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Background: Adjuvant chemotherapy offers survival benefit to patients with gastric cancer. Only 50-65% of patients who undergo neoadjuvant chemotherapy and gastrectomy are able to receive adjuvant therapy. It is optimal to start adjuvant therapy within 8 weeks after gastrectomy. We compared the rate of return to intended oncologic therapy (RIOT) between minimally invasive gastrectomy (MIG) and open gastrectomy (OG)., Method: Retrospectively, we analyzed patients who underwent gastrectomy within a multi-hospital university-based health system (2019-2022). Data on patient demographics, comorbid conditions, operative approach, and postoperative outcomes were assessed with univariate analysis and multivariable analysis (MVA) to determine the association with RIOT., Results: Among 87 eligible patients, 33 underwent MIG and 54 underwent OG. There were no differences in demographics, performance status, comorbid conditions, or type of gastrectomy between the two groups. MIG patients were significantly more likely to RIOT compared with OG patients (87.9% vs. 63%, p = 0.003), with 73.1% of MIG patients starting adjuvant therapy within 8 weeks compared with 53.1% of OG patients. Factors associated with higher odds of RIOT included MIG and age <65 years, while major postoperative complications (Clavien-Dindo grade ≥IIIa) was associated with lower odds of RIOT. On MVA, MIG was independently associated with higher odds of RIOT compared with OG (odds ratio 6.05, 95% confidence interval 1.47-24.78, p = 0.008)., Conclusion: The minimally invasive approach may benefit patients undergoing gastrectomy, irrespective of the extent of gastric resection for adenocarcinoma. MIG is associated with a higher likelihood of (1) RIOT and (2) starting adjuvant therapy within the optimal time period after gastrectomy., Competing Interests: Disclosures: Mihir M. Shah is a Proctor with Intuitive Inc., for robotic surgery. Andee Koo, Parit T. Mavani, Caitlin Sok, Subir Goyal, Seth Concors, Meredith C. Mason, Joshua H. Winer, Maria C. Russell, Kenneth Cardona, Edward Lin, Shishir K. Maithel, David A. Kooby, and Charles A. Staley III have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Background: Incisional hernia (IH) results in significant morbidity to patients and financial burden to healthcare systems. We aimed to determine the incidence of IH in distal pancreatectomy (DP) patients, stratified by specimen extraction sites., Method: Imaging in DP patients in our institution from 2016 to 2021 were reviewed by radiologists blinded to the operative approach. Specimen extraction sites were stratified as upper midline/umbilical (UM) versus Pfannenstiel. IH was defined as fascial defect on postoperative imaging. Patients without preoperative and postoperative imaging were excluded., Results: Of the 219 patients who met our selection criteria, the median age was 64 years, 54% were female, and 64% were White. The majority were minimally invasive (MIS) procedures (n = 131, 60%), of which 52% (n = 64) had a UM incision for specimen extraction, including 45 hand-assist and 19 purely laparoscopic procedures. MIS with Pfannenstiel incisions for specimen extraction was 48% (n = 58), including 44 robotic and 14 purely laparoscopic procedures. Mean follow-up time was 16.3 months (standard deviation [SD] 20.8). Follow-up for MIS procedures with UM incisions was 16.6 months (SD 21.8) versus 15.5 months (SD 18.6) in the Pfannenstiel group (p = 0.30). MIS procedures with UM incisions for specimen extraction had a 17.8 times increase in odds of developing an IH compared with MIS procedures with Pfannenstiel extraction sites (p = 0.01). The overall odds of developing an IH increased by 4% for every month of follow-up (odds ratio 1.04; p < 0.001)., Conclusion: A Pfannenstiel incision should be performed for specimen extraction in cases with purely laparoscopic or robotic distal pancreatectomy, when feasible., (© 2024. Society of Surgical Oncology.)

Competing Interests: Disclosure. Dr. Shah is a Proctor with Intuitive Inc. for Robotic Surgery

Competing Interests: Disclosures The authors declare that they have no conflict of interest.

Competing Interests: Disclosure: Dr. Shah is a proctor with Intuitive Inc. for Robotic Surgery.

Background: The information on the clinicopathologic/outcome differences between ampullary adenocarcinoma (AC) and pancreatic adenocarcinoma (PC) has been conflicting to the extent that it still is questioned whether ACs need to be recognized separately from PCs., Methods: The characteristics of 413 ACs were compared with those of 547 PCs., Results: The ACs had a better prognosis than the PCs (5-year survival, 57 % vs 23 %; p < 0.001). Even the pancreatobiliary (PB)-type ACs had a better prognosis (5-year survival, 46 % vs 23 %; p < 0.001). Several differences also were identified as contributing factors: (1) the preinvasive adenomatous component often constituted a significant proportion of the mass in ACs (>50 % of the tumor in 16 % vs 1.5 %; p < 0.001); (2) the mean size of the carcinoma was smaller in ACs (2.5 vs 3.2 cm; p < 0.001): when matched for invasion size, the survival advantage of AC was minimized, and when matched for invasion size larger than 2 cm, the survival advantage of AC lost its statistical significance; (3) lymph node (LN) metastases were less common in ACs (49 % vs 71 %; p < 0.001); (4) the definitive R1 rate was lower in ACs (4 % vs 23.5 %; p < 0.001); and (5) non-PB and non-tubular adenocarcinoma types were more common in ACs (17 % vs 3 %; p < 0.001)., Conclusions: Comparatively, ACs have better clinical survival than PCs. Potential contributing factors are the relative abundance of the preinvasive component, smaller invasion, lower LN metastasis rate, higher resectability, and common occurrence of less aggressive histologic phenotypes (intestinal, medullary, mucinous). However, this survival advantage is sustained even in PB-type ACs, highlighting the importance of accurately determining the site of origin., (© 2024. Society of Surgical Oncology.)

