Effect of Diabetes Mellitus on Complication Rates of Coronary Artery Bypass Grafting.

Previous studies have shown that diabetes mellitus (DM) is a risk factor for postoperative coronary artery bypass grafting (CABG) complications. More contemporary studies are needed to guide revascularization decisions in DM patients. We performed a single-center study of patients who underwent CABG. Patients with no DM were compared with patients with DM, subgrouped according to whether or not DM was treated with insulin before admission (Insulin and No Insulin Groups). Multivariable logistic regression was used to determine whether DM was a significant predictor of mortality, combined postoperative events, and specific postoperative complications after controlling for other predictive clinical variables. Of 11,590 consecutive patients who underwent CABG, 5,013 (43%) had DM and 6,577 (57%) had no DM. Of the patients with DM, 3,433 (68%) were not treated with insulin and 1,580 (32%) were treated with insulin before admission. Multivariable logistic regression analyses showed that DM was not significantly associated with in-hospital mortality or combined postoperative events after considering other clinical variables. The No Insulin Group was significantly associated with stroke, and the Insulin Group was significantly associated with surgical site infection and new renal failure. In conclusion, this study of consecutively treated CABG patients shows that DM is not a predictor of in-hospital mortality or combined in-hospital postoperative events after adjusting for other clinical factors. DM is a predictor of permanent stroke, surgical site infection, and new renal failure. These findings may help with case selection and management of DM patients undergoing CABG.

The Paradoxical Relationship Between Donor Distance and Survival After Heart Transplantation.

BACKGROUND: Concerns over prolonged allograft ischemia have limited the widespread adoption of long-distance organ procurement in heart transplantation (HT). We sought to assess whether donor distance from the center of transplantation independently affects mortality. METHODS: We queried the United Network for Organ Sharing (UNOS) database for adults undergoing isolated HT from 2005 to 2012. Risk-adjusted Cox proportional hazards models were constructed for the primary outcomes of 30-day and 1-year mortality, and the independent impact of donor distance from transplantation center at the time of procurement was assessed. RESULTS: We included 14,588 heart transplant recipients. The mean distance from location of the donor heart to transplantation center was 184.4 ± 214.6 miles; 1,214 HTs (8.3%) occurred at the same location as the donor heart. Ischemic times were inversely related to the distance from the site of donor procurement to recipient transplantation. After risk adjustment, longer donor distances (in miles) were associated with a significantly lower risk of mortality at both 30 days (hazard ratio [HR] 0.9993, 95% confidence interval [CI]: 0.9988 to 0.9998, p < 0.01) and 1 year (HR 0.9994, 95% CI: 0.9989 to 0.9999, p = 0.015). Risk-adjusted hazards for mortality were significantly reduced in recipients receiving hearts from more than 25 miles away. The hazard reduction was greatest in recipients receiving donor hearts from more than 500 miles away (1-year HR 0.64, p < 0.01; 30-day HR 0.47, p < 0.01). CONCLUSIONS: Longer distances between donor location and center of heart transplantation are associated with a reduced hazard for survival at 30 days and 1 year, despite greater ischemic times. Future studies are necessary to elucidate the protective factors surrounding long-distance heart donation.

Late Complications Following Continuous-Flow Left Ventricular Assist Device Implantation.

Left ventricular assist devices have become standard therapy for patients with end-stage heart failure. They represent potential long-term solutions for a growing public health problem. However, initial enthusiasm for this technology has been tempered by challenges posed by long-term support. This review examines these challenges and out current understanding of their etiologies.

Mediastinal Fibrosis of the Pulmonary Artery Secondary to Tuberculosis.

Mediastinal fibrosis is an uncommon disease involving the esophagus, respiratory tract, and great vessels. We report a man who presented with dyspnea on exertion. Computed tomography of the chest demonstrated granulomatous disease with dense calcifications leading to severe stenosis of the main pulmonary artery (PA) and narrowing of the superior vena cava. The results of tuberculosis (TB) interferon-γ release assay and TB-polymerase chain reaction were positive for Mycobacterium tuberculosis. The patient received 2 weeks of treatment for latent TB before undergoing resection of fibrotic tissue and replacement of the main and branch PAs using a homograft.

Palliative iliac vein-to-right atrium bypass in a patient with a prior vena cava ligation for invasive renal cell carcinoma.

