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Background: Healthcare policies have focused on centralizing care to high-volume centers in an effort to optimize patient outcomes; however, little is known about patients' and caregivers' considerations and selection process when selecting hospitals for care. We aim to explore how patients and caregivers select hospitals for complex cancer care and to develop a taxonomy for their selection considerations., Methods: This was a qualitative study in which data were gathered from in-depth interviews conducted from March to November 2019 among patients with hepatopancreatobiliary cancers who were scheduled to undergo a pancreatectomy (n = 20) at a metropolitan, urban regional, or suburban medical center and their caregivers (n = 10)., Results: The interviews revealed six broad domains that characterized hospital selection considerations: hospital factors, team characteristics, travel distance to hospital, referral or recommendation, continuity of care, and insurance considerations. The identified domains were similar between participants seen at the metropolitan center and urban/suburban medical centers, with the following exceptions: participants receiving care specifically at the metropolitan center noted operative volume and access to specific services such as clinical trials in their hospital selection; participants receiving care at urban/suburban centers noted health insurance considerations and having access to existing medical records in their hospital selection., Conclusions: This study delineates the many considerations of patients and caregivers when selecting hospitals for complex cancer care. These identified domains should be incorporated into the development and implementation of centralization policies to help increase patient access to high-quality cancer care that is consistent with their priorities and needs.

As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic., (Published by Elsevier Ltd.)

Background: Treatments that generate T cell-mediated immunity to a patient's unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galα1-3Galβ1-4GlcNAc (α-Gal) in situ leading to opsonization with pre-existing natural anti-α-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity., Methods: Various immunological effects of coating tumor cells with α-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI-134 mediated complement dependent cytotoxicity (CDC) in cancer cells. The anti-tumoral activity of AGI-134 alone or in combination with an anti-programmed death-1 (anti-PD-1) antibody was tested in melanoma models in anti-Gal expressing galactosyltransferase knockout (α1,3GT -/- ) mice. CDC and phagocytosis data were analyzed by one-way ANOVA, ADCC results by paired t-test, distal tumor growth by Mantel-Cox test, C5a data by Mann-Whitney test, and single tumor regression by repeated measures analysis., Results: In vitro, α-Gal labelling of tumor cells via AGI-134 incorporation into the cell membrane leads to anti-Gal binding and complement activation. Through the effects of complement and ADCC, tumor cells are lysed and tumor antigen uptake by APCs increased. Antigen associated with lysed cells is cross-presented by CD8α+ dendritic cells leading to activation of antigen-specific CD8+ T cells. In B16-F10 or JB/RH melanoma models in α1,3GT -/- mice, intratumoral AGI-134 administration leads to primary tumor regression and has a robust abscopal effect, i.e., it protects from the development of distal, uninjected lesions. Combinations of AGI-134 and anti-PD-1 antibody shows a synergistic benefit in protection from secondary tumor growth., Conclusions: We have identified AGI-134 as an immunotherapeutic drug candidate, which could be an excellent combination partner for anti-PD-1 therapy, by facilitating tumor antigen processing and increasing the repertoire of tumor-specific T cells prior to anti-PD-1 treatment., Competing Interests: Competing interestsAll of the authors are or were employees, have or had executive roles and/or are consultants to, and may have stocks or shares of Agalimmune Ltd. or BioLineRx, and may hold patents related to the described work. Several of the authors are or were involved in efforts to develop AGI-134 as cancer immunotherapy. AGI-134 is currently in Phase 1/2a clinical trials in the United Kingdom and Israel with BioLineRx as sponsor., (© The Author(s) 2019.)

Background: Our previous case series suggested that a 1-week, low-calorie and low-fat diet was associated with decreased intraoperative blood loss in patients undergoing liver surgery., Objective: The current study evaluates the effect of this diet in a randomized controlled trial., Methods: We randomly assigned 60 patients with a body mass index ≥25 kg/m(2) to no special diet or an 800-kcal, 20 g fat, and 70 g protein diet for 1 week before liver resection. Surgeons were blinded to diet assignment. Hepatic glycogen stores were evaluated using periodic acid Schiff (PAS) stains., Results: Ninety four percent of the patients complied with the diet. The diet group consumed fewer daily total calories (807 vs 1968 kcal, P < 0.001) and fat (21 vs 86 g, P < 0.001) than the no diet group. Intraoperative blood loss was less in the diet group: mean blood loss 452 vs 863 mL (P = 0.021). There was a trend towards decreased transfusion in the diet group (138 vs 322 mL, P = 0.06). The surgeon judged the liver to be easier to manipulate in the diet group: 1.86 versus 2.90, P = 0.004. Complication rate (20% vs 17%), length of stay (median 5 vs 4 days) and mortality did not differ between groups. There was no difference in hepatic steatosis between groups. There was less glycogen in hepatocytes in the diet group (PAS stain score 1.61 vs 2.46, P < 0.0001)., Conclusions: A short-course, low-fat, and low-calorie diet significantly decreases bleeding and makes the liver easier to manipulate in hepatic surgery.

Background and Objectives: Lymphatic mapping (LM) and blue dye injections are essential to identification of sentinel lymph nodes (SLN) for melanoma. LM is performed the day before (DB) or the same day (SD) of surgery, but the optimal timing is unknown. Similarly, methylene blue (MB), used during SLN biopsy (SLNB), is administered diluted (dMB) or undiluted (uMB), but the relative efficacies are unknown., Methods: Patients who underwent SLNB for melanoma from 2009 to 2013 at our institution were evaluated. Outcomes included operative correlation with LM, SLN identification, and postoperative complications., Results: One hundred seventy-one patients underwent SLNB. Sixty-seven (39%) had DB LM. Sixty-seven (39%) received uMB. Operative findings correlated with both LM groups, though the DB patients had lower background count (P = 0.018) and lower highest SLN radioactive signal count (P = 0.046). More uMB patients had blue SLNs (90% vs. 68%, P = 0.001). There was no difference in the total number of SLNs or complication rates in the LM and MB groups., Conclusions: This is the first study to compare the use of DB LM with SD LM and the efficacy of uMB versus dMB. DB LM and uMB offer advantageous alternatives for patients and their surgeons without loss of accuracy or increased morbidity. J. Surg. Oncol. 2016;114:947-950. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy., Methods: Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection., Results: 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency., Conclusion: Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Peritoneal dissemination of cancer is a terminal condition with limited therapeutic options. Because the peritoneal cavity is a single enclosed space, regional treatment approaches for isolated peritoneal cancrinomatosis are appealing. There is a potential role for gene therapy in the management of peritoneal cancrinomatosis., Materials and Methods: An adenoviral construct of the human p14ARF gene (a tumor suppressor) and a 22 amino acid sequence of the ARF gene product, which has cell membrane penetrating properties, were assayed for proapoptotic properties in a human colorectal cancer cell line (Clone A) cells in vitro. Peritoneal carcinomatosis derived from Clone A cells was also established in nude mice and then treated with intraperitoneal administration of an adenoviral construct of the human p14ARF gene., Results: Treatment of ARF-negative Clone A cells with Ad-hARF in vitro reestablished ARF function. However, the cell penetrating ARF-related peptide did not restore ARF function in Clone A cells. Treatment of Clone A peritoneal xenografts with a single intraperitoneal dose of Ad-hARF (9 × 10(6) viral particles) suppressed the progression of peritoneal disease. Weekly (six times) administration of the Ad-hARF at a lower dose (3 × 10(6) viral particles) also suppressed tumor progression., Conclusions: Treatment of peritoneal carcinomatosis by intraperitoneal administration of adenoviral constructs of inactivated tumor suppressor genes may be a feasible clinical approach, and ARF may represent a suitable molecular target for tumors where the ARF gene is inactivated., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The increasing use of computed tomography (CT) scans in the evaluation of trauma patients has led to increased detection of incidental radiologic findings. Incidental findings (IFs) of the abdominal viscera are among the most commonly discovered lesions and can carry a risk of malignancy. Despite this, patient notification regarding these findings is often inadequate., Methods: We identified patients who underwent abdominopelvic CTs as part of their trauma evaluation during a recent 1-year period (9/2011-8/2012). Patients with IFs of the kidneys, liver, adrenal glands, pancreas and/or ovaries had their charts reviewed for documentation of the lesion in their discharge paperwork or follow-up. A quality improvement project was initiated where patients with abdominal IFs were verbally informed of the finding, it was noted on their discharge summary and/or were referred to specialists for evaluation. Nine months after the implementation of the IF protocol, a second chart review was performed to determine if the rate of patient notification improved., Results: Of 1,117 trauma patients undergoing abdominopelvic CT scans during the 21 month study period, 239 patients (21.4%) had 292 incidental abdominal findings. Renal lesions were the most common (146 patients, 13% of all patients) followed by hepatic (95/8.4%) and adrenal (38/3.4%) lesions. Pancreatic (10/0.9%) and ovarian lesions (3/0.3%) were uncommon. Post-IF protocol implementation patient notification regarding IFs improved by over 80% (32.4% vs. 17.7% pre-protocol, p = 0.02)., Conclusion: IFs of the solid abdominal organs are common in trauma patients undergoing abdominopelvic CT scan. Patient notification regarding these lesions is often inadequate. A systematic approach to the documentation and evaluation of incidental radiologic findings can significantly improve the rate of patient notification.

