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Background: Resection of colorectal hepatic metastases is an accepted treatment modality for stage IV colorectal cancer. Concurrent or sequential pulmonary metastasectomy continues to be a controversial strategy. We analyzed factors that predicted pulmonary recurrence in patients with resected hepatic metastases and examined the efficacy of these combined interventions in the treatment of metastatic colorectal cancer.Methods: A retrospective review of a database of patients who underwent resection of colorectal hepatic metastases was performed to identify patients who either had synchronous pulmonary metastases (defined as pulmonary recurrence at the time of or within 3 months of hepatic metastasectomy) or subsequently experienced pulmonary metastases. Patient demographics, operative interventions, and overall survival were analyzed. Statistical methods included unpaired Student's t-test, actuarial survival and log-rank analysis.Results: Twenty-one patients (19%) had pulmonary metastases after hepatic resection, of which 12/21(57%) underwent pulmonary resection. No differences were observed between the resection group, the nine patients with pulmonary metastases who did not undergo resection, and the 87 patients without pulmonary metastases with regard to age, sex, race, or extent of hepatic metastases. When comparing the resected versus the unresected pulmonary recurrences, the disease-free interval from hepatic resection to detection of pulmonary metastases was 21 +/- 20 months (range, 3-72 months) versus 16 +/- 8 months (range, 4-25 months), respectively. All patients with pulmonary recurrence who underwent pulmonary metastasectomy had unilateral disease. Seven of 12 (58%) underwent wedge/segmental resections, and the remaining five (42%) required lobectomy in order to obtain a complete resection. Four patients who underwent pulmonary resection had multiple lung metastases (two to four lesions), and eight had isolated metastasis. There were no perioperative deaths in the pulmonary metastasectomy group. Contraindications to pulmonary resection included extensive pulmonary disease and concurrent extrapulmonary disease. A survival benefit was noted at 3 years for the resected versus the unresected group (60% vs 31%). Survival was no different between the resected pulmonary recurrence patients and the resected hepatic metastases only patients (60% vs 54%).Conclusions: Pulmonary metastasectomy can be performed safely and effectively in patients with recurrent disease after hepatic resection for colorectal metastases. Prolonged survival can be achieved with resection of isolated pulmonary recurrence after hepatic resection for colorectal cancer. Further studies that delineate selection criteria for pulmonary resection of colorectal metastases are warranted. [ABSTRACT FROM AUTHOR]

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials. [ABSTRACT FROM AUTHOR]

Objective: To determine the disease-free survival (DFS) and recurrence after the treatment of patients with rectal cancer with open (OPEN) or laparoscopic (LAP) resection., Background: This randomized clinical trial (ACOSOG [Alliance] Z6051), performed between 2008 and 2013, compared LAP and OPEN resection of stage II/III rectal cancer, within 12 cm of the anal verge (T1-3, N0-2, M0) in patients who received neoadjuvant chemoradiotherapy. The rectum and mesorectum were resected using open instruments for rectal dissection (included hybrid hand-assisted laparoscopic) or with laparoscopic instruments under pneumoperitoneum. The 2-year DFS and recurrence were secondary endpoints of Z6051., Methods: The DFS and recurrence were not powered, and are being assessed for superiority. Recurrence was determined at 3, 6, 9, 12, and every 6 months thereafter, using carcinoembryonic antigen, physical examination, computed tomography, and colonoscopy. In all, 486 patients were randomized to LAP (243) or OPEN (243), with 462 eligible for analysis (LAP = 240 and OPEN = 222). Median follow-up is 47.9 months., Results: The 2-year DFS was LAP 79.5% (95% confidence interval [CI] 74.4-84.9) and OPEN 83.2% (95% CI 78.3-88.3). Local and regional recurrence was 4.6% LAP and 4.5% OPEN. Distant recurrence was 14.6% LAP and 16.7% OPEN.Disease-free survival was impacted by unsuccessful resection (hazard ratio [HR] 1.87, 95% CI 1.21-2.91): composite of incomplete specimen (HR 1.65, 95% CI 0.85-3.18); positive circumferential resection margins (HR 2.31, 95% CI 1.40-3.79); positive distal margin (HR 2.53, 95% CI 1.30-3.77)., Conclusion: Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.

