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Immune thrombocytopenic purpura (ITP) is an uncommon condition resulting from the autoimmune destruction of platelets. A man in his mid-30s, who had received three doses of the SARS-CoV-2 vaccine a year prior, was diagnosed with ITP 3 weeks after contracting COVID-19. Mechanisms of SARS-CoV-2 induced thrombocytopenia may include bone marrow depletion, coagulation consumption, mutations resulting in cytokine release or molecular mimicry leading to autoimmunity. Initial treatment involved glucocorticoids, but the disease course progressed into glucocorticoid-resistant ITP. Subsequently, the patient was diagnosed with ITP refractory to intravenous immunoglobulin, thrombopoietin receptor agonist, rituximab, cyclophosphamide, inhibitors of BTK and SYK, and other pharmacological agents. Despite exhaustive medical interventions, bleeding diathesis and platelet counts worsened, so the patient underwent a splenectomy resulting in the resolution of the thrombocytopenia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation., Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants., Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22)., Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique., Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-509/coif). KZ, GSL, XT and SDW are full-time employees of AME Publishing Company, the publisher of Hepatobiliary Surgery and Nutrition. RHP has received speaker fees from Medtronic, AMBU, Medela and AstraZeneca and is the Advisory Board member of AstraZeneca, MSD and Roche. CSHN has received consulting fees from Medtronic & Johnson and Johnson. AT reports consulting fee from Intuitive. MFJ has received consulting and lecture fees from Medtronic and Intuitive. AYO reports educational and research grants from Artivion and Terumo Aortic to his institution. The other authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Objectives: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement., Study Design and Setting: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021., Results: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description., Conclusion: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease., Methods: This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods., Results: Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR)., Conclusions: The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease., (© 2022. The Author(s).)

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

Background: Standardized and transparent reporting of surgical technique is the cornerstone of effective dissemination, implementation and improvement. However, current reporting of surgical techniques is inadequate. The existing guidelines potentially applied to guide surgical technique reporting are with a minimal highlight of the surgical technique, lack requirements explaining what extent and dimensions need to be described in detail, or are unlikely to extrapolate to a wide range of surgical techniques. This study aims to formulate a rigorous protocol to develop a surgical technique reporting checklist and standards (SUPER) that defines what a clear, comprehensive and detailed surgical technique report should be contained., Methods: This protocol is designed following the classic guidance for developing reporting guidelines recommended by the EQUATOR network., Results: The development team will consist of surgeons (~80%), methodologists, and journal editors. The draft checklist sources will include a scoping review of existing reporting guidelines related to surgical technique, surgical technique articles from 15 top journals published in the last year, and brainstorming by the multidisciplinary development team. The final SUPER checklist will be formed after three rounds of Delphi surveys, one round of face-to-face meeting, and a month-long pilot test. The SUPER checklist will be published as open-access and be used in combination with existing reporting guidelines related to surgical techniques (e.g., IDEAL). This protocol will steer the SUPER checklist's development, allowing us to further elaborate surgical technique reporting for all surgical specialties, and enabling a more favorable experience for surgeons, nurses, medical students, residents, editors, and reviewers., Trial Registration: This trial is registered at the EQUATOR network on December 18th, 2020. Available at: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-312). ADLS receives Speaker’s honoraria from Medtronic and is the consultancy of Medela. AF declares a pending patent (PCT/IT2018/00000S) related to the project. FD declares a licensed patent (Italian patent application “TO2013A000038”) related to the project. RHP receives speaker fee from Medtronic and is the advisory board member for AstraZeneca. KZ, GSL, XT and SDW are staff of AME publishing company (the publisher of Gland Surgery). The other authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Background: The reporting of surgical techniques is of mixed quality, with most at a very minimal level. Reporting guidelines that could be applied to guide surgical technique reporting vary in methodology for development, discipline coverage, dimension coverage and detail requested. However, a scoping review that could indicate the gaps and efforts needed in surgical technique reporting guidelines is lacking and warranted. This study aims to design a methodological rigour protocol to guide the development of a scoping review of surgical technique reporting guidelines., Methods: This protocol is designed following the 2020 manual proposed by the Joanna Briggs Institute. To further ensure the soundness of the protocol, we also included multidisciplinary professionals (including methodologists, clinicians, and journal editors) to refine the protocol., Discussion: Seven key steps for developing the scoping review are identified and presented in detail, including (I) identifying the research questions; (II) inclusion criteria; (III) search strategy; (IV) source of evidence selection; (V) data extraction; (VI) analysis of the evidence; and (VII) presentation of the results. Guided by this protocol, the subsequent scoping review will inform us the overview of surgical technique reporting guidelines and precisely guide our direction and next steps in improving surgical technique reporting guidelines., Trial Registration: This protocol is not registered as the PROSPERO database only accepts registration of systematic review protocols while does not accept registration of scoping review protocols., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-311). AF declares a pending patent (PCT/IT2018/00000S) related to the project. ADLS receives Speaker’s honoraria from Medtronic and is the consultancy of Medela. FD declares a licensed patent (Italian patent application “TO2013A000038”) related to the project. RHP receives Speaker fee from Medtronic and Advisory Board member AstraZeneca. KZ, GSL, XT and SDW are staff of AME publishing company (the publisher of Gland Surgery). The other authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Esophageal resection is a key component of the multidisciplinary management of esophageal cancer. Robotic-assisted minimally invasive esophagectomy is gaining widespread approval amongst few centers with promising early data. There is significant variability in the operative approach utilized by different centers and this review describes, step-by-step, the operative technique at a high-volume tertiary center. The cornerstone of management is individualized surgical approach, based on patient, tumor and technical factors. Although our approach is based on aforementioned factors, our preferred approach is an Ivor Lewis esophagectomy and this review focuses on that. The procedure is broken down into three key parts, starting with an abdominal exploration and creation of the gastric conduit, placement of jejunostomy tube, moving to thoracic mobilization and creation of the side-side 6 cm stapled esophagogastric anastomosis with a final abdominal portion to assure proper positioning of the conduit and reducing redundancy. This approach is fully robotic and a side to side anastomosis facilitates the creation of a widely patent anastomosis therefore minimizing the risk of anastomotic leaks and strictures. Our experience with minimally invasive esophagectomy, as has been previously published, is associated with a 5.1% of anastomotic leak and 7.6% of anastomotic stricture. The robotic platform further optimizes this technique and helps us safely accomplish a side to side stapled anastomosis. Superior instrument dexterity in a restricted thoracic space is facilitated by intracorporeal suturing and robotic stapling. Thus, it obviates the need for a larger thoracotomy incision, which is typically needed for an EEA anastomosis, and that is traditionally associated with higher stricture rate.