Background/objectives: Heated intraperitoneal chemotherapy (HIPEC) kills cancer cells via thermal injury and improved chemotherapeutic cytotoxicity. We hypothesize that higher HIPEC flow rates improve peritoneal heating and HIPEC efficacy., Methods: (1) A HIPEC-model (30.8 L cooler with attached extracorporeal pump) was filled with 37°C water containing a suspended 1 L saline bag (SB) wrapped in a cooling sleeve, creating a constant heat sink. (2) HIPECs were performed in a swine model. Inflow, outflow, and peritoneal temperatures were monitored as flow rates varied. (3) Flow rates and temperatures during 20 HIPECs were reviewed., Results: Higher flow rates decreased time required to increase water bath (WB) and SB temperature to 43°C. With a constant heat sink, the minimum flow rate required to reach 43°C in the WB was 1.75 L/min. Higher flow rates lead to greater temperature gradients between the WB and SB. In the swine model, the minimum flow rate required to reach 43°C outflow was 2.5-3.0 L/min. Higher flows led to more rapid heating of the peritoneum and greater peritoneal/outflow temperature gradients. Increased flow during clinical HIPEC suggested improved peritoneal heating with lower average visceral temperatures., Conclusions: There is a minimum flow rate required to reach goal temperature during HIPEC. Flow rate is an important variable in achieving and maintaining goal temperatures during HIPEC., (© 2014 Wiley Periodicals, Inc.)

Background: A novel data warehouse based on automated retrieval from an institutional health care information system (HIS) was made available to be compared with a traditional prospectively maintained surgical database., Methods: A newly established institutional data warehouse at a single-institution academic medical center autopopulated by HIS was queried for International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes for pancreatic neoplasm. Patients with ICD-9-CM diagnosis codes for pancreatic neoplasm were captured. A parallel query was performed using a prospective database populated by manual entry. Duplicated patients and those unique to either data set were identified. All patients were manually reviewed to determine the accuracy of diagnosis., Results: A total of 1107 patients were identified from the HIS-linked data set with pancreatic neoplasm from 1999-2009. Of these, 254 (22.9%) patients were also captured by the surgical database, whereas 853 (77.1%) patients were only in the HIS-linked data set. Manual review of the HIS-only group demonstrated that 45.0% of patients were without identifiable pancreatic pathology, suggesting erroneous capture, whereas 36.3% of patients were consistent with pancreatic neoplasm and 18.7% with other pancreatic pathology. Of the 394 patients identified by the surgical database, 254 (64.5%) patients were captured by HIS, whereas 140 (35.5%) patients were not. Manual review of patients only captured by the surgical database demonstrated 85.9% with pancreatic neoplasm and 14.1% with other pancreatic pathology. Finally, review of the 254 patient overlap demonstrated that 80.3% of patients had pancreatic neoplasm and 19.7% had other pancreatic pathology., Conclusions: These results suggest that cautious interpretation of administrative data rely only on ICD-9-CM diagnosis codes and clinical correlation through previously validated mechanisms., (Published by Elsevier Inc.)

Background: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. A minority of patients present with localized disease and surgical resection still offers patients the only hope for long-term survival. Locally advanced pancreatic cancer is defined as surgically unresectable, but has no evidence of distant metastases. The purpose of this study is to evaluate the efficacy and safety of cetuximab in combination with gemcitabine and 5-FU along with radiation therapy in locally advanced non-resectable, pancreatic adenocarcinoma, using progression free survival as the primary end point., Methods: This was a prospective, single arm, open label pilot phase II study to evaluate the anti-tumor activity of gemcitabine (200 mg/m(2) per week) and cetuximab (250 mg/m(2) per week after an initial 400 mg/m(2) loading dose) with continuous infusion 5-FU (800 mg/m(2) over 96 hours) and daily concurrent external beam radiation therapy (50.4 Gy total dose) for six weeks (cycle 1) in patients with non-metastatic, locally advanced pancreatic adenocarcinoma. Following neoadjuvant treatment, subjects were re-evaluated for response and surgical candidacy with restaging scans. After resection, or also if not resected; subjects received further therapy with four 28-day cycles (cycles 2-5) of weekly gemcitabine (1000 mg/m(2)) and cetuximab (250 mg/m(2)) on days 1, 8, and 15., Results: Between 2006 and 2011, twenty-six patients were screened and eleven of them were enrolled in the study. Most common reasons for screen failures were having resectable disease, metastatic disease or co-morbidity. Ten patients were able to tolerate and complete cycle 1 of chemoradiotherapy. One patient stopped the study prematurely due to grade III diarrhea. All except this one patient received planned radiation therapy. The response evaluation after cycle 1 showed one Partial Response, eight Stable Disease and two Progressive Disease. Four patients subsequently underwent surgical resection of the tumor. All patients had R0 resections. There was one preoperative mortality due to multiple organ failure. Median progression free survival (PFS) for four resected patients was 9.0 months while for unresected patients median PFS was 7.1 months. Median overall survival (OS) for four resected patients was 47.4 months and for unresected patients median OS was 17.0 months. Most common adverse events were hematologic (27%). Only two patients developed grade 3 neutropenia. Most common treatment related non-hematologic adverse events were diarrhea (10 of 11), nausea (8 of 11) and skin rash (10 of 11 patients). Only 9.5% of all reported non-hematologic adverse events were grade 3 or higher., Conclusions: The combination of cetuximab, weekly gemcitabine and continuous infusion of 5-FU with radiotherapy was quite well tolerated with intriguing clinical benefit and survival results in carefully selected patients with locally advanced pancreatic adenocarcinoma. A trial with larger sample size will be necessary to confirm these results.