Renal cell carcinoma can involve the inferior vena cava and extend into the right atrium. Cure is rarely achieved in patients with concomitant metastases, but cytoreductive nephrectomy and eradication of the entire tumor thrombus can extend survival and prevent symptoms of venous congestion; however, the invasive nature of the tumor thrombus can make resection with negative margins difficult. We present a patient with aggressive renal cell carcinoma that demanded an iliac vein-to-right atrium bypass after inferior vena cava ligation during a previous attempt at curative resection with nephrectomy and caval thrombectomy.

Simulation in cardiothoracic surgical training: where do we stand?

OBJECTIVES: Simulation may reduce the risks associated with the complex operations of cardiothoracic surgery and help create a more efficient, thorough, and uniform curriculum for cardiothoracic surgery fellowship. Here, we review the current status of simulation in cardiothoracic surgical training and provide an overview of all simulation models applicable to cardiothoracic surgery that have been published to date. METHODS: We completed a comprehensive search of all publications pertaining to simulation of cardiothoracic surgical procedures by using PubMed. RESULTS: Numerous cardiothoracic surgical simulators at various stages of development, assessment, and commercial manufacturing have been published to date. There is currently a predominance of models simulating coronary artery bypass grafting and bronchoscopy and a relative paucity of simulators of open pulmonary and esophageal procedures. Despite the wide range of simulators available, few models have been formally assessed for validity and educational value. CONCLUSIONS: Surgical simulation is becoming an increasingly important educational tool in training cardiothoracic surgeons. Our next steps forward will be to develop an objective, standardized way to assess surgical simulation training compared with the current apprenticeship model.

Valve surgery for infective endocarditis is associated with high hospital charges.

BACKGROUND AND AIM OF THE STUDY: Half of all patients with infective endocarditis (IE) will require early surgical intervention, and another 40% will eventually undergo surgical treatment for their disease. Although the surgical management of IE is effective, the financial impact of the disease has never been assessed. METHODS: All patients who underwent valve surgery for native valve IE at the present authors' institution over a 10-year period (1996-2006) were reviewed retrospectively. Hospital charges were identified and adjusted to reflect US$ in 2006. A logistic regression analysis was performed to identify factors affecting charges and the patients' length of stay (LOS). RESULTS: A total of 369 patients (252 males, 117 females; mean age 53 +/- 15 years) underwent surgery for IE. Of these patients, 121 (33%) had preoperative renal failure and 70 (20%) were intravenous drug users. In addition, 159 patients (43%) had aortic IE, 112 (30%) had mitral IE, and 45 (12%) had both aortic and mitral valve IE. Right- and left-sided IE was identified in 42 patients (11%), and 11 (3%) had isolated right-sided IE. The median hospital charges were US$ 60,072 (interquartile range (IQR) US$ 39,386-103,960), with a median LOS of 15 days (IQR 9-29 days). Both, hospital charges and LOS were higher for patients undergoing emergent operations, or those with active IE (p < 0.001). The 30-day mortality was 2.7%. Regression analyses showed preoperative renal failure (p = 0.007), intraoperative transfusion (p = 0.028) and postoperative gastrointestinal complications (p < 0.001), renal failure (p = 0.012), heart block (p < 0.001), in-hospital mortality (p < 0.001), and patients undergoing emergent procedures (p < 0.001), or with active infection (p < 0.001) to be associated with significantly increased hospital charges. Factors that significantly affected LOS were other non-white race (p = 0.039), postoperative gastrointestinal complications (p = 0.001), stroke (p = 0.014), heart block (p < 0.001), and patients undergoing emergent procedures (p < 0.001) or with active infection (p < 0.001). CONCLUSION: The present series was among the largest to include patients with IE, and the first in which risk factors were assessed for increased hospital charges and resource utilization following surgery for endocarditis. Operations for IE are associated with a significant financial burden to the healthcare system, despite a relatively low percentage of complications. Patients with significant preoperative comorbidities, those with postoperative complications, and those who underwent emergent procedures or who had active IE, were associated with a prolonged LOS and increased hospital charges.

Mithramycin represses basal and cigarette smoke-induced expression of ABCG2 and inhibits stem cell signaling in lung and esophageal cancer cells.

