Sentinel Lymph Node Mapping for Adenocarcinoma of the Colon Does Not Improve Staging Accuracy

PURPOSE This study was designed to: determine the efficacy of sentinel lymph node mapping in patients with intraperitoneal colon cancer; and create an algorithm to predict potential survival benefit by using best-case estimates in favor of sentinel node mapping and lymph node ultraprocessing techniques. METHODS Forty-one patients with intraperitoneal colon cancer undergoing colectomy with curative intent were studied prospectively. After mobilization of the colon and mesentery, 1 to 2 ml of isosulfan blue dye was injected subserosally around the tumor. The first several nodes highlighted with blue dye were identified as sentinel nodes. Additional nodes were identified by the pathologist in routine fashion by manual dissection of the mesentery. All nodes were processed in routine fashion by bivalving and hematoxylin and eosin staining. To create an algorithm to predict potential survival benefit of sentinel node mapping and lymph node ultraprocessing techniques, assumptions were made using data from the literature. All bias was directed toward success of the techniques. RESULTS Three of 41 patients (7 percent) did not undergo injection of dye and were excluded from further analysis. Stage of disease in the remaining 38 patients was: I, n = 10 (26 percent); II, n = 15 (39 percent); III, n = 11 (29 percent); IV, n = 2 (5 percent). At least one sentinel node was identified in 30 of 38 patients (79 percent). The median number of sentinel nodes identified was two (range, 1–3). Median total nodal retrieval was 14 (range, 7–45). All nodes were negative in 26 of 38 patients (68 percent). Sentinel nodes and nonsentinel nodes were positive in 2 of 38 patients (5 percent). Sentinel nodes were the only positive nodes in 1 of 38 patients (3 percent). Sentinel nodes were negative and nonsentinel nodes were positive in 9 of 38 patients (24 percent). Thus, sentinel node mapping would have potentially benefited only 3 percent, and failed to accurately identify nodal metastases in 24 percent of the patients in our study. To create a survival benefit algorithm, we assumed the following: combined fraction of Stage I and II disease (0.5); fraction understaged by bivalving and hematoxylin and eosin staining that would have occult positive nodes by more sophisticated analysis (0.15); fraction of occult positive nodes detected by sentinel node mapping (0.9); and survival benefit from chemotherapy (0.33). Thus, the fraction of patients benefiting from sentinel lymph node mapping and lymph node ultraprocessing techniques would be 0.02 (2 percent). CONCLUSIONS Sentinel node mapping with isosulfan blue dye and routine processing of retrieved nodes does not improve staging accuracy in patients with intraperitoneal colon cancer. Even using best-case assumptions, the percentage of patients who would potentially benefit from sentinel lymph node mapping is small. Read at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.     

In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer

Introduction

Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called “sentinel nodes” and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques.

Methods

Patients with colon cancer UICC stage I–III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients.

Results

Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node.

Conclusion

Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

     

Ex Vivo Sentinel Lymph Node Mapping in Colorectal Cancer

INTRODUCTION Sentinel lymph node mapping has been used in clinical work in malignant melanoma and breast cancer and shown an advantage over routine regional lymphadenectomy. The technique has been applied to colorectal cancer, but concerns over accuracy and high false-negative rates have restricted its use in the routine clinical setting. Most published series have used the in vivo technique and only three studies have been published in which the ex vivo technique was used. The aim of this study was to report the results of a larger study of ex vivo sentinel node mapping.METHODS All patients with colorectal cancer were considered for the trial, except patients who received preoperative radiotherapy for rectal cancer. All specimens were examined in the operating room within 30 minutes of resection. After opening the bowel, 0.5 ml of patent blue dye was injected submucosally at four sites immediately adjacent to the tumor (2 ml). The pathologic examination of the sentinel nodes and of an equal number of nonsentinel nodes consisted of standard hematoxylin and eosin sectioning, followed by multiple sectioning for further hematoxylin and eosin staining and immunohistochemistry if initial samples did not show tumor metastases.RESULTS A total of 58 tumors in 57 patients were studied. One or more sentinel nodes were found in relation to 56 tumors, with one of the two failures being attributed to gross mesenteric metastases obstructing lymphatic flow. A mean of 2.93 (0–8) sentinel nodes were found per patient. There was concordance between the sentinel nodes and nonsentinel nodes in 43 patients (76.8 percent). There were nine false-negative sentinel nodes (16 percent). Two patients were upstaged by detailed pathologic examination of the sentinel nodes (micrometastases), and in a further two patients the sentinel node was the only positive node on simple hematoxylin and eosin sectioning.CONCLUSIONS The technique of ex vivo sentinel node mapping is feasible and accurate in defining sentinel nodes in colorectal cancer. There is, however, a significant false-negative rate making the sentinel nodes not representative of the lymph node basin. This precludes the use of this technique in routine clinical practice. There may be a role in a research setting to help define the prognostic significance of micrometastases.Supported by grants from AP-HP, Paris, France, Contrat de Recherche Clinique 01018.Read at the meeting of the American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.Reprints are not available.     