Unlabelled: AIM/ BACKGROUND: To determine the feasibility and safety of intratumoral α-gal glycolipids injection for conversion of human tumors into autologous Tumor Associated Antigens (TAA) vaccine. α-Gal glycolipids bind anti-Gal--the most abundant antibody in humans. Pre-clinical studies indicated that injected α-gal glycolipids insert into tumor cell membranes, bind anti-Gal and target tumor cells to Antigen Presenting Cells, thereby converting tumors into autologous TAA vaccines. We hypothesized that α-gal glycolipids might have similar utility in humans., Patients and Methods: Eleven patients with advanced solid tumors received one intratumoral injection of 0.1 mg, 1 mg, or 10 mg α-gal glycolipids. The primary endpoint was dose-limiting toxicity (DLT) within 4 weeks. Secondary endpoints included long-term toxicity, autoimmunity, radiological tumor response and survival., Results: There were no DLT and no clinical or laboratory evidence of autoimmunity, or any other toxicity. Few patients had an unexpectedly long survival., Conclusion: Intratumoral injection of α-gal glycolipids is feasible and safe for inducing a protective anti-tumor immune response.

Background: Because of the malignant potential, resection has been recommended for some intraductal papillary mucinous neoplasms (IPMN). We hypothesize that a large cancer database could be used to evaluate national resection rates and survival for malignant IPMN., Materials and Methods: Using the Surveillance Epidemiology and End Results (SEER) database, 1988-2003, cases of malignant IPMN were identified using histology codes. Age-adjusted incidence rates were calculated; Cochran-Armitage tests evaluated trends over time. Predictors of resection were evaluated using χ(2) and logistic regression. Kaplan-Meier curves and Cox models were constructed to evaluate survival., Results: Of 1834 patients, 209 (11.4%) underwent resection. Annual age-adjusted incidence decreased over the study time-course (P<0.05), while annual proportion of patients presenting with localized lesions and the proportion being resected increased (P<0.05). Predictors of resection on multivariate analysis included localized stage [versus distant, adjusted odds ratio (OR) 31; 95% confidence interval (CI) 17-56], and more recent diagnosis [referent 1988-1991; 2000-2003, OR 3.0 (95%CI 1.7-5.3)]. Median survival for resected patients was 16 mo versus 3 mo without resection (P<0.0001). After adjusting for age, gender, stage, year, and tumor location, surgical resection remained a significant predictor of survival [hazard ratio 0.44 (95% CI 0.36-0.54), P<0.0001]., Conclusions: In this population-based cohort, detection of malignant IPMNs is decreasing, with an increasing proportion of patients diagnosed at local stages and undergoing resection. Increased awareness of IPMN may be contributing to earlier detection, which might include benign/premalignant lesions, and greater utilization of resection for appropriate candidates; thus, we may be improving survival for this most treatable form of pancreatic cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Adrenalectomy remains the definitive therapy for most adrenal neoplasms. Introduced in the 1990s, laparoscopic adrenalectomy is reported to have lower associated morbidity and mortality. This study aimed to evaluate national adrenalectomy trends, including major postoperative complications and perioperative mortality., Methods: The Nationwide Inpatient Sample was queried to identify all adrenalectomies performed during 1998-2006. Univariate and multivariate logistic regression were performed, with adjustments for patient age, sex, comorbidities, indication, year of surgery, laparoscopy, hospital teaching status, and hospital volume. Annual incidence, major in-hospital postoperative complications, and in-hospital mortality were evaluated., Results: Using weighted national estimate, 40,363 patients with a mean age of 54 years were identified. Men made up 40% of these patients, and 77% of the patients were white. The majority of adrenalectomies (83%) were performed for benign disease. The annual volume of adrenalectomies increased from 3,241 in 1998 to 5,323 in 2006 (p < 0.0001, trend analysis). The overall in-hospital mortality was 1.1%, with no significant change. Advanced age (< 45 years as the referent; ≥ 65 years: adjusted odds ratio [AOR], 4.10; 95%; confidence Interval [CI], 1.66-10.10) and patient comorbidities (Charlson score 0 as the referent; Charlson score ≥ 2: AOR, 4.33; 96% CI, 2.34-8.02) were independent predictors of in-hospital mortality. Indication, year, hospital teaching status, and hospital volume did not independently affect perioperative mortality. Major postoperative in-hospital complications occurred in 7.2% of the cohort, with a significant increasing trend (1998-2000 [5.9%] vs 2004-2006 [8.1%]; p < 0.0001, trend analysis). Patient comorbidities (Charlson score 0 as the referent; Charlson score ≥ 2: AOR, 4.77; 95% CI, 3.71-6.14), recent year of surgery (1998-2000 as the referent; 2004-2006: AOR, 1.40; 95% CI, 1.09-1.78), and benign disease (malignant disease as the referent; benign disease: AOR, 1.98; 95% CI, 1.55-2.53) were predictive of major postoperative complications at multivariable analyses, whereas laparoscopy was protective (no laparoscopy as the referent; laparoscopy: AOR, 0.62; 95% CI, 0.47-0.82)., Conclusion: Adrenalectomy is increasingly performed nationwide for both benign and malignant indications. In this study, whereas perioperative mortality remained low, major postoperative complications increased significantly.

The CtBP transcriptional corepressors promote cancer cell survival and migration/invasion. CtBP senses cellular metabolism via a regulatory dehydrogenase domain, and is antagonized by p14/p19(ARF) tumor suppressors. The CtBP dehydrogenase substrate 4-methylthio-2-oxobutyric acid (MTOB) can act as a CtBP inhibitor at high concentrations, and is cytotoxic to cancer cells. MTOB induced apoptosis was p53-independent, correlated with the derepression of the proapoptotic CtBP repression target Bik, and was rescued by CtBP overexpression or Bik silencing. MTOB did not induce apoptosis in mouse embryonic fibroblasts (MEFs), but was increasingly cytotoxic to immortalized and transformed MEFs, suggesting that CtBP inhibition may provide a suitable therapeutic index for cancer therapy. In human colon cancer cell peritoneal xenografts, MTOB treatment decreased tumor burden and induced tumor cell apoptosis. To verify the potential utility of CtBP as a therapeutic target in human cancer, the expression of CtBP and its negative regulator ARF was studied in a series of resected human colon adenocarcinomas. CtBP and ARF levels were inversely-correlated, with elevated CtBP levels (compared with adjacent normal tissue) observed in greater than 60% of specimens, with ARF absent in nearly all specimens exhibiting elevated CtBP levels. Targeting CtBP may represent a useful therapeutic strategy in human malignancies.

Background: Pancreatectomy for cancer continues to have substantial perioperative risk, and the factors affecting mortality are ill defined. An integer-based risk score based on national data might help clarify the risk of in-hospital mortality in patients undergoing pancreatic resection., Methods: Records with the diagnosis of pancreatic cancer were queried from the Nationwide Inpatient Sample for 1998-2006. Procedures were categorized as proximal, distal, or nonspecified pancreatectomies on the basis of ICD-9 codes. Logistic regression and bootstrap methods were used to create an integer risk score for estimating the risk of in-hospital mortality using patient demographics, comorbidities (Charlson comorbidity score), procedure, and hospital type. A random sample of 80% of the cohort was used to create the risk score with a 20% internal validation set., Results: A total of 5715 patient discharges were identified. Composite in-hospital mortality was 5.8%. Predictors used for the final model were age group, Charlson score, sex, type of pancreatectomy, and hospital volume status (low-, medium-, or high-volume center). Integer values were assigned to these characteristics and then used for calculating an additive score. Three clinically useful score groups were defined to stratify the risk of in-hospital mortality (mortality was 2.0, 6.2, and 13.9%, respectively; P < 0.0001), with a 6.95-fold difference between the low- and high-risk groups. There was sufficient discrimination of both the derivation set and the validation set, with c statistics of 0.71 and 0.72, respectively., Conclusions: An integer-based risk score can be used to accurately predict in-hospital mortality after pancreatectomy and may be useful for preoperative risk stratification and patient counseling.

