Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Lamivudine treatment for hepatitis B in dialysis population : case reports and literature review.

It is well known that chronic hepatitis B plays a detrimental role on survival in patients on long-term dialysis and after kidney transplantation. The advent of nucleos(t)ide analogues offers the opportunity to change the natural history of hepatitis B in patients with chronic kidney disease. We report our experience on lamivudine use in two patients with HBV-related liver disease on long-term dialysis. At the beginning, both the patients were HBsAg positive and HBeAg positive with high viral load; after long-term lamivudine therapy, clearance of HBV viremia from serum was observed in both. Raised aminotransferase levels fell into the normal range and one patient experienced clearance of HBsAg by anti-HBV therapy. Tolerance to lamivudine was satisfactory and lamivudine resistance was not detected. Information on antiviral therapy with lamivudine in HBsAg positive patients on regular dialysis is extremely limited; we identified by an extensive review of the literature five studies with a total of 38 unique patients, most of them being renal transplant candidates. Lamivudine proved to be effective as the clearance of HBV viraemia from serum ranged between 56% and 100% ; the clearance of HBeAg from serum was less evident (between 37.5% and 100%). No significant side-effects due to lamivudine were observed and emergence of lamivudine-resistant strains was observed in two (5%) patients. Only a minority of patients experienced HBsAg loss (13%). We conclude that anti-HBV treatment with a nucleoside analogue such as lamivudine gives satisfactory results in some patients on long-term dialysis. Clinical trials are in progress to assess efficacy and safety of last-generation nucleos(t)ide analogues for anti-HBV therapy in dialysis population.

Musculoskeletal findings in obese subjects before and after weight loss following bariatric surgery.

OBJECTIVE: To determine the point prevalence of painful musculoskeletal (MSK) conditions in obese subjects before and after weight loss following bariatric surgery. DESIGN: Longitudinal, interventional, unblended. SUBJECTS: Forty-eight obese subjects (47 women, one man, mean age 44+/-9 years; mean body mass index (BMI) 51+/-8 kg/m(2)) recruited from an academic medical center bariatric surgery program. MEASUREMENTS: Comorbid medical conditions; MSK findings; BMI; Western Ontario McMaster Osteoarthritis Index (WOMAC) for pain, stiffness and function; and SF-36 for quality of life. METHODS: Consecutive subjects were recruited from the University Hospitals of Cleveland Bariatric Surgery Program. Musculoskeletal signs and symptoms and non-MSK comorbid conditions were documented at baseline and at follow-up. SUBJECTS completed the SF-36 and the WOMAC questionnaires. Analyses were carried out for each MSK site, fibromyalgia syndrome (FMS) and for the cumulative effect on the spine, upper and lower extremities. The impact of change in comorbid medical conditions, BMI, physical and mental health domains of the SF-36 on the WOMAC pain subscale score was evaluated. SF-36 outcomes were compared to normal published controls. RESULTS: Forty-eight subjects were available for baseline and a follow-up assessment 6-12 months after gastric bypass surgery. They lost an average of 41+/-15 kg and the mean BMI decreased from 51+/-8 to 36+/-7 kg/m(2). Baseline comorbid medical conditions were present in 96% before surgery and 23% after weight loss. There was an increased prevalence of painful MSK conditions at baseline compared to general population frequencies. Musculoskeletal complaints had been present in 100% of obese subjects before, and 23% after weight loss. The greatest improvements occurred in the cervical and lumbar spine, the foot and in FMS (decreased by 90, 83, 83 and 92%, respectively). Seventy-nine percent had upper extremity MSK conditions before and 40% after weight loss. Before surgery, 100% had lower extremity MSK conditions and only 37% did after weight loss. The WOMAC subscale and composite scores all improved significantly, as did the SF-36((R)). Change in BMI was the main factor impacting the WOMAC pain score. CONCLUSION: There was a higher frequency of multiple MSK complaints, including non-weight-bearing sites compared to historical controls, before surgery, which decreased significantly at most sites following weight loss and physical activity. These benefits may improve further, as weight loss may continue for up to 24 months. The benefits seen with weight loss indicate that prevention and treatment of obesity can improve MSK health and function.