Indication and Benefit of Pelvic Sidewall Dissection for Rectal Cancer

Purpose This study was designed to clarify indication and benefit of pelvic sidewall dissection for rectal cancer. Methods The retrospective, multicenter study collected the data of rectal cancer patients who underwent surgery between 1991 and 1998 and were prospectively followed. Results Of 1,977 patients with rectal cancers, 930 underwent pelvic sidewall dissection without adjuvant radiotherapy. Positive lateral lymph nodes were found in 129. Multivariate analysis disclosed a significantly increased incidence of positive lateral lymph nodes in female gender, lower rectal cancers, non-well-differentiated adenocarcinoma, tumor size of ≥4 cm and T3-T4. The five-year survival rate for 1,977 patients was 79.7 percent. The survival of patients with positive lateral lymph nodes was significantly worse than that of Stage III patients with negative lateral lymph nodes (45.8 vs. 71.2 percent, P<0.0001). Multivariate analysis showed significantly worse prognosis in male gender, pelvic sidewall dissection, lower rectal cancers, T3-T4, perirectal lymph node metastasis, and positive lateral lymph nodes. During the median follow-up time of 57 months, recurrence developed in 19.7 percent: 17 percent in negative and 58.1 percent in positive lateral lymph nodes (P<0.0001). Local recurrence was found in 8 percent: 6.8 percent in negative and 25.6 percent in positive lateral lymph nodes (P<0.0001). Multivariate analysis disclosed that lower rectal cancers, non-well-differentiated adenocarcinoma, T3-T4, perirectal lymph node metastasis, and positive lateral lymph nodes were significantly associated with an increased local recurrence. Conclusions Positive lateral lymph node was the strongest predictor in both survival and local recurrence. Pelvic sidewall dissection may be indicated for patients with T3-T4 lower rectal cancers because of the greater provability of positive lateral lymph nodes. Study Group for Rectal Cancer Surgery of the Japanese Society for Cancer of the Colon and Rectum. Presented at the United States-Japan Clinical Trial Summit Meeting, Maui, Hawaii, February 10–13, 2005.     

Sentinel Node Mapping does not Improve Staging of Lymph Node Metastasis in Colonic Cancer

Purpose  This study was designed to evaluate the reliability of the sentinel node concept in colonic cancer. Methods  Patent blue was used as tracer. The four blue nodes closest to the tumor were defined as the sentinel node(s) by the pathologist. All nodes were examined by routine microscopy (hematoxylin-eosin staining). If no metastases were detected, all lymph nodes were examined immunohistochemically with antibody to cytokeratin. Results  Two hundred colon specimens were examined. Sentinel node(s) were identified in 93 percent. Sixty contained metastases in hematoxylin-eosin sections. In 32 these were found in sentinel nodes (sensitivity 53 percent). Twenty-eight patients had metastases in nonsentinel nodes only, giving a false-negative rate of 47 percent. Immunostaining revealed 39 (30 percent) micrometastases or submicrometastases in 131 TNM Stages I and II patients, and in 17 of these patients metastases were found in nonsentinel nodes only (false-negative rate 44 percent). Conclusions  Sentinel lymph node mapping shows low sensitivity for detection of ordinary metastases, micrometastases, and submicrometastases. If only the sentinel nodes had been examined, approximately half of the metastases would have been lost after routine staining, as well as half of the micrometastases and submicrometastases when immunohistochemical examination was added. Presented as one of six best papers at the meeting of the European Society of Coloprotology-ESCP, Portomaso, Malta, September 26 to 29, 2007. An erratum to this article can be found at     

