Neoadjuvant Chemotherapy is Associated With Decreased Survival in Early-Stage Gastric Cancer.

BACKGROUND: Although randomized controlled trials on neoadjuvant chemotherapy for gastric cancer have included some T1-staged tumors, overall survival (OS) has not been analyzed for this subset. Due to the low negative predictive value of clinical staging and the benefits of neoadjuvant chemotherapy for locally advanced disease, identifying patient groups with early-stage gastric cancer that may benefit from neoadjuvant chemotherapy is of merit. AIMS: The objective of this study was to evaluate the relationship between OS and sequence of surgical therapy for clinical T1 gastric cancer. METHODS: The 2017 National Cancer Database was used to compare patients who had surgery-first and those who received neoadjuvant chemotherapy for T1-stage gastric cancer. OS was analyzed using a parametric regression survival-time model adjusted for covariates. The effects of these covariates on OS based on surgical sequence were examined. RESULTS: 11,219 patients were included, of which 10,191 underwent surgery as their first or only treatment. When adjusted for covariates, neoadjuvant chemotherapy followed by curative-intent surgery was significantly associated with increased risk of death (HR 1.15, 95% CI 1.01-1.31, P = .030). In multivariate analysis, clinical N0 stage, non-minorities, and patients with high socioeconomic status had improved OS if they did not have neoadjuvant chemotherapy and instead had upfront surgery. CONCLUSION: Neoadjuvant chemotherapy is associated with decreased OS for early-stage gastric adenocarcinoma, even for patients with clinically positive nodal disease. In addition, the lack of survival improvement with a surgery-first approach in patients with disparities deserves further study.

Synchronous Upper Intestinal Neurofibromas and Duodenal Periampullary Well-Differentiated Neuroendocrine Tumor Associated With Neurofibromatosis 1.

Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder associated with characteristic skin findings, as well as a fourfold increase in risk of malignancy. NF1 patient malignancies commonly include the central and peripheral nervous system, but these patients are also at high risk of developing gastrointestinal (GI) tumors. While most often these GI tumors are benign upper GI neurofibromas; clinicians should have a high suspicion for malignant tumors, degeneration into a malignant peripheral nerve sheath tumor or less common associated malignancies such as well-differentiated neuroendocrine tumor (formerly carcinoid tumor), when patients present with multiple GI tumors. Our patient underwent a Whipple for symptomatic neurofibromas associated with NF1 and was unexpectedly discovered to have a metastatic duodenal well-differentiated neuroendocrine tumor. The patient is a 66-year-old man with NF1 who presented with hematemesis and was found to have large gastric neurofibromas and an ampullary neurofibroma based on endoscopy and radiological imaging. Another ostensive neurofibroma was noted distally. A pancreatoduodenectomy was performed. Pathological examination identified the neurofibromas but the tumor measuring 1.4cm and arising from the minor duodenal papilla was, in fact, a synchronous well-differentiated neuroendocrine tumor metastatic to regional lymph nodes, consistent with pT2 pN1, Stage IIIB cancer. NF1 patients with multiple GI tumors are at an increased risk for malignancy. Therefore, a high index of suspicion for malignancy in any patient with NF1 presenting with gastrointestinal symptoms has implications for a surgeon, warranting not only a further diagnostic investigation, but also an appropriate surgical intervention and sampling for nodal spread. Because of the possibility of a simultaneous cancer, it is crucial to assess all suspicious tumors even if the masses appear endoscopically benign.

What is Elective Oncologic Surgery in the Time of COVID-19? A Literature Review of the Impact of Surgical Delays on Outcomes in Patients with Cancer.

BACKGROUND: The impact of the COVID-19 pandemic has spread beyond those infected with SARS-CoV-2. Its widespread consequences have affected cancer patients whose surgeries may be delayed in order to minimize exposure and conserve resources. METHODS: Experts in each surgical oncology subspecialty were selected to perform a review of the relevant literature. Articles were obtained through PubMed searches in each cancer subtype using the following terms: delay to surgery, time to surgery, outcomes, and survival. RESULTS: Delays in surgery > 4 weeks in breast cancer, ductal carcinoma in situ, T1 pancreatic cancer, ovarian cancer, and pediatric osteosarcoma, negatively impacted survival. Studies on hepatocellular cancer, colon cancer, and melanoma (Stage I) demonstrated reduced survival with delays > 3 months. CONCLUSION: Studies have shown that short-term surgical delays can result in negative impacts on patient outcomes in multiple cancer types as well as in situ carcinoma. Conversely, other cancers such as gastric cancer, advanced melanoma and pancreatic cancer, well-differentiated thyroid cancer, and several genitourinary cancers demonstrated no significant outcome differences with surgical delays.