Cigarette smoking at diagnosis or during therapy correlates with poor outcome in patients with lung and esophageal cancers, yet the underlying mechanisms remain unknown. In this study, we observed that exposure of esophageal cancer cells to cigarette smoke condensate (CSC) led to upregulation of the xenobiotic pump ABCG2, which is expressed in cancer stem cells and confers treatment resistance in lung and esophageal carcinomas. Furthermore, CSC increased the side population of lung cancer cells containing cancer stem cells. Upregulation of ABCG2 coincided with increased occupancy of aryl hydrocarbon receptor, Sp1, and Nrf2 within the ABCG2 promoter, and deletion of xenobiotic response elements and/or Sp1 sites markedly attenuated ABCG2 induction. Under conditions potentially achievable in clinical settings, mithramycin diminished basal as well as CSC-mediated increases in AhR, Sp1, and Nrf2 levels within the ABCG2 promoter, markedly downregulated ABCG2, and inhibited proliferation and tumorigenicity of lung and esophageal cancer cells. Microarray analyses revealed that mithramycin targeted multiple stem cell-related pathways in vitro and in vivo. Collectively, our findings provide a potential mechanistic link between smoking status and outcome of patients with lung and esophageal cancers, and support clinical use of mithramycin for repressing ABCG2 and inhibiting stem cell signaling in thoracic malignancies.

Thoracic outlet syndrome caused by fibrous dysplasia of the first rib.

Fibrous dysplasia causing thoracic outlet syndrome is rare. A 41-year-old woman presented with neurogenic thoracic outlet syndrome with imaging that demonstrated a large tumor of her proximal left first rib. Transaxillary excision was unsuccessful due to involvement of the subclavian vasculature and brachial plexus. Subsequent posterolateral thoracotomy and resection of her first rib revealed fibrous dysplasia. Thoracotomy should be considered in these cases for optimal vascular control and identification of thoracic outlet anatomy.

Polycomb repressor complex-2 is a novel target for mesothelioma therapy.

PURPOSE: Polycomb group (PcG) proteins are critical epigenetic mediators of stem cell pluripotency, which have been implicated in the pathogenesis of human cancers. This study was undertaken to examine the frequency and clinical relevance of PcG protein expression in malignant pleural mesotheliomas (MPM). EXPERIMENTAL DESIGN: Microarray, quantitative reverse transcriptase PCR (qRT-PCR), immunoblot, and immunohistochemistry techniques were used to examine PcG protein expression in cultured MPM, mesothelioma specimens, and normal mesothelial cells. Lentiviral short hairpin RNA techniques were used to inhibit EZH2 and EED expression in MPM cells. Proliferation, migration, clonogenicity, and tumorigenicity of MPM cells either exhibiting knockdown of EZH2 or EED, or exposed to 3-deazaneplanocin A (DZNep), and respective controls were assessed by cell count, scratch and soft agar assays, and murine xenograft experiments. Microarray and qRT-PCR techniques were used to examine gene expression profiles mediated by knockdown of EZH2 or EED, or DZNep. RESULTS: EZH2 and EED, which encode components of polycomb repressor complex-2 (PRC-2), were overexpressed in MPM lines relative to normal mesothelial cells. EZH2 was overexpressed in approximately 85% of MPMs compared with normal pleura, correlating with diminished patient survival. Overexpression of EZH2 coincided with decreased levels of miR-101 and miR-26a. Knockdown of EZH2 orEED, or DZNep treatment, decreased global H3K27Me3 levels, and significantly inhibited proliferation, migration, clonogenicity, and tumorigenicity of MPM cells. Common as well as differential gene expression profiles were observed following knockdown of PRC-2 members or DZNep treatment. CONCLUSIONS: Pharmacologic inhibition of PRC-2 expression/activity is a novel strategy for mesothelioma therapy.

Operative management for recurrent and metastatic adrenocortical carcinoma.

