Different prognosis of patients with esophageal carcinoma with M1a and regional node involvement

Background and purposeBased on the 6th edition of the American Joint Commission on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC), M1a node involvement was classified as regional node involvement in the revised 7th/8th edition. However, the clinical significance of M1a node involvement is unclear. Thus, we analyzed the prognostic value of M1a node involvement in patients with ESCC after definitive concurrent chemoradiotherapy (CCRT).Materials and methodsIn total, 188 patients with ESCC had M0 disease according to the 7th/8th edition AJCC. We reclassified 31 (16.5%) of these patients as having M1a disease according to the 6th edition. After definitive CCRT, we compared baseline characteristics between the two groups and analyzed the rates of responders and recurrence. Finally, we compared prognoses according to overall survival (OS), disease-specific OS, and disease-free survival (DFS).ResultsAmong 31 patients reclassified to have M1a disease, 21 (67.7%) had supraclavicular lymph node metastasis and 10 (32.3%) had celiac lymph node metastasis. The number of responders was significantly lower for M1a disease based on univariate (p = 0.004) and multivariate (p = 0.011) analyses. Significantly lower survival rates were observed in individuals with M1a disease (median OS, 16.4 vs. 42.7 months; 5-year OS, 10.8% vs. 41.2%).ConclusionsM1a node involvement should be differentiated from regional node involvement.     

Comparison of morphological features in lymph node metastasis between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinomas

BackgroundVarious studies have reported inconsistent results regarding the use of lymph node size for the prediction of metastasis in pancreatic cancer. Further, there is even less information in pNENs. Thus, the clinical accuracy and utility of using lymph node size to predict lymph node metastasis in pNENs has not been fully elucidatedObjectivesThis study aimed to examine differences in lymph node morphology between pancreatic neuroendocrine neoplasms (pNENs) and pancreatic ductal adenocarcinomas (PDACs) to create more accurate diagnostic criteria for lymph node metastasis.MethodsWe assessed 2139 lymph nodes, 773 from pNEN specimens and 1366 from PDAC specimens, surgically resected at our institute between 1994 and 2016. We evaluated the number, shape, size, and presence of metastasis.ResultsSixty-eight lymph nodes from 16 pNEN patients and 109 lymph nodes from 33 PDAC patients were metastatic. There were more lymph nodes sampled per case in the PDAC group than in the pNEN group (31.8 vs. 18.0). Metastatic lymph nodes in pNEN patients were larger and rounder than those in PDAC patients (minor axis: 5.15 mm vs. 3.11 mm; minor axis/major axis ratio: 0.701 vs. 0.626). The correlation between lymph node size and metastasis was stronger in pNENs (r = 0.974) than in PDACs (r = 0.439).ConclusionsLymph node status and morphology are affected by differences in tumor histology. The lymph node minor axis is a reliable parameter for the prediction of lymph node metastasis and has more utility as a predictive marker in pNENs than in PDACs.     

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC pa     

The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy

Background

Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood.

Methods

This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients.

Results

FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy.

Conclusions

This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.

     

Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases

BackgroundThe aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy.MethodsConsecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers.ResultsIn the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97–2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09–2.69) were independent poor prognostic factors in the resected cohort.ConclusionPatients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.     

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.     

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer

ObjectiveDNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC.Patients and MethodsPatients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed.Results130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48–9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04–3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13–5.48, p = 0.023) and high post-operative CA 19–9 level (>100 IU/ml) (HR:2.61 95% CI 1.40–4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53.ConclusionContrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.     

Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy

BackgroundThe decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas.ObjectivesWe aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs.MethodsThis single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis.ResultsAfter excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group.ConclusionsIn patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.     

Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma

Background/objectiveWe evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0–1) based on anatomical (A) and biological dimensions (B).MethodsFrom 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 < 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; n = 53) groups.ResultsThe 3 groups were comparable according to patient characteristics (except for back pain (P < .01) and CA 19-9 (P < .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P < .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P < .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P < .001), respectively.ConclusionsThe 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.     