Background: The association between vitamin D-binding protein (VDBP) and 25-hydroxyvitamin D (25 (OH)D) with colorectal cancer (CRC) is still ambiguous. This study was to further investigate the relationship between serum VDBP, 25 (OH)D levels and the clinical and pathological features of patients with CRC., Methods: Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay were used to analyze the VDBP and 25(OH)D concentrations in serum. Pearson's correlation analysis was applied to evaluate the association between serum VDBP and 25(OH)D levels in CRC. Conditional logistic regression was performed to analyze the prediction value of serum VDBP or 25(OH)D as a risk factor for CRC., Results: The serological levels of 25(OH)D in patients were significantly lower than in healthy individuals, while VDBP levels were significantly higher than in healthy controls. The serum VDBP in pre-operative was significantly lower than in post-operative samples, while the serum 25(OH)D from pre-operative patients was significantly higher than post-operative patients. Patients with tumors with higher stage and increased lymph node involvement had lower serum post-operative VDBP levels. In addition, our results showed that the pre-operative VDBP level is a risk factor of CRC., Conclusions: The levels of serum 25(OH)D and VDBP were both associated with CRC. Thus, serum 25(OH)D and VDBP levels might be of value in evaluating the pathogenesis and risk of CRC in the future. Moreover, serum VDBP or 25(OH)D levels were associated with patient's clinical and pathological features providing data for risk and prognostic prediction., (© 2019 Wiley Periodicals, Inc.)

Tetraspanins have been implicated in multiple biological functions including protein networking and cell signaling. NET-6 (TSPAN 13) has been demonstrated to be a tumor suppressor gene in breast cancer, while CD151 is more likely to act as an oncogene. However, the biological function of both proteins is still inconclusive. Immunohistochemistry was used to analyze the expression of NET-6 and CD151 proteins in breast tumors and benign epithelial cells. The cellular expression of both markers was correlated with HER2, ER, and PR status as well as tumor grade, Ki-67 scores, invasion, and metastasis. Expression of NET-6 and CD151 was variable both in tumors and in benign epithelial cells. Expression of NET-6 and CD151 was stronger in tumors than in benign epithelial cells. The expression of NET-6 was also stronger in HER2-negative, low-grade, lymphovascular invasion-negative, and non-metastatic breast tumors. There was no correlation between NET-6 expression and ER, or PR, or triple-negative status. There was no correlation between CD151 expression and HER2, ER, PR, or triple-negative status, tumor grade, or Ki-67 scores, invasion, and metastasis. The expression of tetraspanins NET-6 and CD151 may indicate an alteration of their biological function during neoplastic transformation. NET-6 expression in tumors might be a potential marker indicating the outcome of breast cancer.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

Background: Biomarkers for early diagnosis and follow-up of cancers are still underutilized in clinical management. Thus, seeking new biomarkers with better sensitivity and specificity is still a challenge. VEGF, VEGFR2, and OPN are newly emerging biomarkers with clinical potential., Methods: ELISA was used to analyze serum VEGF, VEGFR2, and OPN from 75 gastrointestinal cancer patients and 75 control subjects. The correlation of pre-operative serum VEGF, VEGFR2, and OPN levels with CEA, Ki-67 as well as clinical features (age, gender, tumor size, TNM stage, tumor stage, lymph node involvement, metastasis, and histological grading) in these patients., Results: The pre-operative and post-operative serum VEGF and VEGFR2 levels and the post-operative OPN level in patients were significantly higher than in controls (p = 0.000, for all mentioned). The post-operative VEGF and OPN levels were significantly higher than that of pre-operative (p = 0.000 and 0.007, respectively). There was no correlation between pre-operative serum VEGF, VEGFR2, and OPN levels and serum CEA concentration. The pre-operative serum VEGF level was significantly correlated with the tumor Ki-67 scores; however, there was no correlation between serum VEGFR2 and OPN and Ki-67 scores. Univariate logistic regression analysis revealed that serum VEGF level was significantly higher in patients with advanced TNM (III - IV) stage and with lymph node involvement than in patients with low TNM stage (I - II) and with no lymph node involvement. High OPN level was correlated with metastasis. Multivariate logistic regression analysis results showed that serum VEGF and VEGFR2 were the two most important factors for the diagnosis of gastrointestinal cancers in this study (p = 0.000, for both). Combinatorial analysis of the biomarkers improved the performance of the assays., Conclusions: Serum VEGF and VEGFR2 are potential biomarkers for the diagnosis and prognosis evaluation of gastrointestinal cancers, while serum OPN is a potential biomarker for the prognostication of gastrointestinal cancers.