OBJECTIVE: A review of all resections for recurrent or metastatic ACC was performed to identify patients who might benefit from a surgical approach, and to identify factors that might aid in prognosis among patients with metastatic disease. SUMMARY BACKGROUND DATA: Adrenocortical carcinoma (ACC) is a rare tumor, with frequent recurrences and metastases even after complete resection. Chemotherapy has limited efficacy, and surgical resection of metastatic ACC remains controversial. METHODS: A retrospective review was performed of all patients who underwent surgical intervention for metastatic ACC in a single tertiary center from 1977 to 2009. All available clinicopathologic data were analyzed to determine potential factors associated with response to treatment and survival. RESULTS: Fifty-seven patients underwent 116 procedures for recurrent or metastatic disease. Twenty-three resections were for liver metastases, 48 for pulmonary metastases, 22 for abdominal disease including local recurrences, and 13 were for metastases at other sites. Median and 5-year survivals from time of first metastasectomy were 2.5 years, and 41%, respectively. The median survival of patients with DFI <12 months was 1.7 years, compared to 6.6 years for patients with DFI >12 months (P = 0.015). Median survival for right versus left-sided primaries was 1.9 years versus 3.8 years (P = 0.03). Liver metastases were more common with right-sided primaries (67% vs. 41%, P = 0.05). Chemotherapy had no impact on survival. CONCLUSIONS: Resection of recurrent or metastatic ACC is safe, and may result in prolongation of survival in selected patients with DFI greater than 1 year.

Pulmonary resection for metastatic adrenocortical carcinoma: the National Cancer Institute experience.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare neoplasm with a high propensity for locoregional recurrences and distant metastases for which there are no effective systemic therapies. This study was undertaken to determine outcomes of patients undergoing pulmonary metastasectomy for ACC. METHODS: A single-institution retrospective review was performed of patients undergoing pulmonary metastasectomy for ACC from 1979 to 2010. RESULTS: Twenty-six patients underwent 60 pulmonary metastasectomies. Fifteen patients (58%) underwent unilateral thoracotomy, 6 (23%) had staged thoracotomies, and 5 (19%) underwent median sternotomy as the initial thoracic procedure. Median number and size of lesions were 6 and 2 cm, respectively. Twenty-three patients (88%) were rendered free of disease in the lung, and 14 (54%) were rendered completely free of disease. Median overall and 5-year actuarial survivals from initial pulmonary metastasectomy were 40 months and 41%, respectively, with a median potential follow-up of 120 months. Median recurrence-free survival (RFS) and 5-year RFS for ipsilateral thoracic recurrences were 6 months, and 25%, respectively. The median RFS in the contralateral thorax was 5 months. Time to first recurrence after adrenalectomy and T stage of the primary tumor, but not adjuvant or neoadjuvant chemotherapy, were associated with increased overall survival after pulmonary metastasectomy. CONCLUSIONS: This study represents the most comprehensive review of outcomes of patients undergoing pulmonary metastasectomy for ACC. Given the lack of effective systemic therapies, pulmonary metastasectomy may be beneficial in properly selected patients.

Association of operative time of day with outcomes after thoracic organ transplant.

CONTEXT: Recent emphasis on systems-based approaches to patient safety has led to several studies demonstrating worse outcomes associated with surgery at night. OBJECTIVE: To evaluate whether operative time of day was associated with thoracic organ transplant outcomes, hypothesizing that it would not be associated with increased morbidity or mortality. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of adult heart and lung transplant recipients in the United Network for Organ Sharing database from January 2000 through June 2010. Primary stratification was by operative time of day (night, 7 PM-7 AM; day, 7 AM-7 PM). MAIN OUTCOME MEASURES: Primary end points were short-term survival, assessed by the Kaplan-Meier method at 30, 90, and 365 days. Secondary end points encompassed common postoperative complications. Risk-adjusted multivariable Cox proportional hazards regression examined mortality. RESULTS: A total of 27,118 patients were included in the study population. Of the 16,573 who underwent a heart transplant, 8346 (50.36%) did so during the day and 8227 (49.64%) during the night. Of the 10,545 who underwent a lung transplant, 5179 (49.11%) did so during the day and 5366 (50.89%) during the night. During a median follow-up of 32.2 months (interquartile range, 11.2-61.1 months), 8061 patients (28.99%) died. Survival was similar for organ transplants performed during the day and night. Survival rates at 30 days for heart transplants during the day were 95.0% vs 95.2% during the night (hazard ratio [HR], 1.05; 95% confidence interval, 0.83-1.32; P = .67) and for lung transplants during the day were 96.0% vs 95.5% during the night (HR, 1.22; 95% CI, 0.97-1.55; P = .09). At 90 days, survival rates for heart transplants were 92.6% during the day vs 92.7% during the night (HR, 1.05; 95% CI, 0.88-1.26; P = .59) and for lung transplants during the day were 92.7% vs 91.7% during the night (HR, 1.23; 95% CI, 1.04-1.47; P = .02). At 1 year, survival rates for heart transplants during the day were 88.0% vs 87.7% during the night (HR, 1.05; 95% CI, 0.91-1.21; P = .47) and for lung transplants during the day were 83.8% vs 82.6% during the night (HR, 1.08; 95% CI, 0.96-1.22; P = .19). Among lung transplant recipients, there was a slightly higher rate of airway dehiscence associated with nighttime transplants (57 of 5022 [1.1%] vs 87 of 5224 [1.7%], P = .02). CONCLUSION: Among patients who underwent thoracic organ transplants, there was no significant association between operative time of day and survival up to 1 year after organ transplant.

