extremely simple.

The abdominal part of the procedure is similar to that of low anterior resection except that the splenic flexure need not be taken down routinely and no distal rectal transection is required. The left lower quadrant premarked colostomy site is used as the placement of SILS port. The patient and surgical team positions are similar to those in Hartmann´s operation. An incision of 2,5 cm located at the marked stoma site on the left side is used to access the abdomen and the SILS port is placed. The surgeon and the camera operator is located on the left side of the patient (Fig. 11). The patient is then placed in steep Trendelenburg position.

Fig. 11. Operative view of self-constructed port position at proposed left-sided colostomy site.

Mesocolic dissection and inferior mesenteric pedicle isolation is achieved with lateral approach by using 5 mm instruments and rectosigmoid colon is suspended towards the abdominal wall with transabdominal sutures**.** The superior rectal artery is divided just below the inferior mesenteric artery. The left ureter is then recognized and subsequently lateral-to-medial dissection is continued until the left colon is mobilised so that it may be brought up comfortably through the stoma site.Then, the posterior aspect of the mesorectum is easily identified and the mesorectal plane dissected with harmonic scalpel, preserving the pelvic nerves. The total mesorectal excision (TME) dissection is continued down to the presacral space in the avascular space towards the pelvic floor untill the level of os coccygis in the posterior level. At the anterior level the dissection is continued till the upper margin of the vagina. By decreasing tension of the transabdominal sutures to the sigmoid colon the anterior dissection can be performed. Lateral dissection is performed until circumferential mobilisation of the rectum is accomplished as mentioned the above. A 5 mm ports is replaced with a 10 mm port inside the device (SILS port). The sigmoid colon is

Single – Incision Laparoscopic Surgery for Rectal Cancer 151

The anterior dissection is carried out immediately behind and to the upper level of the transversus perineal muscles and the dissection is completed with the division of the puborectalis muscle on both sides. In cases of anterior tumours with local invasion, a portion of the prostate or the posterior vaginal wall may be resected en bloc with the anorectum. In some cases, venous bleeding from the posterior and posterolateral aspect of the prostate or vagina can be troublesome. Meticulous haemostasis by diathermy or stitching can control this bleeding. When the specimen is removed and hemostasis is secured, the perineal wound is closed in layers using interrupted sutures with vicryl 2/0

and vicryl rapid 3/0 in the skin.

**7. Complications**

**8. Discussion**

Fig. 12b. Patient in the prone jack-knife position (perineal view)

perineal wound should remain unchanged.

We have seen no specific complications following SILS for rectal cancer compared to conventional multiport laparoscopic surgery or conventional open surgery. There is no report about visceral or vascular injuries in the literature at present. We believe that there is a theoretical risk for unrecognized injury to viscera caused by the use of laparoscopic instruments away from the surgical field as in laparoscopic surgery. Wound complications will probably be shown to be decreased. However, complications with stoma and the

The SILS technique for rectal surgery is still in its infancy and the published studies are highly inhomogeneous. To date, a total of ten articles as single case reports and small case series have been available in the English literature on single-access laparoscopic rectal surgery. Table 1. summarizes the technical aspects and operative outcomes of SILS for rectal surgery. Operative outcomes are comparable with CLS in these very limited preliminary data. The data reviewed in this chapter shows the safety and feasibility of the procedure.

divided with a blue EndoGIA 60 stapler (Covidien Ltd., Norwalk, Conn. USA). The abdomen is deflated and the divided left colon is brought out to form a colostomy in the SILS aperture and then the left-sided colostomy is fashioned with interrupted 3/0 vicryl sutures**.**

#### **6.3.2 Perineal dissection**

The patient is then turned into jack-knife position with legs spread to enable the surgeon to stand between the legs with one assistant on each side (Fig. 12a). A purse–string suture is tied tightly to close the anus. After the skin is prepared, a drop formed incision around the anus is made and extended cranially to the coccyx (Fig. 1b).  The perineal incision is deepened into ischiorectal fossa on both sides and the outer side of the levator muscle is identified all around. A small transverse incision is made immediately proximal of the tip of os coccyx, which is disarticulated from the sacrum and Waldeyer´s fasciae divided (19). The pelvic or presacral cavity is entered and the incision into it enlarged by cutting the levator ani muscles on both sides, from posterior to anterior. The specimen is gently withdrawn and dissected off the prostate or posterior vaginal wall.

Fig. 12a. Patient in the prone jack-knife position (lateral view)

divided with a blue EndoGIA 60 stapler (Covidien Ltd., Norwalk, Conn. USA). The abdomen is deflated and the divided left colon is brought out to form a colostomy in the SILS aperture and then the left-sided colostomy is fashioned with interrupted 3/0 vicryl

The patient is then turned into jack-knife position with legs spread to enable the surgeon to stand between the legs with one assistant on each side (Fig. 12a). A purse–string suture is tied tightly to close the anus. After the skin is prepared, a drop formed incision around the anus is made and extended cranially to the coccyx (Fig. 1b).  The perineal incision is deepened into ischiorectal fossa on both sides and the outer side of the levator muscle is identified all around. A small transverse incision is made immediately proximal of the tip of os coccyx, which is disarticulated from the sacrum and Waldeyer´s fasciae divided (19). The pelvic or presacral cavity is entered and the incision into it enlarged by cutting the levator ani muscles on both sides, from posterior to anterior. The specimen is gently

withdrawn and dissected off the prostate or posterior vaginal wall.

Fig. 12a. Patient in the prone jack-knife position (lateral view)

sutures**.**

**6.3.2 Perineal dissection**

The anterior dissection is carried out immediately behind and to the upper level of the transversus perineal muscles and the dissection is completed with the division of the puborectalis muscle on both sides. In cases of anterior tumours with local invasion, a portion of the prostate or the posterior vaginal wall may be resected en bloc with the anorectum. In some cases, venous bleeding from the posterior and posterolateral aspect of the prostate or vagina can be troublesome. Meticulous haemostasis by diathermy or stitching can control this bleeding. When the specimen is removed and hemostasis is secured, the perineal wound is closed in layers using interrupted sutures with vicryl 2/0 and vicryl rapid 3/0 in the skin.

Fig. 12b. Patient in the prone jack-knife position (perineal view)

### **7. Complications**

We have seen no specific complications following SILS for rectal cancer compared to conventional multiport laparoscopic surgery or conventional open surgery. There is no report about visceral or vascular injuries in the literature at present. We believe that there is a theoretical risk for unrecognized injury to viscera caused by the use of laparoscopic instruments away from the surgical field as in laparoscopic surgery. Wound complications will probably be shown to be decreased. However, complications with stoma and the perineal wound should remain unchanged.

#### **8. Discussion**

The SILS technique for rectal surgery is still in its infancy and the published studies are highly inhomogeneous. To date, a total of ten articles as single case reports and small case series have been available in the English literature on single-access laparoscopic rectal surgery. Table 1. summarizes the technical aspects and operative outcomes of SILS for rectal surgery. Operative outcomes are comparable with CLS in these very limited preliminary data. The data reviewed in this chapter shows the safety and feasibility of the procedure.

Table 1. Studies showing outcomes of single-incision laparoscopic rectal surgery

Single – Incision Laparoscopic Surgery for Rectal Cancer 153

Although operative times seems to be longer in some series, nevertheless the results are in general comparable with conventional multiport laparoscopic rectal procedures. Another

The adequacy of lymph node retrieval plays an important role in tumor staging and prognosis. A minimum number of 12 lymph nodes have been endorsed as a consensus standard of performance in colorectal resections (20). However, many factors affect the number of lymph nodes examined, including extent of surgical resection, patient age, tumor location, pathologist, surgeon and the method of specimen preparation. The data shows that the number of harvested lymph nodes in malignant cases appears oncologically satisfactory. The reported number of median or mean lymph nodes extraction in these cases are comparable to multiport laparoscopic series and population based studies (21-24). However, the given data regarding pathological examination and the shortness of follow-up are inadequate to evaluate the oncological outcome. A more detailed pathological report including margin clearance and the quality of mesorectal fasciae would be important to

The potential advantages of a small skin incision include, not only better cosmetic appereance, but decreasing rate of port-site related complications. The final length of the skin and fasciae incision depends on specimen size. This is particularly important in rectal surgery due to relatively fast mesorectum. Extraction difficulties may often be encountered for the patients with large rectal tumors or thickened mesorectum. In addition, when the colon is full of stool in the case of distal stenosis, it is also difficult to bring the rectosigmoid colon out. The length of skin and fascia incision is often enlarged to permit the intact extraction of the specimen. Another expected advantage of a small incision is the reduction of postoperative pain. None of the published reports assessed the postoperative pain or analgesic requirements (32-35). Technical difficulties of single-access as the lack of triangulation and exposure, the inaxis view and conflicts between instruments are the most important challenges. The handling of both a grasper and an energi-based device in parallel with the laparoscope through the single port decreases the possibility of the surgeons manoeuvre and result in inadequate exposure and difficult dissection in the surgical field

To ensure an adequate and timely traction and to have a better surgical view and dissection, transparietal sutures are applied through abdominal wall. A 300 laparoscope and articulating or curved graspers are also helpful to improve view and dissection. The possibility of using a planned ileostomy or sigmoidostomy site as the port placement and extraction of the specimen reduced parietal trauma and improved cosmesis as a real no-scar procedure in some cases. The case studies in literature have shown that the length of stay did not appear to be decreased using SILS in rectal cancer. Health care systems have the duty to offer the citizen the best available medical care, taking economic cost and priority into consideration. SILS colorectal procedures stands now where conventional laparoscopic surgery stood in the early 1990s. Today, SILS for rectal cancer is under trial. Larger comparative studies to conventional laparoscopic surgery with oncologic outcomes, cost analysis and long-term results are necessary to determine patient benefits. Another important issue is the education of surgeons in the future. SILS for rectal procedures presents a challenge for teaching residents and surgeons. There are some similarities between SILS and Transanal Endoscopic Microsurgery (TEM). The colorectal surgical

issue is the adequacy of oncological results of SILS for rectal cancer.

make long-term comparisons.

(Fig. 13).

Table 1. Studies showing outcomes of single-incision laparoscopic rectal surgery

Although operative times seems to be longer in some series, nevertheless the results are in general comparable with conventional multiport laparoscopic rectal procedures. Another issue is the adequacy of oncological results of SILS for rectal cancer.

The adequacy of lymph node retrieval plays an important role in tumor staging and prognosis. A minimum number of 12 lymph nodes have been endorsed as a consensus standard of performance in colorectal resections (20). However, many factors affect the number of lymph nodes examined, including extent of surgical resection, patient age, tumor location, pathologist, surgeon and the method of specimen preparation. The data shows that the number of harvested lymph nodes in malignant cases appears oncologically satisfactory. The reported number of median or mean lymph nodes extraction in these cases are comparable to multiport laparoscopic series and population based studies (21-24). However, the given data regarding pathological examination and the shortness of follow-up are inadequate to evaluate the oncological outcome. A more detailed pathological report including margin clearance and the quality of mesorectal fasciae would be important to make long-term comparisons.