Objective: Postoperative pancreatic fistula is a potentially devastating complication after pancreatoduodenectomy (PD). The purpose of this study was to identify features on preoperative computed tomography (CT) imaging that correlate with an increased risk of postoperative pancreatic fistula (POPF)., Methods: Patients who underwent PD at our high-volume pancreatic surgery center from 2019 to 2021 were included if CT imaging was available within 8 weeks of surgical intervention. Pancreatic neck thickness (PNT), abdominal wall thickness (AWT), and intra-abdominal distance from pancreas to peritoneum (PTP) were measured by two board-certified radiologists who were blinded to the clinical outcomes. Radiographic measurements, as well as preoperative patient characteristics and intraoperative data, were assessed with univariate and multivariable analysis (MVA) to determine risk for clinically relevant POPF (CR-POPF, grades B and C)., Results: A total of 204 patients met inclusion criteria. Median PTP was 5.8 cm, AWT 1.9 cm, and PNT 1.3 cm. CR-POPF occurred in 33 of 204 (16.2%) patients. MVA revealed PTP > 5.8 cm (odds ratio [OR] 2.86, p = 0.023), PNT > 1.3 cm (OR 2.43, p = 0.047), soft pancreas consistency (OR 3.47, p = 0.012), and pancreatic duct size ≤ 3.0 mm (OR 4.55, p = 0.01) as independent risk factors for CR-POPF after PD. AWT and obesity were not associated with increased risk of CR-POPF. Patients with PTP > 5.8 cm or PNT > 1.3 cm were significantly more likely to suffer a major complication after PD (39.6% vs. 22.3% and 40% vs. 22.1%, p < 0.008)., Conclusions: Patients with a thick pancreatic neck and increased intra-abdominal girth have a heightened risk of CR-POPF after pancreatoduodenectomy, and they experience more serious postoperative complications. We defined a simple CT scan-based measurement tool to identify patients at increased risk of CR-POPF., (© 2023. Society of Surgical Oncology.)

Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors., (© 2023. Society of Surgical Oncology.)

Background: Major pathologic response (MPR) following neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. We sought to determine whether racial disparities exist in MPR rates following NAT in patients with PDAC undergoing resection., Methods: Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ± radiation followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Self-reported race was dichotomized as Black and non-Black, and multivariable models evaluated the association between race and MPR (i.e., pathologic complete response [pCR] or near-pCR). Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS)., Results: Results of 486 patients who underwent resection following NAT (mFOLFIRINOX 56%, gemcitabine/nab-paclitaxel 25%, radiation 29%), 67 (13.8%) patients were Black. Black patients had lower CA19-9 at diagnosis (median 67 vs. 204 U/mL; P = 0.003) and were more likely to undergo mild/moderate chemotherapy dose modification (40 vs. 20%; P = 0.005) versus non-Black patients. Black patients had significantly lower rates of MPR compared with non-Black patients (13.4 vs. 25.8%; P = 0.039). Black race was independently associated with worse MPR (OR 0.26, 95% confidence interval [CI] 0.10-0.69) while controlling for NAT duration, CA19-9 dynamics, and chemotherapy modifications. There was no significant difference in DFS or OS between Black and non-Black cohorts., Conclusions: Black patients undergoing pancreatectomy appear less likely to experience MPR following NAT. The contribution of biologic and nonbiologic factors to reduced chemosensitivity in Black patients warrants further investigation., (© 2022. Society of Surgical Oncology.)

Background: Carbohydrate antigen (CA) 19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB)., Methods: The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I-II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98 U/mL and CA19-9 ≥ 98 U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported., Results: Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1%) and II (60%) patients had CA19-9 ≥ 98 U/mL. Stage I-II patients with CA19-9 < 98 U/mL had improved OS rates (stage I: 67.5%, 42.6%; stage II: 59.8%, 32.8%) compared with stage I and II patients with CA19-9 ≥ 98 U/mL (stage I: 50.7%, 26.9%; stage II: 48.1%, 22%). Among resected stage I patients, CA19-9 <98 U/mL was associated with improved OS (< 98: 80.5%, 56%; ≥ 98: 70.2%, 42.8%), and a similar trend was seen in resected stage II patients (< 98: 77.6%, 49.9%; ≥ 98: 71%, 39.2%). Unresected stage I patients with lower CA19-9 had improved OS (< 98: 42.1%, 17.5; ≥ 98: 29.9%, 10%), with similar findings in unresected stage II patients (< 98: 41.1%, 15.3%; ≥ 98: 33.4%, 10.6%)., Conclusions: Our study demonstrated the prognostic value of CA19-9 in patients with clinical stage I-II PC, with a value < 98 U/mL demonstrating improved survival. Surgery significantly improved survival at 12 and 24 months irrespective of CA19-9., (© 2022. Society of Surgical Oncology.)

Background: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting. The impact of neoadjuvant therapy on this practice and its relationship with overall survival (OS) is incompletely understood., Methods: We reviewed PDAC patients (80% borderline resectable/locally advanced [BR/LA]) undergoing pancreaticoduodenectomy after neoadjuvant therapy at seven, academic, high-volume centers (2010-2018). Multivariable models examined the association of PS:R0, PS:R1, and converted-R0 margins with OS., Results: Of 272 patients receiving at least 2 (median 4) cycles of neoadjuvant chemotherapy (71% mFOLFIRINOX or gemcitabine/nab-paclitaxel) and undergoing pancreaticoduodenectomy with intraoperative frozen-section assessment of the transected pancreatic neck margin, PS:R0 (n = 220, 80.9%) was observed in a majority of patients; 18 patients (6.6%) had converted-R0 margins following additional resection, whereas 34 patients (12.5%) had persistently positive PS:R1 margins. At a median follow-up of 42 months, PS:R0 resection was associated with improved OS compared with either converted-R0 or PS:R1 resection (median 25 vs. 14 vs. 16 months, respectively; p = 0.023), with no survival difference between the converted-R0 and PS:R1 groups (p = 0.9). On Cox regression, SMA margin positivity (hazard ratio 2.2, p = 0.012), but not neck margin positivity (hazard ratio 1.2, p = 0.65), was associated with worse OS., Conclusions: In this multi-institutional cohort of predominantly BR/LA PDAC patients undergoing pancreaticoduodenectomy following modern neoadjuvant therapy, pursuing a negative neck margin intraoperatively if the initial margin is positive does not appear to be associated with improved survival., (© 2022. Society of Surgical Oncology.)

Background: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer., Methods: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm. Best models were selected using the Bayesian information criterion (BIC). The performance of the models was internally cross-validated via the bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index and accuracy was evaluated using calibration plots. Nomograms were made available as online tools., Results: Overall, 895 patients met inclusion criteria. Age (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.17-1.84), presence of preoperative comorbidities (HR 1.66, 95% CI 1.14-2.41), lymph node ratio (LNR; HR 1.72, 95% CI 1.42-2.01), and lymphovascular invasion (HR 1.81, 95% CI 1.33-2.45) were associated with overall survival (OS; all p < 0.01), whereas tumor location (HR 1.93, 95% CI 1.23-3.02), T category (Tis-T1 vs. T3: HR 0.31, 95% CI 0.14-0.66), LNR (HR 1.82, 95% CI 1.45-2.28), and lymphovascular invasion (HR 1.49; 95% CI 1.01-2.22) were associated with disease-free survival (DFS; all p < 0.05) The models demonstrated good discrimination on internal validation relative to OS (C-index 0.70) and DFS (C-index 0.74)., Conclusions: A web-based nomograms to predict OS and DFS among gastric cancer patients following resection demonstrated good accuracy and discrimination and good performance on internal validation., (© 2021. Society of Surgical Oncology.)

