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Background: For patients with periampullary adenocarcinoma (PAC), pancreatoduodenectomy (PD) provides the best survival. Surgery on a subset of patients is aborted during PD. We analyzed these patients., Methods: Patients who underwent laparotomy for planned PD for PAC were identified (2006-2019). From operative notes, we identified the subset with intraoperative decision to abort. Patient, treatment, and outcome data were analyzed. The subset with pancreatic ductal adenocarcinoma (PDAC) was analyzed for survival., Results: Only 6.7% (n = 55/819) of cases were aborted. Majority 78% (n = 43) had pathologically-confirmed diagnoses at time of surgery, and 18.2% (n = 10) received preoperative chemotherapy. Reasons for aborted PD included: distant metastases (65.5%, n = 36) and local invasion (34.5%, n = 19). Of patients with metastatic disease, 75% (n = 27) had liver metastases. Eighty-nine percent (n = 49) of patients underwent at least one palliative bypass procedure and 81.8% (n = 45) had both gastric and biliary bypass. Patients with computed tomography (CT) scans before surgery more commonly had missed metastatic disease (79.2% CT compared to 54.8% magnetic resonance imaging [MRI], χ 2  = 3.54, p = 0.059). In PDAC, 61.4% (n = 27/44) were aborted for metastatic disease and 38.7% (n = 17/44) for local invasion. Median overall survival for all PDAC patients after aborted PD was 334 days., Conclusion: Majority of pancreatoduodenectomies for periampullary adenocarcinoma are done to completion. Liver metastases is the most common reason for aborting. Preoperative MRI may help identify hepatic metastases., (© 2022 Wiley Periodicals LLC.)

Background: Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct outcomes, treatment strategies, and response profiles to therapy. Adenosquamous carcinoma (ASC) is thought to behave more aggressively than each of its counterparts. The aim of this study is to determine ifASC is best managed as AC or SCC., Methods: National Cancer Database (2004-2015) was queried for patients with nonmetastatic esophageal ASC. The analysis was stratified by clinical node-negative (cN0) or clinical node-positive (cN1-3). Treatment was categorized into chemoradiation alone, surgery alone, or preoperative chemoradiation followed by surgery. The primary outcome was 5-year overall survival (OS)., Results: Among 352 patients, 43% were cN0 (n = 151), 57% were cN1-3 (n = 201) and 55% had chemoradiation alone (n = 194), 15% surgery alone (n = 53), and 30% preoperative chemoradiation (n = 105). Among patients who had preoperative chemoradiation, 20% had pathologic complete response (n = 17). For either cN0 or cN1-3, Charlson-Deyo Comorbidity Index did not differ among the treatment groups(all p > 0.05). On Kaplan-Meier analysis for cN0, treatment with surgery alone had comparable OS to preoperative chemoradiation (47% vs 34%; P = .5) and each had improved OS compared to chemoradiation alone (30%; P = .02; P = .06). On univariate analysis for cN0, clinical T category was not associated with OS. For cN1-3, however, preoperative chemoradiation was associated with improved OS when compared to chemoradiation alone or surgery alone (27% vs 19% vs 0%; P < .001). This persisted when accounting for age and clinical T category (hazard ratio: 0.45; P < .001)., Conclusion: Esophageal ASC behaves more like AC in response to chemoradiation and survival based on treatment modality. A complete response to chemoradiation is only 20% unlike what has been shown for SCC, where chemoradiation is an acceptable definitive therapy. Esophageal ASC should be managed more like AC., (© 2020 Wiley Periodicals LLC.)

