Results of vascular resections during pancreatectomy from two European centres: an analysis of survival and disease-free survival explicative factors

Objectives

The object of our study was to report on the experience with vascular resections at pancreatectomy in two European specialist hepatopancreatobiliary centres and evaluate outcome and prognostic factors.

Patients and methods

From 1989 to 2002, 45 patients (21 men, 24 women) underwent pancreatectomy for a pancreatic mass: Whipple''s procedure (n=33), total pancreatectomy (n=10) or left splenopancreatectomy (n=2), along with a vascular resection, i.e. venous (n=39), arterial (n=1) or venous + arterial (n=5).

Results

Operative mortality was nil, postoperative mortality was 2.2% (n=1); 34 patients had an uneventful postoperative course. Reoperations were performed for portal vein thromobosis (n=1), pancreatic leak (n=1), gastric outlet syndrome (n=1) and gastrointestinal bleeding (n=1). In all, 43 patients had cancer on pathology examination, with retropancreatic invasion in 72% and lymph node extension in 62.8%. Resection was R0 in 21 cases. Vessel wall invasion was present in 13 cases and 19 had perivascular invasion. Disease-free survival (DFS) at 1, 2 and 3 years was 36.0%, 15.0% and 12.0%, respectively. Median DFS length was 8.7 months (95% CI: 7.2; 10.2). Overall survival rates were 56.6%, 28.9% and 19.2%, respectively. Median survival length was 14.2 months (95% CI: 9.8; 18.6). A multivariate analysis of prognostic variables identified tumour location (other than head of pancreas), neoadjuvant chemotherapy and advanced disease stage as adverse factors for DFS.

Conclusion

Survival and DFS rates of these patients are comparable to those without vascular resection. Tumour localization, tumour stage, neoadjuvant treatment and tumour recurrence are explanatory variables of survival. Tumour localization, tumour stage and neoadjuvant treatment were explanatory variables for DFS. However, the type and extent of vascular resections as well as vessel wall invasion does not affect survival and DFS.     

Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage IA and pathological stage T1 non-small cell lung cancer

Purpose  To explore the appropriate method of mediastinal lymph node dissection for selected clinical stage IA (cIA) non-small cell lung cancer (NSCLC). Methods  From 1998 through 2002, the curative-intent surgery was performed to 105 patients with cIA NSCLC who had been postoperatively identified as pathologic-stage T1. According to the method of intraoperative medistinal lymph node dissection, they were divided into radical systematic mediastinal lymphadenectomy (LA) group (n = 42) and mediastinal lymph-node sampling (LS) group (n = 63). The effects of LS and LA on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Also, associations between clinicopathological parameters and survival were analyzed. Results  The mean numbers of dissected lymph nodes per patient in the LA group was significantly greater than that in the LS group (15.59 ± 3.08 vs. 6.46 ± 2.21, P < 0.001), and the postoperative overall morbidity rate was higher in the LA group than that in the LS group (26.2 vs. 11.1%, P = 0.045). There were no significant difference in migration of N staging, OS and DFS between two groups. However, for patients with lesions between 2 and 3 cm, the 5-year OS in LA group was significantly higher than that in LS group (81.6 vs. 55.8%, P = 0.041), and the 5-year DFS was also higher (77.9 vs. 52.5%, P = 0.038). For patients with lesions of 2 cm or less, 5-year OS and DFS were similar in both groups. Multivariate analysis showed that lymph node metastasis was the unique unfavorable prognostic factor (P < 0.001). Conclusions  After being intraoperatively identified as stage T1, patients with lesions between 2 and 3 cm in cIA NSCLC should be performed with LA to get a potentially better survival, and patients with lesions of 2 cm or less should be performed with LS to decrease invasion.     

Indications and Techniques for Endoscopic Mucosal Resection in the Lesions of A Colorectal Tumor

We evaluated the possibility of an extended application of endoscopic treatment for submucosal‐invading colorectal cancers, and describe the method of endoscopic mucosal resection (EMR) using a one channel colonoscope. A total of 328 submucosal‐invading cancers were examined from July 1985 to September 2002. The patterns of infiltrating growth into the submucosal layer were further divided into two groups: expanding growth, and infiltrating growth. Lymph node metastasis occurred in sm2 and extension cancer in more advanced stages. The lowest measurement of submucosal invading cancer with lymph node metastasis was 1250 µm. As for patterns of invasion, the frequencies of lymph node metastasis in the groups of expanding growth and infiltrating growth were 0% (0/87) and 14.5% (16/110), respectively, (P = 0.0002, Fisher's direct method). Results showed that endoscopic treatment is suitable for sm1 extension without vessel invasion, but there is a possibility that some sm2 extension cancers can be cured radically when the pattern of submucosal invasion shows expanding growth with a distinct border.     