Bariatric surgery in the field of gynecological oncology.

Obesity has become a foremost health problem. More than half of US adults are overweight or obese. This has been due to sedentary lifestyles, increased intake of refined carbohydrates, and fat-rich diets. Obese women are particularly susceptible to a variety of health risks including cancer, especially cancers of the breast, endometrium, and colon. Bariatric surgery appears to be a viable option for the treatment of severe obesity. As the role of surgery in the management of this condition becomes increasingly frequent, it is important for gynecological oncologists to recognize the potential for gynecological malignancies in this patient population.

Crohn's disease of the foregut.

Historically, Crohn's disease of the esophagus, stomach, and duodenum has been reported only rarely. With more frequent use of upper endoscopy, however, upper gastrointestinal involvement has been found to be more common than previously suspected. The surgeon with an interest in Crohn's disease needs to be familiar with all areas that are potentially affected in this perplexing and sometimes devastating disease. This article examines the literature on foregut Crohn's and discusses the incidence, clinical manifestations, diagnosis, medical management, surgical indications, and operative techniques.

Intracavitary urokinase for enhancement of percutaneous abscess drainage: phase II trial.

OBJECTIVE: To evaluate the effectiveness of urokinase as an abscess-cavity irrigant during percutaneous abscess drainage. SUBJECTS AND METHODS: In a prospective study, approved by the Food and Drug Administration and the review board at our institution, urokinase and saline were used as abscess-cavity irrigants. In the study group of 42 patients, half the patients were randomly placed into the urokinase group and the other half were placed into the control saline group. Doses used varied with the size of the abscess. Data collected from patient charts were evaluated with standard statistical methods. RESULTS: The results indicate definite benefits of the urokinase treatment. The length of stay (p = 0.0025) and treatment costs (p = 0.0021) were significantly less for the urokinase group. Other clinical parameters, including the febrile course, elevated WBC, and days of drainage, trended in a favorable fashion. CONCLUSION: Urokinase injected intracavitarily is an effective technique for shortening the treatment time and improves the clinical course for patients treated with percutaneous drainage techniques.

Laparoscopic implant instrument for the placement of intramuscular electrodes in the diaphragm.

We have developed an endoscopic instrument that will allow a surgeon to safely, dependably and accurately place intramuscular (IM) electrodes in the diaphragm. This instrument has been used to implant 28 IM electrodes in the diaphragms of eleven acute and four chronic dogs. All electrodes achieved full activation of the diaphragm muscle, producing tidal volumes up to 130% V(TCRIT), the critical volume necessary for basal ventilatory support, with unilateral stimulation. The surgeon is able to control the angle of the IM electrode insertion needle, which enables the needle to approach the diaphragm at an angle that is parallel to the surface of the muscle. This insures good control over the depth of needle penetration into the muscle, which greatly reduces the risk of accidentally passing the needle through the diaphragm and entering the thorax. Endoscopic placement of IM electrodes into the diaphragm opens opportunities to provide cost effective negative pressure ventilation to patients who are unable to effect sufficient ventilation by central nervous system (CNS) control of respiration.

Laparoscopic placement of electrodes for diaphragm pacing using stimulation to locate the phrenic nerve motor points.

Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.

The role of fluorodeoxyglucose and positron emission tomography in the evaluation of pancreatic disease.

BACKGROUND: The difficulties involved in the timely and accurate diagnosis of pancreatic disease are well known. The usual imaging modalities usually identify abnormalities but may not always differentiate malignancy from other condition such as scar tissue or chronic inflammation. The purpose of our study was to determine if fluorodeoxyglucose positron emission tomography (FDG PET) can accurately diagnose pancreatic disease. METHODS: The records of 15 patients presenting with pancreatic disease were retrospectively reviewed. The diagnosis suspected by imaging modalities was compared with the final tissue diagnosis. Two patients were excluded because no tissue was obtained. RESULTS: Adenocarcinoma was diagnosed in 9 patients. A mass consistent with this diagnosis was seen in 8 of 9, 6 of 9, 6 of 8, and 5 of 5 patients by PET, computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS), respectively. Chronic pancreatitis (CP) was diagnosed in 2 patients. The unique appearance on FDG PET made the diagnosis in both these patients. Both patients with CP were thought to have a malignancy by CT and EUS and 1 of 2 by ERCP. Neuroendocrine tumors were diagnosed in 2 other patients. One of 2 was seen by FDG PET and both by CT. CONCLUSIONS: FDG PET can accurately differentiate a pancreatic adenocarcinoma from chronic pancreatitis in a patient with a suspicious pancreatic mass. Thus, FDG PET may help in establishing a diagnosis and subsequently managing a patient with pancreatic disease.