Background: The path of the biliopancreatic limb for reconstruction of the pancreatic anastomosis during pancreatoduodenectomy for pancreatic ductal adenocarcinoma can be trans-mesocolon or through the ligament of Treitz. Even after curative intent pancreatoduodenectomy, incidence of recurrence in the surgical bed remains high and may lead to obstruction of the biliopancreatic limb. However, the association between path of jejunal limb and incidence of biliopancreatic limb obstruction has not been studied. Primary aim was to determine whether path of reconstruction predisposes to biliopancreatic limb obstruction in the setting of local recurrence., Methods: Patients who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma (2008-2018) from a single institution were identified. As disease recurrence is the predominant cause of biliopancreatic limb obstruction, analysis was limited to patients with known recurrence at date of last follow-up. Given a known median time to recurrence of 8 to 10 months after resection for pancreatic ductal adenocarcinoma, analysis was further limited to patients with at least 8 months of follow-up. Primary outcome was incidence of biliopancreatic limb obstruction., Results: Among the 517 patients identified, 182 were included. Median age was 65 years; 51% were male. Median follow-up was 22 months. Path of reconstruction was trans-mesocolon in 35% (n = 64) and through ligament of Treitz in 65% (n = 118). There was no difference between the two groups in clinicopathologic factors including age, tumor differentiation, grade, T-stage, N-stage, LVI, or PNI (all p > 0.05). Importantly, there was no difference in retroperitoneal margin positivity between groups (trans-mesocolon 8% vs ligament of Treitz 10%, p = 0.79). Both groups had similar post-operative outcomes including median length-of-stay (trans-mesocolon 6 days vs ligament of Treitz 6 days, p = 0.89) and median follow-up (trans-mesocolon 21 months vs ligament of Treitz 23 months, p = 0.68). Biliopancreatic limb obstruction was detected in 8% (n = 14) of which 14% (n = 2) were in the trans-mesocolon group and 86% (n = 12) were in the ligament of the Treitz group. Therefore, incidence of biliopancreatic limb obstruction was 3.1% in the trans-mesocolon group and 10.4% in the ligament of the Treitz group resulting in an absolute risk increase of 7.3%, risk ratio of 3.4, and relative risk increase of 2.3. There was no difference in median time to biliopancreatic limb obstruction between the groups (17.6 months vs 18.5 months, p = 1.0). Biliopancreatic limb obstruction was caused by locally recurrent pancreatic ductal adenocarcinoma in 93% (n = 13) and kinking of the duodenojejunal anastomosis in 7% (n = 1). Intervention was performed in 71% (n = 10) and included surgical bypass in 29% (n = 4), percutaneous drain in 21% (n = 3), and endoscopic/surgical decompression in 21% (n = 3)., Conclusion: Biliopancreatic limb obstruction is a known complication after pancreatoduodenectomy for pancreatic ductal adenocarcinoma due to local recurrence in the surgical bed. This study shows that path of jejunal limb through the ligament of Treitz may be associated with a higher incidence of biliopancreatic limb obstruction compared with trans-mesocolon as the position of the biliopancreatic limb in the surgical bed may be more predisposed to obstruction after local recurrence. Larger studies are needed; however, given this potential risk of subsequent obstruction, these data suggest that the reconstruction paths may not be equivalent when performing pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

Background: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database., Methods: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM)., Results: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups., Conclusions: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers., (© 2019 American Cancer Society.)

Purpose: Preclinical studies have shown synergy between everolimus, an mTOR inhibitor, radiation, and platinum agents. We conducted a phase IB trial to determine the recommended phase II dose of everolimus with carboplatin and radiation., Materials and Methods: Patients with stage II/III esophageal cancer were enrolled. Following 2 cycles of Capecitabine/Oxaliplatin (XELOX), patients with no disease progression, received 50.4 Gy in 28 fractions and concurrent weekly carboplatin (area under the curve=2), with escalating doses of everolimus. A standard 3+3 dose escalation design was used., Results: Nineteen patients were enrolled. Two patients were screen failures and 4 were removed due to poor tolerance to XELOX (n=2) or disease progression (n=2). All treated patients had adenocarcinoma. Median age was 58 (44 to 71 y) and 85% were male patients. One patient at dose level 1 was replaced due to ongoing anxiety. One of 6 patients had a dose-limiting toxicity of bowel ischemia that was fatal. At dose level 2, two of 6 patients had a dose-limiting toxicity (fever with neutropenia and nausea). The recommended phase II dose of everolimus was 2.5 mg QOD. Grade ≥3 toxicities included lymphopenia (11%), nausea (10%), low white blood cell (8.0%) vomiting (5.5%), decreased neutrophils (4.0%). All patients achieved an R0 resection with a pathologic response rate of 40% and a pathologic complete response (ypCR) rate of 23%. The 2-year progression-free survival and overall survival were 50% and 49.6%, respectively., Conclusions: The recommended phase II dose of everolimus with concurrent weekly carboplatin and radiation is 2.5 mg QOD.