National Cluster-Randomized Trial of Duty-Hour Flexibility in Surgical Training.

BACKGROUND: Concerns persist regarding the effect of current surgical resident duty-hour policies on patient outcomes, resident education, and resident well-being. METHODS: We conducted a national, cluster-randomized, pragmatic, noninferiority trial involving 117 general surgery residency programs in the United States (2014-2015 academic year). Programs were randomly assigned to current Accreditation Council for Graduate Medical Education (ACGME) duty-hour policies (standard-policy group) or more flexible policies that waived rules on maximum shift lengths and time off between shifts (flexible-policy group). Outcomes included the 30-day rate of postoperative death or serious complications (primary outcome), other postoperative complications, and resident perceptions and satisfaction regarding their well-being, education, and patient care. RESULTS: In an analysis of data from 138,691 patients, flexible, less-restrictive duty-hour policies were not associated with an increased rate of death or serious complications (9.1% in the flexible-policy group and 9.0% in the standard-policy group, P=0.92; unadjusted odds ratio for the flexible-policy group, 0.96; 92% confidence interval, 0.87 to 1.06; P=0.44; noninferiority criteria satisfied) or of any secondary postoperative outcomes studied. Among 4330 residents, those in programs assigned to flexible policies did not report significantly greater dissatisfaction with overall education quality (11.0% in the flexible-policy group and 10.7% in the standard-policy group, P=0.86) or well-being (14.9% and 12.0%, respectively; P=0.10). Residents under flexible policies were less likely than those under standard policies to perceive negative effects of duty-hour policies on multiple aspects of patient safety, continuity of care, professionalism, and resident education but were more likely to perceive negative effects on personal activities. There were no significant differences between study groups in resident-reported perception of the effect of fatigue on personal or patient safety. Residents in the flexible-policy group were less likely than those in the standard-policy group to report leaving during an operation (7.0% vs. 13.2%, P<0.001) or handing off active patient issues (32.0% vs. 46.3%, P<0.001). CONCLUSIONS: As compared with standard duty-hour policies, flexible, less-restrictive duty-hour policies for surgical residents were associated with noninferior patient outcomes and no significant difference in residents' satisfaction with overall well-being and education quality. (FIRST ClinicalTrials.gov number, NCT02050789.).

ERCP in potentially resectable malignant biliary obstruction is frequently unsuccessful when performed outside of a comprehensive pancreaticobiliary center.

BACKGROUND AND OBJECTIVES: ERCP prior to pancreaticoduodenectomy is unnecessary in select patients. When performed, it should be in conjunction with endoscopic ultrasound (EUS) to increase diagnostic sensitivity and allow for metal stent placement. The aim of this study was to determine differences in endoscopic practice patterns at community medical centers (CMC) and a comprehensive pancreaticobiliary referral center (PBRC). METHODS: Retrospective cohort study of all patients seen at a PBRC for endoscopic and/or surgical management of potentially resectable malignant distal biliary obstruction from 1/2011 to 6/2014. RESULTS: Of 75 patients, 30 underwent endoscopic management at a CMC and 45 were initially managed at our PBRC. ERCP was attempted in 92% of patients. EUS was performed more frequently (100% vs. 13.3 %, P < 0.0001), ERCP was more successful (93% vs. 69%, P = 0.02), and metal stent placement more likely (41% vs. 5%, P = 0.005) at our PBRC compared to a CMC. The majority (81%) of patients undergoing initial endoscopy at a CMC required repeat endoscopy at our PBRC. CONCLUSIONS: Patients who are candidates for pancreaticoduodenectomy frequently undergo ERCP. At a CMC, ERCP is often unsuccessful, is rarely accompanied by EUS, and often requires repeat endoscopy. Our findings support regionalizing the management of suspected pancreatic malignancy into dedicated specialty centers. J. Surg. Oncol. 2016;113:647-651. © 2016 Wiley Periodicals, Inc.

Development of the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial Protocol: A National Cluster-Randomized Trial of Resident Duty Hour Policies.