Endoscopic ultrasonography versus cholangiography for the diagnosis of choledocholithiasis.

BACKGROUND: Choledocholithiasis is a major source of morbidity among patients undergoing cholecystectomy for symptomatic gallstones. There is no consensus on the best approach to diagnosing bile duct stones. We compared the safety, accuracy, diagnostic yield, and cost of EUS- and ERCP-based approaches. METHODS: Sixty-four consecutive pre- and post-cholecystectomy patients referred for endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis were prospectively evaluated in a blinded fashion. All were stratified into risk groups using predefined criteria. Endoscopic ultrasonography (EUS) and ERCP were sequentially performed by two endoscopists. RESULTS: The success rates of EUS and ERCP were 98% and 94%, respectively. The accuracy of EUS for diagnosing choledocholithiasis was 94%. EUS provided an additional or alternative diagnosis to bile duct stones in 21% of patients. The complication rate of EUS was significantly lower than diagnostic ERCP. An EUS-based strategy costs less than diagnostic ERCP in patients with low, moderate, or intermediate risk. CONCLUSIONS: EUS is comparably accurate, but safer and less costly than ERCP for evaluating patients with suspected choledocholithiasis. It is useful in patients with an increased risk of having common bile duct stones based on clinical criteria and those with contraindications for or prior unsuccessful ERCP. EUS may enable selective performance of ERCP and improve the cost-effectiveness of diagnosing choledocholithiasis.

Cholescintigraphy in the diagnosis of bile leak after laparoscopic cholecystectomy.

Bile leaks are a recognized complication of laparoscopic cholecystectomy (LC). Different diagnostic approaches have been employed when this condition is suspected. We present our experience with cholescintigraphy as a primary imaging technique for the detection of bile leaks. The medical records of all patients who had cholescintigraphy after LC during a 58-month period were reviewed. Patients were selected for cholescintigraphy if fever unusual abdominal pain, nausea, vomiting, or jaundice were present beyond 36 hours after LC. Bile leaks were suspected in 25 out of 744 patients (3.36%). The nuclear imaging study was true positive in 7 cases and true negative in 18 cases, for a 100 per cent sensitivity, specificity, and accuracy in the detection of bile leaks. Five patients were treated by endoscopic retrograde cholangiopancreatography with stent and/or sphincterotomy, and two patients underwent exploratory laparotomy. None of the patients who underwent endoscopic retrograde cholangiopancreatography required peritoneal drainage. We conclude that cholescintigraphy is sensitive and accurate in the diagnosis of bile leaks. Its use along with a high index of suspicion of a bile leak may prevent the development of bile peritonitis.

Staple penetration and staple histological response for attaching an epimysial electrode onto the abdominal surface of the diaphragm using a laparoscopic approach.

BACKGROUND: Laparoscopic stapling was found to be a viable option for attaching epimysial electrodes onto the abdominal surface of the diaphragm. Stapling was preferable to suturing due to its simplicity and speed. METHODS: Of the two staplers tested in this study, the Ethicon Endopath was preferred over the Autosuture Endo Hernia because the staples did not penetrate the diaphragm when an electrode tab thickness greater than 0.75 mm was used. RESULTS: The thickness of the electrode tab was an important factor in determining staple penetration but large variation in penetration depth indicated that other factors may also play a role. An electrode tab thickness of 1.0-1.25 mm was suggested to minimize the risk of diaphragm perforation. CONCLUSIONS: The histological reaction to staples implanted up to 14 months was unremarkable, reflecting the safety of laparoscopic staples for permanently anchoring electrodes on the diaphragm.

Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer.