The role of sentinel lymph node mapping in staging of colon and rectal cancer

PURPOSE: Nodal metastasis is the best predictor of survival for patients with colon cancer. Statistical models based on random distribution of positive lymph nodes suggest that to correctly classify nodal status with 95 percent confidence, 20 nodes are needed for T1 lesions, 17 nodes for T2, and 15 nodes for T3. The mean number of nodes identified in American patients is 8, suggesting that they might not be accurately staged. Patients in our tumor registry staged as "node-negative" had a short survival when they had < or =10 lymph nodes evaluated when compared with patients with >10 lymph nodes evaluated (p < 0.01). We hypothesized that the use of sentinel lymph node may assist in the staging of colon cancer. METHODS: Thirty-eight consecutive patients with colon lesions were prospectively enrolled into this trial between February 1998 and November 1999. Thirty-one patients met criteria for analysis. During surgery, Lymphazurin blue dye was injected subserosally into the area around the tumor. Routine nodal evaluation, with extra cuts of all sentinel nodes, was undertaken. RESULTS: At least one sentinel lymph node was found in 18 of 31 patients (58 percent). Sensitivity of 67 percent, specificity and positive predictive value of 100 percent, and negative predictive value of 94 percent were found when sentinel lymph nodes were identified. In 2 of these 18 patients, the sentinel lymph node was the only positive lymph node found. CONCLUSIONS: Application of the sentinel lymph node technique to colon cancer may make it easier to identify lymph nodes most likely to contain metastatic disease, potentially "down-staging" more patients. This may have implications in postoperative care.     

Sentinel Node Mapping for Colorectal Cancer With Radioactive Tracer

PURPOSE: The aim of this study was to test the feasibility and accuracy of radioactivity-guided mapping of the first lymph nodes found in draining the primary tumor site for colorectal cancer. METHODS: We enrolled 56 consecutive patients with preoperative diagnosis of curatively resectable colorectal cancer. Endoscopic injection of technetium Tc 99m-labeled tin colloid (15 MBq) was performed preoperatively, and radioactive sentinel nodes were identified intraoperatively with a gamma probe. Standard radical resection with lymph node dissection was performed in all patients, and all resected nodes were evaluated by routine histopathologic examination. RESULTS: Radioactivity-guided methods were used to detect sentinel nodes in 51 (91 percent) of 56 patients. The number of lymph nodes resected was 23.9 +/- 15.2 per case. The number of sentinel nodes was 3.5 +/- 2.1 (range, 0-8) per case. In 18 of 22 patients with lymph node metastasis, the sentinel node was positive. The incidence of metastasis in the sentinel node (22 percent) was significantly higher than that in nonsentinel nodes (3 percent, P < 0.01). Diagnostic accuracy according to sentinel node status was 92 percent (47/51). Four false-negative cases in this study were advanced cases with T3 primary tumors. The detection rate and diagnostic accuracy for patients with T1 or T2 primary tumors (29 cases) were 100 percent each. CONCLUSION: Intraoperative radioactivity-guided sentinel node mapping was accurate for patients with colorectal cancer with T1 or T2 tumors. The results suggest that sentinel node mapping and intraoperative biopsy may be a sensitive and specific diagnostic method for detecting metastasis in regional lymph nodes in patients with colorectal cancer.     

All patients with small intramural rectal cancers are at risk for lymph node metastasis