The potential advantages of a small skin incision include, not only better cosmetic appereance, but decreasing rate of port-site related complications. The final length of the skin and fasciae incision depends on specimen size. This is particularly important in rectal surgery due to relatively fast mesorectum. Extraction difficulties may often be encountered for the patients with large rectal tumors or thickened mesorectum. In addition, when the colon is full of stool in the case of distal stenosis, it is also difficult to bring the rectosigmoid colon out. The length of skin and fascia incision is often enlarged to permit the intact extraction of the specimen. Another expected advantage of a small incision is the reduction of postoperative pain. None of the published reports assessed the postoperative pain or analgesic requirements (32-35). Technical difficulties of single-access as the lack of triangulation and exposure, the inaxis view and conflicts between instruments are the most important challenges. The handling of both a grasper and an energi-based device in parallel with the laparoscope through the single port decreases the possibility of the surgeons manoeuvre and result in inadequate exposure and difficult dissection in the surgical field (Fig. 13).

To ensure an adequate and timely traction and to have a better surgical view and dissection, transparietal sutures are applied through abdominal wall. A 300 laparoscope and articulating or curved graspers are also helpful to improve view and dissection. The possibility of using a planned ileostomy or sigmoidostomy site as the port placement and extraction of the specimen reduced parietal trauma and improved cosmesis as a real no-scar procedure in some cases. The case studies in literature have shown that the length of stay did not appear to be decreased using SILS in rectal cancer. Health care systems have the duty to offer the citizen the best available medical care, taking economic cost and priority into consideration. SILS colorectal procedures stands now where conventional laparoscopic surgery stood in the early 1990s. Today, SILS for rectal cancer is under trial. Larger comparative studies to conventional laparoscopic surgery with oncologic outcomes, cost analysis and long-term results are necessary to determine patient benefits. Another important issue is the education of surgeons in the future. SILS for rectal procedures presents a challenge for teaching residents and surgeons. There are some similarities between SILS and Transanal Endoscopic Microsurgery (TEM). The colorectal surgical

Single – Incision Laparoscopic Surgery for Rectal Cancer 155

improve cosmetic results. However, the existing clinical evidence is limited, and potential benefits or disadvantages of SILS procedures require further evaluation. There is a need to standardize the technique and carefully evaluate its oncological outcomes. Prospective comparative studies between SILS and conventional laparoscopic colorectal surgery are

SILS is a major step after CLS and represents the crossing link between robotic surgery and NOTES (Fig. 14). The huge developments in the fields of imaging, data processing, simulation and virtual reality in the future have the potential to help SILS mature as computer-assisted single-access surgery through a single transabdominal incision or a natural orifice. It is believed that the future of minimally invasive surgery will be a hybrid

**NOTES Computer-assisted**

**Single-access Surgery**

needed to clearly determine its short- and long-term outcome

**SIL SPA LESS SILS E-NOTES TUES NOTUS**

**Robotic Surgery**

Fig. 14. The development of minimally invasive surgery in the future.

nephrectomy. J Endouro, l17,493-49413.

insertion. JSLS, 5, 293-295.

[1] Bonjer H.J., Hop W.C., Nelson H., et al.(2005). Laparoscopically assisted vs open colectomy for colon cancer: a metaanalysis. Arch Surg, 142, 298-303. [2] Schwenk W., Haase O., Neudecker J., Muller J.M. (2008). Short term benefits for

[3] Lowry P.S., Moon T.D., D'Alessandro A., Nakada S.Y. (2003). Symptomatic port-site

[4] Marcovici I. (2003). Significant abdominal wall hematoma from an umbilical port

laparoscopic colorectal resection. Cochrane Database of Systematic Reviews.

hernia associated with a non-bladed trocar after laparoscopic live-donor

form of SILS, NOTES and robotic surgery.

**10. The future**

**Conventional Laparoscopic Surgery**

**11. References**

CD003145.

community should use the experiences in training of surgeons in TEM for teaching SILS in the procedure.

Fig. 13. External view of the instruments working in parallel position through a selfconstructed single port.

#### **9. Conclusions**

SILS for rectal cancer is a challenging procedure that seems to be feasible. These technical challenges could explain why the operating time may be considerably lengthened. When using SPA for complex procedures such as rectal cancer surgery, advanced laparoscopic experience is mandatory. In addition to this a significant learning curve must be expected. It can be performed safely on slim patients with no bulky tumour using one incision, either through the patient´s umbilicus or through a chosen stoma site which may become the diversion ileostomy or end-sigmoidostomy aperture. SILS has a potential of reducing postoperative pain. The decrease in incision number may decrease the development of wound infection or hernias and the formation of intra-abdominal adhesions as well as improve cosmetic results. However, the existing clinical evidence is limited, and potential benefits or disadvantages of SILS procedures require further evaluation. There is a need to standardize the technique and carefully evaluate its oncological outcomes. Prospective comparative studies between SILS and conventional laparoscopic colorectal surgery are needed to clearly determine its short- and long-term outcome

#### **10. The future**

154 Rectal Cancer – A Multidisciplinary Approach to Management

community should use the experiences in training of surgeons in TEM for teaching SILS in

Fig. 13. External view of the instruments working in parallel position through a self-

SILS for rectal cancer is a challenging procedure that seems to be feasible. These technical challenges could explain why the operating time may be considerably lengthened. When using SPA for complex procedures such as rectal cancer surgery, advanced laparoscopic experience is mandatory. In addition to this a significant learning curve must be expected. It can be performed safely on slim patients with no bulky tumour using one incision, either through the patient´s umbilicus or through a chosen stoma site which may become the diversion ileostomy or end-sigmoidostomy aperture. SILS has a potential of reducing postoperative pain. The decrease in incision number may decrease the development of wound infection or hernias and the formation of intra-abdominal adhesions as well as

the procedure.

constructed single port.

**9. Conclusions**

SILS is a major step after CLS and represents the crossing link between robotic surgery and NOTES (Fig. 14). The huge developments in the fields of imaging, data processing, simulation and virtual reality in the future have the potential to help SILS mature as computer-assisted single-access surgery through a single transabdominal incision or a natural orifice. It is believed that the future of minimally invasive surgery will be a hybrid form of SILS, NOTES and robotic surgery.

Fig. 14. The development of minimally invasive surgery in the future.

#### **11. References**

Single – Incision Laparoscopic Surgery for Rectal Cancer 157

[22] Park J.S., Kang S.B., Kim D.W., Lee K.H., Kim Y.H.(2009). Laparoscopic versus open

[24] Baxter N.N., Virnig D.J., Rothenberger D.A., Morris A.M., Jessurun J, Virnig BA. (2005).

[25] Chambers W., Bicsak M., Lamparelli M., Dixon A. (2011). Single-incision laparoscopic

[26] Gash K.J., Goede A.C., Chambers W., Greenslade G.L., Dixon A.R. (Published on line 24

[27] Hamzaoglu I., Karahasanoglu T.; Baca B., et al. (2011). Single-port laparoscopic

[28] Ramos-Valadez D.I., Chirag B. Patel, M.R., Pickron T.B., Haas E.M. (Published on

[29] Uematsu D., Akiyama G., Narita M., Magishi A. (2011). Single-access laparoscopic low

[30] Katsuno G., Fukunaga M., Nagakari K., Yoshikawa S., Ouchi M., Hirasaki Y. (2011).

[31] Bulut O., Nielsen C.B. and Jespersen N. (2011). Single-port access laparoscopic

[32] Adair J., Gromski M.A., Lim R.B., Nagle D. (2010). Single-incision laparoscopic right

[34] Chen W.T.L., Chang S.C., Chiang H.C. et al. (Published on line 27 february 2011).

laparoscopic right hemicolectomy. Dis Colon Rectum, 53,1549-1554. [33] Waters J.A., Guzman M.J., Fajardo A.D., et al. (2010). Single-port laparoscopic right

flexure mobilization. Surg Laparosc Endosc Percutan Tech, 19, 62–68. [23] Kang S.B., Park J.W., Jeong S.Y., et al.(1010). Open versus laparoscopic surgery for mid

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1481-4.

Natl Cancer Inst, 97, 219-225.

cases. Arch Surg, 146,75-81.

cases. Dis Colon Rectum, 54,705-710.

just cosmesis. Colorectal Dis, 13, 393-398.

resection without splenic flexure mobilization for the treatment of rectum and sigmoid cancer: a study from a single institution that selectively used splenic

or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): shortterm outcomes of an open-label randomised controlled trial. Lancet Oncol, 11, 37-

Lymph node evaluation in colorectal cancer patients: a population-based study. J

surgery (SILS) in complex colorectal surgery: a technique offering potential and not

august 2010). Laparoendoscopic single site surgery is feasible in complex colorectal resections and could enable day case colectomy. Surg Endosc, DOI 10.1007/s00464-

sphincter-saving mesorectal excision for rectal cancer. Report of the first 4 human

line: 29 march 2011). Single-incision laparoscopic colectomy: outcomes of an emerging minimally invasive technique. Int J Colorectal Dis, DOI10.1007/s00384-

anterior resection with vertical suspension of the rectum. Dis Colon Rectum, 54,

Single-incision laparoscopic colectomy for colon cancer: Early experience with 31

surgery for rectal cancer: Initial experience with 10 cases. Dis Colon Rectum, 54,

colectomy: Experience with 17 consecutive cases and comparison with multiport

hemicolectomy: A safe alternative to conventional laparoscopy. Dis Colon Rectum,

Single-incision laparoscopic versus conventional laparoscopic right hemicolectomy: a comparison of short-term surgical results. Surg Endosc. DOI 10.1007/s00464-010-

[5] Dunker M.S., Stiggelbout A.M., van Hogezend R.A., Ringers J., Griffioen G., Bemelman

[6] Raman J.D., Bagrodia A., Cadeddu J.A. (2009). Single-incision, umbilical

[7] Podolsky E.R., Curcillo P.G. 2nd. (2010). Single Port Access (SPA) Surgery-a 24-Month

[8] Ahmed K., Wang T.T., Patel V.M., et al. (2011). The role of single-incision laparoscopic surgery in abdominal and pelvic surgery: a systematic review, 25, 378-396. [9] Remzi F.H., Kirat H.T., Kaouk J.H., Geisler D.P. (2008). Single port laparoscopy in

[10] Remzi F.H., Kirat H.T., Geisler D.P. (2010). Laparoscopic single-port colectomy for

[11] Bucher P., Pugin F., Morel P. (2008). Single port access laparoscopic right

[12] Bucher P., Pugin F., Morel P. (2009). Single-port access laparoscopic radical left

[13] Law W, Fan J.K.M., Poon J.T.C. (2010). Single-incision laparoscopic colectomy: early

[14] Wong M.T.C., Ng K.H. , Ho K.S., Eu K.W. (2010). Single-incision laparoscopic surgery

[15] Geisler D.P., Condon E.T., Remzi F.H. (2010).  Colorectal Dis, 12, 941-943. [16] Ramos-Valadez D.I., Chirag B. Patel, M.R., Pickron T.B., Haas E.M. (Published online

[17] Bulut O. and Nielsen C.B.(2010). Single-incision laparoscopic low anterior resection for

[18] Bulut O. and Nielsen C.B. (2011). Single-incision laparoscopic low anterior resection

[19] Holm T., Ljung A., Haggmark T., Jurell G. and Lagergren J.(2007). Extended

[20] Nelson H., Petrelli N., Carlin A., et al. (2001). Guidelines 2000 for colon and rectal

[21] Guillou P.J., Quirke P., Thorpe H., et al.(2005). MCR CLASICC trial group. Short-term

