Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

AIM: To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma.METHODS: Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays.Forty-three (41%) of the 106 patients were staged as pT1/2, 63 (59%) as pT3/4, 51 (48%) as pN0, and 55 (52%)as pN1. The study population included 59 (56%) patients exhibiting G1/2, and 47 (44%) patients with G3 tumors.Patients received no adjuvant chemo- or radiation therapy and were followed up for a median of 12 (range:3.5 to 139) mo.RESULTS: Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as "tumor free" by conventional histopathology in 73(69%) out of the 106 patients. Twenty-nine (57%)of 51 patients staged histopathologically as pN0 had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free (relative risk 2.92,P=0.005) and overall (relative risk 2.49, P=0.009) survival.CONCLUSION: The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports may help to improve risk stratification of patients with pancreatic cancer.     

Prognostic assessment of different lymph node staging methods for pancreatic cancer with R0 resection: pN staging,lymph node ratio,log odds of positive lymph nodes

Background and aimsSurvival after surgical resection of pancreatic adenocarcinoma is poor. Several prognostic factors such as the status of the resection margin, lymph node status, or tumour grading have been identified. The aims of the present study were to evaluate and compare the prognostic assessment of different lymph nodes staging methods: standard lymph node (pN) staging, metastatic lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in pancreatic cancer after pancreatic resection.Materials and methodsData were retrospectively collected from 143 patients who had undergone R0 pancreatic resection for pancreatic ductal adenocarcinoma. Survival curves (Kaplan–Meier and Cox proportional hazard models), accuracy, and homogeneity of the 3 methods (LNR, LODDS, and pN) were compared to evaluate the prognostic effects.ResultsMultivariate analysis demonstrated that LODDS and LNR were an independent prognostic factors, but not pN classification. The scatter plots of the relationship between LODDS and the LNR suggested that the LODDS stage had power to divide patients with the same ratio of node metastasis into different groups. For patients in each of the pN or LNR classifications, significant differences in survival could be observed among patients in different LODDS stages.ConclusionLODDS and LNR are more powerful predictors of survival than the lymph node status in patients undergoing pancreatic resection for ductal adenocarcinoma. LODDS allows better prognostic stratification comparing LNR in node negative patients.     

Value of rectal ultrasound in predicting staging and outcome in patients with rectal adenocarcinoma

PURPOSE: Transrectal ultrasonography is considered the best method to stage rectal cancer, and thus the need for preoperative radiotherapy. This retrospective study was designed to determine the prognostic value of uTN classification on survival of patients treated by preoperative radiotherapy and surgery.METHODS: A total of 218 patients with proven rectal adenocarcinoma were staged by transrectal ultrasonography before treatment. Transrectal ultrasonography reports were reviewed for TN classification, quality of examinations, and downstaging (pT < uT).RESULTS: Transrectal ultrasonography stages were as follows: uT1, n = 2; uT2, n = 61; uT3, n = 145; uT4, n = 10; uN0, n = 94; uN+, n = 124. After radiotherapy, based on operative specimen, lesions were staged as pT0, n = 27; pT1, n = 20; pT2, n = 60; pT3/4, n = 111; pN0, n = 160; pN+, n = 58; pM+, n = 10. Downstaging (measured as a reduction in TN level determined by transrectal ultrasonography and pathology of resected specimen) occurred in 42.6 percent for T and 38.1 percent for N. Five-year overall and disease-free survivals were 71.3 and 62.7 percent, respectively (median follow-up, 62 months). In univariate or multivariate analysis including parameters available before treatment, uT and age but not uN were statistically significant prognosis factor for overall survival. Patients with TN downstaging had significantly better overall survival. In multivariate analysis, including all parameters, only age, gender, pT, and pN+ status predicted poor outcome.CONCLUSIONS: In patients with rectal adenocarcinoma treated by preoperative radiotherapy, uT classification determined by transrectal ultrasonography before radiotherapy, pT and pN classification determined after radiotherapy, and tumor downstaging were predictors of survival contrary to uN. Only pTN classification, age, and gender were independent predictors in multivariate analysis.Presented at the meeting of the American Society for Gastrointestinal Endoscopy, Atlanta, Georgia, May 20 to 23, 2001.     