Objective: This study aims to define the role of surgery and assess different therapies for nonagenarians with localized, nonmetastatic pancreatic adenocarcinoma (PDAC)., Methods: The National Cancer Database (NCDB) was queried for patients ≥ 90 years of age with nonmetastatic, localized PDAC from 2004-2016. Postoperative mortality was assessed at 30 and 90 days in patients receiving pancreatoduodenectomy or total pancreatectomy. Overall survival (OS) was compared between three treatment groups: surgery alone, chemotherapy alone, and chemoradiation (chemoRT) alone., Results: Of 380,524 patients with PDAC, 98 patients ≥ 90 years of age underwent curative-intent resection; 55% were female and 75% had a Charlson-Deyo comorbidity score of 0. A total of 17% received postoperative chemotherapy, 51.1% had poorly differentiated tumors with a median tumor size of 3 cm, 55.1% had positive lymph nodes, and 19.4% had positive resection margins. Postoperative median length of stay was 11 days. Postoperative 30- and 90-day mortality was 10.0% and 18.9%, respectively. Median OS for the surgery alone group was 11.6 months compared with 20.4 months in those receiving adjuvant therapy (p = 0.01). Among nonoperative PDAC patients, median OS in patients receiving chemotherapy only (n = 207) was 7.2 months, while chemoRT only (n = 100) was similar to surgery only (11 versus 11.6 months, p = 0.97)., Conclusions: Even in well-selected nonagenarians, pancreatoduodenectomy or total pancreatectomy carries a high mortality rate. While adjuvant therapy after resection provides the best survival, it is seldom achieved, and chemoRT alone affords identical survival statistics as surgery alone. These data suggest it is reasonable to consider chemoRT as initial therapy, then reassess candidacy for resection if performance status allows.

Background: Pancreatoduodenectomy (PD) for duodenal adenoma (DA) resection may be associated with excessive surgical risk for patients with potentially benign lesions, given the absence of pancreatic duct obstruction. We examined factors associated with final malignant pathology and evaluated the postoperative course of patients with DA versus pancreatic ductal adenocarcinoma (PDAC)., Methods: We retrospectively analyzed patients with DA who underwent PD from 2008 to 2018 and assessed the accuracy rate of preoperative biopsy and factors associated with final malignant pathology. Complications for DA patients were compared with those of matched PDAC patients., Results: Forty-five consecutive patients who underwent PD for DA were identified, and the preoperative biopsy false negative rate was 29. Factors associated with final malignant pathology included age over 70 years, preoperative biliary obstruction, and common bile duct diameter > 8 mm (p < 0.05). Compared with patients with PDAC (n = 302), DA patients experienced more major complications (31% vs. 15%, p < 0.01), more grade C postoperative pancreatic fistulas (9% vs. 1%, p < 0.01), and greater mortality (7% vs. 2%, p < 0.05). Propensity score matched patients with DA had more major complications following PD (32% vs. 12%, p < 0.05)., Conclusions: Preoperative biopsy of duodenal adenomas is associated with a high false-negative rate for malignancy, and PD for DA is associated with higher complication rates than PD for PDAC. These results aid discussion among patients and surgeons who are considering observation versus PD for DA, especially in younger patients without biliary obstruction, who are less likely to harbor malignancy.

Background: Surgery alone is standard-of-care for stage I gastric adenocarcinoma; however, clinicians can offer preoperative therapy for clinical stage I disease with signet ring cell histology, given its presumed aggressive biology. We aimed to assess the validity of this practice., Methods: The National Cancer Database (2004-2015) was reviewed for patients with clinical stage I signet ring cell gastric adenocarcinoma who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical/pathologic stage. Primary outcome was overall survival (OS)., Results: Of 1018 patients, median age was 60 years (±14); 53% received surgery alone (n = 542), 5% received perioperative chemotherapy (n = 47), 12% received neoadjuvant therapy (n = 125), and 30% received adjuvant therapy (n = 304). For clinical stage I disease, surgery alone was associated with an improved 5-year OS rate (71%) versus perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) [overall p < 0.01]. For pathologic stage I, surgery alone had equivalent or improved survival compared with perioperative, neoadjuvant, and adjuvant therapy (5-year OS: 78% vs. 89% [p = 0.77] vs. 64% [p = 0.04] vs. 84% [p = 0.99]). Adjuvant therapy was associated with improved 5-year OS compared with pretreatment for those patients upstaged (37%) to pathologic stage II/III (55% vs. 36% and 34% vs. 7%; all p < 0.01)., Conclusions: This stage-specific study demonstrates improved survival with surgery alone for clinical stage I signet ring cell gastric adenocarcinoma. Despite 37% of clinical stage I patients being upstaged to pathologic stage II/III, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared with those treated preoperatively. Surgery alone also affords similar or improved survival for pathologic stage I disease versus multimodality therapy. This study challenges the bias to overtreat stage I signet ring cell gastric adenocarcinoma.

Background: The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3-20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately., Methods: The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS)., Results: Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1-1.99%, n = 23), and group C (2-2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1-2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0-70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage., Conclusions: PanNETs with a Ki-67 of 1-2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

Background: Despite randomized trials addressing adjuvant therapy (AT) for pancreas cancer, the ideal time to initiate therapy remains undefined. Retrospective analyses of the ESPAC-3 trial demonstrated that time to initiation of AT did not impact overall survival (OS). Given the absence of confirmatory data outside of a clinical trial, we sought to determine if AT timing in routine clinical practice is associated with OS differences., Methods: Perioperative data of pancreatectomies for ductal adenocarcinoma from five institutions (2005-2015) were assessed. Delay in AT was defined as initiation >12 weeks after surgery. Multivariate analysis was performed to identify predictors of mortality., Results: Of 867 patients, 172 (19.8%) experienced omission of AT. Improved OS was observed in patients who received AT compared with patients who did not (24.8 vs. 19.1 months, p < 0.01). Information on time to initiation of AT was available in 488 patients, of whom 407 (83.4%) and 81 (16.6%) received chemotherapy ≤12 and >12 weeks after surgery, respectively. There were no differences in recurrence-free survival or OS (all p > 0.05) between the timely and delayed AT groups. After controlling for perioperative characteristics and tumor pathology, patients who initiated AT ≤ 12 or > 12 weeks after surgery had a 50% lower odds of mortality than patients who only underwent resection (p < 0.01)., Conclusions: In a multi-institutional experience of resected pancreas cancer, delayed initiation of AT was not associated with poorer survival. Patients who do not receive AT within 12 weeks after surgery are still appropriate candidates for multimodal therapy and its associated survival benefit.