Objectives: Our objectives were to (1) compare 30- and 90-day mortality rates after esophagectomy, (2) compare drivers of 30- and 90-day mortality, and (3) examine whether 90-day mortality affects hospital rankings., Background: Operative mortality has traditionally been assessed at 30 days. Ninety-day mortality has been suggested as a more appropriate indicator of quality, particularly after complex cancer surgery., Methods: Esophagectomies for nonmetastatic esophageal cancer patients diagnosed between 2007 and 2011 were identified in the National Cancer Data Base. Mortality rates were examined by patient demographics, tumor characteristics, and hospital procedural volume. Risk-adjusted hierarchical logistic regression models examined hospital performance for mortality., Results: A total of 15,796 esophagectomy patients at 977 hospitals were available for analysis. Ninety-day overall mortality was more than double the 30-day mortality (8.9% vs 4.2%; P < 0.0001). In multivariate analysis, while both 30- and 90-day mortality were associated with patient factors such as age, comorbidity, and hospital volume, only 90-day mortality was influenced by tumor- and management-related variables such as stage, tumor location, and receipt of neoadjuvant therapy. Hospital performance was examined as top 10%, middle 10% to 90%, and lowest 10% as ranked using risk-adjusted odds of mortality. There was moderate correlation between ranking based on 30- and 90-day mortality [weighted κ = 0.45 (95% confidence interval, 0.39-0.52)]. Compared with 30-day mortality rankings, nearly 20% of hospitals changed their ranking category when 90-day mortality rankings were used., Conclusions: Examination of 90-day mortality after esophagectomy reflects cancer patient management decisions and may provide actionable targets for quality improvement.

Objective: To prospectively evaluate the additional value of geriatric assessment (GA) for predicting surgical outcomes in a cohort of older patients undergoing a pancreaticoduodenectomy (PD) for pancreatic tumors., Background: Older patients are less often referred for possible PD. Standard preoperative assessments may underestimate the likelihood of significant adverse outcomes. The prospective utility of validated GA has not been studied in this group., Methods: PD-eligible patients were enrolled in a prospective outcome study. Standard preoperative assessments were recorded. Elements of validated GA were also measured, including components of Fried's model of frailty, the Vulnerable Elders Survey (VES-13), and the Short Physical Performance Battery (SPPB). All postoperative adverse events were recorded, systematically reviewed, and graded using the Clavien-Dindo system by a surgeon blinded to the GA results. Multivariate regression analyses were conducted., Results: Seventy-six older patients underwent a PD. Significant unrecognized vulnerability was identified at the baseline: Fried's "exhaustion" (37.3%), SPPB <10 (28.5%), and VES-13 >3 (15.4%). Within 30 days of PD, 46% experienced a severe complication (Clavien-Dindo grade ≥III). In regression analyses controlling for age, the body mass index, the American Society of Anesthesiologists score, and comorbidity burden, Fried's "exhaustion" predicted major complications [odds ratio (OR) = 4.06; P = 0.01], longer hospital stays (β = 0.27; P = 0.02), and surgical intensive care unit admissions (OR = 4.30; P = 0.01). Both SPPB (OR = 0.61; P = 0.04) and older age predicted discharge to a rehabilitation facility (OR = 1.1; P < 0.05) and age correlated with a lower likelihood of hospital readmission (OR = 0.94; P = 0.02)., Conclusions: Controlling for standard preoperative assessments, worse scores on GA prospectively and independently predicted important adverse outcomes. Geriatric assessment may help identify older patients at high risk for complications from PD.

Objective: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes., Methods: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity., Results: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year., Conclusions: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.

Concurrent chemotherapy and radiotherapy (chemoradiotherapy) for the management of pancreatic adenocarcinoma in either adjuvant or locally regional advanced settings produces predictable acute toxicities that are proportional in severity to the intensity and type of systemic therapy and to the parameters of radiotherapy. In addition, relevant to the adjuvant setting, surgery for pancreatic cancer often produces physiologic alterations that may impact a patient's ability to tolerate chemoradiotherapy. Failures to anticipate, monitor, and proactively manage the effects of surgery and toxicities of chemoradiotherapy can result in the need for unplanned treatment interruptions and/or inability to complete all planned therapy. In this review, complications of pancreatic cancer itself and of pancreatic resection as well as toxicities of chemoradiotherapy are delineated, and approaches to their management before, during, and after chemoradiotherapy are presented. Planning for the treatment of side effects before the anticancer therapy begins facilitates therapy administration and improves patient tolerance.

Chemo-inducible cancer gene therapy is a potential new treatment for solid tumors that may in part enhance the anti-tumor effects of chemotherapy while minimizing toxicity. This approach combines viral vectors expressing cytotoxic transgenes that can be transcriptionally activated by DNA-damaging agents. The development of chemo-inducible gene therapy has numerous implications for the treatment of both localized and metastatic disease in patients with solid tumors.

Minimally invasive surgical approaches were designed to enhance quality of care and improve patient outcome by minimizing postoperative pain, shortening hospital stay, reducing costs, and facilitating early return to work and presurgical lifestyle. The hand-assisted laparoscopic approach for resection of cancer is still in its formative stage, and this review places it in proper perspective within the context of minimally invasive surgery currently being performed for both benign and malignant disease. The review also outlines the potential advantages and disadvantages, techniques, and site-specific procedures of hand-assisted laparoscopic surgery for cancer.