Background: The three-delays model describes delays in seeking, reaching, and receiving care for vulnerable populations needing treatment. The dominant delay for patients with gastric adenocarcinoma (GAC) is unknown. We aimed to define patients with GAC who reached and received care at our regional safety-net hospital (Grady Memorial Hospital [GMH]) and our neighboring quaternary referral hospital (Emory University Hospital [EUH])., Methods: Clinicopathologic data from National Cancer Database (NCDB) participating academic centers were compared with GMH from 2004 to 2014. Outcomes of patients undergoing surgery at GMH were compared to those at EUH., Results: At presentation, compared to NCDB centers (n = 69 662), GMH patients (n = 154) were more often black (85.1 vs 17.2%; P < 0.001), uninsured (30.5 vs 4.7%; P < 0.001), have stage IV disease (43.5 vs 30.1%; P = 0.017), and received no treatment (40.3 vs 18.4%; P < 0.001). When only comparing patients who underwent curative-intent resection at GMH (n = 23) to EUH (n = 137), median overall survival was similar between both groups (GMH: median not reached; EUH: 59.8 mos; P = 0.785)., Conclusion: Although vulnerable patients with GAC within a safety-net hospital present with later stages of the disease, those who received surgery have acceptable outcomes. Thus, efforts should be made to overcome barriers in seeking care., (© 2018 Wiley Periodicals, Inc.)

Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by T or N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population.

Background: Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival., Methods: We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression., Results: Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001)., Conclusions: Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

Background: Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC)., Methods: Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS)., Results: Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034)., Conclusions: Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.

Unlabelled: Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC., Implications for Practice: Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized., (©AlphaMed Press.)

Background: The effect of routine drainage after abdominal surgery with enteric anastomoses is controversial. In particular, the role of peritoneal drain (PD) placement after total gastrectomy for adenocarcinoma is not well established., Methods: Patients who underwent total gastrectomy for gastric adenocarcinoma (GAC) at seven institutions from the US Gastric Cancer Collaborative, from 2000 to 2012, were identified. The association of PD placement with postoperative outcomes was analyzed., Results: Overall, 344 patients were identified and 253 (74 %) patients received a PD. The anastomotic leak rate was 9 %. Those with PD placement had similar American Society of Anesthesiologists score, tumor size, TNM stage, and the need for additional organ resection when compared with their counterparts. No difference was observed in the rate of any complication (54 vs. 48 %; p = 0.45), major complication (25 vs. 24 %; p = 0.90), or 30-day mortality (7 vs. 4 %; p = 0.51) between the two groups. In addition, no difference in anastomotic leak (9 vs. 10 %; p = 0.90), the need for secondary drainage (10 vs. 9 %; p = 0.92), or reoperation (13 vs. 8 %; p = 0.28) was identified. On multivariate analysis, PD placement was not associated with decreased postoperative complications. Subset analysis, stratified by patients who did not undergo concomitant pancreatectomy (n = 319) or those who experienced anastomotic leak (n = 31), similarly demonstrated no association of PD placement with reduced complications or mortality., Conclusions: PD placement after total gastrectomy for GAC is associated with neither a decrease in the frequency and severity of adverse postoperative outcomes, including anastomotic leak and mortality, nor a decrease in the need for secondary drainage procedures or reoperation. Routine use of PDs is not warranted.

Background: Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC)., Methods: All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analyses were performed., Results: A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage-specific analyses showed no association between SRC and RFS or OS., Conclusions: SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet-ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.

Objectives: To determine pathologic features associated with recurrence and survival in patients with lymph node-negative gastric adenocarcinoma., Study Design: Multi-institutional retrospective analysis., Background: Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established., Methods: Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively., Results: Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2-3.6) to be associated with decreased overall survival., Conclusions: Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.