Background: The purpose of this study was to characterize disparities among centers performing major surgery for esophageal or gastric cancer stratified by case volume., Methods: The National Cancer Data Base (NCDB) was queried for cases of esophagectomy or total gastrectomy. Centers were compared based on number of cases during 2004-2013: low volume [1-99], middle [100-200], and high [>200]., Results: For esophagectomy, 17,547 patients were included; 73.5% were treated in low volume centers, 14.6% in middle, and 11.9% in high. For gastrectomy, 20,059 patients were included, with 87.5%, 8.3%, and 4.3%, respectively. Patients treated at low volume centers were more likely to be of racial/ethnic minorities, uninsured, and have lower socioeconomic status. Overall survival (OS) was superior for patients treated at high volume centers. On multivariable analysis for either procedure, a higher number of disparate factors was identified in the low and middle volume centers compared to the high volume centers, which were associated with poorer OS., Conclusions: This study identified higher numbers of disparate patient factors associated with low/middle volume centers compared to high volume centers, which were associated with worse OS, and further makes the case for performance of esophagectomy and total gastrectomy at high volume centers., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Importance: Failure to rescue (FTR), or death after a potentially preventable complication, is a nationally endorsed, publicly reported quality measure. However, little is known about the impact of frailty on FTR, in particular after low-risk surgical procedures., Objective: To assess the association of frailty with FTR in patients undergoing inpatient surgery., Design, Setting, and Participants: This study assessed a cohort of 984 550 patients undergoing inpatient general, vascular, thoracic, cardiac, and orthopedic surgery in the National Surgical Quality Improvement Program between January 1, 2005, and December 31, 2012. Frailty was assessed using the Risk Analysis Index (RAI), and patients were stratified into 5 groups (RAI score, ≤10, 11-20, 21-30, 31-40, and >40). Procedures were categorized as low mortality risk (≤1%) or high mortality risk (>1%). The association between RAI scores, the number of postoperative complications (0, 1, 2, or 3 or more), and FTR was evaluated using hierarchical modeling., Main Outcomes and Measures: The number of postoperative complications and inpatient FTR., Results: A total of 984 550 patients were included, with a mean (SD) age of 58.2 (17.1) years; women were 549 281 (55.8%) of the cohort. For patients with RAI scores of 10 or less, major complication rates after low-risk surgery were 3.2%; rates of those with RAI scores of 11 to 20, 21 to 30, 31 to 40, and more than 40 were 8.6%, 13.5%, 23.8%, and 36.4%, respectively. After high-risk surgery, these rates were 13.5% for those with scores of 10 or less, 23.7% for those with scores of 11 to 20, 31.1% for those with scores of 21 to 30, 42.5% for those with scores of 31 to 40, and 54.4% for those with scores of more than 40. Stratifying by the number of complications, significant increases in FTR were observed across RAI categories after both low-risk and high-risk procedures. After a low-risk procedure, odds of FTR after 1 major complication for patients with RAI scores of 11 to 20 increased 5-fold over those with RAI scores of 10 or less (odds ratio [OR], 5.3; 95% CI, 3.9-7.1). Odds ratios were 8.1 (95% CI, 5.6-11.7) for patients with RAI scores of 21 to 30; 22.3 (95% CI, 13.9-35.6) for patients with scores of 31 to 40; and 43.9 (95% CI, 19-101.1) for patients with scores of more than 40. For patients undergoing a high-risk procedure, the corresponding ORs were likewise consistently elevated (RAI score 11-20: OR, 2.5; 95% CI, 2.3-2.7; vs RAI score 21-30: 5.1; 95% CI, 4.6-5.5; vs RAI score 31-40: 8.9; 95% CI, 8.1-9.9; vs RAI score >40: 18.4; 95% CI, 15.7-21.4)., Conclusions and Relevance: Frailty has a dose-response association with complications and FTR, which is apparent after low-risk and high-risk inpatient surgery. Systematic assessment of frailty in preoperative patients may help refine estimates of surgical risk that could identify patients who might benefit from perioperative interventions designed to enhance physiologic reserve and potentially mitigate aspects of procedural risk, and would provide a framework for shared decision-making regarding the value of a given surgical procedure.

Background: Esophagectomy is a major surgical procedure associated with high rates of morbidity. The purpose of this study was to determine if the immediate first postesophagectomy chest X-ray (pCXR) is associated with morbidity or mortality., Methods: This was a single-institution analysis of patients undergoing esophagectomy, 2005-2015. A pCXR was routinely performed. A pCXR score was developed based on the number of objective abnormal findings. A statistical analysis was performed using patient/tumor variables and the pCXR score to derive adjusted odds ratios (ORs) on short-term outcomes., Results: One hundred eighty-two patients had pCXRs. Scores ranged from 0 (normal) to 4 depending on the number of abnormalities, with a mean score of 1.6. The mean patient age was 60.7 y. Within the cohort, 92.9% had adenocarcinoma, 39.6% had T3/T4 tumors, and 48.4% were node positive. Open surgeries were performed in 51.6%, and 74.2% had chest anastomoses. The 30- and 90-d mortality rates were 2.2% and 3.9%, respectively. Increasing pCXR scores were associated with increased risk of prolonged intubation (OR: 1.67, 95% confidence interval [CI]: 1.21-2.36, P = 0.002) and tracheostomy (OR: 2.12, 95% CI: 1.08-4.16, P = 0.029). Multivariable analysis adjusting for age, comorbidities and performance status, histology, pathologic stage, surgical approach, and operative time confirmed a statistically significant association with the pCXR score and respiratory failure requiring tracheostomy (OR: 2.13, 95% CI: 1.03-4.39, P = 0.041)., Conclusions: This is the first study to show an association between the first pCXR and respiratory failure, providing new evidence that the first pCXR has important implications for pulmonary care after esophagectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma., Study Design: We performed retrospective analyses using the National Cancer Data Base, 2004-2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S)., Results: Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67-0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68-1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC., Conclusion: Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted., (© 2017 Wiley Periodicals, Inc.)