Significance of isolated tumor cells in lymph nodes among gastric cancer patients

Purpose To determine the frequency and prognostic impact of isolated tumor cells (ITC) in regional lymph nodes judged to be tumor free in conventional histopathology among gastric cancer patients.Methods Among 161 patients who underwent gastrectomy and D2-lymphadenectomy, 56 were staged pN0 (35%). Archival paraffin blocks of 1148 resected regional lymph nodes of those pN0 patients were reevaluated for ITC using monoclonal antibody Ber-EP4. Patients with and without ITC were compared with regard to the distribution of various clinicopathological factors. Prognostic impact of ITC was tested in uni- and multivariate analysis.Results Of 56 pN0 patients, 33 (59%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of ITC was not dependent on other clinicopathological factors. ITC impaired patients prognoses significantly in uni- as well as multivariate analyses [estimated 5-year survival rate: 82% for pN0_(i–) vs 58% for pN0_(i+) (p=0.059) and 15% for pN1/2 (p=0.0005 and p<0.0001, respectively)].Conclusion ITC are a frequent event in apparently tumor-free lymph nodes of gastric cancer patients and are overlooked by conventional histopathology. They are encountered even in limited stages of disease and impair patients prognoses. This should be borne in mind when advocating local resection for early gastric cancer.     

Metastasis of rectal cancer to lymph nodes and tissues around the autonomic nerves spared for urinary and sexual function

PURPOSE: To clarify the indications for autonomic nerve-sparing operations for rectal cancer, the presence of lymph nodes and metastasis in the tissue around the autonomic nerve were examined in 28 rectal cancer patients. These were staged as pT2 in 8 patients, pT3 in 19 patients, and pT4 in 1 patient histopathologically. METHODS: The specimens of the autonomic nerve including the inferior mesenteric plexus, preaortic plexus, superior hypogastric plexus, hypogastric nerve, and pelvic plexus were removed with radical abdominopelvic lymphadenectomy after the autonomic nerve-sparing rectal cancer operation. RESULTS: In the tissue around the autonomic nerve, lymph nodes were 11.2±9.6 in number and 2.6±2.4 mm in size (mean ± standard deviation). The frequency of presence of lymph nodes was higher and the number of lymph nodes was larger in the inferior mesenteric plexus (70.4 percent; 3.6) and the preaortic plexus (66.7 percent; 2.1) than in the left and right pelvic plexuses (39.1 percent, 1; 36 percent, 1). Metastasis to the lymph nodes or lymphatic permeation in the tissue around the autonomic nerve were observed in four cases (14.3 percent) of lower rectal cancer, consisting of three with Stage III cancer (pT3, pN1-3, and M0) and one with Stage IV cancer (pT4, pN1, and pM1 (HEP)). CONCLUSION: Radical rectal excision that includes lymph nodes and adjacent tissue around the autonomic nerves may result in metastatic tumor removal that would otherwise be left in situ with nerve-sparing techniques for advanced rectal cancer in Stage III.     

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.     

Limitations and pitfalls of transrectal ultrasonography for staging of rectal cancer

PURPOSE: This study was designed to evaluate the accuracy of preoperative staging by transrectal ultrasonography (TRUS) and to clarify the limitations and pitfalls of TRUS by clinicopathologic analysis for staging errors. MATERIALS AND METHODS: Results of TRUS for 164 consecutive patients with rectal cancer were compared prospectively with histopathologic findings according to the newest TNM classification. Clinicopathologic factors that may influence staging errors were analyzed by reviewing both resected specimens and hard copies of TRUS. RESULTS: There were 13 patients histopathologically staged as pTis, 21 as pT1, 34 as pT2, 84 as pT3, 12 as pT4, 73 as pN0, and 91 as pN1–3. Of these, 85, 86, 56, 93, 75, 74, and 77 percent, respectively, were correctly staged by TRUS. Excluding 12 cases with incomplete examinations because of annular constricting tumors, overstaging of tumor invasion depth was mostly caused by tumor invasion close to the deeper uninvolved layer, inflammatory cell aggregation, desmoplastic change, and hypervascularity around the tumor, mimicking tumor invasion on TRUS. The understaging was mostly the result of microscopic invasion beyond the estimated layers and difficulties in examination because of the tumor location being close to the anal canal or on the Houston's valves or the tumor shapes being polypoid or bulky and fungating. Overstaging in lymph node status was caused by reactive lymph node swelling and understaging by the presence of only small involved node and metastasis in the extramesorectal nodes. CONCLUSIONS: An awareness of the limitations and pitfalls of TRUS, as demonstrated by the present study, should improve staging accuracy and contribute to optimum clinical decision-making.     