Meta-analysis of randomized clinical trials of adjuvant chemotherapy for resected biliary tract cancers

BackgroundThis meta-analysis was performed by analyzing randomized controlled trials (RCTs) to assess the potential prognostic value of adjuvant chemotherapy (ACT) for patients with resected biliary tract cancers (BTCs).MethodsPubMed, EMBASE, and the Cochrane Library were searched for relevant articles published. Only RCTs affected by tumors of gallbladder, intrahepatic, perihilar, and distal bile ducts were considered. Data were pooled using a random-effects model. The primary endpoint of the study was overall survival (OS).ResultsThe study identified 1192 patients who met the inclusion and exclusion criteria. ACT had nearly reached a significant better OS (HR, 0.88; 95% CI, 0.77–1.01; P = 0.07) and achieved a significant better RFS (HR, 0.83; 95% CI, 0.69–0.99; P = 0.04). The effectiveness of ACT for OS was significantly modified by fluorouracil-based ACT (HR, 0.83; 95% CI, 0.70–0.99; P = 0.04), but not by gemcitabine-based ACT (HR, 0.91; 95% CI, 0.74–1.12; P = 0.36). The survival benefit was also not modified by primary disease site, resection margin status, and lymph node status.ConclusionsACT is correlated with favorable relapse-free survival compared with non-ACT for resected BTCs patients. Fluorouracil-based ACT could be viewed as a standard practice for resected BTCs patients regardless of the primary cancer site, lymph node or margin status.     

EUS-guided reverse bevel fine-needle biopsy sampling and open tip fine-needle aspiration in solid pancreatic lesions – a prospective,comparative study

Objectives: Different diagnostic entities can present as solid pancreatic lesions (SPL). This study aimed to explore the utility of endoscopic ultrasound-guided reverse bevel fine-needle biopsy sampling (EUS-FNB) in SPLs.

Material and methods: In 2012–2015, consecutive patients with SPLs were prospectively included in a tertiary center setting and subjected to dual needle sampling with a 22 gauge reverse bevel biopsy needle and a conventional 25 gauge open tip aspiration needle (EUS-FNA). The outcome measures were the diagnostic accuracy of sampling, calculated for each modality separately and for the modalities combined (EUS-FNA?+?FNB), and the adverse event rate related to sampling.

Results: In 68 unique study subjects, the most common diagnostic entities were pancreatic neuroendocrine tumor, PNET, (34%), pancreatic ductal adenocarcinoma, PDAC, (32%), pancreatitis (15%) and metastasis (6%). The overall diagnostic accuracy of EUS-FNB was not significantly different from that of EUS-FNA, (69% vs. 78%, p?=?.31). EUS-FNA?+?FNB, compared with EUS-FNA alone, had a higher sensitivity for tumors other than PDAC (89% vs. 69%, p?=?.02) but not for PDACs (95% vs. 85%, p?=?.5). No adverse event was recorded after the study dual-needle sampling procedures.

Conclusions: Endoscopic ultrasound-guided tissue acquisition performed with a 22 gauge reverse bevel biopsy needle is safe but not superior to conventional fine-needle aspiration performed with a 25 gauge open tip needle in diagnosing solid pancreatic lesions. However, the performance of both these modalities may facilitate the diagnostic work-up in selected patients, such as cases suspicious for pancreatic neuroendocrine tumors and metastases. NCT02360839.     