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive disease and current treatment regimens fail to effectively cure PDAC. Development of resistance to current therapy is one of the key reasons for this outcome. Nimbolide (NL), a triterpenoid obtained from Azadirachta indica, exhibits anticancer properties in various cancer including PDAC cells. However, the underlying mechanism of this anticancer agent in PDAC cells remains undefined. We show that NL exerts a higher level of apoptotic cell death compared to the first-line agent gemcitabine for PDAC, as well as other anticancer agents including sorafenib and curcumin. The anticancer efficacy of NL was further evidenced by a reduction in the CD44 + as well as cancer stem-like cell (CSC) population, as it causes decreased sphere formation. Mechanistically, the anticancer efficacy of NL associates with reduced mutant p53 as well as increased mitochondrial activity in the form of increased mitochondrial reactive oxygen species and mitochondrial mass. Together, this study highlights the therapeutic potential of NL in mutant p53 expressing pancreatic cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Gemcitabine with capecitabine (gem-cap) is an established regimen for advanced biliary cancer (ABC) supported by our previously reported phase II trial. Here, we provide our updated experience., Methods: Single institution, retrospective study from 2005 to 2015 of ABC treated with gem-cap., Results: A total of 372 patients with ABC were identified, of whom 227 (61.0%) were treated with chemotherapy. 153 patients (67.4%) received gem-cap, of which 129 (56.8%) received it in the first line. Thirty two point six percent (42/129) were locally advanced, 67.4% (87/129) had metastatic disease, and 18.6% (24/129) received it as adjuvant therapy. Disease sites included 48.8% [63] intrahepatic cholangiocarcinoma (IHCC), 24.0% [31] extrahepatic cholangiocarcinoma (EHCC) and 27.1% [35] gallbladder carcinoma (GBC). Median follow-up was 49.7 months (mo). The median PFS and OS were 8.0 mo [95% confidence intervals (CI): 6.0-9.3] and 13.0 mo (95% CI: 10.7-17.4), respectively. Overall, 53.5% (69/129) experienced a grade 3/4 toxicity. The most common (35.7%) was a hematologic toxicity (neutropenia or thrombocytopenia) followed by infection (25.6%)., Conclusions: Gem-cap provides similar survival outcomes to gemcitabine/cisplatin based on historical comparison to the ABC-2 trial (median PFS =8.0 mo and OS =11.7 mo). Gem-cap may offer the advantage of fewer adverse events compared to the levels reported in ABC-2 (grade 3/4 events 70.7%)., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Introduction: An 18F-fluorodeoxyglucose positron emission tomography-computerized tomography (PET-CT) scan is performed after neoadjuvant chemoradiation (nCRT) to restage esophageal cancer. The purpose of this study was to determine the ability of PET-CT to accurately identify interval metastatic disease following nCRT., Methods: This was a single-institution retrospective review (January 2005-February 2012) of patients with esophageal cancer treated with nCRT who underwent pre- and post-nCRT PET-CT., Results: A total of 283 patients were treated with nCRT, of whom 258 (91.2%) had both a pre- and post-nCRT PET-CT. On the post-nCRT PET-CT, 64 patients (24.8%) had interval findings concerning for metastatic disease. Of these patients, only 10 (15.6%) had true-positive findings of metastatic disease (six biopsy proven). The sites of interval metastases included bone (4), liver (3), peritoneum (1), mediastinal lymph nodes (1), and cervical lymph nodes (1). The positive predictive value of post-nCRT PET-CT for interval metastases was 15.6% (10/64), and the yield for detecting metastases since the pre-nCRT PET-CT was 3.9% (10/258). The work-up of the 54 patients (20.9% of the initial starting group) with false-positive post-nCRT findings included biopsy (24.6%) and immediate additional imaging (45.2%). A total of 208 patients proceeded with surgery: 163 (78.4%) had no new findings on post-nCRT PET-CT, and 45 (21.6%) had new false-positive findings. False-positive sites mainly included the lung (15) and liver (14)., Conclusions: The yield of post-nCRT PET-CT for the detection of new metastatic disease was 3.9%. Post-nCRT PET-CT often leads to a high proportion of false positives and subsequent investigational work-up.

Pancreatic cancer has one of the lowest survival rates of all cancers. The mechanism underlying chemo-resistance of pancreatic cancer is not well understood. Our previous article reported that small molecule YM155 induced apoptosis in pancreatic cancer cells via activation of death receptor 5. In this study, we aim to continuously address death receptor 5-mediated apoptosis in chemo-resistant pancreatic carcinoma. We found that in comparison to paired pancreatic cancer tissues and adjacent normal tissues, five of the six cancer tissues had downregulated death receptor 5 and upregulated Bcl-xL. Mono treatment with lexatumumab was not sufficient to induce apoptosis in pancreatic cancer cells, whereas focal adhesion kinase inhibitor PF573228 significantly sensitized lexatumumab-induced apoptosis. Western blotting analysis revealed that lexatumumab and PF573228 combination treatment increased death receptor 5 but decreased Bcl-xL expression. Interestingly, pre-treatment with Bcl-xL inhibitor ABT263 reversed the insensitivity of panc-1 cells to lexatumumab or PF573228-induced apoptosis. Specific small interfering RNA-mediated gene silencing of Bcl-xL effectively sensitized pancreatic cancer cells to lexatumumab or PF573228-induced apoptosis. Furthermore, lexatumumab and PF573228 combination was shown to exhibit significant xenograft pancreatic tumor growth inhibition in SCID mice. Our data provide fundamental evidence to support the notion that lexatumumab and PF573228 co-treatment could be a potentially effective regime for patients with pancreatic cancer.

Background: Our group reported that patients with clinically node-negative esophageal adenocarcinoma do not derive overall survival (OS) benefit from neoadjuvant chemoradiation (nCRT) compared with clinically node-positive patients. The aim of this study was to develop a calculator that could more easily identify which patients derive OS benefit from nCRT., Study Design: Using the National Cancer Data Base (2006 to 2012), patients with clinical status T1b to T4a, N-/+, M0 adenocarcinoma of the esophagus who underwent resection were selected. Of this cohort, 80% were randomly selected to develop and test the prediction model using Cox regression. The remaining 20% were used to internally validate the model, and performance was evaluated using receiver operating characteristic curves and area under the curves., Results: A total of 8,974 patients met study criteria. Using the model testing cohort (7,179 patients), variables that were independently associated with OS in multivariable analysis were included in the model. These variables included Charlson-Deyo comorbidity score, tumor grade, clinical T and N status, and nCRT before surgery. Factors associated with increased risk of death were higher grade and higher T or N status. Receipt of nCRT was associated with improved OS. After validation, model performance showed an area under the curve of 0.630 and 0.682 for 1-year and 3-year OS, respectively., Conclusions: A novel OS calculator was developed for esophageal adenocarcinoma that reasonably predicts which patients are expected to derive OS benefit from nCRT. This tool can be helpful in determining OS benefit from nCRT to assist with treatment decision making., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease., (Copyright © 2016 by the National Comprehensive Cancer Network.)