IMPORTANCE: Debate continues regarding whether to further restrict resident duty hour policies, but little high-level evidence is available to guide policy changes. OBJECTIVE: To inform decision making regarding duty hour policies, the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial is being conducted to evaluate whether changing resident duty hour policies to permit greater flexibility in work hours affects patient postoperative outcomes, resident education, and resident well-being. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic noninferiority cluster-randomized trial of general surgery residency programs with 2 study arms. Participating in the study are Accreditation Council for Graduate Medical Education (ACGME)-approved US general surgery residency programs (n = 118), their affiliated hospitals (n = 154), surgical residents and program directors, and general surgery patients from July 1, 2014, to June 30, 2015, with additional patient safety outcomes collected through June 30, 2016. The data collection platform for patient outcomes is the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), thus only hospitals participating in the ACS NSQIP were included. INTERVENTIONS: In the usual care arm, programs adhered to current ACGME resident duty hour standards. In the intervention arm, programs were allowed to deviate from current standards regarding maximum shift lengths and minimum time off between shifts through an ACGME waiver. MAIN OUTCOMES AND MEASURES: Death or serious morbidity within 30 days of surgery measured through ACS NSQIP, as well as resident satisfaction and well-being measured through a survey delivered at the time of the 2015 American Board of Surgery in Training Examination (ABSITE). RESULTS: A total of 118 general surgery residency programs and 154 hospitals were enrolled in the FIRST Trial and randomized. Fifty-nine programs (73 hospitals) were randomized to the usual care arm and 59 programs (81 hospitals) were randomized to the intervention arm. Intent-to-treat analysis will be used to estimate the effectiveness of assignment to the intervention arm on patient outcomes, resident education, and resident well-being compared with the usual care arm. Several sensitivity analyses will be performed to determine whether there were differential effects when examining only inpatients, high-risk patients, and emergent/urgent cases. CONCLUSIONS AND RELEVANCE: To our knowledge, the FIRST Trial is the first national randomized clinical trial of duty hour policies. Results of this study may be informative to policymakers and other stakeholders engaged in restructuring graduate medical training to enhance the quality of patient care and resident education. TRIAL REGISTRATION: clinicaltrials.org Identifier: NCT02050789.

Surgical duration and risk of venous thromboembolism.

IMPORTANCE: There is a paucity of data assessing the effect of increased surgical duration on the incidence of venous thromboembolism (VTE). OBJECTIVE: To examine the association between surgical duration and the incidence of VTE. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective cohort of 1,432,855 patients undergoing surgery under general anesthesia at 315 US hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2011. EXPOSURE: Duration of surgery. MAIN OUTCOMES AND MEASURES: The rates of deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE within 30 days of the index operation. Surgical duration was standardized across Current Procedural Terminology codes using a z score. Outcomes were compared across quintiles of the z score. Multiple logistic regression models were developed to examine the association while adjusting for patient demographics, clinical characteristics, and comorbidities. RESULTS: The overall VTE rate was 0.96% (n = 13,809); the rates of DVT and PE were 0.71% (n = 10,198) and 0.33% (n = 4772), respectively. The association between surgical duration and VTE increased in a stepwise fashion. Compared with a procedure of average duration, patients undergoing the longest procedures experienced a 1.27-fold (95% CI, 1.21-1.34; adjusted risk difference [ARD], 0.23%) increase in the odds of developing a VTE; the shortest procedures demonstrated an odds ratio of 0.86 (95% CI, 0.83-0.88; ARD, -0.12%). The robustness of these results was substantiated with several sensitivity analyses attempting to minimize the effect of outliers, concurrent complications, procedural differences, and unmeasured confounding variables. CONCLUSIONS AND RELEVANCE: Among patients undergoing surgery, an increase in surgical duration was directly associated with an increase in the risk for VTE. These findings may help inform preoperative and postoperative decision making related to surgery.

Association between hospital imaging use and venous thromboembolism events rates based on clinical data.

OBJECTIVE: The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. BACKGROUND: Hospital VTE rates are publicly reported and used in pay-for-performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. METHODS: Data (2009-2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk-adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Association) and hospital imaging use rates on VTE event rates. RESULTS: The mean risk-adjusted VTE event rates at 30 days after surgery increased across VTE imaging use rate quartiles: 1.13% in the lowest quartile to 1.92% in the highest quartile (P < 0.001). This statistically significant trend remained when examining only the inpatient period. Hospital VTE imaging use rate was the dominant driver of hospital VTE event rates (P < 0.001), as no other hospital characteristics had significant associations. CONCLUSIONS: Even when examined with clinically ascertained outcomes and detailed risk adjustment, VTE rates reflect hospital imaging use and perhaps signify vigilant, high-quality care. The VTE outcome measure may not be an accurate quality indicator and should likely not be used in public reporting or pay-for-performance programs.

