Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Local production of lactate, ribose phosphate, and amino acids within human triple-negative breast cancer.

BACKGROUND: Upregulated glucose metabolism is a common feature of tumors. Glucose can be broken down by either glycolysis or the oxidative pentose phosphate pathway (oxPPP). The relative usage within tumors of these catabolic pathways remains unclear. Similarly, the extent to which tumors make biomass precursors from glucose, versus take them up from the circulation, is incompletely defined. METHODS: We explore human triple negative breast cancer (TNBC) metabolism by isotope tracing with [1,2-13C]glucose, a tracer that differentiates glycolytic versus oxPPP catabolism and reveals glucose-driven anabolism. Patients enrolled in clinical trial NCT03457779 and received IV infusion of [1,2-13C]glucose during core biopsy of their primary TNBC. Tumor samples were analyzed for metabolite labeling by liquid chromatography-mass spectrometry (LC-MS). Genomic and proteomic analyses were performed and related to observed metabolic fluxes. FINDINGS: TNBC ferments glucose to lactate, with glycolysis dominant over the oxPPP. Most ribose phosphate is nevertheless produced by oxPPP. Glucose also feeds amino acid synthesis, including of serine, glycine, aspartate, glutamate, proline and glutamine (but not asparagine). Downstream in glycolysis, tumor pyruvate and lactate labeling exceeds that found in serum, indicating that lactate exchange via monocarboxylic transporters is less prevalent in human TNBC compared with most normal tissues or non-small cell lung cancer. CONCLUSIONS: Glucose directly feeds ribose phosphate, amino acid synthesis, lactate, and the TCA cycle locally within human breast tumors.

Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.

Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFß) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFß1 knockdown was 100%, and TGFß2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC.

Improved pancreatic islet isolation outcome in autologous transplantation for chronic pancreatitis.

Total or partial pancreatectomy followed by autologous islet transplantation is a therapeutic option for the treatment of refractory chronic pancreatitis (CP). Maximization of islet yields from fibrotic and inflamed organs is crucial for prevention of posttransplant diabetes. We adapted technical advancements developed for islet allotransplantation toward islet autotransplantation. Eight patients (two men, six women; ages 24-58 years) underwent total (n = 7) or partial (n = 1) pancreatectomy for the treatment of CP refractory to maximal medical management. Pancreata were preserved in UW solution (UW group) in initial three cases and the last five pancreata were preserved with pancreatic ductal injection followed by ET-Kyoto/oxygenated PFC solutions (DI+TLM group). Islets were isolated by modified Ricordi method and were purified only in one case. All islet infusions were performed under general anesthesia via direct vein injection into the portal venous system with pressure monitoring. Total islet yields (129,314 ± 51,627 vs. 572,841 ± 116,934 IEQ, p < 0.04), islet yield/pancreas weight (1,233 ± 359 vs. 6,848 ± 847 IEQ/g, p < 0.003), and islet yield/patient body weight (1,951 ± 762 vs. 7,305 ± 1,531 IEQ/kg, p < 0.05) were significantly higher in the DI+TLM group when compared to the UW group. Pellet size was also higher (5.3 ± 0.3 vs. 13.5 ± 3.4 ml) in the DI+TLM group, suggesting that this method of preservation effectively protected pancreatic tissue against autolysis. First month posttransplant basal C-peptide and the secretory unit of islet transplant objects (SUITO) index were also higher in the DI+TLM group when compared to the UW group (2.0 ± 0.3 vs. 1.4 ± 0.4 ng/ml and 42.6 ± 12.7 vs. 14.6 ± 5.6, respectively). There were no technical complications related to the infusion. Our results suggest that higher islet yields can be achieved even from chronically inflamed and fibrotic organs using DI+TLM. The techniques applied for islet isolations from normal pancreata are showing promise for fibrotic pancreata from CP patients.

Pneumocystis cell wall beta-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells.

BACKGROUND: Respiratory failure secondary to alveolar inflammation during Pneumocystis pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with Pneumocystis infection predicts severity of the infection and death. Several previous studies indicate that airway epithelial cells release the neutrophil chemoattractant proteins, MIP-2 (rodents) and IL-8 (humans), in response to Pneumocystis and purified Pneumocystis cell wall beta-glucans (PCBG) through the NF-kappaB-dependent pathway. However, little is known about the molecular mechanisms that are involved in the activation of airway epithelium cells by PCBG resulting in the secretion of IL-8. METHOD: To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo- cells, a human airway epithelial cell line. RESULTS: Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-kappaB and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for beta-glucans in human airway epithelial cells. Preincubation of the cells with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) a potent inhibitor of the glycosphingolipids synthesis, prior to PCBG stimulation, significantly decreased IL-8 production. CONCLUSION: These data indicate that PCBG activates calcium dependent MAPK signaling resulting in the release of IL-8 in a process that requires glycosphingolipid for optimal signaling.

Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study.

BACKGROUND: Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD). Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. METHODS: The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells). The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke. RESULTS: In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired. CONCLUSIONS: These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells. Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD.

Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer.

Circulating tumor cells (CTCs) have been detected in patients with a variety of metastatic cancers, including colorectal, and may be a significant prognostic variable in patients with liver metastases. This prospective study involved 20 patients (13 men and 7 women) undergoing surgical excision or ablation of liver metastases from a colon or rectal primary tumor. Four 7.5-mL vials of peripheral blood were drawn preoperatively, 2 weeks postoperatively, and during mobilization of the liver or at the beginning of radiofrequency ablation. The samples were centrifuged, the sera combined to a final volume of 7.5 mL, and the CellSearch system used to identify circulating epithelial cells. A CTC count >2 was defined as clinically significant. Preoperative CTC levels averaged 3.9 (range, 0-56) and were significant in 2 patients (10%). Postoperative CTC levels averaged 1.0 (in 18 patients; range, 0-9) and were significant in 1 patient (5%). Intraoperative CTC levels averaged 28.2 (range, 0-315) and were significant in 10 patients (50%). At a median follow-up of 11.5 months (range, 5-25), 6 patients (30%) were dead of disease, 6 patients (30%) showed no evidence of disease, and 8 patients (40%) were alive with disease. Statistical analysis suggested a correlation between the presence of postoperative CTCs and survival (P = 0.036), as well as with disease-free survival (P = 0.036). Thus, CTCs are present and quantifiable in many patients with colorectal hepatic metastases, and peripheral CTCs are present in greater quantity during intraoperative liver manipulation. This preliminary study suggests a relationship between the presence of postoperative CTCs and outcome. Further accrual and follow-up of this group is needed to confirm these findings.

Clinical utility of breast magnetic resonance imaging in patients presenting with primary breast cancer.

Since magnetic resonance imaging (MRI) of the breast has been shown to be sensitive in identifying the extent of the primary tumor and other foci of cancer, we examined its clinical utility in the surgical management of breast cancer patients. From January 2004 to April 2007, 117 patients with newly diagnosed breast cancer underwent bilateral MRI prior to definitive surgical management. Additional lesions were found in 27 patients (23.1%) in the ipsilateral breast and 19 patients (16.2%) in the contralateral breast. Twelve patients (10.3%) had more than one new lesion identified. Six patients (5.1%) had a larger area of tumor than detected by mammography or ultrasound. Additional biopsies were performed in 27 patients (23.1%). Additional foci of cancer were identified in 17 patients (14.5%): 12 (10.2%) in the ipsilateral breast and 5 (4.3%) in the contralateral breast. This information changed the clinical management in 23 cases (19.7%). Further studies are needed to confirm the benefits of MRI relative to its costs and to further identify the appropriate patients to undergo this imaging procedure.

p53 therapy in a patient with Li-Fraumeni syndrome.

Li-Fraumeni syndrome is an autosomal dominant disorder that greatly increases the risk of developing multiple types of cancer. The majority of Li-Fraumeni syndrome families contain germ-line mutations in the p53 tumor suppressor gene. We describe treatment of a refractory, progressive Li-Fraumeni syndrome embryonal carcinoma with a p53 therapy (Advexin) targeted to the underlying molecular defect of this syndrome. p53 treatment resulted in complete and durable remission of the injected lesion by fluorodeoxyglucose-positron emission tomography scans with improvement of tumor-related symptoms. With respect to molecular markers, the patient's tumor had abnormal p53 and expressed coxsackie adenovirus receptors with a low HDM2 and bcl-2 profile conducive for adenoviral p53 activity. p53 treatment resulted in the induction of cell cycle arrest and apoptosis documented by p21 and cleaved caspase-3 detection. Increased adenoviral antibody titers after repeated therapy did not inhibit adenoviral p53 activity or result in pathologic sequelae. Relationships between these clinical, radiographic, and molecular markers may prove useful in guiding future application of p53 tumor suppressor therapy.

Management of ampullary lesions.