Background: Jejunostomy feeding tubes (J-tubes) are often placed during resection for gastric adenocarcinoma (GAC). Their effect on postoperative complications and receipt of adjuvant therapy is unclear., Methods: Patients who underwent curative-intent resection of GAC at seven institutions of the U.S. Gastric Cancer Collaborative from 2000 to 2012 were identified. The associations of J-tubes with postoperative complications and receipt of adjuvant therapy were determined., Results: Of 837 patients, 265 (32%) received a J-tube. Patients receiving J-tubes demonstrated greater incidence of preoperative weight loss, lower BMI, greater extent of resection, and more advanced TNM stage. J-tube placement was associated with increased infectious complications (36% vs. 19%; P < 0.001), including surgical-site (14% vs. 6%; P < 0.001) and deep intra-abdominal (11% vs. 4%; P < 0.001) infections. On multivariate analysis, J-tubes remained independently associated with increased risk of infectious complications (all: HR = 1.93; P = 0.001; surgical-site: HR = 2.85; P = 0.001; deep intra-abdominal: HR = 2.13; P = 0.04). J-tubes were not associated with increased receipt of adjuvant therapy (HR = 0.82; P = 0.34). Subset analyses of patients undergoing total and subtotal gastrectomy similarly demonstrated an association of J-tubes with increased risk of infectious outcomes and no association with increased receipt of adjuvant therapy., Conclusions: J-tube placement after resection of gastric adenocarcinoma is associated with increased postoperative infectious outcomes and is not associated with increased receipt of adjuvant therapy. Selective use of J-tubes is recommended., (© 2015 Wiley Periodicals, Inc.)

Background: A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established., Methods: Patients who underwent curative-intent resection for proximal GAC from 2000 to 2012 at 7 centers in the US Gastric Cancer Collaborative were included. PM length was sequentially dichotomized and analyzed at 0.5 cm increments (0.5-6.5 cm). Outcomes after negative margin (R0) and positive microscopic margin (R1) resections were compared. Primary endpoints were local recurrence (LR) and overall survival (OS)., Results: All patients (n = 162) had R0 distal margins. 151 (93.2%) had an R0-PM with mean length of 2.6 cm (median:1.7 cm; range:0.1-15 cm). A greater PM distance was not associated with LR or OS. An R1-PM was associated with higher N-stage (N3:73% vs. 26%; P = 0.007) and increased LR (HR6.1; P = 0.009) but not associated with decreased OS. On multivariate analysis, an R1-PM was also not independently associated with LR., Conclusions: For resection of proximal gastric adenocarcinoma, proximal margin length is not associated with local recurrence or overall survival. An R1 margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing resection of proximal gastric adenocarcinoma, efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned., (© 2015 Wiley Periodicals, Inc.)

Background: The proximal gastric margin dictates the extent of resection for gastric adenocarcinoma (GAC). The value of achieving negative margins via additional gastric resection after a positive proximal margin frozen section (FS) is unknown., Methods: The US Gastric Cancer Collaborative includes all patients who underwent resection of GAC at seven institutions from 2000-2012. Intraoperative proximal margin FS data and final permanent section (PS) data were classified as R0 or R1, respectively; positive distal margins were excluded. The primary aim was to evaluate the impact on local recurrence of converting a positive proximal FS-R1 margin to a PS-R0 final margin by additional resection. Secondary endpoints were recurrence-free survival (RFS) and overall survival (OS)., Results: Of 860 patients, 520 had a proximal margin FS and 67 were positive. Of these, 48 were converted to R0 on PS by additional resection. R0 proximal margin was achieved in 447 patients (86 %), PS-R1 in 25 (5 %), and converted FS-R1-to-PS-R0 in 48 (9 %). The median follow-up was 44 months. Local recurrence was significantly decreased in the converted FS-R1-to-PS-R0 group compared to the PS-R1 group (10 vs. 32 %; p = 0.01). Median RFS was similar between the FS-R1-to-PS-R0 and PS-R1 cohorts (25 vs. 20 months; p = 0.49), compared to 37 months for the PS-R0 group. Median OS was similar between the FS-R1-to-PS-R0 conversion and PS-R1 groups (36 vs. 26 months; p = 0.14) compared to 50 months for the PS-R0 group. On multivariate analysis, increasing T-stage and N-stage were associated with worse OS; the FS-R1-to-PS-R0 proximal margin conversion was not significantly associated with improved RFS (p = 0.68) or OS (p = 0.44)., Conclusion: Conversion of a positive intraoperative proximal margin frozen section during gastric cancer resection may decrease local recurrence, but it is not associated with improved RFS or OS. This may guide decisions regarding the extent of resection.