PURPOSE: Although local excision can be curative in patients with early-stage rectal cancer, approximately 20 percent of patients will develop local recurrence, many as a result of unrecognized and unresected regional lymph node metastases. Our objective was to determine if standard pathologic factors can predict lymph node metastases in small intramural rectal cancers and provide a basis for patient selection for nonradical surgery. METHODS: Between June 1986 and September 1996, 318 patients with T1 or T2 rectal cancers underwent radical resection at our institution. Of these, 159 patients (48 T1 and 111 T2) were potentially eligible for curative local excision (4 cm in size, 10 cm from the anal verge, no synchronous metastases), and the prevalence of lymph node metastases based on T stage and other pathologic factors was analyzed in this group. RESULTS: The overall frequency of lymph node metastasis was 15 percent (24/159 patients). T stage (T1, 10 percent; T2, 17 percent), differentiation (well-differentiated or moderately differentiated, 14 percent and poorly differentiated, 30 percent), and lymphatic vessel invasion (lymphatic vessel invasion-negative, 14 percent and lymphatic vessel invasion-positive, 33 percent) influenced the risk of lymph node metastasis. However, only blood vessel invasion (blood vessel invasion-negative, 13 percent and blood vessel invasion-positive, 33 percent) reached statistical significance as a single predictive factor (P=0.04). Tumors with no adverse pathologic features (low-risk group) had a lower overall frequency of lymph node metastasis (11 percent) compared with the remaining tumors (high-risk group, 31 percent;P=0.008). However, even in the most favorable group (T1 cancers with no adverse pathologic features) lymph node metastases were present in 7 percent of patients. CONCLUSION: In rectal cancer patients potentially eligible for local excision, the overall risk of undetected and untreated lymph node metastases is considerable (15 percent). The use of pathologic factors alone after local excision does not reliably assure the absence of lymph node metastases.Presented at the 51st Annual Cancer Symposium of the Society of Surgical Oncology, San Diego, California, March 26 to 29, 1998.     

Combining Radioisotopic and Blue-Dye Technique Does Not Improve the False-Negative Rate in Sentinel Lymph Node Mapping for Colorectal Cancer

Purpose This study was designed to assess the feasibility of a combined colorimetric and radioisotopic technique in the detection of the sentinel lymph node in colorectal cancer. Methods This prospective dual-center study included 64 patients. Using endoscopy on D0, a radiolabeled colloid was injected into the peritumoral submucosa, followed by a lymphoscintigraphy. Intraoperatively, on D1, lymphatic mapping was performed by using a visual method and radioguided detection after subserosal peritumoral injection of patent blue. Twenty-nine patients were injected only with the patent blue, 18 patients only with the radioactive tracer, and the other 17 patients benefited from both techniques. Results The detection rate was 92 percent. The average number of sentinel nodes harvested was 2.8. Twenty-four of 59 patients were pN+ (40 percent) and in 12 cases the sentinel lymph node was histologically negative, although there was a positive nonsentinel node (false-negative rate, 50 percent). The false-negative rate for the combined, radioisotopic, and colorimetric techniques were 63, 60, and 36 percent, respectively. In four patients, the sentinel node was the only metastatic site (4/24, 17 percent), and in two of these four patients, the sentinel lymph node presented with micrometastases (<2 mm). The radioisotopic technique allowed us to highlight a lateral drainage of two rectal cancers (2/13, 15 percent). The concordance between the blue and radioactive sentinel nodes was 43 percent. Conclusions The addition of a radioisotopic method using submucosal injection does not improve the false-negative rate. The sentinel lymph node technique in colorectal cancer is feasible, although the false-negative rate is such that the technique should still be considered as experimental. Supported by the “H?pital Universitaire de Saint Etienne” and by a grant from the French Ministry of Research (PHRC national 2001). Presented at the Congrès Fran?ais de Chirurgie, Paris, France, September 27 to 30, 2005.     

Analysis of regional lymph node metastases from rectal carcinoma by the clearing method