Outcome after surgery for invasive intraductal papillary mucinous neoplasia compared to conventional pancreatic ductal adenocarcinoma – A Swedish nationwide register-based study

BackgroundThe clinical importance of intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Long-term survival after resection for invasive IPMN (inv-IPMN) compared to conventional pancreatic ductal adenocarcinoma (PDAC) is not thoroughly delineated.ObjectiveThis study, based on the Swedish national pancreatic and periampullary cancer registry aims to elucidate the outcome after resection of inv-IPMN compared to PDAC.MethodsAll patients ≥18 years of age resected for inv-IPMN and PDAC in Sweden between 2010 and 2019 were included. Clinicopathological variables were retrieved from the national registry. The effect on death was assessed in two multivariable Cox regression models, one for patients resected 2010–2015, one for patients resected 2016–2019. Median overall survival (OS) was estimated using the Kaplan-Meier method.ResultsWe included 1909 patients, 293 inv-IPMN and 1616 PDAC. The most important independent predictors of death in multivariable Cox regressions were CA19-9 levels, venous resection, tumour differentiation, as well as T-, N-, M-stage and surgical margin. Tumour type was an independent predictor for death in the 2016–2019 cohort, but not in the 2010–2015 cohort. In Kaplan-Meier survival analysis, inv-IPMN was associated with longer median OS in stage N0-1 and in stage M0 compared to PDAC. However, in stage T2-4 and stage N2 median OS was similar, and in stage M1 even shorter for inv-IPMN compared to PDAC.ConclusionIn this population-based nationwide study, outcome after resected inv-IPMN compared to PDAC is more favourable in lower stages, and similar to worse in higher.     

A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion

Background: The purpose of this study was to re-evaluate echo features of lymph nodes during endoscopic ultrasound and assess the utility of these echo features and endoscopic ultrasound–guided fine-needle aspiration in predicting malignant lymph node invasion. Methods: Thirty-five lymph nodes in 25 patients with lung, esophageal, and pancreatic cancer were evaluated by endoscopic ultrasound. Endoscopic ultrasound examinations were performed with a radial scanning echoendoscope. Confirmation of benign lymph nodes was obtained by surgical resection while malignant lymph nodes were confirmed by real-time endoscopic ultrasound–guided fine-needle aspiration with a linear array echoendoscope. Results: Nineteen benign lymph nodes and 16 malignant lymph nodes in the mediastinum, celiac axis, and the peripancreatic area were included in the study. The following echo features were compared between benign and malignant lymph nodes: size greater than 1 cm, hypoechoic, distinct margins, and round shape. No single feature independently predicted malignant invasion. When all four of the above features were present in the same lymph node, the accuracy for predicting malignant invasion was 80%. However, all four features of malignant involvement were present in only 25% (4 of 16) of malignant lymph nodes. Our study also suggests that the above echo features may be a less reliable predictor of malignant invasion in pulmonary malignancies when compared to gastrointestinal cancers. Endoscopic ultrasound–guided fine-needle aspiration of lymph nodes in 22 patients revealed malignant lymph node invasion in 16 and benign cells in 6 patients. Conclusion: Endoscopic ultrasound–guided fine-needle aspiration is an important adjunct for accurate lymph node assessment for malignancy. (Gastrointest Endosc 1997;45:474-9.)     

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/ lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared =21.94;P <0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.Read at the meeting of the Japanese Society of Gastroenterological Surgery, Tokyo, Japan, February 24 to 25, 1994.     

Factors influencing receipt of adjuvant chemotherapy after surgery for pancreatic cancer: a two-center retrospective cohort study

Objective: The addition of adjuvant chemotherapy after surgical resection has improved survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). However, outside clinical trials, many operated patients still do not receive adjuvant chemotherapy due to clinical and tumor-related factors. The aim of this study was to investigate factors that may influence the receipt of adjuvant chemotherapy and the effect on long-term survival.

Materials and methods: Patients undergoing macroscopically curative resection for PDAC at the University Hospitals in Lund and Linköping, Sweden, between 1 January 2007 and 31 December 2015, were retrospectively reviewed. Clinical and pathological data were compared between adjuvant and non-adjuvant chemotherapy groups and factors affecting chemotherapy receipt were analyzed by multiple logistic regression. Multivariable Cox regression analysis was performed to select predictive variables for survival.