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for right hemicolectomy: our initial experience with 10 cases. Tech Coloproctol, 14,

ahead of print 2010).Single-incision laparoscopic right hemicolectomy: safety and feasibility in a series of consecutive cases. Surg. Endosc, DOI: 10.1007/s00464-010-

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**9**

*Bulgaria*

**Intraoperative Sentinel Lymph Node**

Krasimir Ivanov, Nikola Kolev and Anton Tonev

*Medical University "Prof. Dr. Paraskev Stoyanov"*

**Mapping in Patients with Colorectal Cancer**

The sentinel lymph node (SLN) is defined as the first lymph node/nodes receiving direct drainage from the tumor and consequently possessing the greatest metastatic potential. (Nieweg OE. et al., 2001; Tanis PJ. Et al, 2002; Saha S et al, 2004; Bilchik A et al., 2001; Wood Th. F. et al, 2001; Bertagnolli M. et al, 2001; Dahl K. Et al, 2005; Feig BW et al, 2001; Patten LC et al, 2001) Sentinel lymph node mapping in colorectal cancer (CRC) is related to two

1. Is the extending of the lymph dissection necessary in certain patients and which are

1. Can the volume of the visceral resection and lymph dissection be decreased (economy resections) in the aspect of implantation of laparoscopic surgery or local tumor excision

2. Can the method help in deciding for sphincter preservation and nerve preservation in

The most important factor affecting the outcomes of the surgical treatment and the survival rate is the presence of metastases. (Bertoglio S et. Al, 2004; Wood Th. F. et al, 2001; Bertagnolli M. et al, 2001; Saha S. et al, 2000; Paramo JC. Et al, 2001; Trocha SD. et al, 2003; Wood TF et al, 2001) The presence of lymph metastases places the patients from first and second stage into third stage and significantly deteriorates the prognosis and the survival rate. (Bilchik AJ et al., 2002; Philips RKS. et al., 1984; O'Connell MJ. et al., 1997; Saha S. et al.,2000) The atypical lymph-drainage occurs in about 8-14% of the patients. (Saha S. et al., 2001; Saha S. et al., 2001; Wood TF et al, 2001; Kitagawa Y. et al., 2002; Bilchik AJ et al., 2001) The failure to detect the atypical drainage is one of the reasons for recurrences due to incorrect staging and adjuvant therapy. (Bilchik AJ et al., 2001; Paramo JC. et al., 2001; Martinez SR et al., 2005) It results from specific anatomical features of the lymph flow. The atypical lymph metastases are observed in terms of the localization level of the metastatic lymph nodes (jumping or "skip" metastases and also in affecting the atypical lymph basin

**1. Introduction**

these patients?

rectal surgery?

questions that are important for the surgeon:

Additional questions that may be answered in the future are:

5. Will sentinel lymph node mapping have clinical application? To answer these questions well-designed trials are needed.

2. Is the staging of the disease correct?

3.  4. Is PET-CT a comparable method?

– endoscopic or transanal?

[35] Champagne B.J., Lee E.C., Leblanc .F, Stein S.L. and Delaney C.P. (2011). Single-incision vs straight laparoscopic segmental colectomy: A case-controlled study. Dis Colon Rectum, 54,183-186.

### **Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer**

#### **1. Introduction**

158 Rectal Cancer – A Multidisciplinary Approach to Management

[35] Champagne B.J., Lee E.C., Leblanc .F, Stein S.L. and Delaney C.P. (2011). Single-incision

Rectum, 54,183-186.

vs straight laparoscopic segmental colectomy: A case-controlled study. Dis Colon

The sentinel lymph node (SLN) is defined as the first lymph node/nodes receiving direct drainage from the tumor and consequently possessing the greatest metastatic potential. (Nieweg OE. et al., 2001; Tanis PJ. Et al, 2002; Saha S et al, 2004; Bilchik A et al., 2001; Wood Th. F. et al, 2001; Bertagnolli M. et al, 2001; Dahl K. Et al, 2005; Feig BW et al, 2001; Patten LC et al, 2001) Sentinel lymph node mapping in colorectal cancer (CRC) is related to two questions that are important for the surgeon:

Additional questions that may be answered in the future are:

To answer these questions well-designed trials are needed.

The most important factor affecting the outcomes of the surgical treatment and the survival rate is the presence of metastases. (Bertoglio S et. Al, 2004; Wood Th. F. et al, 2001; Bertagnolli M. et al, 2001; Saha S. et al, 2000; Paramo JC. Et al, 2001; Trocha SD. et al, 2003; Wood TF et al, 2001) The presence of lymph metastases places the patients from first and second stage into third stage and significantly deteriorates the prognosis and the survival rate. (Bilchik AJ et al., 2002; Philips RKS. et al., 1984; O'Connell MJ. et al., 1997; Saha S. et al.,2000) The atypical lymph-drainage occurs in about 8-14% of the patients. (Saha S. et al., 2001; Saha S. et al., 2001; Wood TF et al, 2001; Kitagawa Y. et al., 2002; Bilchik AJ et al., 2001) The failure to detect the atypical drainage is one of the reasons for recurrences due to incorrect staging and adjuvant therapy. (Bilchik AJ et al., 2001; Paramo JC. et al., 2001; Martinez SR et al., 2005) It results from specific anatomical features of the lymph flow. The atypical lymph metastases are observed in terms of the localization level of the metastatic lymph nodes (jumping or "skip" metastases and also in affecting the atypical lymph basin

Krasimir Ivanov, Nikola Kolev and Anton Tonev *Medical University "Prof. Dr. Paraskev Stoyanov" Bulgaria*

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 161

a) b)

c) Fig. 1. Intraoperative view of stained lymph nodes and lymph vessels with Patent Blue V.

We performed intraoperative sentinel mapping in 103 consecutive patients operated for colon or rectal cancer. An algorithm was worked out for sentinel mapping in colorectal

Histological diagnosis and preoperative staging performed not later than 3 months

**2. Methodology**

**2.1 Intraoperative procedure**

before the surgery;

Class after ASA I–III.

a. Indications or inclusion criteria:

Presence of distant metastases;

Recurrent colorectal cancer;

Patients with invasive colorectal cancer

b. Contraindications and exclusion criteria:

cancer. The dying method with Patent Blue V was used.

Life expectancy over 5 years (age up to 80 years);

 Preceding Previous local excision of the primary tumor; Metachronous colorectal cancer (with some exceptions);

(aberrant lymph drainage) for the given localization of the primary tumor. (Kitagawa Y. et al., 2000; Bilchik AJ et al., 2002; Wood TF et al., 2002)

In CRC the resection volume and the lymph dissection are determined by the tumor localization and they have been standardized to a great extent. (Schlag PM et al., 2004) The metastatic lymph nodes in the presence of aberrant lymph drainage can be found beyond the lines of the standard lymph dissection. In these cases the radicality of the surgery requires extension of the lines of lymph dissection. (Paramo JC et al., 2001; Tsioulias G. et al., 2002; Kitajima M. et al., 2004) It is important to apply a method for lymph metastases detection. The possibilities of the intraoperative examination and palpation as well as the existing methods for imaging diagnostics of the lymph basin in CRC are not sufficiently reliable. Their sensitivity varies between 20% and 50%, only lymph nodes with size over 5mm are detected and the metastatic potential is determined based on the increased size. (Kitagawa Y. et al., 2000) According to literary data 50% to 78% of the metastatic lymph nodes are sized under 5 mm. (Saha S. et al., 2004; Rodriguez-Bigas MA et al., 1996; Haboubi NY et al., 1992; Paramo JC et al., 2002). This is a reason for the unsatisfactory capability of the preoperative and intraoperative diagnostics of the lymph metastases. Lymph node mapping with dye visualizes the lymph vessels and the SLN very well in the surgical field even if they are very small in size less than 5mm, otherwise undetectable. (Saha S. et al., 2004; Rodriguez-Bigas MA et al., 1996; Haboubi NY et al., 1992; Paramo JC et al., 2002).

The direct tumor drainage in the SLN is demonstrated by means of blue stained lymph vessel linking the tumor to the SLN, when marked with dye (Fig.1.a), b), c))

Recurrences are observed in 20 – 40% of the operated patients in the first and second stage. (Martinez SR & AJ Bilchik , 2005; Rodriguez-Bigas MA et al., 1996; Wolmark N. et al., 1986) In half of the patients with recurrences it was established that they were due to metastatic lymph nodes, which have not been detected and remove during the surgery. (Dimitrov V. et al., 2003; Macintosh E., 1997; Makela J.& Kiviniemi H., 2000; Morson BC et al., 1963; Pietra N. et al., 1998) For these patients the following was true: adequate lymph dissection was not performed; the disease has not been correctly staged; no indications have been given for adjuvant therapy (Saha S. et al., 2000; Cohen AM et al., 1998).

According to the TNM system the micrometastases are designated with the index "mi" and their presence stages the disease as third stage, determining a relevant treatment and prognosis. (Bilchik AJ et al., 2003; Sobin LH, 2002)

For the assessment of the lymph status it is obligatory to investigate morphologically at least 12 lymph nodes. (Martinez SR& Bilchik AJ, 2005; Rodriguez-Bigas MA et al., 1996). If lymph metastases are not detected, it is advisable to search for micrometastases (MM) A great number of authors in the literature suggest that the presence of MM is a poor prognostic factor and therefore are indicative for adjuvant therapy which would improve the prognosis in these "troublesome" 30% of the patients "without metastases". The prognostic value of the metastases in CRC requires further investigations in the future. In their studies a number of authors confirm the prognostic value of MM (Broll R. et al., 1997; Greenson JK et al., 1994; Isaka N. et al., 1999; Palma RT et al., 2003; Yasuda K. et al., 2001; Liefers GJ et al., 1998), others aren't support this suggestion.  If the all LNs are to be investigated, the methods for micrometastases detection are costly, expensive and time consuming.  Intraoperative view of stained lymph nodes and lymph vessels with Patent Blue V.