Effect of perioperative blood transfusions on survival of patients after radical surgery for colorectal cancer

The effect of perioperative blood transfusion on the survival of patients with colorectal cancer was evaluated in 128 patients undergoing curative surgery between 1980 and 1988. The following clinical and histopathological variables were also studied: age, sex, duration of symptoms, presence of intestinal obstruction, tumour site, extent of spread through the bowel wall, lymph node involvement, Dukes' stage, grade of differentiation, venous invasion and type of surgical procedure performed. The need for perioperative blood transfusion was unrelated to the stage of disease. In the transfused patients (n=73) the 5-year recurrence-free survival, calculated by the Kaplan-Meyer technique, was 37% and in the non-transfused (n=55) was 60% (P=0.0027, Mantel-Cox). Similar differences were found in the comparison of the groups with (n=68) and without (n=60) transfusions on the day of operation. The deleterious effect of transfusion was evident in patients who received only one unit of blood (n=19) — these had a 5-year survival rate of 45% compared those who had more than one unit of blood (n=54) (5-year survival rate 35%) (P=0.0062). With a multivariate analysis, using a Cox proportional hazard model, taking into account all the variables studied, a significant and independent effect on survival was found for lymph node involvement (beta coefficient=3.97), blood transfusion (beta coefficient=2.16) and extent of bowel wall spread (beta coefficient=1.75). This result leads to the conclusion that perioperative blood transfusion has had an adverse influence on prognosis and that this effect is dose related.

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Résumé L'effet des transfusions sanguines periopératoires sur la survie de 128 patients ayant un cancer colo-rectal, soumis à une résection à visée curative entre 1980 et 1988, a été étudié. Les variables cliniques et histopathologiques suivantes ont été soumises à une analyse multifactorielle: âge, sexe, durée des symptômes, présence de l'occlusion, localisation du tumeur, invasion pariétale et ganglionnaire, degré de différentiation, type du cancer et invasion veineuse et lymphatique. La necessité de transfusions sanguines periopératoires n'a pas eu de relation avec le stade tumoral. La survie (Kaplan-Meier) à 5 ans des malades ayant reçu des transfusions (n=73) a été de 37% par rapport à une survie de 60% des malades (n=55) pas transfusés (P=0,0027, Mantel-Cox). Des différences significatives ont aussi été retrouvées quand on a comparé les groupes ayant réçu (n=68) et n'ayant pas reçu (n=60) des transfusions seulement le jour de l'íntervention. L'effet nocif des transfusions s'est montré même chez les patients ayant reçu une seule unité de sang (n=19): leur survie à 5 ans a été de 45% significativemente différente (P=0,0062) de celle observée chez les malades ayant reçu plus qu'une unité (35%). L'analyse multifactorielle selon la methode de Cox tenant compte tous les facteurs étudiés, a montré que les variables suivantes ont influencié la survie d'une façon significative et indépendante: invasion ganglionnaire (coefficient beta=3,97), transfusions sanguines (coefficient beta=2,16) et invasion parietale (coefficient beta=1,75). Devant ces résultats on peut conclure que les transfusions periopératoires semblent aggraver, d'une façon statistiquement significative, le prognostique des patients ayant un cancer colo-rectal et que cet effet est cumulatif.

     

The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P<0.0001), the volume-corrected mitotic index (P<0.0001), histological grade (P<0.0001), the apoptotic index (P<0.0001), oestrogen and progesterose receptor content (P<0.0001 for both) and p53 accumulation (P=0.001). No correlation was found between Ki-67 expression and lymph node status (P=0.25), metastasis at operation (n=0.81) or tumour size (n=0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P=0.001) and in axillary-lymph-node-negative (ANN) patients (P=0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P=0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P=0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.Abbreviations M/V index the volume-corrected mitotic index - ANN axillary lymph node negative - ANP axillary lymph node positive     

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3–T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

Introduction Local excision is considered inappropriate treatment for T3–T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision.Method The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3–T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed.Results Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour.Conclusion Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.On behalf of the Mount Vernon Colorectal Cancer Network     