Oral contraceptive pills (OCP) are the most commonly used form of contraception throughout the United States of America. The prolonged usage of oral contraceptives leads to a variety of complications, ranging from subclinical modifications of liver function tests to the development of benign and malignant tumors of the liver. Spontaneous hepatic hemorrhage secondary to oral contraceptive use was only reported once in the early 1980s. We report a case of spontaneous hepatic hemorrhage secondary to prolonged ingestion of combined OCPs followed by multiple pulmonary emboli without underlying thrombophilia., ((c) 2009. Published by Elsevier GmbH.)

Objective: To evaluate the effect of surgical resection and radiotherapy (RT) in retroperitoneal or abdominal sarcoma., Design: Retrospective cohort., Setting: Surveillance, Epidemiology, and End Results, 1988-2005., Patients: Patients 18 years or older with initial diagnosis of primary retroperitoneal and nonvisceral abdominal sarcoma., Main Outcome Measures: Survival for 2 years after diagnosis. Kaplan-Meier survival was stratified based on surgery and RT status. Cox proportional hazards model was used to assess adjusted effects of surgery and RT on survival in patients with locoregional disease., Results: Of 1901 patients with locoregional disease, 1547 (81.8%) underwent resection; 447 (23.5%) received RT. Overall, patients who received both surgery and RT demonstrated improved survival compared with patients who underwent either therapy alone; patients undergoing monotherapy in turn had more favorable survival compared with patients who received neither therapy (P < .001, log rank). Cox analysis demonstrated that surgical resection (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.21-0.29; P < .001) and RT (0.78; 0.63-0.95; P = .01) independently predicted improved survival in locoregional disease only. In adjusted analyses stratified for American Joint Commission on Cancer (AJCC) stage, for stage I disease (n = 694), RT provided an additional benefit (HR, 0.49; 95% CI, 0.25-0.96; P = .04) independent of that from resection (0.35; 0.21-0.58; P < .001). For stage II/III (n = 552), resection remained protective (HR, 0.24; 95% CI, 0.18-0.32; P < .001); however, RT was no longer associated with a significant benefit (0.78; 0.58-1.06; P = .11)., Conclusions: In a national cohort of retroperitoneal and abdominal sarcomas, surgical resection was associated with significant survival benefits for AJCC disease stages I to III. Radiotherapy provided additional benefit for patients with stage I disease. Resection should be offered to reasonable surgical candidates with nonmetastatic retroperitoneal/abdominal sarcomas; radiotherapy may most benefit patients with early-stage disease.

Background: Recent studies have shown adjuvant therapy improves outcomes from pancreatic cancer (PC). This study investigates receipt and timing of PC treatments, and association with outcomes., Methods: The analysis cohort consisted of patients with newly-diagnosed PC at a single institution over 5 years. Primary Endpoints were (i) receipt of recommended therapy, and (ii) overall survival (OS)., Results: Among 102 patients, 52 underwent resection. Out of 36 localized resected and 16 locally advanced resected (LAR) patients, 26 and 13, respectively, received adjuvant therapy. Six of the latter group received neoadjuvant therapy. Median OS for resected patients was 15.7 months (range 0.6-51.4), compared with 7.7 for unresected patients (range 0.4-32.0) (P < 0.001), and 14.0 months for patients with resection alone (range 0.6-24.4) vs. 16.1 for patients who also received adjuvant therapy (range 3.2-51.4) (P= 0.027). Out of 46 patients undergoing up-front resection, 33 had R0 surgical margins. For the six LAR patients undergoing neoadjuvant therapy, all margins were R0., Conclusion: After resection, a substantial proportion of patients do not receive adjuvant therapy, and have worse survival. In this study, neoadjuvant treatment increased both the proportion of patients receiving all components of recommended therapy and the R0 resection rate.

Autologous melanoma associated antigens (MAA) on murine melanoma cells can elicit a protective anti-tumor immune response following a variety of vaccine strategies. Most require effective uptake by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-tumor T cells. One potential problem with clinical melanoma vaccines against autologous tumors may be that often tumor cells do not express surface markers that label them for uptake by APC. Effective uptake of melanoma cells by APC might be achieved by exploiting the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. This approach has been developed in a syngeneic mouse model using mice capable of producing anti-Gal. Anti-Gal binds specifically to α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). Injection of glycolipids carrying α-gal epitopes (α-gal glycolipids) into melanoma lesions results in glycolipid insertion into melanoma cell membranes, expression of α-gal epitopes on the tumor cells and binding of anti-Gal to these epitopes. Interaction between the Fc portions of bound anti-Gal and Fcγ receptors on APC induces effective uptake of tumor cells by APC. The resulting anti-MAA immune response can be potent enough to destroy distant micrometastases. A clinical trial is now open testing effects of intratumoral α-gal glycolipid injections in melanoma patients.

Objectives: To develop a population-based risk score for stratifying patients by risk of in-hospital mortality following procedural intervention for hepatic neoplasm., Background: There has been growing support for the value of surgical management of hepatic neoplastic disease, both primary and metastatic. Advances in surgical and ablative technologies have contributed to a decrease in the mortality associated with these procedures. However, multiple patient-, disease- and treatment-related factors can contribute to perioperative morbidity and mortality., Methods: Using the Nationwide Inpatient Sample from 1998 to 2005, a retrospective cohort of patient-discharges for hepatic procedures with a concurrent diagnosis of hepatic primary or metastatic neoplasm to the liver was assembled. Procedures were categorized as lobectomy, wedge resection, or enucleation/ablation. Logistic regression and bootstrap methods were used to create an integer score for estimating the risk of in-hospital mortality using patient demographics, comorbidities, procedure type, tumor type, and hospital characteristics. A randomly selected sample of 80% of the cohort was used to create the risk score. Testing was conducted in the remaining 20% validation-set., Results: In total, 12,969 patient-discharges were identified. Overall in-hospital mortality was 3.45%. Predictive characteristics incorporated into the model included: age, sex, Charlson comorbidity score, procedure type, hospital type, and type of neoplasm. Integer values were assigned to these, and used to calculate an additive score. Five clinically relevant groups were assembled to stratify risk, with a 36-fold gradient in mortality. Rates in the groups were as follows: 0.9%, 2.5%, 6.8%, 17.6%, and 35.9%. In the derivation set, as well as in the validation set, the simple score discriminated well, with c-statistics of 0.76 and 0.70, respectively., Conclusions: An integer-based risk score can be used to predict in-hospital mortality after hepatic procedure for neoplasm, and may be useful for preoperative risk stratification and patient counseling.