Results: A total of 233 patients were analyzed. Adjuvant chemotherapy was administered to 167 patients (71.7%). The likelihood of receiving adjuvant chemotherapy decreased with age, OR 0.91, 95% CI 0.86–0.95, p?<?.001. Moreover, patients with severe postoperative complications (Clavien–Dindo grade ≥?III) were less likely to receive adjuvant chemotherapy, OR 0.31, 95% CI 0.14–0.71, p?=?.005. The presence of lymph node metastases on histopathological reporting was associated with increased likelihood of initiating adjuvant chemotherapy, OR 2.19, 95% CI 1.09–4.40, p?=?.028. Adjuvant chemotherapy was an independent factor for prolonged survival on multivariable Cox regression analysis, HR 0.45 (95% CI 0.31–0.65), p?<?.001.

Conclusions: Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.     

Relationship of apical lymph node involvement to survival in resected colon carcinoma

In a prospective study of 197 patients with resected colon carcinoma treated between 1974 and 1985, we explored the relationships between pathologic parameters, and the effect of the latter on survival, to identify the parameter whose systematic measurement would improve the predictive capacity of pathologic staging. Prognostic characteristics were studied by univariate analysis. The results showed significant relationships between the location and number of lymph nodes involved, blood vessel invasion, depth of tumor penetration, and metastases. The five-year survival rates were 45 percent and 17 percent (P < 0.001) for patients without and with apical lymph node involvement, respectively, and 44 percent and 6 percent (P <0.05) for those with four or less nodes involved and more than four involved, respectively. Among the patients treated by incomplete resection, the respective survival rates of those resected for metastases and of those resected for apical lymph node involvement did not differ significantly. We conclude that the involvement of apical lymph nodes has a significant effect on prognosis and suggest systematic pathologic examination of these nodes to allow simpler and more reproducible selection of patients for treatment by incomplete resection who are at high risk of disease-related death.     

Ultrastaging of Rectal Cancer Based on Identification of Micrometastases in Sentinel Lymph Node

AbstractBackground and Purpose: Almost one third of patients with node-negative rectal carcinoma develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. In this study sentinel lymph node (SLN) mapping and a focused pathologic examination were combined to detect occult nodal metastases in rectal carcinoma.Patients and Methods: Since 1999, SLN mapping has been performed in 53 consecutive patients undergoing surgery for rectal carcinoma. Peritumoral injection of 0.5–1.0 ml of patent blue dye was performed to demonstrate the SLNs. All lymph nodes in the resected specimen were examined by routine hematoxylin-eosin (HE) staining. In addition, a focused examination of multiple sections of the negatively stained HE lymph node was performed using anti-carcinoembryonic antigen and monoclonal anti-cytokeratin.Results: Overall, lymphatic mapping was successful in 47 patients (88.7%). The number of patients with negative SLN and positive non-SLN amounted to four (skip lesion), two of them detected by HE staining and the others by immunostaining. Sensitivity was 81.6%, specificity 80%, and negative predictive value 63.2%. Negative HE staining and positive immunostaining were observed in 13 of 28 patients (stage B; 46%), nine SLN and four non-SLN. SLN detection proved to be successful when there was no evident lymph node involvement. Focused examination of the SLN identified seven cases (17.5%) of additional upstaging disease for stage pT1–3 N0 M0 tumor.Conclusion: Upstaging by combination of immunostaining and SLN mapping may have important implications for adjuvant treatment in future protocols.     