A comparison of computed tomography and endorectal ultrasound in staging rectal cancer

Endorectal ultrasound was used prospectively to stage 85 patients with rectal cancer. All patients had surgical exploration and histological analysis. Demonstration of tumour, extension into perirectal fat and lymph node involvement were evaluated. Eighty-one tumours were successfully imaged by endorectal ultrasound. The results suggest that: (1) endorectal ultrasound is more accurate than CT in detecting the site of tumour; (2) endorectal ultrasound is more accurate than CT in detecting perirectal fat infiltration; (3) endorectal ultrasound is slightly more accurate than CT in detecting level II lymph node involvement.     

Direct Tumor Invasion in Colon Cancer: Correlation with Tumor Spread and Survival

Purpose  This study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival. Methods  A cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied. Results  The depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation. Conclusion  Two types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion. Reprints are not available.     

Significance of para-aortic lymph node dissection in advanced gastric cancer.

BACKGROUND/AIMS: Since surgical results in advanced gastric cancer remain poor and para-aortic lymph node dissection may contribute to survival, it is useful to determine the significance of para-aortic lymph node dissection. METHODOLOGY: Para-aortic lymph node dissection was provisionally indicated for patients with invasion depth deeper than the subserosal layer. Clinicopathologic variables were retrospectively analyzed using univariate analysis and multivariate analysis to predict para-aortic lymph node metastasis. Similarly, they were analyzed using univariate analysis and the Cox's proportional hazards regression model to estimate the prognostic factor in 120 patients who underwent para-aortic lymph node dissection. Surgical results and post-operative complications were compared between para-aortic lymph node dissection and D2 dissection. RESULTS: Univariate analysis revealed that the mean diameter, the degree of lymph node metastasis, and the invasion depth were significant predictors of para-aortic lymph node metastasis. Multivariate analysis showed that n2 was the only independent predictive factor as to para-aortic lymph node metastasis. Univariate analysis revealed tumor site, tumor diameter, lymph node metastasis, number of positive lymph nodes, INF, and stage were significantly associated with 5-year survival. The Cox's proportional hazards regression model showed that the number of positive lymph nodes and the number of positive para-aortic lymph nodes were independent prognostic factors. Patients with < or = 10 positive lymph nodes in any stage or < or = 3 positive para-aortic lymph nodes in stage IVb had significantly better surgical results. Surgical results for patients who underwent para-aortic lymph node dissection with n2 or invasion depth deeper than the exposed serosa were significantly higher than those in D2. As to post-operative complications, pancreatic fistula and respiratory complications were significantly frequent after para-aortic lymph node dissection. CONCLUSIONS: n2 is helpful in predicting para-aortic lymph node metastasis. Whereas, post-operative morbidity such as pancreatic fistula and respiratory complications after para-aortic lymph node dissection were significantly higher, they were controllable. Para-aortic lymph node dissection should be indicated in advanced gastric cancer patients in which lymph node metastasis is over n2 or invasion depth is deeper than the exposed serosa. But the number of positive para-aortic lymph nodes must be less than three.     

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study

BackgroundPancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma.MethodsA total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively.ResultsSixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival.ConclusionDirect invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.     

Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer

To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123–1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053–1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288–1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420–1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425–2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248–2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249–1.852) correlated with the 5-year survival rate.Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.     

Longterm survival after pancreaticoduodenectomy for periampullary adenocarcinomas

Objectives

The aim of this study was to identify predictors for longterm survival following pancreaticoduodenectomy (PD) for pancreatic and other periampullary adenocarcinomas.

Methods

Clinicopathological factors were compared between short-term (<5 years) and longterm (≥5 years) survival groups. Rates of actual 5-year and actuarial 10-year survival were determined.

Results

There were 109 (21.8%) longterm survivors among a sample of 501 patients. Patients with ampullary adenocarcinoma represented 76.1% of the longterm survivors. Favourable factors for longterm survival included female gender, lack of jaundice, lower blood loss, classical PD, absence of postoperative bleeding or intra-abdominal abscess, non-pancreatic primary cancer, earlier tumour stage, smaller tumour size (≤2 cm), curative resection, negative lymph node involvement, well-differentiated tumours, and absence of perineural invasion. Independent factors associated with longterm survival were diagnosis of primary tumour, jaundice, intra-abdominal abscess, tumour stage, tumour size, radicality, lymph node status and cell differentiation. The prognosis was best for ampullary adenocarcinoma, for which the rate of actual 5-year survival was 32.8%, and poorest for pancreatic head adenocarcinoma, for which actual 5-year survival was only 6.5%.