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.

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: Current nodal staging (N-staging) of ampullary carcinoma in the TNM staging system distinguishes between node-negative (N0) and node-positive (N1) disease but does not consider the metastatic lymph node (LN) number., Methods: Overall, 313 patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma were categorized as N0, N1 (1-2 metastatic LNs), or N2 (≥3 metastatic LNs), as proposed by Kang et al. Clinicopathological features and overall survival (OS) of the three groups were compared., Results: The median number of LNs examined was 11, and LN metastasis was present in 142 cases (45 %). When LN-positive cases were re-classified according to the proposed staging system, 82 were N1 (26 %) and 60 were N2 (19 %). There was a significant correlation between proposed N-stage and lymphovascular invasion, perineural invasion, increased tumor size (each p < 0.001), and surgical margin positivity (p = 0.001). The median OS in LN-negative cases was significantly longer than that in LN-positive cases (107.5 vs. 32 months; p < 0.001). Patients with N1 and N2 disease had median survivals of 40 and 24.5 months, respectively (p < 0.0001). In addition, 1-, 3-, and 5-year survivals were 88, 76, 62 %, respectively, for N0; 90, 55, 31.5 %, respectively, for N1; and 68, 34, 30 %, respectively for N2 (p < 0.001). Even with multivariate modeling, the association between higher proposed N stage and shorter survival persisted (hazard ratio 1.6 for N1 and 1.9 for N2; p = 0.018)., Conclusions: Classification of nodal status in ampullary carcinomas based on the number of metastatic LNs has a significant prognostic value. A revised N-staging classification system should be incorporated into the TNM staging of ampullary cancers.

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.

Background: Clinicians may order Octreoscan or positron emission tomography (PET) scan for staging patients with neuroendocrine tumors (NETs). (111)In-Octreoscan (Octreoscan) identifies tumors by radiolabeled targeting of somatostatin receptors, while 18F-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) measures differential tissue glucose transport. We assessed the sensitivity of both nuclear imaging modalities with pathologic correlation to define the best initial choice for NET staging after standard cross-sectional imaging., Methods: We identified all patients diagnosed with NETs of gastrointestinal or pancreatic origin who underwent nuclear imaging staging by Octreoscan and/or PET from 2000 to 2013. Imaging results were correlated with tumor differentiation and grade of pathology specimens., Results: Imaging and pathology results were identified for 153 patients. Of these, 131 underwent Octreoscan, 43 underwent PET, and 21 patients had both performed. Overall sensitivity of Octreoscan and PET for NET detection was similar (77 vs. 72 %; p = not significant). For well-differentiated NETs, Octreoscan (n = 124) demonstrated sensitivity of 80 vs. 60 % (p = 0.28) for PET (n = 30). For poorly-differentiated NETs, Octreoscan (n = 7) proved significantly less sensitive than PET (n = 13) (57 vs. 100 %; p = 0.02). The sensitivity of Octreoscan versus PET varied similarly when analyzed by WHO tumor grade: Grade 1 (79 vs. 52 %; p = 0.16), Grade 2 (85 vs. 86 %; p = not significant), and Grade 3 (57 vs. 100 %; p = 0.02)., Conclusions: Tumor differentiation can be used to guide selection of nuclear imaging modalities for staging gastrointestinal and pancreatic NETs. Octreoscan appears more sensitive than (18)FDG-PET for well-differentiated NETs, whereas (18)FDG-PET demonstrates superior sensitivity for poorly-differentiated NETs.

Background: A proximal margin distance of 5 cm is advocated for resection of gastric adenocarcinoma (GAC). We assessed the prognostic value of proximal margin (PM) distance on survival outcomes after resection of distal GAC., Methods: All patients who underwent resection of distal GAC (antrum/body) from 2000 to 2012 at seven institutions of the U.S. Gastric Cancer Collaborative were included. Patients with positive distal margins or macroscopic residual disease were excluded. The prognostic value of PM distance (assessed in 0.5-cm increments) on overall (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier and multivariate regression analysis., Results: A total of 465 patients underwent resection of distal GAC. Of these, 435 had R0 resections; 30 patients had a positive PM. 143 patients had stage I, and 322 had stage II-III tumors. Median follow-up was 44 months. Average PM distance was 4.8 cm. Median OS for patients with PM of 3.1-5.0 cm (n = 110) was superior to patients with PM ≤ 3.0 cm (n = 176) (48.1 vs. 29.3 months; p = 0.01), while a margin >5.0 cm (n = 179) offered equivalent survival to PM 3.1-5.0 cm (50.6 months, p = 0.72). The prognostic value of margin distance was stage specific. On multivariate analysis of stage I patients, PM 3.1-5.0 cm remained associated with improved OS [hazard ratio (HR), 0.16; 95 % confidence interval (95 % CI), 0.04-0.60; p = 0.01]. In stage II-III, neither PM 3.1-5.0 cm nor PM > 5.0 cm was significantly associated with OS; OS was dictated by T stage and nodal involvement., Conclusions: The prognostic value of proximal margin distance after resection of distal gastric cancer appears stage specific. In stage I, a 3.1- to 5.0-cm proximal margin is associated with the same improved OS as a > 5.0-cm margin. In stage II-III disease, other adverse pathologic factors more strongly impact survival than proximal margin distance.

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: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Overall surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of GIST are limited to small, single-institution experiences., Methods: A total of 397 patients who underwent open surgery (n = 230) or MIS (n = 167) for a gastric GIST between 1998 and 2012 were identified from a multicenter database. The impact of MIS approach on recurrence and survival was analyzed using propensity-score matching by comparing clinicopathologic factors between patients who underwent MIS versus open resection., Results: There were 19 conversions (10 %) to open; the most common reasons for conversion were tumor more extensive than anticipated (26 %) and unclear anatomy (21 %). On multivariate analysis, smaller tumor size and higher body mass index (BMI) were associated with receipt of MIS. In the propensity-matched cohort (n = 248), MIS resection was associated with decreased length of stay (MIS, 3 days vs open, 8 days) and fewer ≥ grade 3 complications (MIS, 3 % vs open, 14 %) compared with open surgery. High rates of R0 resection and low rates of tumor rupture were seen in both groups. After propensity-score matching, there was no difference in recurrence-free or overall survival comparing the MIS and the open group (both p > 0.05)., Conclusions: An MIS approach for gastric GIST was associated with low morbidity and a high rate of R0 resection. The long-term oncological outcome following MIS was excellent, and therefore the MIS approach should be considered the preferred approach for gastric GIST in well-selected patients.