Adenomatous lesions of the ampulla of Vater are relatively rare neoplasms that raise many questions regarding standard management. Adenocarcinoma often will be found in ampullary lesions and should be treated by pancreaticoduodenectomy (PD). Benign-appearing adenomas may be treated by PD, transduodenal ampullectomy (AMP), or endoscopic ampullectomy (EA). AMP and EA have decreased morbidity and mortality compared with PD but are limited by concerns for appropriate resection margins, high recurrence rates, and the need for surveillance endoscopy or additional procedures. Preoperative endoscopic biopsies should be obtained to identify carcinoma, but they have high false-negative rates and cannot be relied upon to rule out malignancy. Intraoperative frozen section evaluation should be requested routinely during AMP, with conversion to PD if carcinoma is demonstrated. The gold standard management of benign adenomas has not been clarified, but the goal for all treatment modalities is complete resection. Patients with familial adenomatous polyposis may be exceptions to this, and routine surveillance endoscopy and biopsy with selective resection have been advocated by some as an alternative to complete resection. Adjuvant chemoradiation has a very limited role in the treatment of ampullary carcinoma and ideally should be offered in the setting of a clinical trial. Metastatic and locally advanced, unresectable lesions may be palliated by surgical or endoscopic bypass, as well as by celiac plexus blockade.

The utility of capsule endoscopy and its role for diagnosing pathology in the gastrointestinal tract.

BACKGROUND: Capsule endoscopy (CE) is a new device that enables visualization of areas of the small bowel that were previously inaccessible through other noninvasive procedures. The purpose of this study is to evaluate this new diagnostic tool and its efficacy in finding occult GI tract pathology. METHODS: A single-institution retrospective review was completed on patients undergoing CE from January 2002 to September 2004. Data evaluated included indications for CE, results of previous studies, CE findings, and complications of the CE study. RESULTS: A total of 702 CE studies in 652 patients were performed during the study period. Suspicious GI bleeding presenting as anemia, guaiac positive stools, or history of gross bleeding were the most common reasons to perform CE (75.8%). Other indications included abdominal pain (11.5%), diarrhea (3.1%), or others (9.5%). In studies performed for GI bleeding (N = 532), a source was found in 49.3% of CE studies. Arteriovenous malformation (AVM) was the most common reported finding (43.9%), followed by ulcer (24.1%), colon or gastric pathology (14.1%), mass/tumor (9.1%), and stricture (6.9%). Patients with abdominal pain (n = 81) had findings 46.9% of the time including edema/ulcer (47.4%), stricture (10.5%), mass/tumor (26.3%), gastric pathology (10.5%), AVM (2.6%), or sprue (2.6%). Patients with diarrhea (n = 22) had findings 45.5% of the time including edema/ulcer (75%), mass/tumor (12.5%), or sprue (12.5%). A total of 66 patients underwent operative exploration after a CE study at this institution either because of the observed findings or for other reasons. There were 12 (1.7%) CE studies in which the capsule was retained and required surgical removal. Pathology at the retention site included benign strictures or adhesions (n = 9, 75%), Crohn's stricture (n = 1, 8.3%) carcinoid tumor (n = 1, 8.3%), and villous adenoma (n = 1, 8.3%). CONCLUSIONS: CE is an accurate study to locate abnormalities in the GI tract that may have either been missed by previous diagnostic studies or cannot be observed through other non-invasive means. When used for diagnostic challenges such as GI bleeding with no apparent source, CE can be helpful in guiding surgical decisions in patients and thus should be integrated as part of the diagnostic workup.

Disruption of parallel and converging signaling pathways contributes to the synergistic antitumor effects of simultaneous mTOR and EGFR inhibition in GBM cells.

Elevated epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) signaling are known to contribute to the malignant properties of glioblastoma multiforme (GBM), which include uncontrolled cell proliferation and evasion of apoptosis. Small molecule inhibitors that target these protein kinases have been evaluated in multiple clinical trials for cancer patients, including those with GBM. Here we have examined the cellular and molecular effects of a combined kinase inhibition of mTOR (rapamycin) and EGFR (EKI-785) in U87 and U251 GBM cells. Simultaneous treatment with rapamycin and EKI-785 results in synergistic antiproliferative as well as proapoptotic effects. At a molecular level, rapamycin alone significantly decreases S6 phosphorylation, whereas EKI-785 alone promotes substantially reduced signal transducer and activator of transcription (STAT3) phosphorylation. Treatment with rapamycin alone also increases Akt phosphorylation on Ser-473, but this effect is blocked by a simultaneous administration of EKI-785. Individually, EKI-785 diminishes while rapamycin promotes the binding of the translation inhibitor eukaryotic initiation factor 4E binding protein (4EBP1) to the eukaryotic translation initiation factor 4E (eIF4E). In spite of these opposing effects, the highest level of 4EBP1-eIF4E binding occurs with the combination of the two inhibitors. These results indicate that the inhibition of EGFR and mTOR has distinct as well as common signaling consequences and provides a molecular rationale for the synergistic antitumor effects of EKI-785 and rapamycin administration.

