Alexander S. Rosemurgy

Consensus statement of the consortium for laparoendoscopic single-site surgery

Inderbir S. Gill • Arnold P. Advincula • Monish Aron • Jeffrey Caddedu • David Canes • Paul G. Curcillo II • Mihir M. Desai • John C. Evanko • Tomasso Falcone • Victor Fazio • Matthew Gettman • Andrew A. Gumbs • Georges-Pascal Haber • Jihad H. Kaouk • Fernando Kim • Stephanie A. King • Jeffrey Ponsky • Feza Remzi • Homero Rivas • Alexander Rosemurgy • Sharona Ross • Philip Schauer • Rene Sotelo • Jose Speranza • John Sweeney • Julio Teixeira

Eating pathology before and after bariatric surgery: A prospective study

OBJECTIVE The objectives of the study were (1) to determine the prevalence of eating pathology in patients before bariatric surgery and at follow-up; (2) to assess the relationship of presurgical eating pathology to various measures of psychopathology; and (3) to assess the relationship between presurgical eating pathology and outcome. METHOD One hundred sixteen patients were evaluated prior to surgery and at follow-up an average of 5.5 years after surgery. RESULTS Preoperative binge eating occurred in 52% of patients, 16% met criteria for binge eating disorder, and 10% had the night eating syndrome. All three forms of presurgical eating pathology were statistically associated with cognitive distortions. At follow-up, 33% of patients were vomiting at least weekly. There was no relationship between presurgical eating pathology and weight outcome or presence of vomiting at follow-up. DISCUSSION Although postoperative vomiting usually does not represent purge behavior, it may represent failed attempts to binge.

Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis.

BACKGROUND Fulminant acute pancreatitis is a disease of complex origin that results in activation of several of the proinflammatory cytokines. Because interleukin-1 (IL-1) is an integral early component of the acute inflammatory process, the use of an IL-1 receptor antagonist (IL-1ra) was investigated in experimental acute pancreatitis to determine the therapeutic potential of proximal cytokine blockade and to further establish the role of inflammatory cytokines in the pathogenesis of acute pancreatitis. METHODS IL-1ra was administered in escalating doses either before or after acute edematous, necrotizing pancreatitis was induced in adult male mice by injection of cerulein. The severity of pancreatitis was quantified by serum amylase, lipase, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels, pancreatic wet weight, and blinded histologic grading. RESULTS Administration of medium (10 mg/kg) and high (100 mg/kg) doses of IL-1ra either before or after the induction of pancreatitis significantly decreased the expected rise in pancreatic wet weight, lipase, IL-6, and TNF-alpha (all, p < 0.01). Serum amylase was significantly reduced when IL-1ra was administered in either dosage before (p < 0.05), but not after, induction of pancreatitis. Pancreatic edema, necrosis, and inflammatory cell infiltrate were significantly diminished (p < 0.05) by histologic grading in all animals receiving medium or high doses of IL-1ra. Low doses of IL-1ra (1.0 mg/kg) had modest effects if given before, but no effect if given after, induction of pancreatitis. CONCLUSIONS The proinflammatory cytokines IL-6 and TNF-alpha are elevated during experimental acute pancreatitis and correlate well with the severity of local pancreatic destruction. Blockade of the cytokine cascade at the level of the IL-1 receptor before or soon after induction of pancreatitis significantly attenuates the rise in these cytokines and is associated with decreased severity of pancreatitis and reduced intrinsic pancreatic damage.

TNFerade Biologic, an Adenovector With a Radiation-Inducible Promoter, Carrying the Human Tumor Necrosis Factor Alpha Gene: A Phase I Study in Patients With Solid Tumors

PURPOSE TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy. PATIENTS AND METHODS TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 x 10(7) particle units [pu] to 4 x 10(11) pu) in patients with solid tumors being treated with radiation. RESULTS Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed. CONCLUSION This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.

Improved Outcome With Cytoreduction Versus Embolization for Symptomatic Hepatic Metastases of Carcinoid and Neuroendocrine Tumors