Background and Objectives: The role of HER2 in patients with early stage/resected gastric cancer is controversial. This study investigates the prevalence and prognostic value of HER2 in patients undergoing curative intent resection for gastric adenocarcinoma., Methods: HER2 status was evaluated in 111 patients with gastric adenocarcinoma treated surgically between 1/00 and 6/11 with tissue available for analysis. Immunohistochemistry (IHC) for HER2 was graded by two blinded pathologists. IHC was scored as 0+/1+: negative, 2+: equivocal, and 3+: positive. Fluorescence in situ hybridization (FISH) for HER2 was performed on equivocal (2+) samples, and in cases of pathologist disagreement., Results: HER2 expression as measured by IHC was negative in 61 (55%), equivocal in 37 (33.3%), and positive in 13 (11.7%) cases. FISH was positive in 8 of 37 samples tested, for a total of 21 HER2-positive cases (18.9%, 95% CI 11.6-26.2%). Patients with HER2-positive tumors were less likely to have signet ring cell features (23.8% vs. 53.9%, P = 0.008). HER2 status was not associated with tumor size, location, perineural or lymphovascular invasion, margin status, nodal metastasis, or stage (P > 0.05). HER2 status was not associated with OS (P = 0.385)., Conclusions: HER2 amplification/over-expression is present in patients with resected gastric adenocarcinoma, but is not associated with the presence of adverse prognostic factors. Our results suggest HER2 is not prognostic for patients with resected gastric adenocarcinoma., (© 2013 Wiley Periodicals, Inc.)

Background: Chronic kidney disease (CKD) is known to adversely affect cardiac and vascular surgery outcomes. We examined the effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection., Study Design: All patients who underwent pancreatic resection between January 2005 and July 2012 were identified. Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease formula. Severe CKD (stages 4-5) was defined as eGFR < 30 mL/min/1.73 m(2). Renal function also was analyzed using serum creatinine (sCr) dichotomized at 1.8 mg/dL. Primary outcomes were any complication, major complications, and respiratory failure. Multivariate models for each endpoint were constructed by including all variables with p value ≤ 0.10 on univariate analysis., Results: There were 1,061 patients identified; 709 underwent pancreaticoduodenectomy, 307 distal pancreatectomy, and 45 central or total pancreatectomy. Median sCr value was 0.86 mg/dL (range 0.30 to 14.1 mg/dL). Eighteen patients (1.7%) had severe CKD and 31 (2.9%) had sCr ≥ 1.8 mg/dL. Complications occurred in 622 patients (58.6%), major complications in 198 (18.7%), and respiratory failure in 48 (4.5%). Both severe CKD and sCr ≥ 1.8 mg/dL were associated with any complication, major complications, and respiratory failure on univariate analysis. On multivariate analysis, severe CKD was associated with increased complications (odds ratio [OR] 5.5; 95% CI 1.3 to 25.5; p = 0.02) and respiratory failure (OR 6.1; 95% CI 1.8 to 20.5; p = 0.03), but not major complications. Using sCr ≥ 1.8 mg/dL as a surrogate marker for renal insufficiency, patients with sCr ≥ 1.8 mg/dL had increased risk of any complication (OR 3.5; 95% CI 1.3 to 9.3; p = 0.01), major complications (OR 2.2; 95% CI 1.04 to 4.8; p = 0.04), and respiratory failure (OR 4.7; 95% CI 1.8 to 12.6; p = 0.002)., Conclusions: Few patients with significant renal insufficiency are candidates for pancreatic resection. Severe CKD (stages 4-5) is associated with increased risk of complication and respiratory failure. Serum creatinine ≥ 1.8 mg/dL may serve as a useful marker of renal insufficiency and identifies patients at significantly increased risk of any complication, major complication, and respiratory failure after pancreatic resection., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Residual disease after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) adversely impacts survival. The value of taking additional neck margin after a positive frozen section (FS) to achieve a negative margin remains uncertain., Methods: All patients who underwent PD for PDAC from January 2000 August 2012 were identified and classified as negative (R0) or positive (R1) based on final neck margin. We examined factors for association with a positive FS neck margin and overall survival (OS). We assessed the value of converting an R1 neck margin to R0 via additional parenchymal resection., Results: A total of 382 patients had FS neck margin analysis, of which 53 (14 %) were positive. Positive FS neck margin was associated with decreased OS (11.1 vs. 17.3 months, p = 0.01) on univariate analysis. On multivariate analysis poor histologic grade (p = 0.007), increased tumor size (p = 0.003), and a positive retroperitoneal margin (p = 0.009) were independently associated with decreased OS, but positive FS neck margin was not. Of the 53 patients with positive FS, 41 underwent additional neck resection and 23 were converted to R0. On permanent section, R0 neck margin was achieved in 322 patients (84 %), R1 in 37 patients (10 %), and R1 converted to R0 in 23 patients (6 %). Both the converted and the R1 groups had significantly poorer OS than the R0 group (11.3 vs. 11.1 vs. 17.3 months respectively; p = 0.04)., Conclusions: Positive FS margin at the pancreatic neck during PD for PDAC is associated with poor survival. Extending the neck resection after a positive FS to achieve R0 margin status does not appear to improve OS.