#### **2. Methodology**

160 Rectal Cancer – A Multidisciplinary Approach to Management

(aberrant lymph drainage) for the given localization of the primary tumor. (Kitagawa Y. et

In CRC the resection volume and the lymph dissection are determined by the tumor localization and they have been standardized to a great extent. (Schlag PM et al., 2004) The metastatic lymph nodes in the presence of aberrant lymph drainage can be found beyond the lines of the standard lymph dissection. In these cases the radicality of the surgery requires extension of the lines of lymph dissection. (Paramo JC et al., 2001; Tsioulias G. et al., 2002; Kitajima M. et al., 2004) It is important to apply a method for lymph metastases detection. The possibilities of the intraoperative examination and palpation as well as the existing methods for imaging diagnostics of the lymph basin in CRC are not sufficiently reliable. Their sensitivity varies between 20% and 50%, only lymph nodes with size over 5mm are detected and the metastatic potential is determined based on the increased size. (Kitagawa Y. et al., 2000) According to literary data 50% to 78% of the metastatic lymph nodes are sized under 5 mm. (Saha S. et al., 2004; Rodriguez-Bigas MA et al., 1996; Haboubi NY et al., 1992; Paramo JC et al., 2002). This is a reason for the unsatisfactory capability of the preoperative and intraoperative diagnostics of the lymph metastases. Lymph node mapping with dye visualizes the lymph vessels and the SLN very well in the surgical field even if they are very small in size less than 5mm, otherwise undetectable. (Saha S. et al., 2004; Rodriguez-Bigas MA et al., 1996; Haboubi NY et al., 1992; Paramo JC et al., 2002). The direct tumor drainage in the SLN is demonstrated by means of blue stained lymph

vessel linking the tumor to the SLN, when marked with dye (Fig.1.a), b), c))

adjuvant therapy (Saha S. et al., 2000; Cohen AM et al., 1998).

prognosis. (Bilchik AJ et al., 2003; Sobin LH, 2002)

AJ, 2005; Bilchik AJ et al., 2003; Doekhie FS et al., 2005)

Recurrences are observed in 20 – 40% of the operated patients in the first and second stage. (Martinez SR & AJ Bilchik , 2005; Rodriguez-Bigas MA et al., 1996; Wolmark N. et al., 1986) In half of the patients with recurrences it was established that they were due to metastatic lymph nodes, which have not been detected and remove during the surgery. (Dimitrov V. et al., 2003; Macintosh E., 1997; Makela J.& Kiviniemi H., 2000; Morson BC et al., 1963; Pietra N. et al., 1998) For these patients the following was true: adequate lymph dissection was not performed; the disease has not been correctly staged; no indications have been given for

According to the TNM system the micrometastases are designated with the index "mi" and their presence stages the disease as third stage, determining a relevant treatment and

For the assessment of the lymph status it is obligatory to investigate morphologically at least 12 lymph nodes. (Martinez SR& Bilchik AJ, 2005; Rodriguez-Bigas MA et al., 1996). If lymph metastases are not detected, it is advisable to search for micrometastases (MM) A great number of authors in the literature suggest that the presence of MM is a poor prognostic factor and therefore are indicative for adjuvant therapy which would improve the prognosis in these "troublesome" 30% of the patients "without metastases". The prognostic value of the metastases in CRC requires further investigations in the future. In their studies a number of authors confirm the prognostic value of MM (Broll R. et al., 1997; Greenson JK et al., 1994; Isaka N. et al., 1999; Palma RT et al., 2003; Yasuda K. et al., 2001; Liefers GJ et al., 1998), others aren't support this suggestion.  If the all LNs are to be investigated, the methods for micrometastases detection are costly, expensive and time consuming.  An algorithm was worked out for sentinel mapping in colorectal cancer. The dying method with Patent Blue V was used.

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 163

paraaortically, the obturatory fosses and along the course of the iliac vessels in order to

We applied the method of the sentinel mapping in five patients with CRC who had been

The SLN tagged by the surgeon are sent to the morphological laboratory together with the specimen where a routine processing to a paraffin block is performed with 10 resections in every 20-25µm. Immunohistochemistry with cytokeratin20 is performed per one resection (usually the fifth one). The remaining resections together with the preparations from the case are dyed with Hematoxilin-Eosin. Micrometastases are defined as a focus of tumor cells sized under 2 mm or a focus detected only by means of immunohistochemistry. (Feezor RJ

The statistical results were reported as detection rate of the sentinel lymph node, accuracy and sensitivity of the test, and false negative rate; formulas, for the assessment of these parameters were as follows: The staging benefit was calculated by comparison between *pN*  staging in the sentinel lymph node group and *pN* staging in the non-sentinel lymph node group. The comparison between groups was performed using the *chi-square* test; the significance was assumed for*p*<0.05 (95% confidence interval). The statistics were performed

detect SLN and the presence of atypical lymph drainage.

operated laparoscopically - figure 3.

**2.2 Morphological investigations**

using XLSTAT 2010 (Addinsoft 1995–2010).

Fig. 3. Laparoscopic view of a SLN.

et al., 2002)

**2.3 Statistical analysis**

Fig. 2. Algorithm for sentinel mapping in colorectal cancer.

After the laparotomy and the exploration of the abdominal cavity in the absence of distant metastases and no palpatory data for the presence of lymph metastases in patients with cancer of the rectum and the left colon, we performed intraoperative colonoscopy. By means of an endoscopic injector we applied submucosally 0,5-2 cc of Patent Blue V peritumorally on 2 to 4 locations. Since in right colon cancer the intraoperative colonoscopy to the caecum is technically difficult and is time-consuming, we injected the dye subserously in these tumor localizations by means of a needle and a syringe (0,5-2cc) peritumorally on 2 to 4 locations. In 1 to 10 minutes time the blue-stained lymph node(s) is visualized, connecting the primary tumor with blue-dyed sentinel lymph node(s). We assume the first 1-4 bluedyed lymph nodes to be sentinel and we mark them with ligatures. It is important that the procedure is performed accurately and precisely timed after the gradually coloring of the whole lymph basin, because the SLN can lose their color with time.

According to the tumor localization we perform thorough exploration of the regional lymph basin, the whole mesocolon, the stem of the mesenterial root of mesentery vessels and paraaortically, the obturatory fosses and along the course of the iliac vessels in order to detect SLN and the presence of atypical lymph drainage.

We applied the method of the sentinel mapping in five patients with CRC who had been operated laparoscopically - figure 3.

#### **2.2 Morphological investigations**

The SLN tagged by the surgeon are sent to the morphological laboratory together with the specimen where a routine processing to a paraffin block is performed with 10 resections in every 20-25µm. Immunohistochemistry with cytokeratin20 is performed per one resection (usually the fifth one). The remaining resections together with the preparations from the case are dyed with Hematoxilin-Eosin. Micrometastases are defined as a focus of tumor cells sized under 2 mm or a focus detected only by means of immunohistochemistry. (Feezor RJ et al., 2002)

#### **2.3 Statistical analysis**

162 Rectal Cancer – A Multidisciplinary Approach to Management

 Presence of cancer in another organ localization during the past 5 years, especially in the cases when the colorectal cancer is difficult to be differentiated histologically; Preceding Previous surgical interventions affecting the anatomy of the lymph basin;

Complicated colorectal cancer (emergency operation);

Fig. 2. Algorithm for sentinel mapping in colorectal cancer.

whole lymph basin, because the SLN can lose their color with time.

After the laparotomy and the exploration of the abdominal cavity in the absence of distant metastases and no palpatory data for the presence of lymph metastases in patients with cancer of the rectum and the left colon, we performed intraoperative colonoscopy. By means of an endoscopic injector we applied submucosally 0,5-2 cc of Patent Blue V peritumorally on 2 to 4 locations. Since in right colon cancer the intraoperative colonoscopy to the caecum is technically difficult and is time-consuming, we injected the dye subserously in these tumor localizations by means of a needle and a syringe (0,5-2cc) peritumorally on 2 to 4 locations. In 1 to 10 minutes time the blue-stained lymph node(s) is visualized, connecting the primary tumor with blue-dyed sentinel lymph node(s). We assume the first 1-4 bluedyed lymph nodes to be sentinel and we mark them with ligatures. It is important that the procedure is performed accurately and precisely timed after the gradually coloring of the

According to the tumor localization we perform thorough exploration of the regional lymph basin, the whole mesocolon, the stem of the mesenterial root of mesentery vessels and

Class ASA IV–V.

The statistical results were reported as detection rate of the sentinel lymph node, accuracy and sensitivity of the test, and false negative rate; formulas, for the assessment of these parameters were as follows: The staging benefit was calculated by comparison between *pN*  staging in the sentinel lymph node group and *pN* staging in the non-sentinel lymph node group. The comparison between groups was performed using the *chi-square* test; the significance was assumed for*p*<0.05 (95% confidence interval). The statistics were performed using XLSTAT 2010 (Addinsoft 1995–2010).

Fig. 3. Laparoscopic view of a SLN.

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 165

The mean number of the lymph nodes in the specimen is 14.7 in cancer of the colon vs. 13.2 in cancer of the rectum. The average number of SLN in cancer of the colon is 1.9 vs. 1.6 in cancer of the rectum. False negative results were reported in the presence of metastases, not detected in the SLN. We observed false negative results in 3 patients. All of them had large T4 tumors infiltrating adjacent organs. Therefore, we suggest that such patients are relatively contraindicated for sentinel mapping. In most cases the SLN were located in proximally to the primary tumor. One, two, three and four SLN were detected in 40%, 39%,

In spite of this we detected a presence of atypical lymph drainage with positive SLN outside the limits of the standard resection in 10 (10%) of the patients. In 3 out of these 10 patients the aberrant SLN were the only site of lymph metastases. In 5 patients we performed extended right hemicolectomy with the inclusion of the lineal flexure and its mesocolon

We extended the size of the lymph dissection in 5 patients with rectal cancer. In one of them we detected SLN in the root of inferior mesenteric atrery artery, which necessitated its high ligation with additional dissection around the root. In the remaining 4 cases we detected SLN in the left or right iliac region and we performed lateral lymph node dissection (Fig. 5). In the rest of the cases when no SLN or enlarged lymph nodes were detected in the lateral ligaments, obturatorialy fosses or along the iliac vessels, we did not consider appropriate to

On Figure 6, it is shown the visualization of direct lymph drainage from cancer of the rectum T2 to SLN from the IIIrd level in the root of inferior mesenteric artery. In the same patient the morphological investigation did not reveal metastases in any of the LN in the surgical preparation. The immunohistochemical study of the only SLN revealed MM, i.e. skip metastasing. In nine of the ten patients with extended resections were found metastases in the lymph nodes, and in one – no metastases. The analysis of the results shows that in 9 of 10 patients with extended resection, based on the results from the intraoperative sentinel lymph node mapping, were dissected metastatic sentinel lymph nodes located beyond the lines of the standard resection, by which we achieved surgical radicalism. In 7 patients with

19% and 2% of the patients, respectively.

Fig. 4. SLN in the region of flexura coli lienalis.

perform lateral lymph node dissection in patients with rectal cancer.

because we detected SLN in the region of the flexure (Fig. 4.).

### **3. Results**

The distribution of the patients is shown on Table 1. The relation between the T stage of the primary tumor and the presence of lymph metastases after sentinel mapping is shown on Table 2. Metastases were detected in 57% of the SLN (105 out of 184) as compared to 9% metastases incidence in the nonsentinel LN (198 out of 2208). In the absence of metastases in SLN the likelihood for metastases occurrence in the nonsentinel LN is only 0,6% (4 out of 657 nonsentinel LN). (Table 3)

Table 1. Distribution of patients according to cancer localization.

Table 2. Relation between tumor stage and metastases, including micrometastases.

Table 3. SLN in colorectal cancer – rate of success, rate of detection, false negative rate, rate of metastases only in SLN, rate of detected micrometastases (MM).

The distribution of the patients is shown on Table 1. The relation between the T stage of the primary tumor and the presence of lymph metastases after sentinel mapping is shown on Table 2. Metastases were detected in 57% of the SLN (105 out of 184) as compared to 9% metastases incidence in the nonsentinel LN (198 out of 2208). In the absence of metastases in SLN the likelihood for metastases occurrence in the nonsentinel LN is only 0,6% (4 out of

Table 1. Distribution of patients according to cancer localization.

Table 2. Relation between tumor stage and metastases, including micrometastases.

Table 3. SLN in colorectal cancer – rate of success, rate of detection, false negative rate, rate

of metastases only in SLN, rate of detected micrometastases (MM).