Conclusions

The majority of longterm survivors after PD for periampullary adenocarcinomas are patients with ampullary adenocarcinoma. The longterm prognosis in pancreatic head adenocarcinoma remains dismal.     

Venous and neural invasion as predictors of recurrence in rectal adenocarcinoma

After radical surgery for rectal adenocarcinoma, the presence of venous and neural invasion of tumor cells was correlated with the pattern of treatment failure, local in the pelvis or distant. Of 128 operation specimens, venous and neural invasion was demonstrated in 22 percent and 32 percent, respectively. A significant decrease of the distant recurrence-free 5-year survival (Kaplan-Meier method) was seen when venous invasion was demonstrated (32.9 percent vs. 84.3 percent; P <0.0001), whereas more local failures were registered in patients with neural invasion. The local recurrence-free 5-year survival in patients with neural invasion was 64.3 percent, compared with 81.1 percent when neural invasion was not demonstrated (P=0.03). Their prognostic value was then studied in a Cox regression model including stage and grade. Neural invasion had the strongest association with local recurrences, whereas venous invasion was found to be the third strongest independent predictor of metastasis, after lymph node status and extent of local tumor infiltration. We conclude that examining for the presence of venous and neural invasion gives reliable prediction of recurrences after radical resection of rectal cancer. Recording of tumor recurrence pattern may lead to a better selection of patients for adjuvant therapy after surgery.     

Risk Factors for Occult Lymph Node Metastasis of Colorectal Cancer Invading the Submucosa and Indications for Endoscopic Mucosal Resection

Purpose Although risk factors for histologically overt lymph node metastasis in patients with early-stage colorectal cancer have been clarified, the risk factors for occult lymph node metastasis are not clear. This study was designed to clarify risk factors for lymph node metastasis, including occult metastasis, in patients with colorectal cancer invading the submucosa and to determine the criteria for endoscopic resection of early colorectal cancer. Methods The risk factors for lymph node metastasis, including occult metastasis, were analyzed in 86 cases of surgically resected colorectal cancer invading the submucosa. The lymph nodes were assessed by immunohistochemistry with cytokeratin antibody CAM5.2. Results The frequencies of overt and occult metastasis to the lymph nodes were 13 percent (11/86) and 13 percent (10/75), respectively. Multivariate analysis showed vascular invasion (P = 0.001) and tumor budding (P = 0.003) to be independent risk factors for lymph node metastasis, including occult metastasis. For tumors with submucosal invasion ≤1,000 μm, no lymph node metastasis was found. The frequencies of lymph node metastasis for tumors with submucosal invasion of 1,000 to 2,000 μm and >2,000 μm were 21 and 37 percent, respectively. In considering combinations of risk factors, there was no lymph node metastasis in tumors having neither vascular invasion nor tumor budding and submucosal invasion of ≤3,000 μm. Conclusions Vascular invasion, tumor budding, and the degree of submucosal invasion were significant risk factors for lymph node metastasis, including occult metastasis. These three factors can be used in combination to identify patients requiring additional surgery after endoscopic resection. Supported in part by a Grant-in-Aid for Scientific Research (no. 15390401) from the Japanese Ministry of Education, Science, and Culture. Presented at the Congress of Japan Surgery Society, Tokyo, Japan, March 29 to 31, 2006. Reprints are not available.     

Prognostic value and interobserver agreement of endoscopic ultrasonography for superficial squamous cell carcinoma of the esophagus: a prospective study