Introduction: National studies on in-hospital pancreatic outcomes have focused on mortality. Non-fatal morbidity affects a greater proportion of patients., Methods: The Nationwide Inpatient Sample 1998-2006 was queried for discharges after pancreatectomy. Rates of major complications (myocardial infarction, aspiration pneumonia, pulmonary compromise, perforation, infection, deep vein thrombosis/pulmonary embolism, hemorrhage, or reopening of laparotomy) were assessed. Predictors of complication(s) were evaluated using logistic regression. Their independent effect on in-hospital mortality, length of stay, and discharge disposition was assessed., Results: Of 102,417 patient discharges, 22.7% experienced a complication. Complication rates did not decline significantly over time, while mortality rates did. Independent predictors of complications included age >or=75 [referent, 19-39; adjusted odds ratio (OR) 1.34, 95% confidence interval (CI) 1.2-1.5, p < 0.0001], total pancreatectomy (vs proximal, OR 1.29, 95%CI 1.1-1.5, p = 0.0025), and low hospital resection volume (vs high, OR 1.61, 95%CI 1.4-1.8, p < 0.0001). Complications were a significant independent predictor of death (OR 7.76, 95%CI 6.7-8.8, p < 0.0001), prolonged hospital stay (OR 6.94, 95%CI 6.2-7.7, p < 0.0001), and discharge to another facility (OR 0.28, 95%CI 0.26-0.3, p < 0.0001)., Conclusions: Despite improvements in mortality, complication rates remain substantial and largely unchanged. They predict in-hospital mortality, prolonged hospital stay, and delayed return to home. The impact on healthcare costs and quality of life deserves further study.

Background: Pancreatic resection can be performed to ameliorate the sequelae of chronic pancreatitis in selected patients. The perceived risk of pancreatectomy may limit its use. Using a national database, this study compared mortality after pancreatic resections for chronic pancreatitis with those performed for neoplasm., Study Design: Patient discharges with chronic pancreatitis or pancreatic neoplasm were queried from the Nationwide Inpatient Sample, 1998 to 2006. To account for the Nationwide Inpatient Sample weighting schema, design-adjusted analyses were used., Results: There were 11,048 pancreatic resections. Malignant neoplasms represented 64.2% of the sample; benign neoplasms and pancreatitis comprised 17.1% and 18.7%, respectively. In-hospital mortality rates were 2.2% and 1.7% for the pancreatitis and benign tumor cohorts, respectively, compared with 5.9% for the malignancy cohort (overall p < 0.01). A multivariable logistic regression examined differences in mortality among diagnoses while adjusting for patient and hospital characteristics; covariates included patient gender, race, age, comorbidities, type of pancreatectomy, payor, hospital teaching status, hospital size, and hospital volume. After adjustment, patients undergoing resection for pancreatitis were at a significantly lower risk of in-hospital mortality when compared with those with malignant neoplasm (odds ratio, 0.43; 95% CI, 0.28 to 0.67)., Conclusions: Pancreatectomies for chronic pancreatitis have lower in-hospital mortality than those performed for malignancy and similar rates as resection for benign tumors. Pancreatic resection, which can improve quality of life in chronic pancreatitis patients, can be performed with moderate mortality rates and should be considered in appropriate patients.

Purpose: Cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) in the treatment of peritoneal carcinomatosis (PC) in 15 patients are described., Summary: Fifteen patients with PC who were treated with CS and IPHC were retrospectively identified between January 2002 and December 2006. All patients underwent cytoreduction immediately followed by IPHC with mitomycin or cisplatin. The time between undergoing CS and IPHC and the date of the last follow-up appointment or the date of death was used to calculate survival data for each patient. Nine patients had complete cytoreduction, and all but one patient had evidence of invasive disease at the time of surgery. Eleven patients required concomitant bowel resection at the time of debulking. Thirteen patients required blood transfusions during the perioperative period. Nine patients were discharged home, and four were discharged to a rehabilitation facility. Two patients died during the perioperative hospital admission, both of whom had a preoperative Eastern Cooperative Oncology Group (ECOG) performance status score of 2. The median survival time was 8.4 months, similar to the findings of previously published studies. Further studies are needed to see if tumor type, ECOG performance status score, degree of cytoreduction, and the chemotherapy agent used in IPHC can be correlated to quality of life and survival in patients with heterogeneous primary sources of intraabdominal malignancies., Conclusion: Combination treatment with CS followed by IPHC in 15 patients with heterogeneous primary sources of intraabdominal malignancies resulted in a median survival time of 8.4 months.

Background: Although surgical resection is generally recommended for patients with localized pancreatic neuroendocrine tumors (PNETs), the impact of resection on overall survival is unknown. The authors investigated the survival advantage of pancreatic resection using a national database., Methods: This is a retrospective survival analysis of patients with PNETs from the Surveillance, Epidemiology, and End Results database (1988-2002)., Results: A total of 728 patients with PNETs were identified with a median survival of 43 months using Kaplan-Meier survival methods. Resection of tumor was associated with significantly improved survival compared with those patients who were recommended for but did not undergo resection (114 months vs 35 months; P < .0001). This survival benefit was demonstrated for patients with localized, regional, and metastatic disease. A multivariable Cox proportional hazards model was constructed to assess the overall effect of surgical resection on survival, and demonstrated an adjusted odds ratio of 0.48 (95% confidence interval, 0.35-0.66) compared with those who were recommended for surgery but did not proceed to surgery., Conclusions: The authors have demonstrated in a large national study that resection of primary tumor in patients with PNETs is associated with improved survival across all disease stages. Patients with localized, regional, and metastatic PNETs who are reasonable operative candidates should be considered for resection of their primary tumors., ((c) 2009 American Cancer Society.)

Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Sp1 is a sequence-specific DNA binding protein that is important in the transcription of a number of regulatory genes involved in cancer cell growth, differentiation, and metastasis. In this study, we investigated Sp1 expression in pancreatic ductal adenocarcinoma and its association with clinical outcome. We studied 42 patients with primary pancreatic adenocarcinoma. The expression of Sp1 in pancreatic adenocarcinoma was evaluated by immunohistochemical staining. All 42 patients had clinical follow-up information and were evaluated for survival. Sp1 protein was aberrantly overexpressed in a subset of primary pancreatic adenocarcinoma. These tumors all developed metastasis, whereas none of the primary tumors without lymph node metastasis showed Sp1 overexpression. Statistically, Sp1 overexpression was associated with higher stage, higher grade, and lymph node metastasis (P < 0.001, P = 0.036, and P < 0.0001, respectively). Additionally, patients of this subset had a much shorter overall survival than patients without Sp1 overexpression, as evidenced by Kaplan-Meier plots and the log-rank test (P = 0.002). The 5-year overall survival rate was 19% in patients with Sp1 overexpression, compared with 55% in patients without Sp1 overexpression. The median survival was only 13 months for patients with Sp1 overexpression, compared with 65 months for patients without Sp1 overexpression. In conclusion, Sp1 is a new biomarker that identifies a subset of pancreatic ductal adenocarcinoma with aggressive clinical behavior. It can be used at initial diagnosis of pancreatic adenocarcinoma to identify patients with an increased probability of cancer metastasis and much shortened overall survival.

Objective: To analyze in-hospital mortality after pancreatectomy using a large national database., Summary and Background Data: Pancreatic resections, including pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy, remain the only potentially curative interventions for pancreatic cancer. The goal of this study was to define factors affecting outcomes after pancreatectomy for neoplasm., Methods: A retrospective analysis was performed using all patients undergoing pancreatic resections for neoplastic disease identified from the Nationwide Inpatient Sample from 1998 to 2003. Crude in-hospital mortality was analyzed by chi. A multivariable model was constructed to adjust for age, sex, hospital teaching status, hospital surgical volume, year of resection, payer status, and selected comorbid conditions., Results: In all, 279,445 patient discharges were identified with a primary diagnosis of pancreatic neoplasm. A total of 39,463 (14%) patients underwent resection during that hospitalization. In-hospital mortality was 5.9% with a significant decrease from 7.8% to 4.6% from 1998 to 2003 by trend analysis (P < 0.0001). Resections done at low (<5 procedures/year)- and medium (5-18/year)-volume centers had higher mortality compared with those at high (>18/year)-volume centers (low-volume odds ratio = 3.3; 95% confidence interval, 2.3-4.; medium-volume, odds ratio = 2.1; 95% confidence interval, 1.5-3.0). The proportion of procedures performed at high volume centers increased from 30% to 39% over the 6-year time period (P < 0.0001) by trend test., Conclusions: This large observational study demonstrates an improvement in operative mortality for patients undergoing pancreatectomy for neoplastic disease from 1998 to 2003. In addition, a greater proportion of pancreatectomies were performed at high-volume centers in 2003. The regionalization of pancreatic surgery may have partially contributed to the observed decrease in mortality rates.