**3. Results**

657 nonsentinel LN). (Table 3)

The mean number of the lymph nodes in the specimen is 14.7 in cancer of the colon vs. 13.2 in cancer of the rectum. The average number of SLN in cancer of the colon is 1.9 vs. 1.6 in cancer of the rectum. False negative results were reported in the presence of metastases, not detected in the SLN. We observed false negative results in 3 patients. All of them had large T4 tumors infiltrating adjacent organs. Therefore, we suggest that such patients are relatively contraindicated for sentinel mapping. In most cases the SLN were located in proximally to the primary tumor. One, two, three and four SLN were detected in 40%, 39%, 19% and 2% of the patients, respectively.

In spite of this we detected a presence of atypical lymph drainage with positive SLN outside the limits of the standard resection in 10 (10%) of the patients. In 3 out of these 10 patients the aberrant SLN were the only site of lymph metastases. In 5 patients we performed extended right hemicolectomy with the inclusion of the lineal flexure and its mesocolon because we detected SLN in the region of the flexure (Fig. 4.).

Fig. 4. SLN in the region of flexura coli lienalis.

We extended the size of the lymph dissection in 5 patients with rectal cancer. In one of them we detected SLN in the root of inferior mesenteric atrery artery, which necessitated its high ligation with additional dissection around the root. In the remaining 4 cases we detected SLN in the left or right iliac region and we performed lateral lymph node dissection (Fig. 5). In the rest of the cases when no SLN or enlarged lymph nodes were detected in the lateral ligaments, obturatorialy fosses or along the iliac vessels, we did not consider appropriate to perform lateral lymph node dissection in patients with rectal cancer.

On Figure 6, it is shown the visualization of direct lymph drainage from cancer of the rectum T2 to SLN from the IIIrd level in the root of inferior mesenteric artery. In the same patient the morphological investigation did not reveal metastases in any of the LN in the surgical preparation. The immunohistochemical study of the only SLN revealed MM, i.e. skip metastasing. In nine of the ten patients with extended resections were found metastases in the lymph nodes, and in one – no metastases. The analysis of the results shows that in 9 of 10 patients with extended resection, based on the results from the intraoperative sentinel lymph node mapping, were dissected metastatic sentinel lymph nodes located beyond the lines of the standard resection, by which we achieved surgical radicalism. In 7 patients with

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 167

cases we followed the protocol on Fig. 7. 100% success rate without false-negative results was achieved by adherence to the protocol of procedure in the cases with immediate postoperative detection (Fig. 8). The only disadvantage in these 7 patients is the presence of higher number SLN (3-5) average 3.6 vs. 1.6 in the patients with intraoperative detection, which is explained with delay in the detection with average 20 minutes, during which time

The practical application of the method is facilitated with the following additional methods:

The intraoperative detection of SLN in rectal cancer is easy, because the blue-stained SLN are in contrast with the yellowish fatty tissue and gain distinction during exploration of the pelvis and are visible through the mesorectal fascia. The visualization of SLN in the mesorectum is helped by transilumination of the mesorectum with halogen light from the

**4.1 Method for immediate ex vivo detection of mesorectal SLN after failure of the**

fibrocolonoscope. The first stained SLN in the mesorectum are easily found.

Fig. 7. Algorithm for immediate detection of SLN in the specimen.

the dye has spread to more lymph nodes.

**intraoperative detection.**

**4. Additional methods of sentinel lymph node mapping**

rectal cancer intraoperative visual detection of SLN during mobilization of the rectum was impeded even after additional introduction of the colonoscope in the mobilized rectum and transilumination, probably due to the fatty tissue and insufficient staining of the SLN.

Fig. 5. SLN in the left ilac region – lateral lymph node dissection.

Fig. 6. Direct lymph drainage from the tumor to the root of inferior mesenteric artery. Case of SLN with micrometastasis – example of skip metastasing.

In the same patients we performed detection of the SLN in the mesorectum after destruction of the fascial layers in the presence of pathologist immediately after the resection of the rectum in the operation room. The detection of the SLN was preceded by making biopsy of the circumferential margin, which is an important predictive factor for the disease. In these 7

rectal cancer intraoperative visual detection of SLN during mobilization of the rectum was impeded even after additional introduction of the colonoscope in the mobilized rectum and transilumination, probably due to the fatty tissue and insufficient staining of the SLN.

Fig. 5. SLN in the left ilac region – lateral lymph node dissection.

of SLN with micrometastasis – example of skip metastasing.

Fig. 6. Direct lymph drainage from the tumor to the root of inferior mesenteric artery. Case

In the same patients we performed detection of the SLN in the mesorectum after destruction of the fascial layers in the presence of pathologist immediately after the resection of the rectum in the operation room. The detection of the SLN was preceded by making biopsy of the circumferential margin, which is an important predictive factor for the disease. In these 7 cases we followed the protocol on Fig. 7. 100% success rate without false-negative results was achieved by adherence to the protocol of procedure in the cases with immediate postoperative detection (Fig. 8). The only disadvantage in these 7 patients is the presence of higher number SLN (3-5) average 3.6 vs. 1.6 in the patients with intraoperative detection, which is explained with delay in the detection with average 20 minutes, during which time the dye has spread to more lymph nodes.

#### **4. Additional methods of sentinel lymph node mapping**

The practical application of the method is facilitated with the following additional methods:

#### **4.1 Method for immediate ex vivo detection of mesorectal SLN after failure of the intraoperative detection.**

The intraoperative detection of SLN in rectal cancer is easy, because the blue-stained SLN are in contrast with the yellowish fatty tissue and gain distinction during exploration of the pelvis and are visible through the mesorectal fascia. The visualization of SLN in the mesorectum is helped by transilumination of the mesorectum with halogen light from the fibrocolonoscope. The first stained SLN in the mesorectum are easily found.

Fig. 7. Algorithm for immediate detection of SLN in the specimen.

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 169

a) b)

c)

pN0 (n) pN1 (n) pN2 (n)

Fig. 9. a),b),c) Intraoperative view of the additional lymph node mapping.

Table 4. Relation of number patients to pT and pN

pT1 18,3 (n = 10) 17,2 (n = 4) –

pT2 17,2 (n = 35) 14,2 (n = 11) 16,1 (n = 5)

pT3 17,6 (n = 19) 16,5 (n = 16) 16,8 (n = 22)

pT4 – 12,1 (n = 7) 12,4 (n = 7)

From these data it is understood, that no clear relation between the tumor infiltration (pT) and the number of metastatic lymph nodes (pN). In pN0 the largest and the least number of examined lymph nodes was established in рТ1 and рТ2 tumors. A larger number of examined lymph nodes are found in patients with pT3 pN2 tumors, comparable to the number of examined lymph nodes in рТ3 рN0 and рТ3 рN1 tumors. The data for the

pN

pT

Fig. 8. Method of immediate postoperative detection. a) the SLN are not visible through fascia propria recti; b)after removal of fascia propria recti one SLN was visualized in the mesorectum; c) the visualized SLN – close view.

#### **4.2 Application of the method of additional lymph node mapping**

An existing problem remains the examination of insufficient number of lymph nodes in patients with colorectal cancer. This leads to decreased probability for discovery of metastatic lymph nodes and inaccurate staging. The main reason is the small size of the lymph nodes, which are not found by palpation in the fatty tissue of the specimen. Aiming maximal increase in the number of discovered and examined lymph nodes we developed method for additional lymph mapping of the specimen and we evaluated the results together with a pathologist. The method of additional lymph mapping was applied in 103 patients with colorectal cancer and SLN mapping. The method was applied on fresh specimen immediately in the operating room. Intraoperative SLN mapping has been performed and the SLN were identified and marked with ligatures. Additionally 2-3cc Patent Blue V was applied subserosally and submucosally. This method vastly stains the whole lymph node basin. Fig 9. (a,b,c)

#### **4.3 Results from the additional methods**

The results we achieved show that the lymphatic system of the specimen facilitates the spread of the dye. In postoperative lymph node mapping the dye stains vastly the lymph nodes and the lymphatic vessels. The evaluation of the lymphatic status in colorectal cancer relies not only on quantitative criteria, e.g. number of examined lymph nodes, but also on qualitative characteristics on the lymph nodes: their size, distance from the primary tumor, sentinel or non-sentinel lymph nodes.

After analyzing the data from the morphological examination after application of the intraoperative SLN mapping and the additional lymph nodes mapping of the specimen we achieved the following results. The number and the average number of examined lymph nodes in relation to pT and pN is shown on Table 4.

a) b) c) Fig. 8. Method of immediate postoperative detection. a) the SLN are not visible through fascia propria recti; b)after removal of fascia propria recti one SLN was visualized in the

An existing problem remains the examination of insufficient number of lymph nodes in patients with colorectal cancer. This leads to decreased probability for discovery of metastatic lymph nodes and inaccurate staging. The main reason is the small size of the lymph nodes, which are not found by palpation in the fatty tissue of the specimen. Aiming maximal increase in the number of discovered and examined lymph nodes we developed method for additional lymph mapping of the specimen and we evaluated the results together with a pathologist. The method of additional lymph mapping was applied in 103 patients with colorectal cancer and SLN mapping. The method was applied on fresh specimen immediately in the operating room. Intraoperative SLN mapping has been performed and the SLN were identified and marked with ligatures. Additionally 2-3cc Patent Blue V was applied subserosally and submucosally. This method vastly stains the

The results we achieved show that the lymphatic system of the specimen facilitates the spread of the dye. In postoperative lymph node mapping the dye stains vastly the lymph nodes and the lymphatic vessels. The evaluation of the lymphatic status in colorectal cancer relies not only on quantitative criteria, e.g. number of examined lymph nodes, but also on qualitative characteristics on the lymph nodes: their size, distance from the primary tumor,

After analyzing the data from the morphological examination after application of the intraoperative SLN mapping and the additional lymph nodes mapping of the specimen we achieved the following results. The number and the average number of examined lymph

mesorectum; c) the visualized SLN – close view.

whole lymph node basin. Fig 9. (a,b,c)

sentinel or non-sentinel lymph nodes.

nodes in relation to pT and pN is shown on Table 4.

**4.3 Results from the additional methods**

**4.2 Application of the method of additional lymph node mapping**

a) b)

Fig. 9. a),b),c) Intraoperative view of the additional lymph node mapping.

Table 4. Relation of number patients to pT and pN

From these data it is understood, that no clear relation between the tumor infiltration (pT) and the number of metastatic lymph nodes (pN). In pN0 the largest and the least number of examined lymph nodes was established in рТ1 and рТ2 tumors. A larger number of examined lymph nodes are found in patients with pT3 pN2 tumors, comparable to the number of examined lymph nodes in рТ3 рN0 and рТ3 рN1 tumors. The data for the

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 171

metastatic lymph nodes in 98% of the cases. The data show that the closer the lymph node to

The examination of higher number of lymph nodes is connected with increased possibility for more accurate evaluation of the lymphatic status. The application of the method made it possible to detect more than 12 lymph nodes in the specimen and to shorten the time for

Fig. 11. Thirty-eight stained lymph nodes subject to morphological evaluation from a rectal

Coecum 12 17,1 27,5 Ascendens 6 16,2 22,1 Hepatic 4 19,7 27,2 Transversum 5 17,3 23,4 Lienalis 1 13,2 15,8 Descendens 9 15,4 25 Sigma 28 12,8 21,2 Rectum 71 14,7 15,7 **Total 136 17 22,2**

Table 6. Number of patients, average number of lymph nodes and average length of the

lymph nodes

Average length of the specimen

Localization Number of patients Average number of

specimen in relation to the tumor localization.

detecting of maximal number lymph nodes in examination of the specimen. Fig. 11

the tumor is, the higher its metastatic potential is.

cancer specimen.

number of patients, average number of examined lymph nodes and the length of the specimen in relation to the tumor localization are shown on Table 5.