Evaluating the adequacy of nodal status in node-negative gallbladder cancer with T1b-T2 stages: use of nodal staging score

BackgroundThe study aimed at establishing a nodal staging score (NSS) to quantify the likelihood that pathologic node-negative gallbladder cancer (GBC) patients are indeed free of lymph node (LN) metastasis.MethodsClinicopathological data of 1374 GBC patients with T1b-T2 stages were collected from the Surveillance, Epidemiology and End Result database (design cohort [DC], n = 1289) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 85). NSS was derived from the count of examined LNs (ELNs) and T stage by using a beta-binomial model, and represented the probability that a node-negative patient is correctly staged. The prognostic value of NSS in node-negative GBC was evaluated by survival analysis.ResultsThe probability of missing a nodal disease in node-negative GBC patients with T1b-T2 stages (pT1bN0 and pT2N0) decreased as the number of ELNs increased. NSS increased as the number of ELNs increased. For pT1bN0 and pT2N0 patients, examination of 5 and 27 lymph nodes could ensure an NSS of 90.0%, respectively. Multivariate analysis revealed that NSS was an independent predictor for overall survival in pT1bN0 and pT2N0 GBC patients (DC, HR:0.53, 95%CI: 0.42–0.66, p < 0.001; VC, HR: 0.33, 95%CI: 0.14–0.76, p = 0.009).ConclusionNSS could evaluate the adequacy of nodal staging and predict the prognosis in pT1bN0 and pT2N0 GBC patients, and hence was helpful to guide their treatment strategies.     

Clinical results of extended lymphadenectomy and intraoperative radiotherapy for pancreatic adenocarcinoma

BACKGROUND/AIMS: The efficacy of extended lymphadenectomy and intraoperative radiotherapy for resectable pancreatic cancer is controversial. The objective of this study was to clarify the surgical outcome after pancreatic resection with extended lymphadenectomy or intraoperative radiotherapy in patients with pancreatic adenocarcinoma. METHODOLOGY: Between 1992 and 2002, 105 patients with pancreatic adenocarcinoma undergoing surgical resection were retrospectively analyzed. Eighty-eight patients had invasive ductal adenocarcinoma and 17 had invasive intraductal papillary mucinous adenocarcinoma. Seventy-six patients underwent pancreatic resection with extended lymphadenectomy and 44 received 20 Gy intraoperative radiotherapy. RESULTS: Patients with invasive intraductal papillary mucinous adenocarcinoma had a similar prognosis to those with invasive ductal adenocarcinoma. There was no significant difference in survival (p = 0.86) between patients with and without extended lymphadenectomy. There was no significant difference in survival (p = 0.053) between patients with and without intraoperative radiotherapy. Patients without lymph node metastasis had a significantly better prognosis (p = 0.0015) than those with nodal involvement. CONCLUSIONS: Neither extended lymphadenectomy nor intraoperative radiotherapy showed a survival advantage in patients with resectable pancreatic adenocarcinoma. Pancreatic cancer patients without nodal involvement had a significantly better prognosis than those with nodal involvement.     

Long term survival after pancreatic resection for pancreatic adenocarcinoma

OBJECTIVE: The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival. METHODS: Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.     