Cholecystitis.

Acute cholecystitis is defined as inflammation of the gallbladder and is usually caused by obstruction of the cystic duct. Cholescintigraphy is the most sensitive imaging modality for cholecystitis. The gold standard treatment of acute cholecystitis is laparoscopic cholecystectomy. Operating early in the disease course decreases overall hospital stay and avoids increased complications, conversion to open procedures, and mortality. Cholecystitis during pregnancy is a challenging problem for surgeons. Operative intervention is generally safe for both mother and fetus, given the improved morbidity of the laparoscopic approach compared with open, although increased caution should be exercised in women with gallstone pancreatitis.

Surgeons' perceptions of public reporting of hospital and individual surgeon quality.

BACKGROUND: Hospital-specific and surgeon-specific public reporting of performance measures is expanding largely due to calls for transparency from the public and oversight agencies. Surgeons continue to voice concerns regarding public reporting. Surgeons' perceptions of hospital-level and individual-level public reporting have not been assessed. This study (1) evaluated surgeons' perceptions of public reporting of surgical quality; and (2) identified specific barriers to surgeons' acceptance of public reporting. METHODS: All surgeons (n=185) at 4 hospitals (university, children's, 2 community hospitals), representing all surgical specialties, received a 41-item anonymous Internet-based survey. Twenty follow-up qualitative interviews were conducted to assess surgeons' interpretation of findings. RESULTS: The survey response rate was 66% (n=122). Most surgeons supported public reporting of quality metrics at the hospital level (80%), but opposed individual reporting (53%, P<0.01). Fewer surgeons expected that individual (26%) or hospital (47%) public reporting would improve outcomes (P<0.01). Few indicated that their practice would change with hospital (11%) or individual (18%) public reporting (P=0.20). Primary concerns regarding public reporting at the hospital level included patients misinterpreting data, surgeons refusing high-risk patients, and outcome metric validity. Individual-surgeon level concerns included outcome metric validity, adequate sample sizes, and patients misinterpreting data. To make public reporting more acceptable, surgeons recommended patient education, simplified data presentation, continued risk-adjustment refinement, and internal review before public reporting. CONCLUSIONS: Surgeons expressed concerns about public reporting of quality metrics, particularly reporting of individual surgeon performance. These concerns must be addressed to gain surgeons' acceptance and to use public reporting to improve health care quality.

Expression of RORγt marks a pathogenic regulatory T cell subset in human colon cancer.

The role of regulatory T cells (T(regs)) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, T(regs) have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different T(reg) subsets. We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive, but compromised anti-inflammatory, properties; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORγt. T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis. Indeed, ablation of the RORγt gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions, suppressed inflammation, improved polyp-specific immune surveillance, and severely attenuated polyposis. Ablation of interleukin-6 (IL-6), IL-23, IL-17, or tumor necrosis factor-α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt. Surprisingly, loss of IL-17A had a dual effect: IL-17A-deficient mice had fewer polyps but continued to have RORγt(+) T(regs) and developed invasive cancer. Thus, we conclude that RORγt has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation, potency of immune surveillance, and severity of disease outcome.

Feast or famine? The variable impact of coexisting fellowships on general surgery resident operative volumes.

OBJECTIVES: Nearly 80% of general surgery residents (GSR) pursue Fellowship training. We hypothesized that fellowships coexisting with general surgery residencies do not negatively impact GSR case volumes and that fellowship-bound residents (FBR) preferentially seek out cases in their chosen specialty ("early tracking"). METHODS: To test our hypotheses, we analyzed the Accreditation Council for Graduate Medical Education Surgical Operative Log data from 2009 American Board of Surgery qualifying examination applicants (N = 976). General surgery programs coexisted with 35 colorectal (CR), 97 vascular (Vasc), 80 minimally invasive (MIS), and 12 Endocrine (Endo) fellowships. We analyzed (1) operative cases for general surgery residency programs with and without coexisting Fellowships, comparing caseloads for FBR and all GSR and (2) operative cases of FBR in their chosen specialties compared to all other GSR. Group means were compared using ANOVA with significance set at P < 0.01. RESULTS: Coexisting fellowships had minimal impact on GSR caseloads. Endocrine fellowships actually enhanced case volumes for all residents. CR impact was neutral while MIS and vascular fellowships resulted in small declines. Endo, CR, and Vasc but not MIS FBR performed significantly more cases in their future specialties than their GSR counterparts, consistent with self-directed, prefellowship tracking. Tracking seems to be additive and FBR do not sacrifice other GSR cases. CONCLUSIONS: Our data establish that the impact of Fellowships on GSR caseloads is minimal. Our data confirm that FBR seek out cases in their future specialties ("early tracking").