Cancer cells often gains a growth advantage by taking up glucose at a high rate and undergoing aerobic glycolysis through intrinsic cellular factors that reprogram glucose metabolism. Focal adhesion kinase (FAK), a key transmitter of growth factor and anchorage stimulation, is aberrantly overexpressed or activated in most solid tumors, including pancreatic ductal adenocarcinomas (PDACs). We determined whether FAK can act as an intrinsic driver to promote aerobic glycolysis and tumorigenesis. FAK inhibition decreases and overexpression increases intracellular glucose levels during unfavorable conditions, including growth factor deficiency and cell detachment. Amplex glucose assay, fluorescence and carbon-13 tracing studies demonstrate that FAK promotes glucose consumption and glucose-to-lactate conversion. Extracellular flux analysis indicates that FAK enhances glycolysis and decreases mitochondrial respiration. FAK increases key glycolytic proteins, including enolase, pyruvate kinase M2 (PKM2), lactate dehydrogenase and monocarboxylate transporter. Furthermore, active/tyrosine-phosphorylated FAK directly binds to PKM2 and promotes PKM2-mediated glycolysis. On the other hand, FAK-decreased levels of mitochondrial complex I can result in reduced oxidative phosphorylation (OXPHOS). Attenuation of FAK-enhanced glycolysis re-sensitizes cancer cells to growth factor withdrawal, decreases cell viability and reduces growth of tumor xenografts. These observations, for the first time, establish a vital role of FAK in cancer glucose metabolism through alterations in the OXPHOS-to-glycolysis balance. Broadly targeting the common phenotype of aerobic glycolysis and more specifically FAK-reprogrammed glucose metabolism will disrupt the bioenergetic and biosynthetic supply for uncontrolled growth of tumors, particularly glycolytic PDAC.

Introduction: Pneumonia and tracheal aspiration remain problematic following esophagectomy. We hypothesized that the incidence of postesophagectomy pneumonia occurs in part because of swallowing dysfunction and more importantly silent tracheobronchial aspiration. Therefore, we instituted a routine prospective formal swallowing evaluation to determine if the aspiration rate and its associated morbidity can be decreased by early identification of patients with silent or vocal aspiration., Methods: Patients undergoing minimally invasive McKeown esophagectomy and receiving neoadjuvant chemoradiotherapy (NACR) were prospectively enrolled between December 2013 to January 2015. A standardized cineradiography observation utilizing the Rosenbek penetration-aspiration (RPA) scale was used to rule out anastomotic leak and/or aspiration., Results: Of 27 patients evaluated, twelve patients were noted to have silent (n = 8) or vocal (cough n = 4) aspiration of thin liquid (n = 8) or nectar-thick consistency (n = 4) on their initial study. Three patients were noted to have an anastomotic leak and vocal aspiration on their initial study. Eight of the nine patients who aspirated but did not have an anastomotic leak on their initial study had a repeat RPA study prior to discharge showing improvement from the initial study. Six patients (22 %) had vocal cord paresis and clinical hoarseness, but only two patients who had clinical diagnosis of pneumonia were noted to have vocal cord paresis and silent aspiration., Conclusions: Swallowing dysfunction remains a common problem after minimally invasive esophagectomy (MIE) with cervical anastomosis and can be readily identified. Silent aspiration likely contributes to pneumonia after MIE.

Although infrequent, esophageal leiomyomas are the most common benign intramural tumors of the esophagus. As malignant potential is not a concern in these lesions, they represent ideal candidates for an organ-preserving approach. Due to their well-circumscribed growth, a minimally invasive approach should be pursued in almost all patients. We present our recent techniques and results associated with totally minimally invasive thoracoscopic and laparoscopic approaches to resection of esophageal leiomyomas. These approaches require technical expertise but can be accomplished with a short learning curve.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ., (Copyright © 2015 by the National Comprehensive Cancer Network.)

Background: The surgical management of esophageal perforation (EP) often results in mortality and significant morbidity. Recent less invasive approaches to EP management include endoscopic luminal stenting and minimally invasive surgical therapies. We wished to establish therapeutic efficacy of minimally invasive therapies in a consecutive series of patients., Study Design: An IRB-approved retrospective review of all acute EPs between 2007 and 2013 at a single institution was performed. Patient demographic, clinical outcomes data, and hospital charges were collected., Results: We reviewed 76 consecutive patients with acute EP presenting to our tertiary care center. Median age was 64 ± 16 years (range 25 to 87 years), with 50 men and 26 women. Ninety percent of EPs were in the distal esophagus, with 67% of iatrogenic perforations occurring within 4 cm of the gastroesophageal junction. All patients were treated within 24 hours of initial presentation with a removable covered esophageal stent. Leak occlusion was confirmed within 48 hours of esophageal stent placement in 68 patients. Median lengths of ICU and hospital stay were 3 and 10 days, respectively (range 1 to 86 days). One-third of the patients were noted to have prolonged intubation (>7 days) and pneumonia that required a tracheostomy. One in-hospital (1.3%) mortality occurred within 30 days. Median total hospital charges for EP were $85,945., Conclusions: Endoscopically placed removable esophageal stents with minimally invasive repair of the perforation and feeding access is an effective treatment method for patients with EP. This multidisciplinary method enabled us to care for severely ill patients while minimizing morbidity and mortality and avoiding open esophageal surgery., (Copyright © 2014 American College of Surgeons. All rights reserved.)

Esophagectomy is a surgical operation which requires technical expertise to decrease the morbidity and mortality frequently associated with this advance procedure. Various minimally invasive esophagectomy techniques have been developed to decrease the negative impact of esophageal resection. Recently, robotic assisted esophagectomies have been described with a wide variety in technique and outcome disparity. This article is a summation review of the current literature regarding the various techniques and surgical outcomes of robotic assisted esophagectomies.

LKB1 is a tumor susceptibility gene for the Peutz-Jeghers cancer syndrome and is a target for mutational inactivation in sporadic human malignancies. LKB1 encodes a serine/threonine kinase that has critical roles in cell growth, polarity and metabolism. A novel and important function of LKB1 is its ability to regulate the phosphorylation of CREB-regulated transcription co-activators (CRTCs) whose aberrant activation is linked with oncogenic activities. However, the roles and mechanisms of LKB1 and CRTC in the pathogenesis of esophageal cancer have not been previously investigated. In this study, we observed altered LKB1-CRTC signaling in a subset of human esophageal cancer cell lines and patient samples. LKB1 negatively regulates esophageal cancer cell migration and invasion in vitro. Mechanistically, we determined that CRTC signaling becomes activated because of LKB1 loss, which results in the transcriptional activation of specific downstream targets including LYPD3, a critical mediator for LKB1 loss-of-function. Our data indicate that de-regulated LKB1-CRTC signaling might represent a crucial mechanism for esophageal cancer progression.

Esophagectomy is a complex operation with significant morbidity and mortality. Minimally invasive esophagectomy (MIE) was described in the 1990s in an effort to reduce operative morbidity. Since then many institutions have adopted and described their series with this technique. This paper reviews the literature on the variety of MIE techniques, clinical and quality of life outcomes with open versus MIE, and controversies surrounding MIE-such as prone positioning, stapling techniques, size of the gastric conduit, and robotic techniques.