This session focused on issues related to implementation of randomized clinical trials in palliative care studies. Topics discussed included what kinds of clinical sites and patient populations were suitable, what types of clinical investigators (clinical specialty) should be involved in or lead the studies, what multisite mechanisms could be used to conduct the trials, and what funding issues were related to these studies. A trial of operative versus nonoperative management for small bowel obstruction caused by recurrent intra-abdominal cancer was considered. The feasibility of such a trial was examined in terms of whether there was "equipoise" for a majority of likely investigators in the field around the trial question, what other issues might impact accrual to the trial, and how many patients would be required to answer which of these two treatment arms was better. This last question is related to selection of a primary endpoint for the trial and was a modestly contentious issue for the trial design group. Both sensible compromises in endpoint selection and the education of the community of investigators for a particular randomized trial in palliative care are crucial steps for successful implementation. A major conclusion of this session is that implementation considerations are intimately related to the architecture of a specific trial and should be addressed practically and early in the design phase of any randomized trial addressing a palliative care question. In this respect, randomized trials in palliative care are no different than in other fields.

Hypothesis: That factors affecting outcomes of surgical resection in the treatment of gastric cancer can be identified using a large US database., Design: Retrospective observational study., Setting: The Nationwide Inpatient Sample from January 1, 1998, through December 31, 2003., Patients: We included 13 354 patient discharges (approximately 66 096 nationally by weighted analysis) who underwent gastric resection for neoplasm., Main Outcome Measure: In-hospital mortality. Univariate analyses were performed by means of chi(2) tests. A multivariate logistic regression was performed to determine which variables were independently predictive of in-hospital mortality., Results: During the study period, 50 738 patients (approximately 250 420 nationally) were discharged with the diagnosis of gastric neoplasm. Of those, 13 354 (26.3%) underwent gastric resection during their hospitalization. In-hospital mortality for patients undergoing surgery was 6.0%, without significant change from 1998 through 2003. Factors predictive of significantly increased in-hospital mortality included low annual hospital surgical volume (lowest [or= 11 gastrectomies per year], 6.8% vs 4.9%; adjusted odds ratio [OR], 1.5; 95% confidence interval [CI], 1.2-1.8]), older patient age (50-69 vs <50 years, 4.0% vs 2.1%; adjusted OR, 1.5; 95% CI, 1.1-2.2) (>or =70 vs <50 years, 8.6% vs 2.1%; adjusted OR, 2.9; 95% CI, 2.0-4.3), male sex (male vs female, 6.7% vs 5.0%; adjusted OR, 1.3; 95% CI, 1.1-1.5), and procedure type (total gastrectomy vs all other resections, 8.0% vs 5.3%; adjusted OR, 1.4; 95% CI, 1.2-1.7)., Conclusions: Higher annual surgical volume is predictive of lower in-hospital mortality for patients undergoing gastric resection for neoplasm. Other factors significantly associated with superior outcomes after gastric resection included diagnosis type, procedure type, younger age, female sex, and fewer comorbid conditions.

KOC (K homology domain containing protein overexpressed in cancer) is a novel oncofetal RNA-binding protein highly expressed in pancreatic carcinomas. Recently, Corixa Corporation developed a monoclonal antibody specific for KOC that can be used with standard immunohistochemical techniques. The purposes of this study were 1) to assess KOC mRNA expression in pancreatic carcinoma, 2) to determine the pattern of KOC immunoexpression among benign, borderline, and malignant pancreatic epithelial lesions, and 3) to evaluate the utility of the KOC antibody in distinguishing between these entities. mRNA was isolated from fresh pancreatic tissues (19 carcinomas, 2 normal pancreas, 1 chronic pancreatitis) and amplified using standard RT-PCR techniques. Fifteen of 19 (79%) carcinomas overexpressed KOC mRNA relative to non-neoplastic tissue samples and expression increased progressively with tumor stage: the mean copy number of KOC mRNA transcripts was 1.5, 11.1, 31, and 28 for stage I, II, III, and IV carcinomas, respectively, compared with 0.9 and 1 for normal pancreatic tissue and chronic pancreatitis, respectively. Immunostains using the KOC antibody were performed on 50 surgical resection specimens (38 invasive adenocarcinomas, 3 intraductal papillary-mucinous neoplasms, 2 mucinous cystic neoplasms, 7 chronic pancreatitis). KOC staining was present in 37 of 38 (97%) carcinomas: the staining reaction was moderate or strong in 36 of 38 (94%) and present in >50% of the tumor cells in 35 of 38 (92%) cases. Severe dysplasia of the ductal epithelium, present in 19 foci of intraductal papillary mucinous carcinoma, mucinous cystadenocarcinoma, and grade 3 pancreatic intraepithelial neoplasia (PanIN3) showed strong or moderate staining in 15 (79%) cases, whereas foci of mild and moderate dysplasia (intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms with adenoma and/or moderate dysplasia, PanIN1, and PanIN2) were uniformly negative for this marker in 25 and 22 cases, respectively. In the normal pancreas, weak background staining of acini was present in 12 of 50 (24%) cases but was easily distinguishable from the type of staining identified in neoplastic epithelium, and benign ducts and ductules were negative in all cases. Four of 38 (11%) foci of chronic pancreatitis, present in the 7 resections performed for chronic pancreatitis as well as 31 foci of peritumoral chronic pancreatitis, showed weak staining in <10% of the ductules. We conclude that KOC is a sensitive and specific marker for carcinomas and high-grade dysplastic lesions of the pancreatic ductal epithelium. Therefore, immunostains directed against KOC may be of diagnostic utility in the evaluation of pancreatic lesions, particularly when biopsy material is limited.

Background: The maximum size of adrenal tumors that should be removed with a laparoscopic approach is controversial. It has been suggested that laparoscopic adrenalectomy is appropriate only for adrenal tumors < 6 cm in size. We report our experience with laparoscopic adrenalectomy in patients with adrenal tumors of > or =6 cm compared with patients with smaller tumors., Methods: We retrospectively reviewed a consecutive series of patients who had a laparoscopic adrenalectomy. Patients were considered candidates for laparoscopic adrenalectomy if their computed tomography (CT) scan showed a well-encapsulated tumor confined to the adrenal gland., Results: Sixty laparoscopic adrenalectomies were performed in 53 patients. Twelve of the adrenalectomies (20%) were for tumors that were > or =6 cm (median, 8 cm; range, 6 to 12 cm). There have been no local or regional recurrences, but one patient with adrenocortical carcinoma developed pulmonary metastases. When the 12 patients with large tumors were compared with the 36 patients with tumors < 6 cm, the median operative time (190 vs. 180 minutes; P =.32), operative blood loss (100 vs. 50 mL; P =.53), and postoperative hospital stay (2 vs. 2 days; P = 1.0) were similar., Conclusions: The size of an adrenal tumor should not be the primary factor in determining whether a laparoscopic adrenalectomy should be performed. Large adrenal tumors that are confined to the adrenal gland on CT can be removed with a laparoscopic approach.