Looking ahead: the SSAT strategic plan for the next decade.

The Society for Surgery of the Alimentary Tract's (SSAT) mission is to advance the science and practice of surgery in the treatment of digestive disease. An essential core value of the SSAT is multidisciplinary collaboration with both its sister societies in the Digestive Disease Week (DDW) Council and other surgical societies in Gastrointestinal Surgery. In order to achieve the society's goals, the strategic plan rests on the society's values of interdisciplinary collaboration, scholarship, education, and discovery. The strategic plan also creates a meritocracy system to foster the development of future leaders for both the SSAT and the broader house of surgery. In the short term, this plan will: Re-organize committee structure and reporting responsibilities; Clarify committee goals and deliverables; Facilitate member participation in the committees and governance of the society; Enhance member services by utilizing enhanced communication strategies; Accelerate efforts to meet the Maintenance of Certification needs of the membership; Re-focus the SSAT's energy on Quality and Outcome Assessment of GI surgery; Clarify and standardize the methodology for allocating funds for new projects. Over the course of the next few years, the SSAT will: Develop a financial model that increases revenue to support the expanded tasks the society intends to undertake; Play an active role in developing the evolving training paradigms for gastrointestinal surgeons through the continuum from residency, fellowship, and early mentored practice; Continue to support development of surgeon scientists through Career Development Award; Enhance relationship with the SSAT Foundation; Continue to improve the experience of members attending DDW; Develop surgeons interested in public policy to be leaders at a national level. The strategic plan is ambitious, and the current leadership realizes that all the tasks and objectives cannot be accomplished in 1 year. There is much to do in order to keep the SSAT the premier professional society for gastrointestinal surgery. Changes in the external environment may require modifications of the priorities or the plan itself in the coming years. Implicit in this plan is the need for annual review by the Board of Trustees at the May Board Meeting so that modifications can be made as the world around us changes.

Developing a practice-based learning and improvement curriculum for an academic general surgery residency.

BACKGROUND: Program directors in surgery are now facing the challenge of incorporating the ACGME's practice-based learning and improvement (PBLI) competency into residency curriculum. We introduced a comprehensive PBLI experience for postgraduate year 2 (PGY2) residents designed to integrate specific competency goals (ie, quality improvement, clinical thinking, and self-directed learning) within the context of residents' clinical practice. STUDY DESIGN: Fourteen PGY2 residents participated in a 3-week PBLI curriculum consisting of 3 components: complex clinical decision making, individual learning plan, and quality improvement (QI). To assess how effectively the curriculum addressed these 3 competencies, residents rated their understanding of PBLI by answering a 12-question written survey given pre- and post-rotation. Resident satisfaction was assessed through standard post-rotation evaluations. RESULTS: Analysis of the pre- and post-rotation surveys from the 14 participants showed an increase in all measured elements, including knowledge of PBLI (p < 0.001), ability to assess learning needs (p < 0.001), set learning goals (p < 0.001), understanding of QI concepts (p = 0.001), and experience with QI projects (p < 0.001). Fourteen QI projects were developed. Although many residents found the creation of measurable learning goals to be challenging, the process of identifying strengths and weaknesses enhanced the resident's self-understanding and contributed to overall satisfaction with the rotation. CONCLUSIONS: The initial implementation of our PBLI curriculum demonstrated that residents report personal progress in their clinical decision making, self-directed learning, and familiarity with QI. This comprehensive PBLI curriculum was accepted by surgical residents as a valuable part of their training. We are encouraged to continue a clinically grounded PBLI experience for PGY2 residents.

Impact of selection bias on the utilization of adjuvant therapy for pancreas adenocarcinoma.