Antiangiogenic therapy has shown promise in the treatment of patients with hepatocellular carcinoma (HCC). Bevacizumab, sorafenib, and sunitinib showed efficacy in patients with HCC; and sorafenib is approved by the FDA for treatment of this cancer. In practice, the clinical benefit of these agents has been heterogeneous; and in patients who do respond, the benefit is modest and/or short-lived. Recent advances in the molecular understanding of tumor angiogenesis along with the rapid development of targeted drug discovery have made it possible to explore novel combination therapy for HCC. We review the clinical trial results, discuss possible molecular mechanisms of resistance, and suggest novel combinations with antiangiogenic therapy.

Background: Isolated limb infusion (ILI) for recurrent or in-transit melanoma is an accepted technique that allows high-dose chemotherapy to be delivered to an extremity with minimal systemic toxicity. Current infusion systems have relied on manual delivery of drugs and circulation of blood during the treatment. Herein, we document our initial results with an automated circuit for ILI as an alternative to the manual technique., Methods: Patients undergoing ILI with an automated circuit for recurrent or advanced malignancy were identified. ILI was performed utilizing a Sarns 8000 roller pump attached to a Cobe 4:1 cardioplegia set with heat exchanger with a total priming volume of 80 ml. Melphalan (7.5 mg/L) and Dactinomycin (75 μg/L) doses which were corrected for ideal body weight were delivered via the infusion circuit after limb temperature reached 38 °C., Results: Fourteen lower extremity infusion procedures were performed in 10 patients. Successful infusion procedures were completed in all patients using the automated circuit. Constant flow rates of 50-70 cc/minute were achievable with the automated circuit. Acute toxicity and clinical results were similar to that reported with manual delivery systems., Conclusion: ILI for advanced malignancy utilizing an automated circuit is feasible and safe. This automated system offers a safe and reliable alternative to the manual infusion technique., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: Preoperative treatment of rectal cancer with combined chemotherapy and radiation therapy has become a widely accepted strategy. The current challenge is to improve outcomes whereas minimizing morbidity and maximizing the potential for a sphincter sparing procedure. This study sought to evaluate the safety and efficacy of a combination of 2 novel approaches-accelerated, hyperfractionated radiation therapy and twice daily oral capecitabine., Methods: Consenting patients with locally advanced T3-T4, N0-1, M0 rectal adenocarcinoma, located no further than 15 cm from the anal verge, were treated with twice daily fractions of 1.2 Gy M-F to a total of 50.4 Gy for T3 lesions and 55.2 Gy for T4 lesions. Concomitantly, the patients received capecitabine 825 mg/m twice per day 7 days per week. Patients were operated on 4 to 6 weeks after completion of therapy., Results: Sixteen of 17 enrolled patients were eligible and all 16 completed the full course of treatment including definitive surgery. Eleven patients had a sphincter sparing procedure and 5 had an abdominoperineal resection. Tumor and/or nodal downstaging occurred in 81% of patients, 100% of resections were R0, and the sphincter preservation rate was 68%. There were 18% pathologic complete remissions and 68% of specimens were node negative with an additional 12% Nx owing to transanal excision. The therapy was well tolerated and there were no unexpected toxicities with only diarrhea reaching grade 3 in 4 patients., Conclusions: This novel approach to preoperative treatment of rectal adenocarcinoma was well tolerated and effective. Comparison with more established approaches appears justified.

Background: Combined resection of both the liver and pancreas for malignancy remains a controversial procedure. To many, the need for such an extended procedure implies an extent of disease that is usually not amenable to surgical control, and the extent of the procedure exposes the patients to substantial operative risks. The purpose of this study was to assess our results with combined resection of the liver and pancreas., Study Design: Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included 26 pancreaticoduodenectomies (PD) and 14 distal pancreatic resections. Liver resections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections., Results: There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy. Mean hospital stay was 14 days (range 7 to 42 days). Median follow-up was 30 months (range 3 to 76 months). Patients undergoing resection for neuroendocrine tumors had a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p = 0.01)., Conclusions: Combined resection of the liver and pancreas can be performed safely. The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindication to resection in selected patients., (Copyright 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Chemoresistance may involve the anti-apoptotic transcriptional regulator, nuclear factor-kappa B (NF-kappa B). The purpose of this study was to determine whether chemotherapy induces NF-kappa B activation in a human colon cancer cell line (SW48) and whether NF-kappa B is constitutively activated in colorectal cancer., Methods: SW48 cells were incubated with gemcitabine hydrochloride (Gemzar) in the presence and absence of the 26s proteasome inhibitor, MG132, and NF-kappa B binding (electrophoretic mobility shift assay), DNA synthesis (tritiated thymidine uptake), cell viability (3-[4,5-dimethylthiazol-2-yl]-diphenyl-tetrazolium bromide assay), and apoptosis (caspase-3 activity) were measured at 24 hours. NF-kappa B binding (electrophoretic mobility shift assay) was also assayed in 10 colorectal cancer tumors., Results: SW48 cells demonstrated constitutive NF-kappa B binding that was enhanced by gemcitabine hydrochloride in a dose-dependent manner. MG132 inhibited NF-kappa B binding and enhanced gemcitabine hydrochloride's inhibition of DNA synthesis (gemcitabine hydrochloride = 73% +/- 1.4% vs gemcitabine hydrochloride + MG132 = 6% +/- 0.4%, P <.05), cell killing (gemcitabine hydrochloride = 87% +/- 2.0 vs gemcitabine hydrochloride + MG132 = 25% +/- 1.3%, P <.05), and caspase-3 activity (gemcitabine hydrochloride = 870 +/- 17.4 vs gemcitabine hydrochloride + MG132 = 1075 +/- 20.4, P <.05). NF-kappa B binding was increased in 8 of 10 colorectal cancer tumors compared with adjacent normal mucosa., Conclusions: Gemcitabine hydrochloride enhances NF-kappa B binding in a colorectal cancer cell line, whereas inhibition of NF-kappa B enhances gemcitabine hydrochloride's antitumor activity. NF-kappa B is also activated in human colorectal cancer. NF-kappa B may identify chemoresistant tumors, whereas inhibition of NF-kappa B may be a novel, biologically based therapy. (Surgery 2001;130:363-9).