Preoperative Standardized Uptake Value of Metastatic Lymph Nodes Measured by 18F-FDG PET/CT Improves the Prediction of Prognosis in Gastric Cancer

This study assessed whether preoperative maximum standardized uptake value (SUVmax) of metastatic lymph nodes (LNs) measured by ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) could improve the prediction of prognosis in gastric cancer.One hundred fifty-one patients with gastric cancer and pathologically confirmed LN involvement who had undergone preoperative ¹⁸F-FDG PET/CT prior to curative surgical resection were retrospectively enrolled. To obtain nodal SUVmax, a transaxial image representing the highest ¹⁸F-FDG uptake was carefully selected, and a region of interest was manually drawn on the highest ¹⁸F-FDG accumulating LN. Conventional prognostic parameters and PET findings (primary tumor and nodal SUVmax) were analyzed for prediction of recurrence-free survival (RFS) and overall survival (OS). Furthermore, prognostic accuracy of survival models was assessed using c-statistics.Of the 151 patients, 38 (25%) experienced recurrence and 34 (23%) died during follow-up (median follow-up, 48 months; range, 5–74 months). Twenty-seven patients (18%) showed positive ¹⁸F-FDG nodal uptake (range, 2.0–22.6). In these 27 patients, a receiver-operating characteristic curve demonstrated a nodal SUVmax of 2.8 to be the optimal cutoff for predicting RFS and OS. The univariate and multivariate analyses showed that nodal SUVmax (hazard ratio [HR] = 2.71, P < 0.0001), pathologic N (pN) stage (HR = 2.58, P = 0.0058), and pathologic T (pT) stage (HR = 1.77, P = 0.0191) were independent prognostic factors for RFS. Also, nodal SUVmax (HR = 2.80, P < 0.0001) and pN stage (HR = 2.28, P = 0.0222) were independent prognostic factors for OS. A predictive survival model incorporating conventional risk factors (pT/pN stage) gave a c-statistic of 0.833 for RFS and 0.827 for OS, whereas a model combination of nodal SUVmax with pT/pN stage gave a c-statistic of 0.871 for RFS (P = 0.0355) and 0.877 for OS (P = 0.0313).Nodal SUVmax measured by preoperative ¹⁸F-FDG PET/CT is an independent prognostic factor for RFS and OS. Combining nodal SUVmax with pT/pN staging can improve survival prediction precision in patients with gastric cancer.     

Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications

PURPOSE: Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy. METHODS: A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m²) and leucovorin (20 mg/m²) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy. RESULTS: Among 60 patients (20 females) there was a mean age of 58.7 (28–84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only). CONCLUSIONS: Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy.Presented at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, June 24 to 29, 2000.     

Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology

BackgroundCurrent treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are related with overall and early recurrence after pancreatectomy for PDAC.MethodsRetrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence.Results261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3–4 Clavien–Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3–4 Clavien–Dindo complications (OR: 3.05) were independent risk factors for early recurrence.ConclusionAlthough overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.     

Long-term results of central inferior (S4a+S5) hepatic subsegmentectomy and pancreatoduodenectomy combined with extended lymphadenectomy for gallbladder carcinoma with subserous or mild liver invasion (pT2-3) and nodal involvement: a preliminary report

BACKGROUND/AIMS: Gallbladder carcinoma, especially advanced cancer that has invaded the subserosal or deeper layers, has a poor prognosis. Recently, radical operations combining resection of the liver and pancreas with extended lymph node dissection have been introduced to improve the prognosis of advanced gallbladder carcinoma. We have introduced central inferior (Couinaud's subsegments 4a and 5; S4a+S5) hepatic subsegmentectomy and pancreatoduodenectomy combined with extended lymphadenectomy for gallbladder carcinoma demonstrating subserous or mild liver invasion (pathological tumor stage pT2-3) and nodal involvement. METHODOLOGY: Morbidity, mortality, clinicopathological features, and long-term outcome were analyzed retrospectively for seven consecutive patients who underwent this radical operation. RESULTS: The postoperative morbidity rate was 57.1% and there was no surgical mortality. All patients had lymph node involvement: two had pN1 disease and five had pN2 disease. All patients underwent curative resection. Only one patient developed gallbladder carcinoma recurrence after resection and it involved the paraaortic lymph nodes. Five patients, three of whom displayed pN2 disease, survived longer than 5 years postoperatively with no evidence of disease. CONCLUSIONS: S4a+S5 hepatic subsegmentectomy and pancreatoduodenectomy combined with extended lymphadenectomy improve the long-term survival of gallbladder carcinoma with pT2-3 and nodal involvement. The presence of pN2 disease is not a contraindication for surgery. Further study is necessary to evaluate the usefulness of this radical procedure, especially as a standard operation.     