Primary aldosteronism is a disorder that is commonly considered in patients referred to the hypertension clinic. The ease of measuring the random aldosterone-to-renin ratio in conjunction with an elevated serum aldosterone level has led to an increased screening for this disorder. Typically, patients undergo a confirmatory test after a positive screening test. However, once primary aldosteronism is confirmed, subtype delineation is critical to decide on the optimal treatment. We report a patient with resistant hypertension and primary aldosteronism with a normal computed tomographic scan of the adrenal glands, a left-sided uptake on adrenal scintigraphy, and a right-sided lateralization of aldosterone after adrenal vein sampling. A repeat adrenal vein sampling confirmed the aldosterone lateralization to the right adrenal gland, which was then removed laparoscopically. The patient had a good clinical and biochemical response, and unilateral adrenal hyperplasia was discovered at histology. Excessive reliance on adrenal scintigraphy without adrenal vein sampling may lead to serious errors in patient management.

Background: The purpose of this study was to evaluate the possibility that laparoscopic cholecystectomy has worsened the prognosis of patients with resected gallbladder cancer; particularly for patients whose cancer was accidentally resected., Study Design: We conducted a retrospective review of Connecticut Tumor Registry data and data extracted from individual patient records at 15 of 30 hospitals in Connecticut reporting data to the Registry, at two separate time points, 1985-1988 (immediate prelaparoscopic era) and 1992-95 (laparoscopic cholecystectomy well established). There were 194 and 208 patients in each 3-year period, respectively. Additional information was extracted from hospital records in 82 and 91 patients, respectively. Twenty-five percent of patients in both data sets presented with "local" or Tis, T1, T2 disease., Results: Three-year survival for localized disease was 29% in the prelaparoscopic period and 34% once laparoscopic cholecystectomy was established. But analysis of individual patient records indicated that 36% of patients from the laparoscopic period did not actually undergo a laparoscopic procedure. Fifty-nine patients had their gallbladder cancer discovered in the specimen postoperatively (serendipitously treated). A higher proportion of cancers were discovered postoperatively in the laparoscopic era (44% versus 24%). Three-year survival for these patients was 25%. If the data from the two eras are grouped according to whether or not the cancer-bearing gallbladder was manipulated laparoscopically, 24 of 59 patients (41%) turned out to be at risk for the possibility of increased laparoscopic dissemination of tumor. Survival of these patients (11-month median survival) was not statistically different from survival of patients whose serendipitously discovered gallbladder cancer was never manipulated laparoscopically (16-month median survival); p = 0.54 by log rank test., Conclusions: The widespread adoption of laparoscopic cholecystectomy did not worsen the survival of patients with gallbladder cancer, and patients with serendipitously treated gallbladder cancers did not have a worse survival after laparoscopic manipulation than after a standard open cholecystectomy. The laparoscopic aspects of operative manipulation of a gallbladder with cancer in it do not appear to be a proximate cause of the poor prognosis in this disease.

Lymph nodes are the most common and earliest site of malignancies arising in epithelia. However, the reason for this pattern of preferential metastasis is not clear. This article reviews features of the metastatic process and lymph node microenvironment which might potentiate lymph node metastases. There is intriguing evidence that preferential lymph node metastasis is due to (1) the efficiency of lymph nodes as filters of the tumor cells which arrive there, and (2) the probability that adhesive interactions, normally governing the generation of different T-cell immune responses, are responsible for this efficiency and may also promote invasion and proliferation of tumor cells in the lymph node. Manipulation of the cytokine environment in a lymph node draining a primary epithelial tumor may alter both the expression of cell adhesion molecules within the node and the subsequent metastatic ability of the tumor cells arriving at it.

Several laparoscopic approaches to the adrenal gland have been described. The lateral transperitoneal approach has several distinct advantages when contrasted with other techniques for laparoscopic adrenalectomy (LA). We present our technique and results obtained in 50 consecutive transperitoneal LAs. We review 50 consecutive laparoscopic adrenalectomies (28 female, 19 male) performed from 1993 to 1998 S.J. Shichman or R.E. Sosa was either the primary surgeon or the first assistant for all cases. The lateral transperitoneal approach described below was used in all cases. Indications for adrenalectomy included Cushing's syndrome (13), aldosteronoma (15), pheochromocytoma (7), nonfunctioning adenoma (11), hyperplasia (2), and 1 case each of Carney's syndrome and metastasis to the adrenal gland. We performed 5 bilateral, 22 left, and 18 right laparoscopic adrenalectomies. The average time needed for bilateral adrenalectomy was 503 min (range 298-690 min); for left adrenalectomy, 227 min (range 121-337 min); and for right LA, 210 min (range 135-355 min). We demonstrated a yearly trend in lower operative times. The largest adrenal gland removed measured 13.8 x 6.7 x 3.5 cm. Intraoperative blood loss was low. Only one patient received a blood transfusion. Conversion to open adrenalectomy was not required. Postoperative analgesic requirements were low. The average length of stay was 3.8 days for bilateral LA and 3 days for unilateral LA. Complications occurred in 5 patients (2 wound infections, 2 hematomas, and 1 pleural effusion). There was no mortality. Lateral transperitoneal adrenalectomy is a safe and efficient technique for the removal of functional and nonfunctional adrenal masses. This technique is associated with low morbidity, a minimal postoperative analgesic requirement, and a short hospital stay and, in our opinion, is more versatile than the retroperitoneal approach.

Background and Objectives: Angiogenesis in malignant neoplasms, as measured by microvessel density, has been shown to correlate with survival or stage in some studies of breast, gastric, and colorectal cancer. We hypothesized that aggressive cancers promote angiogenesis in normal tissue adjacent to the invading neoplasm., Methods: To test this hypothesis, 36 specimens of colon adenocarcinoma curatively resected between 1986 and 1990 were sectioned and stained for factor VIII-related antigen, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8). Microvessel density was measured within the colon cancer and in adjacent, histologically normal tissue. Clinical/pathological variables were examined using multivariate analysis and Student t-test., Results: Microvessel density was higher in the neoplasms (26.0+/-1.66/ 0.25 mm2) than in the surrounding normal tissue (22.3+/-1.88/0.25 mm2) (P=0.03). The difference was primarily due to smaller neoplasms (T1 and T2) which had vessel counts of 10.6+/-0.74/0.25 mm2 in the adjacent normal tissue compared to vessel counts of 18.9+/-3.02/0.25 mm2 within these tumors (P=0.02). T3 and T4 neoplasms had equivalent amounts of angiogenesis within the lesion (26.9+/-1.81/0.25 mm2) and in the histologically normal margin (24.2+/-1.98/0.25 mm2) (P=0.12). VEGF was present in the tumor microenvironment in 100% and IL-8 in 45% of specimens stained for these angiogenic cytokines. Microvessel density did not correlate with 5-year survival., Conclusions: Our data suggest that colon cancers that invade through the muscularis propria may have a greater ability to induce angiogenesis in adjacent normal tissue.