Introduction: Our objective was to compare the efficacy of CT alone to CT followed by laparoscopy in determining resectability of pancreatic nonfunctioning islet (NFI) cell tumors., Methods: A retrospective analysis from 1993 to 1999 revealed 48 patients who underwent surgical evaluation for NFI cell tumors. Of these, 34 (71%) patients underwent laparoscopy and CT for either diagnostic purposes or tumor staging. CT and laparoscopic criteria for curative resectability were defined and the sensitivity, specificity, and predictive value of both modalities in determining resectability were calculated., Results: The most frequent tumor location and presenting symptoms were pancreatic head (n = 27, 56%) and abdominal pain (n = 31, 65%), respectively. Median tumor size was 4.0 cm. In the laparoscopy group, curative resection was performed in 20 cases (59%). CT followed by laparoscopy was more sensitive than CT alone in predicting resectability (93% vs. 50%, P = 0.03) with similar specificity (both 100%). The predictive value for tumor resectability was 74% for CT alone and 95% for CT followed by laparoscopy. Reasons for unresectability identified at laparoscopy but not indicated by CT were liver metastases (n = 6) or nodal disease (n = 1). Four of these patients were spared a laparotomy while the other three patients underwent surgical palliation and all are alive with disease (AWD). In those not undergoing laparoscopy (n = 14), curative resection was performed in 64% (n = 9). Four of these patients underwent resection, despite having metastases, and three are AWD., Conclusions: NFI cell tumors of the pancreas present as large masses with frequent metastases. Despite metastatic disease, prolonged survival is often achieved with or without open surgical treatment. Laparoscopy can be used in diagnosis and accurately identifies metastases not seen on CT, thus sparing laparotomy in some patients.

Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival., (Copyright 2002 Wiley-Liss, Inc.)

Gastric cancer patients in the United States have a poor prognosis with a collective 5-year survival rate of less than 15%. We identified a subset of actual 5-year survivors (long-term survivors) and analyzed clinicopathologic variables predictive of recurrence and survival beyond the 5-year mark. A review of our prospective database from July 1985 to February 1993 revealed 154 patients who were long-term survivors and 280 patients who died of disease prior to 5 years (short-term survivors) following curative resection (R0). Tumor (T) stage, nodal (N) status, tumor location, and median number of positive nodes were compared between the two groups. Univariate and multivariate analysis of disease-free and greater than 5-year disease-specific survival was performed within the long-term survivors. Among the long-term survivors, 29% were classified as "early gastric cancers" (T1NX). The median number of positive nodes (0 vs. 5; P <0.001) and percentage of lesions that were T1/T2 (60% vs. 19%; P <0.001), node negative (58% vs. 15%; P <0.001), or proximal (40% vs. 65%; P <0.001) was significantly different in long-term survivors vs. short-term survivors, respectively. Of the 154 five-year survivors, gastric cancer recurred in 23, and 13 patients (8%) died of the disease at a median of 84 months from the original diagnosis. On univariate and multivariate analysis of prognostic factors in the long-term survivors, only the Lauren histologic classification predicted disease-specific and disease-free survival with diffuse histologic types faring significantly less well. T stage and N status are powerful prognostic factors of outcome within the first 5 years after curative resection of gastric carcinoma. However, the Lauren histologic type emerges as the dominant predictor of outcome once a patient with gastric cancer has survived for 5 years or more.

We present a case of giant cavernous hemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by enucleation. The 51 year old woman presented with increased abdominal girth and easy bruisability. Workup elsewhere revealed a massive hepatic hemangioma and she was started on radiation therapy to the lesion and offered an orthotopic liver transplant. After careful preoperative preparation, we felt that resection was possible and she underwent a successful enucleation. The operation and postoperative course were complicated by bleeding but she recovered and remains well in followup after 6 months. All coagulation parameters have returned to normal. Enucleation should be considered the treatment of choice for hepatic hemangiomas, including those presenting with Kasabach-Merritt syndrome. The benefits of enucleation as compared to liver transplantation for these lesions are discussed.

Background: Although early gastric cancer (T1, NX) in Japan has been reported to have an excellent prognosis, the experience with this cancer in the United States is limited. The treatment of these tumors in Japan is becoming less aggressive as "good prognostic factors" are increasingly recognized. Our objective was to identify predictors of nodal disease and survival in a large cohort of Western patients with T1 tumors., Methods: A retrospective review of our prospective data base from July 1985 to March 1998 revealed 165 patients undergoing surgical resection for T1 gastric tumors. Clinicopathological factors analyzed and compared included presence of positive nodes, tumor size (> or =4.5 vs. <4.5 cm), depth (mucosal vs. submucosal), grade (poor vs. moderate and well), and tumor site (proximal vs. distal), presence of venous or perineural invasion, and Lauren's classification. Factors predicting lymph node involvement and disease-specific survival were evaluated by univariate and multivariate analysis., Results: Median follow-up time was 36 months. The actuarial 5-year survival was 88%. Thirteen patients (8%) died of disease. Lymph node involvement was present in 31 tumors (19%), with a 5-year survival of 91% with negative nodes vs. 78% with positive nodes. On univariate and multivariate analysis, the presence of tumor submucosal invasion (P<.05), venous invasion (P = .02), and size of 4.5 cm and larger (P = .02) was significantly associated with an increased risk for nodal positivity. On univariate analysis of survival, node-positive tumors (P = .02) and tumors 4.5 cm and larger (P = .008) were significantly associated with decreased survival. On multivariate analysis, only node-positive tumors were significantly (P = .01) associated with decreased survival. Those tumors that were limited to the mucosa and less than 4.5 cm in size (n = 47) had a 4% rate of positive nodes. In contrast, those tumors that were 4.5 cm and larger and had penetrated into the submucosa (n = 16) had a 56% chance of positive nodes., Conclusions: Early gastric carcinoma in North America has an excellent prognosis, similar to that in Japan. Tumors that are limited to the mucosa and smaller than 4.5 cm could be considered for limited resection without lymphadenectomy.