Background and Aims. Submucosal invasion of superficial esophageal cancer (SEC) is related to the prognosis. We prospectively analyzed outcomes of SEC in patients staged by endoscopic ultrasonography (EUS). Patients and Methods. We staged 31 endoscopically diagnosed SEC cases using a 20/15-MHz thin probe. The EUS tumor stage was classified as EUSM (limited within mucosa), EUS-SM (with submucosal invasion), or EUS-MP over (invading the muscularis propria or deeper). Lymph node metastasis and 2-yr survival were analyzed according to the EUS tumor stage in 29 squamous cell carcinoma cases. Interobserver agreement of the EUS stage was tested between the examiner and a blind reviewer. Results. Lymph node metastasis was significantly frequent in the EUS-SM group (8 of 18 cases [44.4%]) compared with the EUS-M group (1 of 10 cases [10%]) (p=0.03). Patient survival at 2 yr after initial therapy was 72.2% in the EUS-SM group and 90% in the EUS-M group. Death from cancer was noted only in the EUS-SM group (three cases). The accuracy rates of EUS tumor staging were 74.1% by the examiner and 66.7% by the blind reviewer, with moderate interobserver agreement (κ=0.46). Conclusions. Thin-probe EUS can classify SEC into two groups: the EUS-M group with excellent outcome and the EUS-SM group with a significant risk of lymph node metastasis.     

Surgical treatment for carcinoma of the papilla of vater

Eighty of 89 patients who underwent radical resection (resectability 89.9%) for carcinoma of the papilla of Vater between 1976 and 1992 were retrospectively reviewed. Seventy-three patients underwent pancreaticoduodenectomy (PD) and 7 underwent pylorus-preserving pancreaticoduodenectomy (PPPD). The postoperative mortality rate was only 3.8% (3 patients). The 3- and 5-year survival rates were 63.6% and 57.4%, respectively. Important factors influencing long-term survival were Stage (clinical stage = Stage), microscopic lymph node metastasis (n), duodenal wall invasion (d), vascular invasion (v), and the epithelium of origin. Early carcinoma of the papilla of Vater is defined as tumor in which invasion is limited within the papilla of Vater; in particular, carcinomatous invasion is within the muscle of Oddi (d₀) with n₀. PD and/or PPPD with radical lymph node dissection should be performed for carcinoma of the papilla of Vater, as these procedures can be performed with low morbidity and mortality.     

The validity of sentinel lymph node biopsy using dye technique alone in patients with gastric cancer

BACKGROUND/AIMS: We investigated whether sentinel lymph node biopsy using dye technique alone is useful or not in decision-making for less invasive surgery in patients with gastric cancer. METHODOLOGY: The subjects were 43 patients who had undergone laparotomy for gastric cancer and consented to undergo sentinel lymph node biopsy using patent blue dye. The patients enrolled were 26 males and 17 females, with a mean age of 62.5 years. The tumor sites were upper third of the stomach in 14, middle third in 16, and lower third in 13 patients. The depth of invasion was mucosa in eight, submucosa in 19, muscularis propria in five, subserosa in five, and serosa in six patients. Total gastrectomy was performed in 12, subtotal gastrectomy in 28, and proximal gastrectomy in three patients. RESULTS: The mean number of sentinel lymph node biopsies per surgery was 3.5 +/- 4.1. We were able to perform blue node biopsy in 40 out of 43 patients, but could not find any blue nodes in three patients. Among the 40 patients in whom blue nodes were identified, 29 patients with no metastasis in blue nodes had no evidence of lymph node metastasis (NO). The depth of invasion was not deeper than subserosa in all these patients. Metastasis was observed in one out of the three patients in whom no blue nodes were found. CONCLUSIONS: When the depth of invasion was not deeper than the subserosa and blue nodes were identified, no metastases in either non-blue nodes or blue nodes could be found in the absence of metastatic blue nodes. Therefore, if the depth of invasion is not deeper than the subserosa in gastric cancer, metastatic search in blue nodes seems sufficient and less invasive surgery can be performed safely. Even when the invasion depth is not deeper than the submucosa, the tumor could be metastatic to Group 2 lymph nodes in patients in whom blue node biopsy revealed metastases. When metastasis is found in lymph nodes by intraoperative frozen section diagnosis, less invasive surgery for gastric cancer is not indicated.     

Postoperative morbidity/mortality and survival rates after total gastrectomy, with splenectomy/pancreaticosplenectomy for patients with advanced gastric cancer