Background: Analysis of portal lymph node (LN) metastases following resection of biliary carcinomas at or above the cystic duct (BC) is used to select patients for adjuvant therapy, but no guidelines exist and LN yield is low. Some consider analysis of 7 LNs necessary for accurate staging. Conventional LN analysis may understage patients., Methods: Portal LNs from 38 node-negative patients following resection of BC from 2000 to 2008 were re-examined in detail for occult metastases (OM) using a modified Weaver protocol. Outcomes measured were discordance in LN positivity and patient survival., Results: On detailed examination, 5 of 38 patients had OM. There was no difference in survival between patients with and without OM (24 vs 17 months; p = .382). There was no association between OM and patient demographics or adverse tumor characteristics. The median LN yield was 3. Of the 27 patients with <7 LNs retrieved, 1 had OM, compared with 4 of 11 patients with ≥7 LNs retrieved (p = .030). OM in these well-staged patients were associated with reduced survival (9 vs 41 months; p = .032)., Conclusions: There is discordance between conventional and detailed LN analysis in resected BC. LN yield ≥7 was associated with OM. The presence of OM may be associated with decreased survival. Conventional LN analysis may understage patients with resected BC.

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.

Purpose: The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB)., Methods: Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias., Results: From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61-0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93-1.18) and NoAdjuvant (index)., Conclusions: Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC.

Background: Duodenal gastrointestinal stromal tumors (GISTs) are a small subset of GISTs, and their management is poorly defined. We evaluated surgical management and outcomes of patients with duodenal GISTs treated with pancreaticoduodenectomy (PD) versus local resection (LR) and defined factors associated with prognosis., Methods: Between January 1994 and January 2011, 96 patients with duodenal GISTs were identified from five major surgical centers. Perioperative and long-term outcomes were compared based on surgical approach (PD vs LR)., Results: A total of 58 patients (60.4%) underwent LR, while 38 (39.6%) underwent PD. Patients presented with gross bleeding (n = 25; 26.0%), pain (n = 23; 24.0%), occult bleeding (n = 19; 19.8%), or obstruction (n = 3; 3.1%). GIST lesions were located in first (n = 8, 8.4%), second (n = 47; 49%), or third/fourth (n = 41; 42.7%) portion of duodenum. Most patients (n = 86; 89.6%) had negative surgical margins (R0) (PD, 92.1 vs LR, 87.9%) (P = 0.34). Median length of stay was longer for PD (11 days) versus LR (7 days) (P = 0.001). PD also had more complications (PD, 57.9 vs LR, 29.3%) (P = 0.005). The 1-, 2-, and 3-year actuarial recurrence-free survival was 94.2, 82.3, and 67.3%, respectively. Factors associated with a worse recurrence-free survival included tumor size [hazard ratio (HR) = 1.09], mitotic count >10 mitosis/50 HPF (HR = 6.89), AJCC stage III disease (HR = 4.85), and NIH high risk classification (HR = 4.31) (all P < 0.05). The 1-, 3-, and 5-year actuarial survival was 98.3, 87.4, and 82.0%, respectively. PD versus LR was not associated with overall survival., Conclusions: Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. PD was associated with longer hospital stays and higher risk of perioperative complications. When feasible, LR is appropriate for duodenal GIST and PD should be reserved for lesions not amenable to LR.

Background: Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to examine the relative efficacy of surgical management versus intra-arterial therapy (IAT) for NELM and determine factors predictive of survival., Methods: A total of 753 patients who had surgery (n = 339) or IAT (n = 414) for NELM from 1985 to 2010 were identified from nine hepatobiliary centers. Clinicopathologic data were assessed with regression modeling and propensity score matching., Results: Most patients had a pancreatic (32%) or a small bowel (27%) primary tumor; 47% had a hormonally active tumor. There were statistically significant differences in characteristics between surgery versus IAT groups (hormonally active tumors: 28 vs. 48%; hepatic tumor burden >25%: 52% vs. 76%) (all P < 0.001). Among surgical patients, most underwent hepatic resection alone without ablation (78%). The median number of IAT treatments was 1 (range, 1-4). Median and 5-year survival of patients treated with surgery was 123 months and 74% vs. 34 months and 30% for IAT (P < 0.001). In the propensity-adjusted multivariate Cox model, asymptomatic disease (hazard ratio 2.6) was strongly associated with worse outcome (P = 0.001). Although surgical management provided a survival benefit over IAT among symptomatic patients with >25% hepatic tumor involvement, there was no difference in long-term outcome after surgery versus IAT among asymptomatic patients (P = 0.78)., Conclusions: Asymptomatic patients with a large (>25%) burden of liver disease benefited least from surgical management and IAT may be a more appropriate treatment strategy. Surgical management of NELM should be reserved for patients with low-volume disease or for those patients with symptomatic high-volume disease.

Background: Hepatocellular carcinoma (HCC) is a vascular tumor that proliferates through angiogenic pathways mediated, in part, by vascular endothelial growth factor receptor 2 (VEGFR2), and platelet-derived growth factor receptor (PDGFR) α and β. We hypothesized that overexpression of these proteins is associated with decreased survival after resection., Methods: A total of 57 patients, with available tissue for analysis, who underwent liver resection for HCC between August 2000 and March 2008 at a single institution were identified from a prospectively maintained database. Tumor specimens were assessed with immunohistochemistry for VEGFR2, PDGFR-α, and PDGFR-β expression and were graded by an experienced pathologist. Primary outcome was overall survival (OS)., Results: Median patient age was 64 years; 65% (n=37) were male. Median follow-up was 24.5 months, and median OS was 25.5 months. Median tumor size and number were 7 cm and 1, respectively. Macro and microvascular invasion was present in 9% (n=5) and 42% (n=24) of patients, respectively. Seventy-five percent of patients had tumors exceeding Milan criteria. 9% had positive resection margins. Thirty-five percent of patients had cirrhosis and the median nonadjusted Model for End-Stage Liver Disease (MELD) score was 7.5. Tumors exhibited differential expression of VEGFR2 (low: 79%, high: 21%), PDGFR-α (low: 93%, high: 7%), and PDGFR-β (low: 96%, high: 4%). After excluding all 30-day deaths (n=7), high PDGFR-α and PDGFR-β expression were independently associated with decreased OS (8.7 vs 29.1 months, P=0.01; 2.8 vs 28.8 months, P<0.001; respectively). High VEGFR2 expression displayed a trend toward decreased OS (20.8 vs 27.5 months, P=0.2). When adjusted for tumor burden, vascular invasion, margin status, and MELD score on independent multivariate analyses, both PDGFR-α and -β high expression were independently associated with decreased survival., Conclusions: High expression of PDGFR-α and PDGFR-β may be independently associated with decreased OS irrespective of margin status, MELD score, and tumor extent. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting.