Table 5. Relation of the average number of examined LN in relation to T/N

We analyzed the data in relation to the size of the examined lymph nodes, the distance from the primary tumor and the localization of the lymph nodes in relation to the rest of the lymph nodes and the primary tumor. The average size of the examined lymph nodes was 4.5mm. The average size of the lymph nodes in colorectal cancer with presence of lymph metastases was larger – 4.7mm in comparison to 4.3mm without presence of lymph metastases, as 53% of the metastatic lymph nodes are less than 5mm.

Along with the size of the examined lymph nodes the distance of the lymph node from the primary tumor and its localization in the mesocolon or the mesorectum also have relationship to the metastatic potential of the lymph node. We analyzed the results in relation to the localization of the sentinel lymph nodes in patients with colorectal cancer. The results for the localization of the SLN are shown on Figure 10.

Fig. 10. a) in 73% of the cases the SLN are localized solely in the pericolic or the perirectal fatty tissue. b) in 24% of the cases the SLN are localized simultaneously on the first and upper levels. c) in 3% of the cases the SLN are localized on the second level.

We established that the average size of the metastatic lymph nodes was larger than that of the non-metastatic lymph nodes. As in 53% of the metastatic lymph nodes their size is less than 5mm, the size is not a certain criteria for evaluating its metastatic potential.

Significantly promising criteria is the result after application of diagnostic method for evaluation of the lymphatic status – intraoperative SLN mapping, which discovers

number of patients, average number of examined lymph nodes and the length of the

pT1 10 4 0 **14**  pT2 35 11 5 **51**  pT3 19 16 22 **57**  pT4 0 7 7 **14 Total 64 38 34 136**

We analyzed the data in relation to the size of the examined lymph nodes, the distance from the primary tumor and the localization of the lymph nodes in relation to the rest of the lymph nodes and the primary tumor. The average size of the examined lymph nodes was 4.5mm. The average size of the lymph nodes in colorectal cancer with presence of lymph metastases was larger – 4.7mm in comparison to 4.3mm without presence of lymph

Along with the size of the examined lymph nodes the distance of the lymph node from the primary tumor and its localization in the mesocolon or the mesorectum also have relationship to the metastatic potential of the lymph node. We analyzed the results in relation to the localization of the sentinel lymph nodes in patients with colorectal cancer.

Fig. 10. a) in 73% of the cases the SLN are localized solely in the pericolic or the perirectal fatty tissue. b) in 24% of the cases the SLN are localized simultaneously on the first and

We established that the average size of the metastatic lymph nodes was larger than that of the non-metastatic lymph nodes. As in 53% of the metastatic lymph nodes their size is less

Significantly promising criteria is the result after application of diagnostic method for evaluation of the lymphatic status – intraoperative SLN mapping, which discovers

upper levels. c) in 3% of the cases the SLN are localized on the second level.

than 5mm, the size is not a certain criteria for evaluating its metastatic potential.

Table 5. Relation of the average number of examined LN in relation to T/N

metastases, as 53% of the metastatic lymph nodes are less than 5mm.

The results for the localization of the SLN are shown on Figure 10.

pN0 pN1 pN2 **Total**

specimen in relation to the tumor localization are shown on Table 5.

pN

pT

metastatic lymph nodes in 98% of the cases. The data show that the closer the lymph node to the tumor is, the higher its metastatic potential is.

The examination of higher number of lymph nodes is connected with increased possibility for more accurate evaluation of the lymphatic status. The application of the method made it possible to detect more than 12 lymph nodes in the specimen and to shorten the time for detecting of maximal number lymph nodes in examination of the specimen. Fig. 11

Fig. 11. Thirty-eight stained lymph nodes subject to morphological evaluation from a rectal cancer specimen.

Table 6. Number of patients, average number of lymph nodes and average length of the specimen in relation to the tumor localization.

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 173

aberrant lymphatic drainage in 2% of patients and skip metastases in 3% of patients with lymph mapping. We expanded the volume of surgical procedure in 7% of the patients in which positive lymph nodes were detected beyond standard lymphatic dissection. In three of them skip metastases were observed and in other three patients was observed aberrant lymphatic drainage. All the patients' sentinel lymph nodes revealed the presence of

The examination of insufficient number of lymph nodes is the reason leading to a reduced chance of detection of metastatic lymph nodes and inaccurate staging of the disease. The cause is the small size of lymph nodes that are not detected by palpation in adipose tissue of the specimen. Our results from the application of the method of additional lymph node mapping indicate that it allows quickly discovering and exploring the maximum number of lymph nodes and contributes to the precise staging of colorectal cancer. We found that the average size of metastatic lymph nodes was 4.7 mm. Our results show that the lymphatic system of the specimen has potential for diffusion of the dye. The postoperative lymph node

We found that in case of right colon cancer it is appropriate to apply the method of intraoperative subserosal SLN mapping. The rectal cancer and the left colon cancer are more suitable to perform intraoperative colonoscopy and to apply the method of intraoperative endoscopic submucous sentinel marking. The analysis of the results from the application of the methods of intraoperative endoscopic submucous SLN mapping and intraoperative subserous SLN mapping indicates that both methods are equally reliable and highly sensitive. Additionally the method of intraoperative SLN mapping is equally applicable to

The ultrastaging of sentinel lymph nodes aids the accurate staging and treatment of patients with colorectal cancer. By application of the method of intraoperative sentinel marking and the ultrastaging of lymph nodes is achieved upstaging of the disease and determination of

The method is convenient because it is not related to the need for expensive equipment and supplies and does not require a complex organization, the training of the surgeons is easy

Our own results and literature data show that intraoperative SLN mapping is a method with high success rate and sensitivity for intraoperative diagnosis of the lymph status. The surgical approach and the volume of lymphatic dissection should respond to the state of the lymphatic basin, estimated using an objective diagnostic method such as intraoperative SLN mapping. This leads to an increase of surgical radicalism in the

Surgeons and oncologists are aware that ensuring of optimal conditions for patients with colorectal cancer requires precise surgery, if necessary combined with adjuvant therapy. In order to provide quality treatment for colorectal cancer a multidisciplinary team including GPs, surgeons, imaging diagnostic specialists, gastroenterologists, oncologists and

SLN mapping increases the number of collected lymph nodes, as well as the sensitivity of nodal assessment. In addition, in cases with aberrant lymph drainage extensive resection is performed, containing remote SLN. A multidisciplinary approach is required to standardize the detection and assessment of the SLN, contributing to colorectal cancer staging. Detection of micrometastases in the lymph nodes is generally recognized as pN1(mi), but the risk of

metastases or micrometastases after ultrastaging.

mapping stains the lymphatic vessels and the lymph nodes.

patients with colon and rectal cancer.

pathologist, etc is required.

exact definitive diagnosis in 20% of patients.

and the staff readily agrees for application of the method.

treatment of colorectal cancer, which is proved in our study.

#### **5. Discussion**

Surgical treatment is the basis of the complex therapeutic approach aimed at a lasting cure for patients with colorectal cancers. The quality of surgery is determined apart from the choice of appropriate operating method, but also the characteristics of the tumor in his lymph drainage and possibilities of preoperative and intraoperative staging.

Carrying out an operation with adequate volume fulfils the oncologic criteria and is a prerequisite for precise morphological staging of cancer, which determines the postoperative treatment. Treatment of colorectal cancer is the most successful in stages I and II of the disease before the tumor is metastatic.

The consequences of inaccurate assessment of lymph status lead to development of recurrence in one third of operated patients with "nonmetastatic" colorectal cancers.

The lymph node status is the most important prognostic factor in colorectal cancer. Not always and everywhere can be done accurate preoperative assessment of the lymph status. Clinical examination and intraoperative exploration are only indicative and have relatively low sensitivity and specificity. Prompt intraoperative histological examination has low sensitivity and cannot detect the presence of lymph node micrometastases.

Leaving metastatic lymph nodes located beyond the standard lymph dissection is the cause for recurrence after the radical surgery. The problem is the lack of method for intraoperative assessment of atypical lymphatic drainage. (Bilchik AJ et al., 2001) According to the literature metastatic lymph nodes in the presence of aberrant lymphatic drainage can be found beyond the standard volume of lymph node dissection. In these cases the oncologic principles require to expand the volume of lymph node dissection. (Kitagawa Y. et al., 2004) SLN mapping changes the volume of resection in 8% of cases. Aberrant drainage is not uncommon in patients with tumors of the digestive tract (Cohen, AM et al., 1993). Some authors (Yamamoto, Y. et al., 1998) shows metastasis in 10% of 452 patients with colorectal cancers. Aberrant lymphatic drainage is found in 29% of cases (Bilchik, A J,& Trocha SD, 2003 ) and may later expand the volume of resection (Bilchik AJ et al., 2001), therefore all the blue stained lymph nodes must be accurately located and marked. Regional lymphatic basin of the colon is removed and sent for morphological examination. Reported values for the successful SLN localization ranged from 58 to 100%. (Bilchik AJ et al., 2001; Bilchik AJ et al., 2003; Tsioulias GJ et al., 2002) Applying this method we achieved success in about 94% of cases. Another important advantage of in vivo SLN mapping in colorectal cancer is detection of patients with aberrant lymphatic drainage occuring in 14% of the cases leading to a change in the initial operational plan (Wood TF et al., 2001). The reccurence in nodalnegative patients is attributed to residual nodal disease after inadequate lymphadenectomy or aberrant lymphatic drainage. (Prandi M. e al., 2002; Schrag, D. et al. 2002) Aberrant lymphatic drainage can be due to anatomical variations or due to altered lymph drainage caused by metastatic involvement of the lymphatic system (Bilchik AJ et al., 2001; Bilchik AJ et al., 2003; Saha S. et al., 2001). In colorectal cancer the standard oncological resection is recommended regardless of the status of SLN. Sometimes, however, it appears that aberrant drainage continues beyond the normal lines of resection. This unusual pattern of lymph drainage was observed in 8% of patients with CRC, where the lines of the lymphatic and organ resection should be extended beyond the conventional (Saha, S. et al. 2004).