PURPOSE: It has been reported that functional outcome following low anterior resection of rectal cancer is improved by construction of a colonic J-pouch compared with straight anastomosis. Hence, we tried to justify use of the sigmoid colon in the construction of a J-pouch by the analysis of regional lymph node metastases. METHODS: A total of 182 patients underwent resection for rectal cancer. Node metastases were examined by the clearing method. According to Japanese General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus (JGR), nodes were classified into the perirectal nodes (PR-N), pericolic nodes (PC-N), central intermediate nodes (C-IM-N), central main nodes (C-M-N), lateral intermediate nodes (L-IM-N), and lateral main nodes (L-M-N). RESULTS: Metastatic rate (number of patients with node metastases/ total number of patients) of PR-N was 57.1 percent. Metastatic rate of C-IM-N was 18.7 percent and that of C-M-N was 7.1 percent. Metastatic rates of L-IM-N and L-M-N were 8.8 and 3.3 percent, respectively, and both were highest in the case of lower rectal cancer. Metastatic rate of PC-N was only 1.1 percent. The number of cases without node metastases (n(–) cases) was 78, that with only PR-N metastases (PR-N cases) was 63, that with intermediate but not main node metastases (IM-N cases) was 29, and that with main node metastases (M-N cases) was 12. Five-year survival rate after curative resection was 88.5 percent for n(–) cases, 70.9 percent for PR-N cases, 65.9 percent for IM-N cases, and 41.7 percent for M-N cases. CONCLUSIONS: In low anterior resection, high ligation of the inferior mesenteric artery and dissection of C-M-N, C-IM-N and PR-N are necessary, with the addition of the L-IM-N and L-M-N in the case of lower rectal cancer. Resection of sigmoid colon is not required, and therefore, a J-pouch can be constructed using the sigmoid colon. Nodal classification according to the JGR was predictive of case distribution and five-year survival rate.Supported, in part, by a Grant-in-Aid for Cancer Research from the Japanese Ministry of Health and Welfare and Scientific Research from the Japanese Ministry of Education, Culture and Science.     

Total Mesorectal Excision Results in Low Local Recurrence Rates in Lymph Node-Positive Rectal Cancer

PURPOSE: Most series report lymph node involvement as the main predictor for local recurrence. The principal lymphatic drainage of the rectum is to nodes in the mesorectum and then nodes along the superior rectal and inferior mesenteric arteries. If total mesorectal excision provides adequate block dissection of the lymphatics of the rectum, good local control with low rates of local recurrence should be achieved even in node-positive disease.METHODS: Prospective data on all rectal cancers have been collected since 1978; 170 patients with Dukes C rectal cancer have undergone anterior resection and total mesorectal excision. We did not perform any internal iliac node dissections. Follow-up data were analyzed for local recurrence and distant recurrence.RESULTS: The local recurrence rate was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes C (P = 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18 percent for Dukes B, and 37 percent for Dukes C (P = 0.0001).CONCLUSIONS: If surgical priority is given to the difficult task of excision of the whole mesorectum, anterior resection with total mesorectal excision in node-positive rectal cancer, local recurrence rates of < 10 percent can be achieved.Presented at the Association of Colorectal Surgeons of Great Britain and Ireland, Harrogate, United Kingdom, June 25 to 27, 2001.     

Distribution of metastatic lymph nodes in colorectal cancer by the modified clearing method

PURPOSE: The aim of this study was to clarify the distribution of lymph node metastasis in colorectal cancer. We also examined the relationship between the primary tumor (T) and the regional node (N) categories of the TNM (primary tumor, regional nodes, metastasis) classification. METHOD: Lymph nodes of surgical specimens in 311 consecutive patients with colorectal cancer were studied using the modified clearing method. RESULTS: Lymph node metastasis was seen in 59.2 percent of the total cases. The upward metastasis rate was 30.7 percent. In the longitudinal spread, most of the lymph node metastasis was seen within 10 cm. On the oral side in rectal cancer, there was no metastasis beyond 4 cm. The lateral metastasis rate in rectal cancer was 8.8 percent and in the lower rectum, the rate of cancer within 6 cm from the anal verge or beyond pT3 was much higher. CONCLUSION: In the TNM classification, there was no significant difference between colon and rectal cancer except pT1 with rectal cancer. In the lower rectal cancer within 6 cm from the anal verge or beyond pT3, there is a high risk of lateral metastasis, and lateral lymph node dissection or radiation therapy should be performed.     

Incidence of metastases from rectal adenocarcinoma in small lymph nodes detected by a clearing technique

The incidence of metastases from primary adenocarcinoma of the rectum in lymph nodes smaller than 5 mm is not known. Lymph nodes measuring 5 mm usually are not detected by manual techniques of examination of the surgical specimen. This retrospective analysis describes the results when a lymph node clearing technique that identifies lymph nodes as small as 1 mm was used to treat surgical specimens from 27 consecutive patients with rectal adenocarcinoma who underwent abdominoperineal resection with a curative intent and for whom all pathologic data were retrievable. Nine hundred thirty lymph nodes were found, with an average of 34 lymph nodes per specimen (range 0–88). Seventy-two of the 345 lymph nodes found in patients with Dukes C tumors were found to have metastases. Fifty-six (78 percent) of these 72 lymph node metastases occurred in lymph nodes measuring 5 mm. Three lymph node metastases were found in the perianal zone, 53 in the perirectal zone, and 16 in the pericolonic zone. Lymph node metastases from rectal adenocarcinomas often will occur in lymph nodes smaller than 5 mm. We concluded that the use of lymph node clearing techniques discovers these metastases, thereby offering the potential for enhanced staging of primary rectal adenocarcinomas.Read at the XIIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Graz, Austria, June 24 to 28, 1990.     