Background: Increased tumor expression of excision repair cross-complementing gene-1 (ERCC1) is associated with decreased survival in patients with various cancers. Its effect in pancreatic adenocarcinoma (PAC) is not defined., Methods: Ninety-five patients were selected from a prospective database of all patients (n = 220) who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Tumor was isolated to perform immunohistochemistry for ERCC1 expression and was graded by a single pathologist. Main outcomes were recurrence-free survival (RFS) and overall survival (OS)., Results: Median age was 63 years; 50 patients (53%) were male and 73 (77%) received adjuvant chemotherapy. Median follow-up was 25 months. Median RFS and OS was 9 and 16 months. Median tumor size was 3 cm; 26% had a positive resection margin, 34% had poorly differentiated tumors, 61% had positive lymph nodes, 88% had perineural invasion, and 45% had lymphovascular invasion. Tumors exhibited differential ERCC1 expression in terms of intensity staining [none-weak: 61%; moderate-strong: 39%], percentage staining [0: 39%; 1-10: 29%; 11-50: 20%; 51-100: 12%], and overall expression [low: 84%; high: 16%]. High ERCC1 expression was associated with reduced RFS (6 vs. 10 months; P = 0.03) and decreased OS (9 vs. 18 months; P = 0.019). After accounting for adverse tumor factors, high ERCC1 expression persisted as a negative prognostic factor on multivariate Cox regression for both RFS and OS [hazards ratio (HR), 2.1; 95% confidence interval (CI), 1.1-3.9; P = 0.02; HR, 3; 95% CI, 1.6-6; P = 0.001, respectively]. A subset analysis of only those 73 patients who received adjuvant therapy revealed the same negative effect of high ERCC1 expression on RFS (4 vs. 15 months; P = 0.001) and OS (9 vs. 20 months; P < 0.001)., Conclusions: Pancreas cancer exhibits differential expression of ERCC1. High ERCC1 expression is associated with both reduced RFS and OS after resection. ERCC1 expression levels may help to predict patient outcome with adjuvant chemotherapy.

Background: The premise that allogeneic red blood cell transfusion (RBCT) contributes to adverse oncologic outcomes after surgery remains controversial. We examined the effects of RBCT during and after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) on disease recurrence and survival., Methods: A prospective database of 220 patients undergoing PD for PDAC from 2000 to 2008 was reviewed and transfusion data collected. Univariate and multivariate analyses were performed for factors influencing RBCT, recurrence-free survival (RFS), and overall survival (OS). The effect of amount and timing (intraoperative vs. postoperative) of RBCT was analyzed., Results: One hundred forty-seven patients (67%) received RBCT: 70 (32%) received 1 to 2 units, and 77 (35%) received >2 units. Median RFS and OS for the entire cohort was 12 and 16 months, respectively. RBCT of >2 units was associated with reduced RFS (9 vs. 15 months; P = 0.033) and OS (14 vs. 20 months; P = 0.003). Stratified by timing of transfusion, postoperative RBCT was associated with shortened RFS and OS. Controlling for age, body mass index, comorbidities, tumor factors, and major complications, each incremental unit of postoperative RBCT was associated with reduced RFS (hazard ratio 1.10, 95% confidence interval 1.02-1.18) and OS (hazard ratio 1.08, 95% confidence interval 1.03-1.12). Low hemoglobin and presence of comorbidities were the only preoperative factors independently associated with RBCT., Conclusions: Allogeneic red blood cell transfusion after PD for PDAC is independently associated with earlier cancer recurrence and reduced survival, in particular when administered postoperatively and in larger quantities. Blood-conservation methods are especially indicated for patients with preoperative anemia and medical comorbidities.

Background: Inguinofemoral lymphadenectomy is associated with frequent and marked incision-related morbidity. Our initial feasibility study of videoscopic inguinal lymphadenectomy (VIL) for melanoma showed appropriate nodal yield and anatomic dissection. Although a limited suprafascial dissection has been reported in the urologic literature, we report our growing experience with VIL applying a comprehensive approach to dissection., Methods: Patients with inguinal metastases from varied malignancies were offered VIL. With institutional review board approval, procedures were performed via three ports: one at the apex of the femoral triangle, a second medial to the adductor, and a third lateral to sartorius. Femoral vessels were skeletonized, and all lymphatic tissue within the femoral triangle to 5 cm up onto the external oblique aponeurosis was resected. Specimens were removed through the apical port via a specimen bag. Clinicopathologic and perioperative outcome data were recorded., Results: Forty-five VILs were performed in 32 patients: 19 had unilateral VILs, and 13 had bilateral VILs for neuroendocrine, extramammary Paget disease, or varied genitourinary malignancies. Nine procedures (20%) were performed in women. Median age was 61 (range 16-87) years. Median body mass index was 30 (range 19-53). Median operative time was 165 (range 75-245) minutes, median length of stay was 1 (range 1-14) day, and median drain duration was 15 days. Median number of collected nodes was 11 (range 4-24), and the largest node removed was 5.6 cm in size. Wound complications were observed in 8 cases (18%). Six patients (13%) developed cellulitis without any wound dehiscences, 1 patient developed a seroma, and 1 patient with diabetes had mild skin flap necrosis, which resolved with minimal local care., Conclusions: VIL is an alternative approach to traditional open inguinal lymphadenectomy. In our growing experience, node retrieval is appropriate and wound complications are substantially fewer than reported via an open approach. Further comparative analysis of VIL and traditional inguinofemoral lymphadenectomy is being pursued in a randomized, prospective trial.

Chemotherapy is integral to the management of patients with advanced colorectal cancer liver metastases. Due to their improved efficacy, modern regimens can sometimes convert unresectable disease to a resectable state. As chemotherapy is often administered prior to hepatic resection, adverse effects on the liver are increasingly being recognized. Investigators have identified a wide spectrum of effects on the underlying liver parenchyma, ranging from mild forms of steatosis to severe steatohepatitis and sinusoidal obstruction syndrome. As the histopathologic definitions of these changes evolve, studies have identified specific patterns of hepatic injury related to the various chemotherapeutic agents. The impact of these changes on perioperative outcome after partial hepatectomy remains controversial. Timing and duration of chemotherapy may play a key role and account for discrepancies in outcomes seen among studies. In this review, we provide an overview of the spectrum of chemotherapy-associated liver injury and discuss its relevance to perioperative management of patients undergoing hepatic resection of colorectal cancer liver metastases.