Liver resection and ablation for metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease without effective chemotherapy treated most appropriately with resection. The aim of this study was to evaluate our experience with liver resection for metastatic ACC. METHODS: This study is a retrospective review of patients who underwent liver resection or radiofrequency ablation (RFA) for ACC from 1979 to 2009. RESULTS: A total of 27 patients were identified. Of the 27, 19 underwent liver resection. Of the 19, 10 had a single liver lesion, and 18 of 19 were rendered free of disease in the liver, although only 11 of 19 were rendered completely free of disease because of extrahepatic disease (EHD). Of the 19, 13 had synchronous EHD. Also, 6 of 17 remained disease free in the liver at a median follow-up of 6.2 years (status of 2 of 19 was unknown). Of the 27 patients, 8 underwent RFA, 7 of 8 became free of disease in the liver, and 5 of 7 had EHD. No patients responded to prior chemotherapy. Median overall survival and survival of patients who underwent liver resection or RFA were both 1.9 years (0.2-12 + years); 5-year actuarial survivals were 29% and 29%, respectively. Disease-free interval (DFI) greater than 9 months from primary resection was associated with longer survival (median 4.1 vs 0.9 years; P = .013). CONCLUSIONS: This study is a tertiary institution series of liver resection and RFA for ACC. Given the lack of effective systemic treatment options and the safety of resection and ablation, liver resection or RFA may be considered in selected patients with ACC metastatic to the liver especially with a long DFI.

Liver resections in metastatic gastric cancer.

BACKGROUND: The 5-year survival of patients receiving standard-of-care chemotherapy for metastatic gastric cancer (MGC) to the liver is <2%. This review examines the published data on liver resections for MGC and analyses the rationale for potentially aggressive surgical management. METHODS: A search of the PubMed and Scopus databases was used to identify studies published in English from 1990 to 2009 that reported on 10 or more patients who underwent liver resections for MGC. All available clinicopathologic data were analysed. In particular, we examined longterm survival and the characteristics of individuals surviving for >5 years. RESULTS: Nineteen studies reported on 436 patients. Median 5-year survival was 26.5% (range: 0-60%). Overall, 13.4% (48/358) of patients were alive at 5 years and studies with extended follow-up reported that 4.0% (7/174) of patients survived for >10 years. Overall in-hospital mortality was 3.5% (12/340 patients); however, the median mortality rate across the studies was 0%. No prognostic factor was found to be consistently statistically significant across these small studies. CONCLUSIONS: Despite the limitations of any analysis of retrospective data for highly selected groups of patients, it would appear that liver resections combined with systemic therapy for MGC can result in prolonged survival.

Pulmonary resection for metastatic gastric cancer.

INTRODUCTION: Sixteen percent of patients with gastric cancer will develop pulmonary metastases. Standard of care for these patients is systemic chemotherapy with a median survival of 6 months and a 5-year survival of only 2%. Our aim was to critically evaluate the published data on pulmonary resection for metastatic gastric cancer (MGC) and to analyze the potential rationale for surgical management to determine which patients may benefit from this approach. METHODS: The Pubmed and SCOPUS databases were queried for all studies reporting on pulmonary resections for MGC. All available clinicopathologic data were analyzed. RESULTS: Twenty-one studies from 1975 to 2008 reported 48 pulmonary resections in 43 patients including five repeat resections and four extrapulmonary metastasectomies. Eighty-two percent (34/43) of patients had solitary lesions with a median size of 24 mm (4-90 mm). Median time from gastrectomy to pulmonary resection was 35 months (0-120 months). At a median follow-up of 23 months, 15 of 43 (35%) patients were alive without disease, and two patients died without disease. Median survival was 29 months (3-84 months) after pulmonary metastasectomy and 65 months (5-180 months) after gastrectomy. Fifty-six percent (24/43) of patients had another recurrence at a median of 12 months (range: 6-48 months) after resection including 30% (13/43) of patients with pulmonary recurrences. Overall 5-year survival was 33%. CONCLUSIONS: Pulmonary metastasectomy for MGC can potentially result in long-term survival in a highly selected group of patients and should be considered for those who present with small, isolated lesions after a prolonged disease-free interval.