The method of intraoperative SLN mapping achieves better intraoperative visualization of the lymph nodes with the highest metastatic potential even if they are very small and detects the presence of aberrant lymphatic drainage and skip metastases. Our study found

Surgical treatment is the basis of the complex therapeutic approach aimed at a lasting cure for patients with colorectal cancers. The quality of surgery is determined apart from the choice of appropriate operating method, but also the characteristics of the tumor in his

Carrying out an operation with adequate volume fulfils the oncologic criteria and is a prerequisite for precise morphological staging of cancer, which determines the postoperative treatment. Treatment of colorectal cancer is the most successful in stages I and

The consequences of inaccurate assessment of lymph status lead to development of

The lymph node status is the most important prognostic factor in colorectal cancer. Not always and everywhere can be done accurate preoperative assessment of the lymph status. Clinical examination and intraoperative exploration are only indicative and have relatively low sensitivity and specificity. Prompt intraoperative histological examination has low

Leaving metastatic lymph nodes located beyond the standard lymph dissection is the cause for recurrence after the radical surgery. The problem is the lack of method for intraoperative assessment of atypical lymphatic drainage. (Bilchik AJ et al., 2001) According to the literature metastatic lymph nodes in the presence of aberrant lymphatic drainage can be found beyond the standard volume of lymph node dissection. In these cases the oncologic principles require to expand the volume of lymph node dissection. (Kitagawa Y. et al., 2004) SLN mapping changes the volume of resection in 8% of cases. Aberrant drainage is not uncommon in patients with tumors of the digestive tract (Cohen, AM et al., 1993). Some authors (Yamamoto, Y. et al., 1998) shows metastasis in 10% of 452 patients with colorectal cancers. Aberrant lymphatic drainage is found in 29% of cases (Bilchik, A J,& Trocha SD, 2003 ) and may later expand the volume of resection (Bilchik AJ et al., 2001), therefore all the blue stained lymph nodes must be accurately located and marked. Regional lymphatic basin of the colon is removed and sent for morphological examination. Reported values for the successful SLN localization ranged from 58 to 100%. (Bilchik AJ et al., 2001; Bilchik AJ et al., 2003; Tsioulias GJ et al., 2002) Applying this method we achieved success in about 94% of cases. Another important advantage of in vivo SLN mapping in colorectal cancer is detection of patients with aberrant lymphatic drainage occuring in 14% of the cases leading to a change in the initial operational plan (Wood TF et al., 2001). The reccurence in nodalnegative patients is attributed to residual nodal disease after inadequate lymphadenectomy or aberrant lymphatic drainage. (Prandi M. e al., 2002; Schrag, D. et al. 2002) Aberrant lymphatic drainage can be due to anatomical variations or due to altered lymph drainage caused by metastatic involvement of the lymphatic system (Bilchik AJ et al., 2001; Bilchik AJ et al., 2003; Saha S. et al., 2001). In colorectal cancer the standard oncological resection is recommended regardless of the status of SLN. Sometimes, however, it appears that aberrant drainage continues beyond the normal lines of resection. This unusual pattern of lymph drainage was observed in 8% of patients with CRC, where the lines of the lymphatic and

recurrence in one third of operated patients with "nonmetastatic" colorectal cancers.

lymph drainage and possibilities of preoperative and intraoperative staging.

sensitivity and cannot detect the presence of lymph node micrometastases.

organ resection should be extended beyond the conventional (Saha, S. et al. 2004).

The method of intraoperative SLN mapping achieves better intraoperative visualization of the lymph nodes with the highest metastatic potential even if they are very small and detects the presence of aberrant lymphatic drainage and skip metastases. Our study found

II of the disease before the tumor is metastatic.

**5. Discussion**

aberrant lymphatic drainage in 2% of patients and skip metastases in 3% of patients with lymph mapping. We expanded the volume of surgical procedure in 7% of the patients in which positive lymph nodes were detected beyond standard lymphatic dissection. In three of them skip metastases were observed and in other three patients was observed aberrant lymphatic drainage. All the patients' sentinel lymph nodes revealed the presence of metastases or micrometastases after ultrastaging.

The examination of insufficient number of lymph nodes is the reason leading to a reduced chance of detection of metastatic lymph nodes and inaccurate staging of the disease. The cause is the small size of lymph nodes that are not detected by palpation in adipose tissue of the specimen. Our results from the application of the method of additional lymph node mapping indicate that it allows quickly discovering and exploring the maximum number of lymph nodes and contributes to the precise staging of colorectal cancer. We found that the average size of metastatic lymph nodes was 4.7 mm. Our results show that the lymphatic system of the specimen has potential for diffusion of the dye. The postoperative lymph node mapping stains the lymphatic vessels and the lymph nodes.

We found that in case of right colon cancer it is appropriate to apply the method of intraoperative subserosal SLN mapping. The rectal cancer and the left colon cancer are more suitable to perform intraoperative colonoscopy and to apply the method of intraoperative endoscopic submucous sentinel marking. The analysis of the results from the application of the methods of intraoperative endoscopic submucous SLN mapping and intraoperative subserous SLN mapping indicates that both methods are equally reliable and highly sensitive. Additionally the method of intraoperative SLN mapping is equally applicable to patients with colon and rectal cancer.

The ultrastaging of sentinel lymph nodes aids the accurate staging and treatment of patients with colorectal cancer. By application of the method of intraoperative sentinel marking and the ultrastaging of lymph nodes is achieved upstaging of the disease and determination of exact definitive diagnosis in 20% of patients.

The method is convenient because it is not related to the need for expensive equipment and supplies and does not require a complex organization, the training of the surgeons is easy and the staff readily agrees for application of the method.

Our own results and literature data show that intraoperative SLN mapping is a method with high success rate and sensitivity for intraoperative diagnosis of the lymph status.

The surgical approach and the volume of lymphatic dissection should respond to the state of the lymphatic basin, estimated using an objective diagnostic method such as intraoperative SLN mapping. This leads to an increase of surgical radicalism in the treatment of colorectal cancer, which is proved in our study.

Surgeons and oncologists are aware that ensuring of optimal conditions for patients with colorectal cancer requires precise surgery, if necessary combined with adjuvant therapy. In order to provide quality treatment for colorectal cancer a multidisciplinary team including GPs, surgeons, imaging diagnostic specialists, gastroenterologists, oncologists and pathologist, etc is required.

SLN mapping increases the number of collected lymph nodes, as well as the sensitivity of nodal assessment. In addition, in cases with aberrant lymph drainage extensive resection is performed, containing remote SLN. A multidisciplinary approach is required to standardize the detection and assessment of the SLN, contributing to colorectal cancer staging. Detection of micrometastases in the lymph nodes is generally recognized as pN1(mi), but the risk of

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 175

examination of the SN allows the pathologist to focus on the regional node(s) most likely to contain tumor cells and thus improve tumor cell detection and accuracy of staging. The tumor occludes the lymphatic vessels resulting in drainage to another (nonsentinel) node. Because these nodes are large and solid, it is unlikely that SN and lymphatic mapping will be of value in this group of patients. The prognostic significance of nodal micrometastases by either CK-IHC or RT-PCR in CRC remains unclear. In a recent study in patients initially reported as node negative, re-examination using CK-IHC and carcinoembryonic antigen (CEA)-IHC demonstrated evidence of micrometastases in 26% of the node negative patients (Bilchik et al., 2001). However, the presence of nodal micrometastases did not significantly affect 5-year survival. Similarly, Jeffers (Jeffers MD et al., 1994) detected CK-IHC micrometastases in 25% of 77 patients who's CRCs were initially staged as Duke's B. Again, the presence of nodal micrometastases had no significant effect on survival; however, random micro sectioning may have missed tumor cells, thereby causing insignificant survival differences between the two groups. More recently, Greenson (Greenson JK et al., 1994) demonstrated that micrometastatic disease missed by routine HE staining but identified by CK-IHC had an adverse effect on survival. The lack of consensus in the literature in part reflects the absence of standard antibody titers and staining techniques; there are considerable interinstitutional variations in the analysis of CRC lymph nodes by CK-IHC. Although to date no randomized study has demonstrated significance for the detection of micrometastases by CKIHC, the American College of Surgeons Oncology Group currently is conducting a multicenter trial (Z-0010) to assess the utility of CK-IHC in detecting micrometastases, of SNs draining primary breast carcinoma. Clinical outcome studies of marker expression in CRC are also limited. Hayashi (Hayashi N. et al., 1995) demonstrated decreased survival in patients with p53 or K-ras mutations in colonic lymph nodes. In another study of patients whose CRC was staged Duke's B by conventional techniques, Liefers (Liefers GJ et al., 1998) reported a 5-year survival rate of 50% for patients whose nodes expressed CEA, versus 91% for those whose nodes did not express CEA. Several other investigators have reported that histologically negative lymph nodes contained evidence of occult metastases by RT-PCR using CK20 30 or guanylyl cyclase C 31 in qualitative assay systems. However, guanylyl cyclase C, CEA, and cytokeratin are expressed by normal tissues and therefore may introduce false-positive results. Our group and others have questioned their utility for the detection of micrometastatic CRC. Our approach has been to use a combination of mRNA markers in a semi-quantitative assay to detect occult micrometastases. Focused analysis of multiple sections of the SN by CK-IHC and RT-PCR provides a unique tool for accurate staging of CRC. As demonstrated in our study, lymphatic mapping of the SN also can identify unexpected nodal drainage patterns that alter the margins of surgical resection. Focused examination of SN diagnoses micrometastatic disease missed by conventional techniques. Although the significance of micrometastatic disease is yet to be defined in CRC, it is likely to be an important stratifying

factor in choosing those who may benefit from adjuvant chemotherapy

The method is an objective criterion for intraoperative surgical behavior.

The method of intraoperative SLN mapping using Patent Blue V is an accurate and objective diagnostic method for assessment of the lymphatic status in patients with colorectal cancer.

**6. Conclusions**

recurrence is unknown. Large prospective studies are essential to determine the clinical significance of nodal micrometastases. The introduction of coordinated screening programs for low-risk patients or tracking of high-risk patients, the application of more sensitive methods for preoperative staging, the advance in treatment and methods of morphological evaluation create opportunities for improving the survival and the quality of life of patients with colorectal cancers.

The accuracy may increase with the increasing of the number of lymph nodes sectioned, and with involving of immunohistochemistry or molecular markers' panels as demonstrated in many studies, but will also increase the cost and the workload for pathologists (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Kelder W. et al., 2007). Even though the accuracy was good for colon and rectal cancer, the sensitivity of the method somewhere is reported very low (66.66% for colon and 50% for rectal cancer), and the false-negative rate was high (23.07% for colon cancer and 18.18% for rectal cancer). The sensitivity of the method varies in the literature between 54% in the study of the Bembenek , and 88.2–89% in the study of Bilchik AJ *et al.*, and Kelder W *et al.* (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Kelder W. et al., 2007). The smallest false-negative rate was achieved by Bilchick AJ *et al.* (7.4%), but other authors reported a significantly higher rate of false-negative results (46% for colon cancer in the study of Bembenek AE *et al.* and 43% in rectal cancer in the study of Baton O *et al.*) (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Baton O. et al., 2005). Thus, with such high risk of failure (lower detection rate, low sensitivity and high false-negativity rate), the technique of sentinel lymph node in rectal cancer is obviously not feasible; in colon cancer, the method may be improved by increasing the number of the examined lymph nodes, and using specific immunohistochemical staining methods. However, doing so, it will not represent a relief for pathologist, but probably will increase the quality of the *pN* staging. In this matter, our study has shown an increase in the detection of the positive lymph nodes (37.2% *N+* in sentinel lymph node group *vs.* 26.67% in the control group), but statistical significance was not reached. Moreover, the quality of the upstaging was not determined by the examination technique itself (micrometastases were detected in only two cases – 9.37% upstaging rate), but probably by the increased number of the identified and examined lymph nodes in the studied group *vs.* comparison group (the blue staining of the lymph node in the study group made it easy to identify them, and probably an increasing awareness and close collaboration between the surgeon and pathologist) (Bilchik AJ&Compton C., 2007). In literature, there are better results in upstaging the *pN* category, using the sentinel lymph node technique, varying from 15% for rectal cancer (Baton O *et al., 2005*) to 18–23.6% in colon cancer (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Kelder W. et al., 2007).