Background: Management of neuroendocrine tumor liver metastasis (NELM) remains controversial, with some advocating an aggressive surgical approach while others have adopted a more conservative strategy. We sought to define the efficacy of the surgical management of NELM in a large multicenter international cohort of patients., Methods: We identified 339 patients who underwent surgical management for NELM from 1985 to 2009 from an international database of eight major hepatobiliary centers. Relevant clinicopathologic data were assessed using Kaplan-Meier and Cox regression models., Results: Most patients had a pancreatic (40%) or small bowel (25%) neuroendocrine tumor (NET) primary. The majority of patients (60%) had bilateral liver disease. At surgery, 78% of patients underwent hepatic resection, 3% ablation alone, and 19% resection + ablation. Major hepatectomy was performed in 45% of patients, and 14% underwent a second liver operation. Carcinoid was the most common NET histological subtype (53%). Median survival was 125 months, with overall 5- and 10-year survival of 74%, and 51%, respectively. Disease recurred in 94% of patients at 5 years. Patients with hormonally functional NET who had R0/R1 resection benefited the most from surgery (P = 0.01). On multivariate analyses, synchronous disease [hazard ratio (HR) = 1.9], nonfunctional NET hormonal status (HR = 2.0), and extrahepatic disease (HR = 3.0) remained predictive of worse survival (all P < 0.05)., Conclusions: Liver-directed surgery for NELM is associated with prolonged survival; however, the majority of patients will develop recurrent disease. Patients with hormonally functional hepatic metastasis without prior extrahepatic or synchronous disease derive the greatest survival benefit from surgical management.

Background: Atypical spitzoid melanocytic neoplasms (ASMN) are cutaneous lesions of uncertain malignant potential, which can be difficult to distinguish from cutaneous melanoma. Sentinel lymph node (SLN) biopsy is a safe and useful prognostic tool for staging melanoma, but its role in staging ASMNs is not established nor is the significance of positive SLNs in these patients known. This study attempts to characterize the significance of nodal disease in ASMN., Methods: Patients with ASMNs who presented to the melanoma service from 1992 to 2007 were identified from a prospective database. Histological review was performed by two dermatopathologists. Demographic, treatment, and outcome data were reviewed., Results: A total of 58 patients with ASMNs were treated during the time analyzed; 31 (53%) underwent wide local excision and observation (WLE); 27 underwent wide excision and SLN biopsy. Median age was 24 (range, 6-60) years. Mean Breslow thickness was 2.9 (range, 0.5-10) mm. Median follow-up was 56 (range, 1-160) months. Ten of 58 (17%) patients had nodal metastasis. Four (13%) of 31 patients who underwent WLE developed nodal recurrences, and 6 of 27 (22%) patients had a positive SLN biopsy. Of patients with positive SLNs, none have recurred after undergoing completion lymphadenectomy. One patient presented with synchronous brain metastasis and inguinal lymphadenopathy and died of disease., Conclusions: Nodal status does not seem to convey the same prognosis that it does in standard melanoma. There may be a limited ability for progression within the nodal basin in patients with these lesions. This subset of patients would benefit from genetic data complementing histologic analysis.

Introduction: Inguinal lymphadenectomy for metastatic melanoma is reported to have a complication rate as high as 50%. Wound dehiscence has been reported to occur in more than half of these patients, and as a result many surgeons routinely use sartorius muscle transposition to protect against the potential for exposed vessels. We report feasibility of minimally invasive inguinal lymphadenectomy intended to minimize wound complications inherent to this procedure., Methods: Five patients with histologically confirmed inguinal metastases from melanoma underwent minimally invasive inguinal lymphadenectomy. Procedures were performed via three ports: one at the apex of the femoral triangle, a second two fingerbreadths medial to the adductors, and the third two fingerbreadths lateral to the sartorius. No inguinal incision was utilized for the purpose of surgery. A standard melanoma dissection was performed through these ports: contents of the femoral triangle and 5 cm up onto the external oblique aponeurosis were removed. To validate this technique, sentinel node biopsy scars were excised to permit visual confirmation of adequate anatomic dissection., Results: Five patients underwent minimally invasive inguinal lymphadenectomy for metastatic melanoma. Median operative time was 180 (range, 142-223) min, median hospital stay was 1 day, and two patients developed cutaneous erythema but neither suffered wound dehiscence. Median nodal yield was 10 (range, 4-13). Blood loss was <100 ml for all procedures. Median duration of drain usage was 8 (range 7-19) days., Conclusions: Minimally invasive inguinal lymphadenectomy is feasible for patients with melanoma as demonstrated by nodal yield and visual inspection. This technique may reduce complication rates and wound dehiscence, and the risk of exposed vessels is minimized by eliminating the inguinal incision. This obviates the need for routine sartorius muscle transposition. A prospective, randomized trial comparing the open versus the videoscopic approach is currently in progress.

Purpose: To assess clinicopathologic features and postresection survival of diabetes mellitus (DM)-associated pancreatic ductal adenocarcinoma (PDAC)., Methods: Records of resected PDAC patients from 2000 to 2007 were reviewed. DM was classified as new-onset (<24 months before PDAC) or longstanding (> or =24 months). Clinicopathologic features were compared by univariate and multivariate analyses. Survival was assessed by Kaplan-Meier method and Cox regression., Results: Of 209 patients, 93 (45%) met criteria for DM (35 longstanding DM, 55 new-onset DM, 3 duration unknown). DM patients were older (DM 66 +/- 9 years, non-DM 63 +/- 12 years, P = 0.06); a majority had additional preoperative comorbidities (DM 64.5%, non-DM 25.9%, P < 0.001). Tumor size was larger in patients with DM (DM 3.8 +/- 1.7 cm, non-DM 3.2 +/- 1.5 cm, P = 0.003). Groups were similar in terms of tumor location, perineural/lymphovascular invasion, and node and margin status. On logistic regression, tumor size >/=3.0 cm was independently associated with both overall DM (odds ratio [OR] 3.60; 95% confidence interval [1.79-7.26]) and new-onset DM (OR 3.69, [1.65-8.24]). Median survival was reduced in patients with DM compared with non-DM (15 versus 17 months, P = 0.015). Multivariate analysis controlling for prognostic variables including age, comorbidities, and tumor size demonstrated that DM was independently associated with reduced survival (hazard ratio [HR] 1.55, [1.02-2.35]). This association was more pronounced for patients with new-onset DM (HR 1.75 [1.10-2.78]) than those with longstanding DM (HR 1.30 [0.75-2.25])., Conclusions: Preexisting DM is associated with reduced survival in patients undergoing resection for PDAC. PDAC with new-onset DM may exhibit increased tumor size and decreased postresection survival. Additional investigation is needed to clarify etiology and impact of PDAC-associated DM.