BackgroundFew data exist regarding outcomes after resection versus embolic treatment of symptomatic metastatic carcinoid and neuroendocrine tumors. The purpose of this study was to determine whether cytoreduction provides any benefit over embolic management of diffuse neuroendocrine tumors.MethodsA prospective database of 734 patients treated at our institution was retrospectively queried for symptomatic metastatic tumors treated with embolization or cytoreduction. Patients were compared with regard to pretreatment performance status, relief of symptoms, and survival.ResultsA total of 120 patients were identified: 59 undergoing embolization and 61 undergoing cytoreduction. Twenty-three patients had palliative cytoreduction (gross residual disease). Pretreatment performance status (Eastern Cooperative Oncology Group) was similar for both groups: .7 ± .70 (embolization) versus .8 ± .72 (cytoreduction; P = .27). Complete symptomatic relief was observed in 59% and partial relief in 32% of patients who underwent embolization, with a mean symptom-free interval of 22 ± 13.6 months. A total of 69% of patients who underwent cytoreduction had complete symptomatic relief, and 23% had partial relief (P = .08 vs. embolization). The mean duration of relief was 35 ± 22.0 months (P < .001 vs. embolization). The mean survival for the patients who underwent embolization was 24 ± 15.8 months versus 43 ± 26.1 months for those who underwent cytoreduction (P < .001). Survival in patients who underwent palliative cytoreduction was 32 ± 18.9 months (P < .001 vs. embolization), whereas it was 50 ± 27.6 months in patients who underwent curative resection (P < .001 vs. embolization; P < .001 vs. palliative).ConclusionsCytoreduction for metastatic neuroendocrine tumors resulted in improved symptomatic relief and survival when compared with embolic therapy in this nonrandomized study. Cytoreduction should be pursued whenever possible even if complete resection may not be achievable.

Outcome of Gastric Restriction Procedures: Weight, Psychiatric Diagnoses, and Satisfaction

Background: Weight losses following bariatric surgery have varied widely, depending on length of follow-up and various pre-surgical characteristics of patients undergoing surgery. Methods: One hundred thirty one patients had a detailed presurgical psychiatric evaluation. Patients were assessed clinically for 2 years after surgery and at follow-up a mean of 5.7 years after surgery. Results: Mean presurgical body mass index (BMI) was 52.9 kg/m2; therefore, many patients had ‘super obesity’. Two-thirds of the patients were located a mean of 5.7 years after surgery. The mean change in BMI at follow-up was 25% and the mean weight loss was 27%. One-third had excellent or good weight outcomes using the Griffen criteria. Five patients had died by follow-up. There was no relationship between age, gender, or fat content presurgically and weight loss at follow-up, although presurgical weight was associated with greater weight loss at follow-up. Weight regain began 2 years after surgery. There was no relationship between the presence or absence of a presurgical psychiatric diagnosis and weight loss at follow-up. There was also no relationship between the presence of a presurgical psychiatric diagnosis and various mental health parameters at follow-up. Satisfaction with the surgery was marginally associated with weight loss but significantly associated with improved mental and physical health. Conclusions: Mean weight losses were less than have been previously reported with gastric restriction procedures but the follow-up was longer than usually reported and many patients had ‘super obesity’ prior to surgery. The implications of ‘super obesity’ for weight loss are discussed.

Marimastat in patients with advanced pancreatic cancer: A dose-finding study

Patients with solid tumors, including carcinoma of the pancreas, express high levels of matrix metalloproteinases (MMP), and these enzymes are believed to be important for the growth, spread, and dissemination of most solid malignant tumors. Marimastat is the first orally available MMP inhibitor (MMPI) to be tested in humans and has been shown to inhibit the spread and growth of pancreatic cancer in animal models. The purpose of the present study was to define the toxicities, safety, and tolerance of various doses of marimastat and also to get an early indication of potential biologic activity in patients with advanced pancreatic cancer. The authors prospectively studied 64 patients with advanced carcinoma of the pancreas in whom standard treatments had failed. Eligible patients had a progressive rise in CA 19/9 levels of >25% over the 4-week period preceding their entry into the study. Patients were studied in groups of 8 to 10, with each group receiving escalating dosages ranging from 5 mg twice daily to 75 mg twice daily and 10 to 25 mg daily. Patients were considered for long-term (beyond 4 weeks) continuation treatment if clinical benefit, in the view of the investigator, was derived. Study endpoints were safety, tolerance, and changes in the rate of rise of CA 19/9, which were used as surrogate markers for disease progression. Marimastat was well tolerated. Musculoskeletal pain, stiffness, and tenderness emerged as dose-limiting toxicity. No other dose-related toxicities were observed. A reduced rate of rise of CA 19/9 was observed at dose levels of 5, 10, and 25 mg twice daily. The overall median survival was 160 days, with a 1-year survival of 21%. Marimastat was associated with an acceptable toxicity profile, and these preliminary data suggest that long-term oral administration is feasible and safe. Doses of 5, 10, and 25 mg twice daily were identified as the optimal doses to be tested in larger randomized studies.