The high incidence of distant metastasis of CRC in patients whose nodes are negative may be due to insufficient numbers or sections of lymph nodes. Bilchik A.&Compton C., 2007 Because multiple sectioning and IHC staining cannot be routinely used to examine all lymph nodes in a CRC specimen, we focused on the first regional node(s) to receive lymphatic drainage from a primary tumor. In melanoma and breast cancer, lymphatic mapping and excision of the SN is used to determine the tumor status of the entire nodal basin and avoid complete lymph node dissection in node-negative patients. The application of the SN technique in CRC is different because all regional lymph nodes are routinely removed en bloc with the primary tumor. However, as in melanoma and breast cancer, examination of the SN allows the pathologist to focus on the regional node(s) most likely to contain tumor cells and thus improve tumor cell detection and accuracy of staging. The tumor occludes the lymphatic vessels resulting in drainage to another (nonsentinel) node.

Because these nodes are large and solid, it is unlikely that SN and lymphatic mapping will be of value in this group of patients. The prognostic significance of nodal micrometastases by either CK-IHC or RT-PCR in CRC remains unclear. In a recent study in patients initially reported as node negative, re-examination using CK-IHC and carcinoembryonic antigen (CEA)-IHC demonstrated evidence of micrometastases in 26% of the node negative patients (Bilchik et al., 2001). However, the presence of nodal micrometastases did not significantly affect 5-year survival. Similarly, Jeffers (Jeffers MD et al., 1994) detected CK-IHC micrometastases in 25% of 77 patients who's CRCs were initially staged as Duke's B. Again, the presence of nodal micrometastases had no significant effect on survival; however, random micro sectioning may have missed tumor cells, thereby causing insignificant survival differences between the two groups. More recently, Greenson (Greenson JK et al., 1994) demonstrated that micrometastatic disease missed by routine HE staining but identified by CK-IHC had an adverse effect on survival. The lack of consensus in the literature in part reflects the absence of standard antibody titers and staining techniques; there are considerable interinstitutional variations in the analysis of CRC lymph nodes by CK-IHC. Although to date no randomized study has demonstrated significance for the detection of micrometastases by CKIHC, the American College of Surgeons Oncology Group currently is conducting a multicenter trial (Z-0010) to assess the utility of CK-IHC in detecting micrometastases, of SNs draining primary breast carcinoma. Clinical outcome studies of marker expression in CRC are also limited. Hayashi (Hayashi N. et al., 1995) demonstrated decreased survival in patients with p53 or K-ras mutations in colonic lymph nodes. In another study of patients whose CRC was staged Duke's B by conventional techniques, Liefers (Liefers GJ et al., 1998) reported a 5-year survival rate of 50% for patients whose nodes expressed CEA, versus 91% for those whose nodes did not express CEA. Several other investigators have reported that histologically negative lymph nodes contained evidence of occult metastases by RT-PCR using CK20 30 or guanylyl cyclase C 31 in qualitative assay systems. However, guanylyl cyclase C, CEA, and cytokeratin are expressed by normal tissues and therefore may introduce false-positive results. Our group and others have questioned their utility for the detection of micrometastatic CRC. Our approach has been to use a combination of mRNA markers in a semi-quantitative assay to detect occult micrometastases. Focused analysis of multiple sections of the SN by CK-IHC and RT-PCR provides a unique tool for accurate staging of CRC. As demonstrated in our study, lymphatic mapping of the SN also can identify unexpected nodal drainage patterns that alter the margins of surgical resection. Focused examination of SN diagnoses micrometastatic disease missed by conventional techniques. Although the significance of micrometastatic disease is yet to be defined in CRC, it is likely to be an important stratifying factor in choosing those who may benefit from adjuvant chemotherapy

#### **6. Conclusions**

174 Rectal Cancer – A Multidisciplinary Approach to Management

recurrence is unknown. Large prospective studies are essential to determine the clinical significance of nodal micrometastases. The introduction of coordinated screening programs for low-risk patients or tracking of high-risk patients, the application of more sensitive methods for preoperative staging, the advance in treatment and methods of morphological evaluation create opportunities for improving the survival and the quality of life of patients with colorectal cancers.

The accuracy may increase with the increasing of the number of lymph nodes sectioned, and with involving of immunohistochemistry or molecular markers' panels as demonstrated in many studies, but will also increase the cost and the workload for pathologists (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Kelder W. et al., 2007). Even though the accuracy was good for colon and rectal cancer, the sensitivity of the method somewhere is reported very low (66.66% for colon and 50% for rectal cancer), and the false-negative rate was high (23.07% for colon cancer and 18.18% for rectal cancer). The sensitivity of the method varies in the literature between 54% in the study of the Bembenek , and 88.2–89% in the study of Bilchik AJ *et al.*, and Kelder W *et al.* (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Kelder W. et al., 2007). The smallest false-negative rate was achieved by Bilchick AJ *et al.* (7.4%), but other authors reported a significantly higher rate of false-negative results (46% for colon cancer in the study of Bembenek AE *et al.* and 43% in rectal cancer in the study of Baton O *et al.*) (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Baton O. et al., 2005). Thus, with such high risk of failure (lower detection rate, low sensitivity and high false-negativity rate), the technique of sentinel lymph node in rectal cancer is obviously not feasible; in colon cancer, the method may be improved by increasing the number of the examined lymph nodes, and using specific immunohistochemical staining methods. However, doing so, it will not represent a relief for pathologist, but probably will increase the quality of the *pN* staging. In this matter, our study has shown an increase in the detection of the positive lymph nodes (37.2% *N+* in sentinel lymph node group *vs.* 26.67% in the control group), but statistical significance was not reached. Moreover, the quality of the upstaging was not determined by the examination technique itself (micrometastases were detected in only two cases – 9.37% upstaging rate), but probably by the increased number of the identified and examined lymph nodes in the studied group *vs.* comparison group (the blue staining of the lymph node in the study group made it easy to identify them, and probably an increasing awareness and close collaboration between the surgeon and pathologist) (Bilchik AJ&Compton C., 2007). In literature, there are better results in upstaging the *pN* category, using the sentinel lymph node technique, varying from 15% for rectal cancer (Baton O *et al., 2005*) to 18–23.6% in colon cancer (Bilchik AJ et al., 2006; Bembenek A. et al., 2007; Kelder W.

The high incidence of distant metastasis of CRC in patients whose nodes are negative may be due to insufficient numbers or sections of lymph nodes. Bilchik A.&Compton C., 2007 Because multiple sectioning and IHC staining cannot be routinely used to examine all lymph nodes in a CRC specimen, we focused on the first regional node(s) to receive lymphatic drainage from a primary tumor. In melanoma and breast cancer, lymphatic mapping and excision of the SN is used to determine the tumor status of the entire nodal basin and avoid complete lymph node dissection in node-negative patients. The application of the SN technique in CRC is different because all regional lymph nodes are routinely removed en bloc with the primary tumor. However, as in melanoma and breast cancer,

Sutton R., 2002; Wood, TF et al., 2001).

et al., 2007).

The method of intraoperative SLN mapping using Patent Blue V is an accurate and objective diagnostic method for assessment of the lymphatic status in patients with colorectal cancer. The method is an objective criterion for intraoperative surgical behavior.

Intraoperative Sentinel Lymph Node Mapping in Patients with Colorectal Cancer 177

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Bilchik AJ, Nora DT, Sobin LH, Turner RR, Trocha S, Krasne D: Effect of lymphatic mapping

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The method of intraoperative SLN mapping is applied with high success in patients with colon and rectal cancer. The method has 100% success rate and 98% sensitivity.

The analysis of the results from the application of methods of intraoperative endoscopic submucous SLN mapping and intraoperative subserous SLN mapping indicates that both methods are equally reliable and highly sensitive.

The method of intraoperative SLN mapping achieves better intraoperative visualization of lymph nodes with the highest metastatic potential, even if they are very small. It was found that the average size of metastatic lymph nodes was 4.7 mm. The method can detect the presence of aberrant lymphatic drainage and lymphatic skip metastases.

The sentinel lymph node reflects with high reliability the status of the entire lymphatic basin. Metastatic lymph nodes beyond the standard volume of lymphatic dissection are detected by intraoperative SLN mapping. By increasing the surgical volume was achieved greater radicalism in 7% of patients with colorectal cancers. It does not increase the postoperative morbidity.

Our study demonstrates that metastases in sentinel lymph nodes are found 6 times more frequently than in other lymph nodes. In 98% of cases the metastases are found in the sentinel lymph nodes.

In the absence of metastases in sentinel lymph nodes, the likelihood of metastases in other lymph nodes is only 0.6%.

Only through the application of the method of intraoperative SLN mapping and the ultrastaging of the lymph nodes it is liable to achieve more precise clinical staging of disease and determining of exact definitive diagnosis in 20% of patients.

The method of additional lymph node mapping allows quick discovery and exploration of maximum number lymph nodes, which contributes to the accurate staging of colorectal cancer.

The endoscopic submucous application of the lymphatic marker is the only appropriate method for intraoperative SLN mapping in case of subperitoneal localization of rectal cancer.

We conclude that SLN mapping in colorectal cancer is a convenient diagnostic method allowing the surgeon to individualize the approach to every single patient. Further studies are needed to validate if routine use of this method will increase the survival rates of patients operated for colorectal cancer.

We can conclude that the operational approach and the volume of the conducted lymphatic dissection must comply with the status of the lymphatic basin, assessed by an objective diagnostic method such as the intraoperative sentinel lymph node mapping. This leads to increased surgical radicalism in the surgical treatment of colorectal cancers. Our recommendation is that the method should be promoted and clinical trials should follow.

#### **7. References**

The method of intraoperative SLN mapping is applied with high success in patients with

The analysis of the results from the application of methods of intraoperative endoscopic submucous SLN mapping and intraoperative subserous SLN mapping indicates that both

The method of intraoperative SLN mapping achieves better intraoperative visualization of lymph nodes with the highest metastatic potential, even if they are very small. It was found that the average size of metastatic lymph nodes was 4.7 mm. The method can detect the

The sentinel lymph node reflects with high reliability the status of the entire lymphatic basin. Metastatic lymph nodes beyond the standard volume of lymphatic dissection are detected by intraoperative SLN mapping. By increasing the surgical volume was achieved greater radicalism in 7% of patients with colorectal cancers. It does not increase the

Our study demonstrates that metastases in sentinel lymph nodes are found 6 times more frequently than in other lymph nodes. In 98% of cases the metastases are found in the

In the absence of metastases in sentinel lymph nodes, the likelihood of metastases in other

Only through the application of the method of intraoperative SLN mapping and the ultrastaging of the lymph nodes it is liable to achieve more precise clinical staging of disease

The method of additional lymph node mapping allows quick discovery and exploration of maximum number lymph nodes, which contributes to the accurate staging of colorectal

The endoscopic submucous application of the lymphatic marker is the only appropriate method for intraoperative SLN mapping in case of subperitoneal localization of rectal

We conclude that SLN mapping in colorectal cancer is a convenient diagnostic method allowing the surgeon to individualize the approach to every single patient. Further studies are needed to validate if routine use of this method will increase the survival rates of

We can conclude that the operational approach and the volume of the conducted lymphatic dissection must comply with the status of the lymphatic basin, assessed by an objective diagnostic method such as the intraoperative sentinel lymph node mapping. This leads to increased surgical radicalism in the surgical treatment of colorectal cancers. Our recommendation is that the method should be promoted and clinical trials should follow.

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lymph nodes is only 0.6%.

patients operated for colorectal cancer.

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