DNA index as a significant indicator of lymph node metastasis and local recurrence of rectal cancer

To confirm the prognostic significance of the DNA index (DI) in cases of rectal cancer, the nuclear DNA content of tumor cells was examined in 184 cases of rectal cancer treated with curative surgery, and the incidence of lymph node metastasis and recurrence of the cancer was analyzed. The incidence of lymph node metastasis was 43.9 percent in cases with aneuploidy (DI above 1.5), being statistically different from the 18.0 percent incidence in cases with diploidy (P <0.001). Although the extent of lymph node metastasis was limited to adjacent lymph nodes in cases with diploidy, distant lymph node metastases were frequent in cases with aneuploidy, especially in those with a DI above 1.5. Furthermore, the incidence of recurrence of cancer, and especially of local recurrence, was significantly higher (P <0.001) in cases with aneuploidy (DI above 1.5) than in cases with diploidy and aneuploidy (DI below 1.4). These findings indicate the significant value of the DNA index for the prediction of lymph node metastasis and local recurrence in patients with rectal cancer.     

Endosonography of pararectal lymph nodes

One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz×cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz×cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.Supported by a grant from the Deutsche Forschungsgemeinschaft Hi 385/1-1     

In vivo lymph node mapping and pattern of metastasis spread in locally advanced mid/low rectal cancer after neoadjuvant chemoradiotherapy

Purpose

The lymph node status is one of the strongest prognostic determinants in rectal cancers. After chemoradiotherapy (CRT), lymph nodes are difficult to detect. This study aims to evaluate the feasibility of lymph node mapping in the mesorectum after CRT to analyze the pattern of metastasis spread and to assess the reliability of blue dye injection in sentinel lymph node detection.

Method

Ten patients with cN+ mid/low RCs after CRT were prospectively enrolled. The protocol scheduled intraoperative blue dye injection, surgery, and specimen examination with fat clearance technique. The mesorectum was divided into three equal “levels” (upper, middle, and lower); each level was divided into three equal “sectors” (right anterolateral, posterior, and left anterolateral). Lymph nodes were defined “small” if ≤5 mm.

Results

Two hundred seventy-six lymph nodes were retrieved in ten patients; 76.5 % were small lymph nodes. Six patients were pN+ (33 metastatic lymph nodes, 76 % small); small lymph node analysis upstaged one patient from N0 to N1 and four patients from N1 to N2. Metastasis distribution across sectors was continuous, without “skip sectors.” The blue dye detected the sentinel lymph node in all patients; in half of the cases, it was out of the tumor sector. Blue dye identified 69.7 % of metastatic lymph nodes; its sensitivity decreased together with the metastatic deposit size (84 % macrometastases, 28.6 % micrometastases, 0 % occult tumor cells; p?=?0.004).

Conclusion

The fat clearance technique should be the standard pathological examination in patients with RCs after CRT; N staging was improved by small lymph node identification. Lymph node metastases have a continuous spread through mesorectal sectors. Blue dye injection is effective in sentinel lymph node detection.     