Background: Surgeons are performing laparoscopic left pancreatectomy (LLP) with increasing frequency; however, determinants of perioperative outcome after LLP are not well defined. We evaluated factors contributing to morbidity after LLP., Methods: Records from patients undergoing LLP from 2000 to 2008 from nine academic medical centers were evaluated to assess risk factors for perioperative complications. Extent of pancreatic resection was determined by the length of the gross pancreatic specimen. Complications and pancreatic fistula rates were assessed, and a model was developed to identify those at risk of postoperative adverse events., Results: Among the 219 LLP cases, indications were cystic neoplasms in 122 (56%), solid neoplasms in 83 (38%), and chronic pancreatitis in 14 (6%). Thirty-day morbidity and mortality were 39% and 0, respectively. Major complications occurred in 11%. Pancreatic fistulae were detected in 23%, with clinically important fistulae (International Study Group on Pancreatic Fistula Definition grade B/C) seen in 10%. On multivariate analysis, only greater estimated blood loss (EBL), higher body mass index (BMI), and longer length of resected pancreas were associated with major complications. A complication risk score consisting of 1 point each for BMI >27, pancreatic specimen length >8 cm, or EBL > or =150 mL predicted an increased risk of complications and pancreatic fistulae., Conclusions: The risk of major complications after LLP is 11%, with clinically important pancreatic fistulae occurring in 10%. A complication risk score incorporating BMI, extent of pancreatic resection, and EBL correlates with all end points evaluated. The complication risk score should be used when quality outcome measures are evaluated.

Background: Liver cell adenoma (LCA) is a benign hepatic tumor with poorly characterized risk for spontaneous rupture and malignant transformation., Methods: Records from five tertiary hepatobiliary centers were reviewed for all patients treated for LCA from 1997 to 2006. Clinicopathological data were collected and analyzed, and factors that were associated with rupture and/or malignant transformation were assessed by using multivariable logistic regression., Results: A total of 124 patients were analyzed, of which 8 (6.5%) were men; 119 patients underwent resection, and 5 patients had embolic therapy only. Mean patient age was 39+/-11 years, and 55% had history of hormone use. Rupture occurred in 31 (25%) cases. Ruptured tumors were larger (10.5+/-4.5 cm vs. 7.2+/-4.8 cm; p=0.001), and no tumor <5 cm ruptured. Patients with ruptured LCAs were more likely to require preoperative blood transfusion (32% vs. 9%, p=0.006), preoperative embolization (16% vs. 1%, p=0.021), and major (>or=3 segments) hepatic resection (65% vs. 32%, p=0.003). By multivariate analysis, increasing tumor size (odds ratio (OR), 7.8; 95% confidence interval (CI), 2.2-26.3; p<0.01) and recent (within 6 months) hormone use (OR, 4.5; 95% CI, 1.5-13.3; p<0.01) remained independently associated with risk of rupture. Five cases (4%) had evidence of underlying malignancy, but none had LCA <8 cm in diameter., Conclusion: In this multicenter analysis of patients with LCAs, risk of rupture correlated with increasing tumor size and recent hormone use. Rupture is associated with greater need for preoperative blood transfusion and major hepatic resection. These data suggest that patients with asymptomatic LCAs approaching 4 cm and those requiring hormonal therapy should undergo surgical therapy.

Background: Central pancreatectomy (CP) is a parenchyma-sparing alternative to extended left pancreatectomy (ELP) for tumors of the pancreatic neck. We compared short- and long-term outcomes for the two approaches., Methods: Patients who underwent CP or ELP from 2000-2007 for neoplasms of the neck were identified. Charts were reviewed for patient, treatment, and outcome data. Long-term and quality-of-life (QoL) data were gathered through Institutional Review Board (IRB)-approved telephone interviews and questionnaires European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and QLQ-PAN26., Results: 31 patients were identified; 13 underwent CP and 18 underwent ELP. Median follow-up was 29 months (range 5-90). Groups did not differ in age, American Society of Anesthesiologists (ASA) class, or preexisting diabetes mellitus (DM). CP patients had less gland resected (5.7 +/- 2.1 cm versus 10.8 +/- 2.8 cm) and lower postoperative mean blood glucose levels (120 +/- 15 mg/dl versus 136 +/- 24 mg/dl). CP patients experienced more complications (92% versus 39%), but no significant difference in major complications (38%, CP versus 17%, ELP; P = 0.17) or hospital stay (9 +/- 3 days, CP versus 7.5 +/- 4 days, ELP). There was one perioperative death in the CP group, unrelated to surgical technique. Questionnaire analysis showed no differences in functional or symptom scales. New-onset exocrine insufficiency was not significantly different between the groups (10%, CP versus 27%, ELP; P = 0.62), but the ELP group had a higher rate of new-onset DM (57% versus 11%; P = 0.04)., Conclusion: CP is associated with more complications than ELP, but no difference in long-term QoL. Due to the lower incidence of postoperative DM, CP can be recommended for healthy patients with indolent tumors of the pancreatic neck.

Background: The role of hepatic resection for metastatic squamous cell carcinoma (SCC) remains unknown. The current study evaluates the role of hepatic resection in patients with metastatic SCC to the liver., Methods: Between 1988 and 2006, 52 patients underwent hepatic resection of metastatic SCC at eight major cancer centers. Clinicopathologic factors were analyzed with regard to disease-free survival (DFS) and overall survival (OS)., Results: Primary SCC site was anal (n = 27), head/neck (n = 12), lung (n = 4), esophagus (n = 2), and other (n = 7). Treatment of primary SCC was chemotherapy +/- radiotherapy alone (n = 29), chemotherapy +/- radiotherapy + surgery (n = 15), or surgery alone (n = 8). Forty-seven patients underwent resection alone, 2 resection + radiofrequency ablation (RFA), and 3 RFA only. At last follow-up, 33 (63.5%) patients had recurred. The median time to recurrence was 9.8 months, and 5-year DFS was 18.6%. Factors associated with reduced DFS were liver tumor size > 5 cm (hazard ratio (HR) = 2.02) and positive surgical margin (HR = 2.33). The overall median survival after hepatic resection was 22.3 months and 5-year actuarial OS was 20.5%. Risk factors associated with worse overall survival included synchronous disease (HR = 4.09), hepatic metastasis > 5 cm (HR = 1.71) and positive surgical resection margin (HR = 1.83)., Conclusions: The majority of patients will recur following hepatic resection of SCC. Long-term survival, however, can be achieved following surgical resection of SCC liver metastasis, especially in patients who present with limited metachronous disease amenable to margin negative resection.