BACKGROUND: Improved outcomes have been associated with the use of adjuvant therapy after resection of pancreas adenocarcinoma. However, the frequency with which patients receive adjuvant therapy and the factors impacting its use remain largely undefined. We hypothesized that nonutilization of adjuvant therapy was primarily associated with patient comorbidity and onset of postoperative complications. METHODS: A prospectively maintained database was reviewed to identify patients who underwent potentially curative resection of histologically confirmed pancreas adenocarcinoma at our institution from January 1996 to May 2007. Clinicopathological data and postoperative treatment history were collected to identify variables associated with receipt of adjuvant therapy. RESULTS: Of 119 patients, 33% did not receive adjuvant therapy. The frequency with which patients underwent adjuvant therapy did not change over time. On multivariate analysis, patient age 70 years or greater, major postoperative complications, distal pancreatectomy, absence of nodal metastases, and absence of perineural invasion were associated with decreased utilization of adjuvant therapy. DISCUSSION: One-third of patients in this contemporary dataset of patients did not go on to receive adjuvant therapy. The likelihood of receiving adjuvant treatment is negatively impacted by the course of postoperative recovery. Moreover, the fact that adjuvant therapy was undertaken less often for older patients and patients with favorable pathological features highlights the selection bias impacting the decision to pursue postoperative therapy for this disease. This selective utilization of postoperative therapy for patients with adverse oncological characteristics is likely to bias any retrospective analysis attempting to measure the efficacy of adjuvant treatment for pancreas adenocarcinoma.

Staging laparoscopy enhances the detection of occult metastases in patients with pancreatic adenocarcinoma.

BACKGROUND: The use of staging laparoscopy has been highly institutional dependent. We sought to assess the incidence of occult intra-abdominal metastases identified at the time of staging laparoscopy for patients with either potentially resectable or locally advanced pancreatic adenocarcinoma (LAPC). We also compared the rate of occult metastases in patients who underwent staging laparoscopy versus laparotomy. METHODS: Patients were confirmed to have potentially resectable or LAPC at a multidisciplinary hepatopancreaticobiliary conference. Patients with potentially resectable lesions were initially explored via staging laparoscopy or laparotomy, based on surgeon preference. RESULTS: Over a 4-year period, 25 patients with potentially resectable tumors and 33 patients with LAPC were staged with laparoscopy, with an equivalent prevalence of occult metastases found at laparoscopy (28% potentially resectable vs. 33% LAPC, P = 0.8). Fifty-two patients with potentially resectable lesions were explored initially via laparotomy. Occult peritoneal metastases were more likely to be detected in patients with potentially resectable tumors that were explored via laparoscopy than via laparotomy (32% vs. 10%, P = 0.018). CONCLUSIONS: Staging laparoscopy is more likely than open exploration to detect occult metastases. Current preoperative imaging inadequately identifies unresectable pancreatic adenocarcinoma; therefore, all patients with potentially resectable disease should undergo staging laparoscopy.

Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma.

PURPOSE: Radiofrequency ablation (RFA) is a common treatment modality for surgically unresectable tumors. However, there is a high rate of both local and systemic recurrence. EXPERIMENTAL DESIGN: In this preclinical study, we sought to enhance the antitumor effect of RFA by combining it with huKS-IL2 immunocytokine [tumor-specific monoclonal antibody fused to interleukin-2 (IL2)] in mice bearing CT26-KS colon adenocarcinoma. Mice were treated with RFA, huKS-IL2 via intratumoral injection, or combination therapy. RESULTS: Treatment of mice bearing s.c. tumors with RFA and huKS-IL2 resulted in significantly greater tumor growth suppression and enhanced survival compared with mice treated with RFA or huKS-IL2 alone. When subtherapeutic regimens of RFA or huKS-IL2 were used, tumors progressed in all treated mice. In contrast, the combination of RFA and immunocytokine resulted in complete tumor resolution in 50% of mice. Treatment of a tumor with RFA and intratumoral huKS-IL2 also showed antitumor effects against a distant untreated tumor. Tumor-free mice after treatment with RFA and huKS-IL2 showed immunologic memory based on their ability to reject subsequent challenges of CT26-KS and the more aggressive parental CT26 tumors. Flow cytometry analysis of tumor-reactive T cells from mice with complete tumor resolution showed that treatment with RFA and huKS-IL2 resulted in a greater proportion of cytokine-producing CD4 T cells and CD8 T cells compared with mice treated with RFA or huKS-IL2 alone. CONCLUSIONS: These results show that the addition of huKS-IL2 to RFA significantly enhances the antitumor response in this murine model, resulting in complete tumor resolution and induction of immunologic memory.