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Importance Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. Objective To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. Design, Setting, and Participants A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female). Patients registered between May 29, 2013, and February 7, 2014. Interventions Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2of irinotecan hydrochloride, 400 mg/m2of leucovorin calcium, and then 2400 mg/m2of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2orally twice daily) prior to pancreatectomy. Main Outcomes and Measures Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. Results The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%-83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%-88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. Conclusions and Relevance The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial’s completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. Trial Registration clinicaltrials.gov Identifier:NCT01821612

Appendiceal carcinoid tumors (ACTs) are rare, and little is known about the long-term prognosis for these tumors because no staging system exists. Therefore, we sought to investigate prognostic factors associated with ACTs and to create a predictive staging system to accurately estimate prognosis.In patients with ACTs, TNM staging will accurately predict prognosis.Retrospective review of 15 983 patients with carcinoid tumors in the Surveillance Epidemiology and End Results (SEER) database from January 1, 1977, to December 31, 2004.SEER database study.Nine hundred patients with ACTs (552 females and 348 males; mean age, 47.1 years [age range, 9-89 years]; mean size of the primary tumor, 2.4 cm [range, 0.1-11.5 cm]). Main Outcome Measure Clinicopathologic features in patients with ACTs that affect prognosis using a newly created TNM staging system incorporating these parameters.Lymph node metastasis was found in 137 patients (24%), and distant metastatic disease in 89 patients (10%). Stage-specific survival was statistically significant between stages (P.001) but not within stages. At multivariate analysis, patient age, primary tumor size, histologic features, lymph node involvement, and distant metastasis were significant factors predicting survival.Our newly developed TNM staging system accurately predicts prognosis in patients with ACTs. A TNM staging system for ACTs will be helpful not only for physician education about factors that affect the outcome with this disease but also to observe trends in prognosis.

Hypothesis The down-regulation of manganese superoxide dismutase (MnSOD) expression plays a role in the progression of Barrett esophagus (BE). Design An evaluation of 92 esophageal samples, including 17 patients with normal esophagus, 22 with intestinal metaplasia, 22 with indefinite/low-grade dysplasia, 16 with high-grade dysplasia (HGD), and 15 with esophageal adenocarcinoma were evaluated for MnSOD expression. We evaluated MnSOD expression using immunohistochemistry and graded it separately on a 2-category ordinal scale in relation to the mucosa and submucosa that ranged from 0 (no staining) to 3 (strong staining). The total grading score of MnSOD immunoreactivity was the addition of mucosa and submucosa intensity, from 0 (no immunoreactivity in any of the anatomic sites) to a maximum score of 6 (strong staining reaction in both of the histoanatomic sites). Setting Study subjects were recruited from the Barrett’s Esophageal Registry at the University of Louisville, Louisville, Ky. Main Outcome Measure Manganese superoxide dismutase expression in established groups of progressive BE. Results Ninety-two samples were evaluated for MnSOD expression. The expression of MnSOD was found to be significantly reduced in samples with specialized intestinal metaplasia (mean score, 1.8), low-grade dysplasia (mean, 2.2), high-grade dysplasia (mean, 2.4), and esophageal adenocarcinoma (mean, 2.4) when compared with normal esophagus (mean, 3.9; P = .002). Manganese superoxide dismutase expression was similar for esophageal adenocarcinoma and high-grade dysplasia. Conclusions Manganese superoxide dismutase expression is significantly reduced in patients with BE with high-grade dysplasia and esophageal adenocarcinoma. Manganese superoxide dismutase is related to the progression of BE and may represent one of the primary factors in oxidative stress protection. Further evaluation within genotypic expression and the role of antioxidants is needed in the effective screening and treatment of BE.

Hypothesis Subareolar or periareolar injection of radioactive technetium sulfur colloid is equivalent to other injection techniques for breast cancer sentinel lymph node (SLN) biopsy. Design and Setting Prospective, multicenter clinical trial. Patients A total of 3961 individuals with clinical stage I and II breast cancer. Interventions All patients underwent attempted SLN biopsy followed by completion axillary dissection. Injection technique was determined by the preference of each participating surgeon. Most surgeons had little or no experience with SLN biopsy before participation in this study. Main Outcome Measures The SLN identification and false-negative rates. Results An SLN biopsy was performed in 3961 patients using blue dye alone or radioactive colloid plus blue dye. Subareolar and periareolar radioactive colloid injection techniques were associated with SLN identification rates of 99.3% and 95.6%, respectively, with false-negative rates of 8.3% and 8.9%, respectively. The identification rates were significantly higher for these 2 techniques than for peritumoral injection of radioactive colloid (91.1%) or the use of blue dye alone (88.5%) ( P Conclusions Although many medical centers have adopted subareolar and periareolar radioactive colloid injections because of their simplicity and convenience, a paucity of data from a few single-institutional studies has existed to substantiate the false-negative rates associated with these techniques. The results of this multicenter study establish the validity of subareolar and periareolar radioactive colloid injections and support the hypothesis that the lymphatic drainage of the entire breast is to the same few SLNs.

Background Ewing sarcoma (ES) is the second most common primary osseous malignancy in childhood and adolescence. The improvement in survival is primarily associated with the combination of surgery and chemotherapy. Hypothesis Little is known about the outcome of adults with soft tissue ES or primitive neuroectodermal tumors (PNET). Certain prognostic factors from soft tissue sarcomas (tumor size, tumor location, margin status, and initial presentation) in adults (>16 years) with ES/PNET will help to identify factors associated with outcome. Methods Between July 1, 1982, and June 30, 2000, we identified 59 adult patients with primary soft tissue ES/PNET. Clinicopathologic factors were correlated with the end points studied: patient factors, tumor factors, pathologic factors, status of surgical margins, adjuvant chemotherapy, and radiation therapy. Results There were 41 male and 18 female patients, with a median age of 27 years (range, 16-72 years). Median tumor size was 8 cm, with all lesions being high grade. The most common site was the trunk (n = 22), with an even distribution of retroperitoneal, pelvis, buttock, and lower extremity (all n = 5). The median follow-up was 29 months (range, 6-222 months), with local recurrence identified in 13 patients (22%), with a median time to recurrence of 15 months (range, 5-200 months). Overall 5-year survival was 60%. Initial presentation was the only predictor of long-term survival, with primary tumor–only presentation having a 5-year survival of 60% (median not reached) compared with primary tumor plus metastatic disease having a 5-year survival of 33% (median, 17 months) ( P = .02). Conclusion Initial presentation of disease represents the only predictor of survival identified in this small group of adult patients with ES/PNET.

• To determine what physiologic changes might contribute to the development of the postthrombotic syndrome, venous outflow, venous refilling time, and valvular competence were assessed in 32 patients (39 limbs) with documented deep venous thrombosis. The follow-up ranged from nine to 144 months (mean, 41 months) after the acute deep venous thrombosis. Pain was noted by 49% of the patients, but more objective end points occurred less frequently (edema, 21%; pigmentation, 26%; ulceration, 3%). Venous outflow was lower in the affected limbs but was not a good indicator of those patients with or without symptoms. Venous refilling time after calf compression was markedly reduced in limbs with incompetent valves (mean ± SD, 8.4 ± 3.8 s v 25.3 ±12.1 s), as well as in those with edema, pigmentation, and ulceration. It appears that most of the sequelae of the postthrombotic syndrome can be attributed to the loss of valvular function. ( Arch Surg 1985;120:424-426)