Objective: To determine the value of operation in patients with bowel obstruction caused by recurrent abdominal cancer., Design: Retrospective case review., Setting: The University of Connecticut Health Center, Farmington., Patients: Ninety-eight patients admitted with a diagnosis of bowel obstruction and malignant neoplasm between November 1, 1987, and June 30, 1995., Results: Data for 75 patients who developed a bowel obstruction within 5 years of a malignant diagnosis were analyzed. Forty-six patients (61%) were treated operatively and 29 (39%) were treated nonoperatively. The operative group included 32 patients (70%) whose obstruction was caused by carcinomatosis; 6 (19%) of these 32 patients had had at least 1 episode of previous obstruction requiring hospitalization. They had a 22% in-hospital mortality, stayed an average of 21 days in the hospital, and survived 7 +/- 6 months (mean +/- SD) after discharge; 5 (16%) had at least 1 episode of postoperative obstruction that required hospitalization. After discharge from the hospital, 53% had an excellent or good quality of life (assessed retrospectively). Of the 29 patients in the nonoperative group, 16 (55%) had carcinomatosis. These 16 patients had a 38% in-hospital mortality (6 of 16), stayed an average of 10 days in the hospital, and survived a mean of 13 +/- 9 months; 3 (19%) had at least 1 episode of recurrent obstruction requiring hospitalization. After discharge from the hospital, 6 (37%) had an excellent or good quality of life., Conclusion: The value of operative intervention for bowel obstruction in patients with cancer is derived from the possibility of a benign cause, not alleviation of the consequences of carcinomatosis.

Background: Local recurrence after transurethral resection of bladder tumors (TURB) is common and might be diminished if free tumor cells within the bladder are prevented from reattaching., Methods: In vitro inhibition of murine bladder tumor cells to an approximation of urothelial matrix with agents that might block attachment to components of the extracellular matrix, and in vivo inhibition of attachment in cautery-injured murine bladder., Results: GRGDS, (0.1-2.5 mg/ml), a fibronectin-related peptide, mannose-6-phosphate, (0.1-20 mg/ml), a carbohydrate, and heparin (1-625 units/ml) all inhibited attachment in vitro in a dose-dependent fashion. YIGSR (0.1-2 mg/ml), a laminin-related peptide, did not. Mannose (10 mg/ml) did not significantly inhibit attachment of tumor cells to cauterized urothelium in vivo, whereas there was a 77% reduction of attachment in bladders irrigated with GRGDS (6.25 mg/ml) (p < 0.05), and the appearance of subsequent tumors in the bladder was inhibited. Finally, GRGDS (6.25 mg/ml) did not inhibit healing of the cautery ulcer., Conclusions: RGD-containing peptides may be useful as adjuvant therapy to decrease local recurrence after TURB and perhaps in other circumstances in which tumor cells spilled into a wound or body cavity threaten surgical success.

Objectives: To correlate patient condition and reasons for obtaining chest radiographs (CXRs) with the utility of CXRs in critical illness and to determine the potential impact of stricter criteria for obtaining a CXR in a surgical intensive care unit (ICU)., Design: Inception cohort study of 1003 CXRs examined prospectively., Patients and Setting: A total of 157 consecutive patients admitted to the general surgical ICU of a 780-bed, urban, university-affiliated, tertiary care hospital., Intervention: Nothing was done to influence the ordering of CXRs., Outcome Measures: Influence of CXR findings on clinical management., Results: The likelihood of a clinically important finding was 17% for CXRs obtained for no clear clinical indication (routine), 26% for those obtained to verify the position of a medical device, and 30% for those obtained for suspected clinical conditions. By univariate analysis, suspected pathophysiologic condition, admission APACHE II (Acute Physiology and Chronic Health Evaluation II) score, presence of a central venous or Swan-Ganz catheter, and length of ICU stay were all predictors of a significant finding. By multivariate analysis, the only independent predictor of a finding was a suspected clinical condition, and the only indwelling medical device that was an independent predictor of a finding was a Swan-Ganz catheter. If the criterion that routine CXRs should only be obtained in patients with Swan-Ganz catheters had been used, 200 CXRs would have been avoided during the 3-month study period. The only findings missed by not obtaining those CXRs would have been two malpositioned nasogastric tubes and one malpositioned central venous catheter., Conclusions: Chest radiographs should only be obtained on surgical ICU patients for specific indications. Routine CXRs for ICU patients are justified only for patients with indwelling Swan-Ganz catheters.

Background: We investigated the possibility that lymph nodes might increase metastatic efficiency of tumor cells lodged there by measuring changes in tumor cell invasiveness after physical contact with an in vitro approximation of a lymph node environment., Study Design: The experimental model involved growing Lewis lung carcinoma (LL) or B16 melanoma cells on microcarrier beads, rolling them on a "lymph node endothelial surface," which was created by growing endothelial cells on a differentiating acid extract of lymph node biomatrix, and testing the ability of those tumor cells to invade across matrigel-coated filters at rest (buffer) and in response to a chemotactic stimulus (3T3 conditioned media)., Results: Compared with contact with plastic, LL invasiveness was increased fivefold (buffer or conditioned media) and B16 invasiveness fourfold (conditioned media). Tumor cell invasiveness was not increased by exposure to the acid extract of biomatrix alone. Invasiveness to buffer or conditioned media after exposure to endothelial cells alone was 70 and 54 percent (LL) and 42 and 80 percent (B16), respectively, of the invasiveness induced by exposure to both. Compared with invasiveness induced by exposure to lymph node (100 percent), exposure to a "lung endothelial surface" induced invasiveness of 63 and 85 percent (LL) and 40 and 52 percent (B16) to buffer and conditioned media, respectively. Exposure to a hepatic endothelial surface induced invasiveness similar to that induced by lymph node; 90 and 82 percent (LL) and 110 and 86 percent (B16) of lymph node-induced invasiveness., Conclusions: A lymph node environment may modulate the metastatic potential of tumor cells.

Episodic abdominal pain, a common clinical problem, can be a diagnostic and therapeutic conundrum when the surgeon encounters it acutely in the emergency department. Appendicitis is often excluded from the differential diagnosis because the natural history of appendicitis is usually appreciated as acute, progressing to some degree of peritonitis quite rapidly and inevitably. However, recurrent and chronic forms of appendicitis occur also and can mislead the clinician. Herein, we describe two patients with recurrent appendicitis that were misinterpreted as other abdominal conditions, and we review the literature implicating recurrent and chronic appendicitis as disease processes, distinct from acute appendicitis, that occur with an incidence of approximately 10 per cent and 1 per cent, respectively.

Background: Adhesion to lymph nodes, rather than growth stimulation, accounted for preferential colonization of lymph nodes by a metastatic B16 melanoma. We investigated these adhesive interactions., Methods: Four classes of molecules were tested for inhibition of melanoma adhesion to cryostat sections of lymph node., Results: Calcium chelators ethylenediaminetetraacetic acid and ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetra ace tic acid completely inhibited adhesion (50% adhesion, half-maximal inhibition, at 1 to 3 mmol/L). Cytochalasin B, which impairs contractile microfilaments, inhibited adhesion (60% adhesion at .001 mmol/L, 28% at .01 mmol/L). Colchicine, which disaggregates microtubules, had a similar effect (20% at .01 mmol/L, lowest dose tested). Trypsin slightly increased adhesion (125% adhesion at 10 micrograms/ml). Neuraminidase, which removed sialic acid residues, inhibited it (50% adhesion at 5 micrograms/ml). Gly-arg-gly-asp-ser, a peptide with a cell binding sequence of fibronectin, did not consistently inhibit adhesion (69% adhesion at 0.1 mg/ml, 83% adhesion at 1 mg/ml) or substantially differ from gly-arg-gly-glu-ser-pro (59% adhesion at 0.1 mg/ml, 90% adhesion at 1 mg/ml). In contrast, a peptide with a cell binding region of laminin (tyr-ile-gly-ser-arg) inhibited adhesion (50% adhesion at .05 mg/ml)., Conclusions: Tumor cell-lymph node adhesion is a calcium-dependent process, requiring a functional cytoskeleton, that is mediated by both sialic acid moieties and trypsin-resistant, laminin-related, adhesion molecules.