Consequences of adrenal venous sampling in primary hyperaldosteronism and predictors of unilateral adrenal disease.

BACKGROUND: In patients with primary hyperaldosteronism, distinguishing between unilateral and bilateral adrenal hypersecretion is critical in assessing treatment options. Adrenal venous sampling (AVS) has been advocated by some to be the gold standard for localization of the responsible lesion, but there remains a lack of consensus for the criteria and the standardization of technique. STUDY DESIGN: We performed a retrospective study of 114 patients with a biochemical diagnosis of primary hyperaldosteronism who all underwent CT scan and AVS before and after corticotropin (ACTH) stimulation. Univariate and multivariate analyses were performed to determine what factors were associated with AVS lateralization, and which AVS values were the most accurate criteria for lateralization. RESULTS: Eighty-five patients underwent surgery at our institution for unilateral hyperaldosteronism. Of the 57 patients who demonstrated unilateral abnormalities on CT, AVS localized to the contralateral side in 5 patients and revealed bilateral hyperplasia in 6 patients. Of the 52 patients who showed bilateral disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS for lateralization was the post-ACTH stimulation value. Factors associated with AVS lateralization included a low renin value, high plasma aldosterone-to plasma-renin ratio, and adrenal mass > or = 3 cm on CT scan. CONCLUSIONS: Because 50% of patients would have been inappropriately managed based on CT scan findings, patients with biochemical evidence of primary hyperaldosteronism and considering adrenalectomy should have AVS. The most accurate measurement for AVS lateralization was the post-ACTH stimulation value. Although several factors predict successful AVS lateralization, none are accurate enough to perform AVS selectively.

Thoracic metastasectomy for adoptive immunotherapy of melanoma: a single-institution experience.

OBJECTIVES: Although refractory to chemotherapy, metastatic melanoma may respond to adoptive immunotherapy. As novel treatments evolve, surgeons may be asked to perform metastasectomy not only for palliation or potential cure but also for isolation of tumor-infiltrating lymphocytes. This study was undertaken to examine outcomes of patients with melanoma undergoing thoracic metastasectomy in preparation for investigational immunotherapy. METHODS: A retrospective review identified 107 consecutive patients who underwent 116 thoracic metastasectomy procedures from April 1998 to July 2009. Indications for surgical intervention included procurement of tumor-infiltrating lymphocytes, rendering of patients to no evaluable disease status, palliation, and diagnosis. Response Evaluation Criteria in Solid Tumors criteria were used to assess tumor response. RESULTS: Thoracotomy, lobectomy, and video-assisted thoracoscopic surgery with nonanatomic resection were the most common procedures. Major complications included 1 death and 1 coagulopathy-induced hemothorax. Seventeen patients were rendered to no evaluable disease status. Virtually all patients with residual disease had tumor specimens cultured for tumor-infiltrating lymphocytes; approximately 70% of tumor-infiltrating lymphocyte cultures exhibited antitumor reactivity. Of the 91 patients with residual or recurrent disease, 24 (26%) underwent adoptive cell transfer of tumor-infiltrating lymphocytes, of whom 7 exhibited objective responses (29% response rate and 8% based on intent to treat). Rapid disease progression precluded tumor-infiltrating lymphocyte therapy in most cases. Actuarial 1- and 5-year survival rates for patients rendered to no evaluable disease status or receiving or not receiving tumor-infiltrating lymphocytes were 93% and 76%, 64% and 33%, and 43% and 0%, respectively. CONCLUSIONS: Relatively few patients currently having thoracic metastasectomy undergo adoptive cell transfer. Continued refinement of tumor-infiltrating lymphocyte expansion protocols and improved patient selection might increase the number of patients with melanoma benefiting from these interventions.

Prospective randomized trial evaluating mandatory second look surgery with HIPEC and CRS vs. standard of care in patients at high risk of developing colorectal peritoneal metastases.

BACKGROUND: The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance. METHODS/DESIGN: This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01095523.