Introduction: Staging laparoscopy (SL) can identify occult, subradiographic metastatic (M1) disease in patients with gastric or gastroesophageal (G/GEJ) cancer who are unlikely to benefit from gastrectomy. The purpose of this study is to determine the yield of repeat SL following neoadjuvant therapy for G/GEJ adenocarcinoma after initial negative pretreatment SL., Methods: Retrospective review of a prospective database identified patients with locoregionally advanced (T3-4Nany or TanyN+) G/GEJ adenocarcinoma who underwent pretreatment SL. The yield of repeat SL following neoadjuvant therapy was determined., Results: From 1994 to 2010, 276 patients with locoregionally advanced G/GEJ adenocarcinoma were identified, of whom 244 proceeded to operation after neoadjuvant therapy, at a median time of 105 days. One hundred sixty-four patients (67 %) underwent repeat SL, and 80 patients (33 %) proceeded directly to laparotomy. Occult M1 disease was identified in 12 (7.3 %) and 6 (7.5 %) patients, respectively. In the repeat SL cohort, M1 disease was identified at laparoscopy in nine patients (5.5 %). M1 disease not identified by laparoscopy was discovered at laparotomy in three patients (1.8 %). The median follow-up for the study population was 31 months. For patients with M1 disease, median overall survival was 15 months, versus 41 months for patients resected without M1 disease (p < 0.0001)., Conclusions: Occult, subradiographic M1 disease develops in approximately 7 % of patients following neoadjuvant therapy for locoregionally advanced G/GEJ adenocarcinoma. These patients have poor prognosis, and repeat SL can be a valuable tool in selecting patients with locoregionally advanced G/GEJ tumors for potentially curative resection after neoadjuvant therapy.

Introduction: Outcome after hepatic resection for colorectal cancer liver metastases (CRLM) is heterogeneous and accurate predictors of survival are lacking. This study analyzes the prognostic relevance of pathologic details of the primary colorectal tumor in patients undergoing hepatic resection for CRLM., Methods: Retrospective review of a prospective database identified patients who underwent resection for CRLM. Clinicopathological variables were investigated and their association with outcome was analyzed., Results: From 1997-2007, 1,004 patients underwent hepatic resection for CRLM. The median follow-up was 59 months with a 5-year survival of 47%. Univariate analysis identified nine factors associated with poor survival; three of these related to the primary tumor: lymphovascular invasion (LVI, p<0.0001), perineural invasion (p=0.005), and degree of regional lymph node involvement (N0 vs. N1 vs. N2, p<0.0001). Multivariate analysis identified seven factors associated with poor survival, two of which related to the primary tumor: LVI (hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.06-1.64, p=0.01) and degree of regional lymph node involvement [N1 (HR 1.3, 95% CI 1.04-1.69, p=0.02) vs. N2 (HR 1.7, 95% CI 1.27-2.21, p<0.0005)]. A significant decrease in survival along the spectrum of patients ranging from LVI negative/N0 to LVI positive/N2 was present. Patients who were LVI-positive/N2 had a median survival of 40 months compared with 74 months for patients who were LVI-negative/NO (p<0.0001)., Conclusions: Histopathologic details of the primary colorectal tumor, particularly LVI and the detailed assessment of the degree of lymph node involvement, are strong predictors of survival. Future biomarker studies should consider exploring factors related to the primary colorectal tumor.

Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by T or N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population. [ABSTRACT FROM AUTHOR]