A prospective trial of transjugular intrahepatic portasystemic stent shunts versus small-diameter prosthetic H-graft portacaval shunts in the treatment of bleeding varices.

OBJECTIVE The authors compare transjugular intrahepatic portasystemic stent shunts (TIPS) to small-diameter prosthetic H-graft portacaval shunts (HGPCS). SUMMARY BACKGROUND DATA Transjugular intrahepatic portasystemic stent shunts have been embraced as a first-line therapy in the treatment of bleeding varices due to portal hypertension, although they have not been compared to operatively placed shunts in a prospective trial. METHODS In 1993, the authors began a prospective, randomized trial to compare TIPS with HGPCSs. All patients had bleeding varices and had failed nonoperative management. Shunting was undertaken as definitive therapy in all. Failure of shunting was defined as an inability to accomplish shunting despite repeated attempts, unexpected liver failure leading to transplantation, irreversible shunt occlusion, major variceal rehemorrhage, or death. Mortality and failure rates were analyzed at 30 days (early) and after 30 days (late) using Fischers exact test. RESULTS There were 35 patients in each group, with no difference in age, gender, Childs class, etiology of cirrhosis, urgency of shunting, or incidence of ascites or encephalopathy between groups. In two patients, TIPS could not be placed despite repeated attempts. Transjugular intrahepatic portasystemic stent shunts reduced portal pressures from 32 +/- 7.5 mmHg (standard deviation) to 25 +/- 7.5 mmHg (p < 0.01), whereas HGPCS reduced them from 30 +/- 4.6 mmHg to 19 +/- 5.3 mmHg (p < 0.01; paired Students test). Irreversible occlusion occurred in three patients after placement of TIPS. Total failure rate after TIPS placement was 57%; after HGPCS placement, it was 26% (p < 0.02). CONCLUSIONS Both TIPS and HGPCS reduced portal pressure. Placement of TIPS resulted in more deaths, more rebleeding, and more than twice the treatment failures. Mortality and failure rates promote the application of HGPCS over TIPS.

Small bowel allografts: sequence of histologic changes in acute and chronic rejection

Using a rat model of accessory small bowel transplantation, the histologic sequence of both acute and chronic rejection in intestinal allograft rejection has been defined. Histologically, all allografts were normal for the first 5 postoperative days. Allografts with caval venous drainage were subject to acute rejection. By 6 to 7 days postoperatively, plasma cells and lymphocytes infiltrated the lamina propria of these grafts (phase I). By 8 to 9 days postoperatively, the cellular infiltration intensified and was associated with villous blunting and scattered epithelial sloughing (phase II). By the 10th day, complete mucosal destruction developed, with heavy transmural infiltration by lymphocytes, plasma cells, and polymorphonuclear leukocytes (phase III). This histologic end point of acute graft rejection was accompanied by death of the host. Grafts with portal venous drainage underwent a similar, although less rapid, sequence of histologic changes (phase I 6 to 9 days, phase II 10 to 13 days, phase III 13 or more days) resulting in graft fibrosis and encapsulation. Some variability was seen among different areas of a given circumferential cross section taken from grafts in phases I and II. Studying circumferential cross sections allowed correct classification into the appropriate phases.

Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease

BACKGROUND Chronic liver failure is associated with high signal abnormalities in the basal ganglia on T1-weighted magnetic resonance imaging of the brain. These abnormalities are strikingly similar to those seen following manganese intoxication. As dietary manganese is normally cleared by the liver, we hypothesize that hepatic dysfunction could lead to manganese overload and account for the MRI abnormalities seen in patients with chronic liver disease. METHODS We measured blood manganese concentrations in eleven patients with biopsy-proven hepatic cirrhosis and eleven healthy age and sex-matched controls. We also performed semi-quantitative measures of T1 signal abnormalities on MRI in the patients with chronic liver disease. RESULTS Patients with cirrhosis had significantly higher blood manganese concentrations (20.6 +/- 10.2 mcg/L) than controls (7.2 +/- 2.7, p = .0013). In addition, semi-quantitative scores of T1-weighted signal hyperintensity on MRI correlated with blood manganese concentration in patients with cirrhosis (r = .65, p = .029). CONCLUSIONS These findings demonstrate that chronic liver disease is associated with manganese overload and suggest that manganese is responsible for the T1-weighted signal hyperintensity seen on MRI of patients with liver disease. As manganese intoxication is known to cause parkinsonism and an encephalopathy similar to those which occur with chronic liver disease, it is possible that manganese toxicity contributes to the development of these symptoms in liver damaged patients and that therapies which prevent or reduce manganese overload may have clinical benefit.