Prognostic value of positive histological margins in patients with pancreatic head ductal adenocarcinoma and lymph node involvement: an international multicentric study

BackgroundResection margin status and lymph node (LN) involvement are known prognostic factors for patients who undergo pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). This study aimed to compare overall survival (OS) and disease-free survival (DFS) by resection margin status in patients with PDAC and LN involvement.MethodsA retrospective international multicentric study was performed including four Western centers. Multivariable Cox analysis was performed to identify prognostic factors of OS and DFS. Median OS and DFS were calculated using Kaplan–Meier curves and compared using log-rank tests.ResultsA cohort of 814 PDAC patients with pancreatoduodenectomy were analyzed. A total of 651 patients had LN involvement (80%). On multivariable analysis R1 resection was not an independent factor of worse OS and DFS in patients with LN involvement (HR 1.1, p = 0.565; HR 1.2, p = 0.174). Only tumor size, grade, and adjuvant chemotherapy were associated with OS and DFS. Median OS and DFS were similar between patients with R0 and R1 resections (23 vs. 20 months, p = 0.196; 15 vs. 14 months, p = 0.080).ConclusionResection status was not identified as predictor of OS or DFS in PDAC patients with LN involvement. Extensive surgery to achieve R0 resection in such patients might not influence the disease course.     

Survival outcomes and prognostic factors of primary small cell carcinoma of the esophagus

BackgroundPrimary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive malignancy. It has a poor survival rate, and there is no consensus as to a standard therapeutic modality. In this study, we aimed to investigate the prognostic factors and evaluate the outcomes of patients with PSCCE who had been treated with different therapeutic methods.MethodsWe retrospectively evaluated 113 consecutive patients with PSCCE who received treatment at our center from 2003 to 2016. The primary endpoint was overall survival (OS). The Cox regression model was used to analyze the prognostic factors. The survival analysis was calculated using the Kaplan-Meier and log-rank methods.ResultsThe 12- and 36-month OS rates of all 113 enrolled patients were 45% and 12%, respectively. A significantly prolonged OS rate was associated with lymph node stages N0–N1 (P=0.022), the Veterans’ Administration Lung Study Group (VALSG) system limited-disease (LD) staging (P=0.040), and multimodality treatments (P=0.047). Patients with regional lymph node metastasis benefited more from surgery combined with chemotherapy than surgery or chemotherapy alone (P=0.046). Concerning chemotherapy, cisplatin plus etoposide was the regimen most commonly used to treat PSCCE patients (67.5%).ConclusionsAn early lymph node stage, the VALSG LD staging, and multimodality treatments were identified as independent prognostic factors of PSCCE. Surgery combined with adjuvant chemotherapy was especially necessary for LD stage PSCCE patients with lymph node stages N1–3.     

The role of hepatic artery lymph node in pancreatic adenocarcinoma: prognostic factor or a selection criterion for surgery

BackgroundHepatic artery lymph node (HALN) metastasis in pancreatic adenocarcinoma reportedly confers a survival disadvantage. This has led some authors to propose it as an indicator against pancreaticoduodenectomy (PD).MethodsConsecutive patients who underwent PD during 2002–2012 were identified from the University of Louisville prospective hepatopancreaticobiliary database. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier analysis. The log-rank test and multivariate Cox proportional hazards regression were used in further analyses.ResultsA total of 420 patients underwent PD during the period of study, of whom 197 had lymph node (LN) metastasis. Among these, 41 (20.8%) patients had disease-positive HALNs. The HALN was the only site of LN metastasis in only three of the 247 patients (1.2%). Median follow-up was 18.5 months (interquartile range: 4.1–28.2 months). Median OS and DFS were 22.7 months [95% confidence interval (CI) 19.0–26.3] and 12.6 months (95% CI 10.2–15.2). There was no significant difference in median OS between HALN-positive patients (18.4 months, 95% CI 12.3–24.0) and HALN-negative patients (19.7 months, 95% CI 16.7–22.6) (P = 0.659). On multivariate analysis, the hazard ratio (HR) of death was highest among patients with an LN ratio of >0.2 (HR 1.2, 95% CI 1.1–1.29; P = 0.012) followed by those with poorly differentiated histology (HR 1.09, 95% CI 1.04–1.11; P = 0.029).ConclusionsIn pancreatic adenocarcinoma patients with LN disease, survival after PD is comparable regardless of HALN status. Therefore, HALN-positive disease should not preclude the performance of PD.