Purpose: Vascular endothelial growth factor (VEGF) is an important mediator of endothelial cell proliferation and survival. The purpose of the present studies was to investigate the role of VEGF in the tumor response to ionizing radiation., Methods: Two ras-transformed murine fibrosarcoma cell lines, VEGF+/+ and VEGF-/- were exposed to ionizing radiation (0, 1, 3, 5, 7 or 9 Gy) in vitro, and clonogenic survival was determined. VEGF+/+ and VEGF-/- xenografts were generated in athymic nude mice and then treated with ionizing radiation (ten 5-Gy fractions = 50 Gy). Mean fractional tumor volume was used to evaluate treatment efficacy. To determine whether VEGF enhances tumor radioresistance by targeting endothelial cells, we performed clonogenic survival assays with human umbilical vein endothelial cells. Surviving fractions were calculated after treatment with ionizing radiation (5 Gy) and recombinant hVEGF165 (0, 1, 10, and 100 ng/mL). To determine whether VEGF neutralization enhances tumor radiosensitivity, we employed anti-VEGF165 monoclonal antibody to treat human tumor xenografts. Tumors were exposed to ionizing radiation (four 5-Gy fractions = 20 Gy) and treated with anti-VEGF antibody (0, 5, and 25 microg/kg in four intraperitoneal doses). Mean fractional tumor volume was used to evaluate treatment efficacy. To elucidate the molecular mechanism contributing to the observed anti-VEGF/ionizing radiation interaction, we exposed human umbilical vein endothelial cells to ionizing radiation (5 Gy) in the presence of anti-VEGF antibody (1 microg/mL). Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell lysates was probed for mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK1/MEK2)., Results: The in vitro radiosensitivities of the VEGF+/+ and VEGF-/- clones were equivalent (D0 = 146 vs 149). However, the VEGF+/+ xenografts were more resistant to the cytotoxic effects of ionizing radiation than the VEGF-/- xenografts. VEGF+/+ xenografts demonstrated a faster doubling time (4.5 vs 6.0 days) and a shorter growth delay (15 vs 23 days) than VEGF-/- xenografts. The surviving fraction of human umbilical vein endothelial cells after exposure to ionizing radiation was significantly enhanced in the presence of VEGF (6.4% vs 12.5%). Western blot analysis demonstrated that stimulation of MAPK and MEK1/MEK2 was abrogated after exposure to anti-VEGF antibody., Discussion: These findings represent the first genetic evidence that factors other than inherent tumor cell radiosensitivity are important determinants of radiocurability. Antitumor strategies targeting VEGF and other endothelial cell survival mechanisms may be used to enhance the cytotoxic effects of radiotherapy.

Trauma to the extrahepatic biliary tract is rare but, if overlooked or improperly managed, may be associated with significant morbidity. The following is our most recent 6-year experience with this unusual injury. Among 949 patients undergoing laparotomy for acute trauma, there were 32 (3%) injuries to the gallbladder and five (0.5%) to the common bile duct. All patients with gallbladder injury underwent abdominal exploration because of associated trauma. Cholecystectomy was preferred for 24 (96%) of the 25 with penetrating wounds and three (43%) of the seven with blunt trauma. Nine (28%) patients developed postoperative complications but none were related to the biliary injury. All common bile duct injuries (CBD) were penetrating. Associated intra-abdominal trauma was always present. Partial lacerations were closed primarily over a T-tube. An intrapancreatic CBD lesion was managed by sphincteroplasty and stented with a T-tube. The one patient with complete transection underwent choledochoenterostomy. Postoperative complications were common (50%) but none were related to the biliary injury.

Conventional policy mandates exploration of retroperitoneal hematomas presumed to contain penetrating injuries of the inferior vena cava (IVC). In clinical practice this maneuver frequently results in torrential blood loss, suggesting the injury may be best managed without exploration and IVC suturing. The present study was undertaken to define the natural history of untreated IVC perforations, and to assess venous access with such injuries. Twelve adolescent Hampshire pigs (20-25 kg) underwent halothane anesthesia and laparotomy. The infrarenal IVC was isolated temporarily and a posterior cruciate incision, equivalent to 50% of the IVC circumference, made via anterior venotomy. Animals were resuscitated with Ringer's lactate. Technetium sulfur colloid was injected 20 min postlaparotomy closure via either a jugular or femoral venous cannula, and count activity measured over the IVC injury site using a mobile gamma camera. The procedure was repeated via the counterpart limb. Background from the first injection was subtracted, and count ratios integrated from 16 to 19 min postinjection. Extravasation following lower extremity infusion was not significantly different from that following central venous administration. One pig succumbed to cryptogenic peritonitis one wk postinjury. The remaining animals were killed at periods ranging from 3 to 12 wk. No animal had clinical evidence of delayed bleeding, pulmonary embolus, or other venous sequelae during the observation period. At autopsy all vena cavae were normal caliber without evidence or pseudoaneurysm of thrombosis. This swine study confirms the efficacy of lower extremity venous access with contained IVC injury, and suggests that isolated retroperitoneal IVC injuries may be treated nonoperatively in very selected patients.