Accurate preoperative staging of pancreatic malignancy aids in directing appropriate therapy and avoids unnecessary invasive procedures. We evaluated the accuracy of magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) in determining resectability of pancreatic malignancy. Twenty-one patients with suspected pancreatic malignancy underwent dynamic, contrast-enhanced breath-hold MRI with MRCP prior to surgical evaluation. Results of this study were correlated with operative results and pathologic findings. The sensitivity, specificity, and accuracy of MRI with MRCP in detecting a mass, determining the nature of the mass, and predicting lymph node involvement and resectability were determined. MRI with MRCP correctly identified the presence of a pancreatic mass in all 21 of these patients. Following pathologic correlation, it was determined that MRI with MRCP was 81% accurate in determining the benign or malignant nature of the pancreatic mass and 43% accurate in predicting lymph node involvement. In predicting resectability, MRI with MRCP had a sensitivity of 100%, specificity of 83%, positive predictive value of 94%, negative predictive value of 100%, and accuracy of 95%. MRI with MRCP is an accurate, noninvasive technique in the preoperative evaluation of pancreatic malignancy. Information obtained from MRI with MRCP including identification of a mass and predicting tumor resectability may be of value in staging and avoiding unnecessary invasive diagnostic procedures in patients with pancreatic cancer.

Background: The indications for preoperative biliary stenting in patients with obstructive jaundice are controversial. We evaluated the effect of preoperative biliary stenting on bacterobilia and infectious complications following surgical treatment of proximal cholangiocarcinoma., Design: A retrospective review was performed of all patients undergoing surgical treatment of proximal cholangiocarcinoma., Setting: A metropolitan cancer surgery service., Patients and Methods: Seventy-one patients underwent palliative biliary bypass or curative resection of proximal cholangiocarcinoma from March 1, 1991, to April 1, 1997, and were entered into a prospective database. Forty-one patients underwent preoperative biliary intubation and stent placement. We analyzed patient, nutritional, laboratory, and operating room factors. Statistical evaluation was performed using Student t test and chi2 analysis., Main Outcome Measure: Data were recorded for a history of cholangitis, operative time, amount of blood loss, incidence of intraoperative bacterobilia, proportion of patients with postoperative infectious and noninfectious complications, and length of hospital stay., Results: All patients (n = 14) with a history of preoperative cholangitis had been subjected to previous endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic biliary drainage. Groups were equivalent for risk for comorbidity, proportion undergoing curative vs palliative procedures, time spent in the operating room, and amount of blood loss. Patients with stents had a significantly lower bilirubin level (P = .005). Patients with stents had a significantly increased risk for bacterobilia (P = .001) and infectious complications (P = .03). Bacterobilia was present in 11 (100%) of 11 patients undergoing endoscopic stenting and in 15 (65%) of 23 patients undergoing percutaneous stenting. There was no increased risk for noninfectious complications, length of hospital stay, or mortality in patients with stents. In 10 (59%) of 17 patients with postoperative infectious complications and positive findings of intraoperative bile culture, the organism was synonymous., Conclusions: Preoperative biliary stenting in proximal cholangiocarcinoma increases the incidence of contaminated bile and postoperative infectious complications. Endoscopic stents frequently do not relieve jaundice in high biliary obstruction and are rarely indicated, especially in light of their high contamination rate.

Background: Increased intestinal permeability may lead to sepsis in resected upper gastrointestinal (GI) cancer patients. This study sought to determine whether these patients demonstrated increased intestinal permeability and if early postoperative enteral nutrition would alter this result., Methods: Nineteen patients undergoing complete resection of upper GI malignancy were randomized into two groups: the nonfed group received IV crystalloid, and the fed group started enteral nutrition by jejunostomy on postoperative day (POD) 1. Six nonoperative volunteers were controls. The lactulose/mannitol test was performed on PODs 1 and 5. Ten grams of lactulose and 5 g of mannitol were given, and urine was collected for 6 hours., Results: All patients (nonfed, 1.895+/-0.34; fed, 0.893+/-0.24) had elevated lactulose/mannitol ratios on POD 1 vs controls (0.262+/-0.1; p < .008 and p = .05). These elevated levels returned toward control levels in both groups by day 5 (nonfed, 0.533+/-0.1, p = .06; fed, 0.606+/-0.12, p = .08)., Conclusions: Major upper GI surgery for malignancy resulted in a significant increase in intestinal permeability on POD 1. With or without enteral nutrition, this measure of intestinal permeability returned to normal on POD 5 in well-nourished patients.

Accurate common bile duct (CBD) imaging in patients with biliary calculi is an important determinant of specific therapy. Noninvasive methods to evaluate calculi in the CBD have limited accuracy and rely mainly on ultrasonography and computed tomography. Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive modality available to evaluate the biliary system. This study was undertaken to assess the accuracy of MRCP in predicting the presence or absence of CBD stones in patients at increased risk for choledocholithiasis. The medical records of 48 patients with a final diagnosis of biliary calculous disease undergoing MRCP between November 1995 and April 1997 were retrospectively reviewed. Three groups were identified: choledocholithiasis (n = 19), gallstone pancreatitis (n 5 11), and uncomplicated cholelithiasis (n = 18). In all patients the presence or absence of CBD calculi, as determined by MRCP, was correlated with the final diagnosis obtained from endoscopic retrograde cholangiopancreatography (ERCP) (n = 19), intraoperative cholangiography (n = 6), CBD exploration (n = 13), or clinical follow-up (n = 10). Sensitivity, specificity, and accuracy of MRCP were determined. The major clinical indications for MRCP in the 48 patients ware abnormal liver function tests followed by hyperamylasemia. Twenty patients were diagnosed with CBD stones and 28 were not. MRCP correctly predicted the presence of CBD stones in 19 of 20 patients and failed to detect CBD stones in one patient with gallstone pancreatitis. MRCP incorrectly predicted the presence of CBD stones in 3 of 28 patients ultimately found to have gallstones and no CBD stones. MRCP correctly predicted the absence of CBD stones in the other 25 patients including 10 patients with gallstone pancreatitis. Overall, MRCP had a sensitivity of 95%, a specificity of 89%, and an accuracy of 92%. MRCP is an accurate, noninvasive test for evaluating the CBD duct for the presence or absence of calculi in patients suspected of having CBD stones. Our data support the use of MRCP in the preoperative evaluation of these patients as findings may influence therapeutic decisions.