Clinical usefulness of intraoperative sentinel-node biopsy in gastric cancer

BACKGROUND/AIMS: Minimally invasive surgery has been used to improve the quality of life after operation in patients with gastric cancer. Sentinel-lymphnode biopsy can help to limit the extent of lymph node dissection, but the diagnostic and therapeutic usefulness of this technique has not been accurately evaluated in gastric cancer. This study was designed to clarify the role of intraoperative sentinel-node biopsy in patients with gastric cancer. METHODOLOGY: We were conducted to evaluate 1) mapping sentinel nodes according to tumor location 2) comparison sentinel node metastases as assessed by frozen section, permanent section (HE stain) and immunohistochemical diagnoses, and 3) comparison non-sentinel node metastases as assessed by permanent section (HE stain) and immunohistochemical diagnosis. RESULTS: All sentinel nodes were identified in the regional perigastric lymph node group close to the tumor. Four of the 43 sentinel lymph nodes were positive for metastasis. Similar diagnostic results were obtained by the 3 different procedures. Lymph node metastasis was found in 10 (4 sentinel nodes and 6 non-sentinel nodes) of 779 lymph nodes (1.28%) on HE staining. Immunohistochemical studies revealed a similar number of positive sentinel nodes as that obtained on HE staining, but identified metastases in 15 in non-sentinel nodes in 2 patients, as compared with only 6 nodes on HE staining. In one patient, sentinel nodes at No. 1 and No. 3 were negative for metastasis, whereas non-sentinel lymph nodes at NO. 3 were positive for metastasis. The other patient had negative sentinel nodes at No. 3 and No. 4d, but positive non-sentinel nodes at No. 4d. CONCLUSIONS: The results of this small study do not yet provide a firm basis for recommending that sentinel-node biopsy is used to reduce the extent of lymph node dissection.     

Lumboaortic and iliac lymphadenectomy: What is the role today?

PURPOSE: The aim of this study was to evaluate the roles of the lymphadenectomy in the surgical treatment of rectal cancer. METHODS: On the basis of our experience of 252 curative operations for rectal cancer, we analyze survival and recurrences in relation to the lymph node involvement and to the level of the lymph nodes where the metastases are located. All patients underwent a lymphadenectomy with high ligation of the inferior mesenteric artery and removal of the lumboaortic lymph nodes from the left renal vein to the aortic bifurcation. Pelvic lymphadenectomy was performed in 16 cases. RESULTS: Five-year survival was 70.6 percent in patients with no lymph node involvement, 68.2 percent in patients with pararectal lymph nodes N+, 25 percent in patients with involvement of intermediate lymph nodes, and 30 percent in patients with involvement of lumboaortic lymph nodes. In no case was there involvement of the hypogastric lymph nodes. On the basis of our experience and from results in the literature, we consider an upward extended lymphadenectomy with high ligation of the inferior mesenteric artery is warranted since it enables the tumor to be staged accurately and may lead to survival even in cases of advanced lymph node involvement.     

Impact of Microscopic Extranodal Tumor Deposits on the Outcome of Patients With Rectal Cancer

PURPOSE: Microscopic mesorectal soft tissue extranodal deposits discontinuous with the primary tumor are identified in many rectal adenocarcinomas. Current guidelines consider them to be involved lymph nodes. We studied the impact of these deposits on the outcome of patients with rectal cancer. METHODS: This was a retrospective study, in which histology slides were reviewed from 55 patients whose resection specimens for rectal cancer were staged as Dukes C or Dukes B with extranodal deposits. Twenty-nine patients had extranodal deposits (19 males), and 26 control patients had lymph node involvement only (14 males). Patient outcome was analyzed in terms of local and systemic control and survival. RESULTS: Distant metastases were diagnosed earlier in patients with extranodal deposits (mean, 14 months) compared with controls (mean, 37 months; P = 0.001). On follow-up, 31.03 percent (9/29) from the extranodal deposit group developed liver metastases compared with 11.5 percent (3/26) of the control group (P = 0.08). Local recurrence was seen in 17.2 percent of patients from the extranodal deposit group and 3.8 percent of the control group (P = not significant). Cancer-related mortality was higher in the extranodal deposit group (16 vs. 7 patients; P = 0.09). The three-year actuarial survival was 48.27 percent in patients with extranodal deposits and 65.38 percent in those without. A significant association was noted between the number of extranodal deposits and intramural vascular invasion (P = 0.017), extramural vascular invasion (P = 0.039), perineural invasion (P = 0.039), and lymph node involvement (P = 0.008). CONCLUSION: These data suggest that extranodal deposit is a distinct form of metastatic disease in patients with rectal cancer. The association with vascular invasion and earlier development of metastases probably infers that a significant proportion of extranodal deposits may represent blood-borne spread. These tumor foci should be considered as indicators of poor prognosis.