BACKGROUND/AIMS: Indications for splenectomy in patients with proximal and middle gastric cancer remain controversial. We investigated characteristic findings in patients with lymph node metastasis to the splenic hilus and the indication of splenectomy with total gastectomy for T2 and T3 advanced gastric cancer. METHODOLOGY: Two hundred and forty-one Japanese patients underwent curative operations for T2 and T3 advanced gastric cancer. RESULTS: The mortality rates were similar, but the morbidity rate for patients who underwent pancreaticosplenectomy was higher than for patients who underwent either total gastrectomy alone or with splenectomy (p<0.007). The rates in cases of lymph node metastasis at the depth of tumor invasion within the subserosa and serosa (T3) were 1.7% and 17.5%, respectively (p<0.003). Lymph node metastasis to the splenic hilus was also evident in patients with T3 or T2 advanced gastric cancer with multiple lymph nodes metastasis (more than 7 nodes). The 10-year survival rates for patients who underwent total gastrectomy alone, with splenectomy, and with pancreaticosplenectomy in T3 advanced gastric cancers were 25%, 42% and 32%, respectively (p=0.184). CONCLUSIONS: Based on these data, the addition of distal pancreaticosplenectomy to total gastrectomy in patients with T2 and T3 advanced gastric cancer increased the risk of complications. Nevertheless, we recommend that total gastrectomy with splenectomy should be done for patients with T3 advanced gastric cancers [and T2 advanced gastric cancer with multiple lymph nodes metastasis (more than 7 nodes)], recognizing the lymph node metastasis to the splenic hilus.     

Mitotic indexes as prognostic predictors in female breast cancer

Summary A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, axillary lymph node status, histological grade, histological type and two mitotic indexes (M/V; MAI) were assessed and related to disease outcome. Primary tumour size (P<0.0001), the volume-corrected mitotic index (M/V) (P<0.0001), the mitotic activity index (MAI) (P=0.0001), and histological grade (P=0.0074) predicted axillary lymph node status. Recurrence as well as recurrence-free survival was significantly related to the axillary lymph node status (P<0.0001), M/V index (P<0.0001), MAI (P<0.0001), tumour size (P=0.0031) and histological grade (P=0.0208). Multivariate analyses disclosed the tumour size and M/V index as independent predictors of axillary metastasis at diagnosis. Recurrence was related independently to M/V index, axillary metastasis and tumour size. Independent predictors of recurrence-free survival in Cox's analysis were M/V index and axillary lymph node status. Axillary lymph node status (P<0.0001), tumour size (P<0.0001), M/V index (P<0.0001), MAI (P<0.0001) and histological grade (P=0.0009) predicted survical in that order. Cox's analysis showed that axillary lymph node status was the most important independent predictor of survival followed by tumour size and M/V index. In a separate Cox's analysis of axillary-lymph-node-negative patients the M/V index and tumour size were independently related to survival. In conclusion the M/V index is an important prognostic factor in breast cancer and also in axillary-lymph-node-negative breast tumours.Abbreviations MAI mitotic activity index - M/V index volume-corrected mitotic index     

Prognostic significance of perigastric lymph nodes metastases on survival in patients with thoracic esophageal cancer

Several publications have showed that the number of metastatic lymph node (LN) should be taken into consideration in nodal category of esophageal cancer, but seldom considered extent of involved regional LNs. The aim of this study is to evaluate the significance of the extent of regional LN metastasis on survival in patients with esophageal cancer. A total of 245 thoracic esophageal cancer patients underwent transthoracic esophagectomy with standard lymphadenectomy between January 2000 and December 2006 were included in the study. Data including demographic factors, pathologic findings, LN parameters and survival outcomes were collected. The survival experience was depicted using Kaplan‐Meier method. A multivariate Cox proportional hazard model was used to screen the significant prognostic factors. The univariate analysis to further explore the significant prognostic factor was done by log‐rank test. After a median follow‐up of 53.2 months, the 5‐year survival rate was 46.3% for the entire cohort. Cox model regression indicated that the LN status and perigastric nodal status, aside from residual tumor status, histological tumor type and depth of invasion, were the independent prognostic factors. Patients without LN metastasis had better 5‐year survival than those with positive nodes (64.2% vs. 18.9%, X²= 35.875, P < 0.001). However, For those patients with nodal involvement, there was no difference in 5‐year survival between patients with involved nodes <3 and ≥3 (27.8% vs. 0%, X²= 0.925, P= 0.336). When considering the location of LN metastasis, patients could be further stratified according to whether the perigastric nodes were involved or not (37.5% vs. 10.0%, X²= 4.295, P= 0.038). In conclusion, involved LN number had no prognostic implication in nodal involved patients based on our data. Whereas, perigastric nodal involvement should be used to refine the N category (N0, no nodal metastasis, N1, non‐perigastric node metastasis, N2, perigastric node metastasis) for the future esophageal cancer staging criteria.