Optimizing outcomes in bariatric surgery: outpatient laparoscopic gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment of severe obesity and one of the fastest growing surgical procedures in the United States. METHODS: A single institution prospective database of patients undergoing outpatient laparoscopic (lap) RYGB over a 3-year period was reviewed. Study end points included hospital discharge within 23 hours, 30-day hospital readmission rate, early (<30 day) and late complication rates, and 30-day perioperative mortality. Variables assessed included surgeon experience, patient demographics, comorbidities, operative time, Roux limb pathway, intraoperative steroid bolus, and use of dexmedetomidine. RESULTS: Two thousand consecutive patients undergoing outpatient lap RYGB were identified, and 84% (n = 1669) were discharged within 23 hours. Of these, 1.7% (n = 34) were readmitted within 30 days. The overall early and late complication rates were 1.9% (n = 38) and 4.3% (n = 86), respectively. The 30-day mortality rate was 0.1% (n = 2), and neither patient was discharged before death. Univariate analysis demonstrated surgeon experience (<50 cases), age (<56 years), body mass index (<60 kg/m), weight (400 lbs), comorbidities (<5), and intraoperative steroid bolus as predictive of successful outpatient discharge. Multivariate analysis revealed surgeon experience, comorbidities, body mass index, and steroid bolus as predictive variables. CONCLUSIONS: These data suggest that outpatient lap RYGB can be performed with acceptable perioperative complication rates, hospital readmission, and mortality rates. Surgeon experience, careful patient selection, and the use of intraoperative steroid bolus predicted optimal patient outcomes.

A prospective randomized trial demonstrating valved implantable ports have fewer complications and lower overall cost than nonvalved implantable ports.

BACKGROUND: The purpose of the current study was to evaluate whether a totally implanted valved subcutaneous port system would have fewer complications as compared to a standard nonvalved port. METHODS: Study subjects requiring port placement were randomized to receive a valved port (PASV; Boston Scientific, Natick, MA) or a nonvalved port (BardPort; Bard Accesss Systems, Salt Lake City, UT). Each port was placed with standard operative technique. Difficulty with blood return, excess time spent accessing the port, and required interventions were reported over the initial 180 days of port usage. RESULTS: Seventy-three patients were randomized to receive either a valved port (n = 37) or a nonvalved port (n = 36). No major complications were identified from port placement, and there were no differences in rates of infection between the 2 ports. A reported inability to withdraw blood was noted in the valved port group on 21 of 364 (5.8%) port accessions and in the nonvalved port group on 37 of 341 (11%) accessions (P = 0.02). Significantly more total time was spent ensuring adequate blood draw from nonvalved ports as opposed to valved ports (750 minutes vs. 1545 minutes, respectively) (P <0.03). CONCLUSIONS: This study revealed that the PASV valved port is associated with significantly fewer instances of poor blood return and less nursing access time, indicating that a port with a PASV valve may be superior to a nonvalved device.

Neuroendocrine Tumors of the Pancreas.

Neuroendocrine tumors (NETs) are rare tumors of the endocrine pancreas that require a high degree of suspicion for timely diagnosis. Diagnosis is often delayed due to the nonspecific and intermittent presentation of symptoms. As many as 45% to 55% of tumors are nonfunctional and are typically diagnosed secondary to mass effect related symptoms or found incidentally. Functional tumors often are symptom specific and are diagnosed at an earlier stage than nonfunctional tumors. The challenging aspects of treating NETs are localizing the tumors, treating extensive or metastatic disease, and palliating symptoms. Most NETs have an indolent course, and aggressive multimodality treatment is often indicated and encouraged.

The role of pelvic exenteration in the management of recurrent rectal cancer.

BACKGROUND: Use of extirpative surgery in the setting of recurrent rectal cancer is controversial given the poor overall outcome of such patients and the morbidity associated with exenteration. METHODS: A retrospective review of patients treated for recurrent rectal cancer from 1990 to 2002 was performed. RESULTS: Twenty-two patients underwent pelvic exenteration. Seventeen underwent potentially curative resection, 5 were for palliation only. There was 1 operative death. Fifteen suffered at least 1 complication; 9 suffered multiple complications. Ten patients required readmission to the hospital. The overall disease-free interval was 11 months. Potentially curative and palliative resections resulted in median survivals of 20.4 and 8.4 months, respectively (P = 0.049). CONCLUSIONS: While patients may derive oncologic and palliative benefits from exenteration, the price in terms of operative morbidity remains high. Newer measures of operative morbidity are necessary to better appraise the value of this radical approach to recurrent rectal cancer.