Worldwide esophageal cancer collaboration

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62 ± 11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3 ± 2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC.     

"Extended" radical cholecystectomy for gallbladder cancer: Long-term outcomes, indications and limitations

AIM: To delineate indications and limitations for "extended" radical cholecystectomy for gallbladder cancer: a procedure which was instituted in our department in 1982.METHODS: Of 145 patients who underwent a radical resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2). Pathological findings were documented according to the American Joint Committee on Cancer Cancer Staging Manual (7th edition).RESULTS: The primary tumor was classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty-three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giving an in-hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the pT classification (P < 0.001) and the nodal status (P = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection, distant metastasis, or extensive extrahepatic organ involvement died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node-positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes).CONCLUSION: Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure.     

EUS in preoperative staging of pancreatic cancer

BACKGROUND: Endoscopic ultrasound (EUS) is believed to be highly accurate in the local (T) and nodal (N) staging of pancreatic cancer. However, there are scant data concerning the predictive value of EUS for resectability of pancreatic adenocarcinoma. This study was performed to determine the accuracy of TNM staging by EUS in patients with pancreatic adenocarcinoma and to evaluate the role of preoperative TNM staging by EUS for determining resectability in patients with pancreatic adenocarcinoma. METHODS: This is a retrospective review of a cohort of 89 patients evaluated preoperatively with EUS for pancreatic adenocarcinoma between January 1995 and December 1997. Preoperative TNM classification by EUS was compared with surgical and histopathologic TNM staging. Resectability rates were determined and compared with the preoperative TNM staging by EUS. RESULTS: The overall accuracy of EUS for T and N staging was found to be 69% and 54%, respectively. The overall proportion of tumors that were deemed resectable by EUS and were actually found to be resectable during surgical exploration was 46%. The proportion of tumors staged as T4 N1, T4 N0, T3 N1 and T3 N0 by EUS that were found to be resectable during surgical exploration was 45%, 37%, 44% and 62%, respectively. CONCLUSIONS: In a tertiary referral patient population, EUS is not as accurate as previously reported in the T and N staging of pancreatic cancer. EUS is also not predictive of resectability in stage T3 or T4 pancreatic cancer.     

Clinicopathologic factors correlated with number of metastatic lymph nodes in oesophageal cancer

BACKGROUND: The number of metastatic lymph nodes is applied to the staging system of gastric cancer and colorectal cancer. However, it has not been evaluated in oesophageal cancer. PATIENTS AND METHODS: Of 258 patients with primary squamous cell carcinoma of the thoracic oesophagus between February 1981 and December 1999, 160 underwent three-field oesophagectomy with a curative intent. Clinicopathologic characteristics of those 160 patients were retrospectively investigated according to the number of metastatic lymph nodes. RESULTS: Seventy-eight patients had no lymph node metastases and 82 (51.3%) had lymph node metastases; 51 [31.9%)] had between 1 and 4 positive lymph nodes, and 31 (19.4%) had > or =5. The number of metastatic lymph nodes was significantly correlated with tumour size, macroscopic classification, histological differentiation, pT, pN, and vessel invasions. Multivariate analysis showed that lymph vessel invasion (relative risk 12.6), histological differentiation (relative risk 4.2), and tumour size (relative risk 3.8) were independent factors correlated with number of metastatic lymph nodes. The number of metastatic lymph nodes was also well correlated with the Japanese nodal level and TNM stage, respectively (p<0.001). The 5-year disease-specific survival rate according to the number of positive lymph nodes was 90% for patients without lymph node metastases, 52.2% with 1-4, and 28.9% with > or =5, respectively, p<0. 0001; 0 vs 1-4, p<0.05; 1-4 vs > or =5). CONCLUSION: The number of positive lymph nodes is well correlated with tumour progression and provides a useful prognostic indicator after oesophagectomy for oesophageal cancer.