Aberrant crypt foci are putative preneoplastic lesions found in the colons of carcinogen-treated rodents and at an increased frequency in humans at increased risk for colon cancer. There is a strong association between aberrant crypt foci and colon cancer, including many shared phenotypic and genetic alterations. The aim of this study is to present further evidence of a relationship between aberrant crypt foci and colon cancer in humans. Multiple aberrant crypt foci from a single patient were identified in unembedded colonic mucosa. Histological sections of the aberrant crypt foci and adjacent mucosa were evaluated for dysplasia, proliferative activity, and pigment-laden macrophages that were characterized with histochemical techniques. The first patient with sporadic colon cancer identified with aberrant crypt foci with carcinoma in situ is described. It is interesting that this 99-year-old patient had multiple carcinomas in situ, pseudomelanosis coli, and two metachronous colon cancers. These data lend support to the hypothesis that aberrant crypt foci are precursors of some colon cancers.

Laparoscopic surgery in a small animal model. A simplified technique of retroperitoneal dissection in the rat.

BACKGROUND: An adequate laparoscopic small-animal model would benefit surgical oncologic research. Immunobiologic data and reagents available for the rodent make them an ideal species. We developed a simple, inexpensive, reproducible technique for laparoscopic surgery in rodents. METHODS: Carbon dioxide pneumoperitoneum is achieved in anesthetized animals. Through a 0.5-cm midline incision a 4.8-mm bronchofiberscope is inserted into the peritoneal cavity and secured with a purse-string suture (PSS). Three additional PSSs are made to introduce the dissectors. Under fiberscopic vision, a blunt dissection of the retroperitoneum exposes the inferior vena cava and aorta. Necropsy 24 h after verifies the adequacy of dissection. RESULTS: Eighteen animals survived. The only death resulted from bleeding. Mortality was 5.26%. Surgical time was 24.72 +/- 8.93 min with all animals active 2 h postlaparoscopy. CONCLUSIONS: Laparoscopic surgery (LS) can be done inexpensively without sophisticated equipment. The rodent is ideal for examining the immunologic consequences of laparoscopic surgery and pneumoperitoneum.

Open versus laparoscopic surgery: a comparison of natural antitumoral cellular immunity in a small animal model.

The scope of laparoscopic surgery has extended to the treatment of cancer. The immunological impact of laparoscopic surgery as compared with open surgery has not been well characterized. A paucity of information is available about differences or similarities of these two methods regarding natural antitumoral cellular immunity, namely, natural killer cell cytotoxicity. This study compared the activity of natural killer cells in rats subjected to pneumoperitoneum, open dissection of the retroperitoneum, and laparoscopic dissection of the retroperitoneum. When compared to control animals, rats subjected to pneumoperitoneum did not show any change in natural killer cell activity. Conversely, the groups of open surgery and laparoscopic surgery revealed significantly decreased natural killer cell cytotoxicity compared with controls (P < 0.0167). When the laparoscopic and the open surgical groups were compared to each other, no difference was found. In this study, both open and laparoscopic surgery had a suppressive effect upon the natural antitumoral cellular immunity. Pneumoperitoneum did not have an immune suppressive effect on natural killer cell activity. In this model, the advantages of laparoscopic surgery do not apply to natural antitumoral cellular immunity.

The clinical spectrum of Clostridium difficile colitis in immunocompromised patients.

Clostridium difficile colitis is a nosocomial infection that continues to cause significant hospital morbidity despite adequate treatment. This morbidity may be especially costly in the immunocompromised patient who now makes up a greater percentage of hospitalized patients. The purpose of this study was to evaluate if patients in immunocompromised states are at risk for relapse of Clostridium difficile colitis, and to determine the efficacy of metronidazole in these patients. A retrospective chart review was conducted of patients with Clostridium difficile colitis over a 1-year period between 1990 and 1991. From this study group, 114 patients were identified who had both positive Clostridium difficile toxin assays of fecal specimens and documented in-house clinical infection. There were 67 immunocompromised patients (59%) in the study group. Oral vancomycin was given alone in 41 (36%) patients, metronidazole was used in 36 (32%) patients, and a combination was given in 15 (13%) patients. Twenty-two (19%) patients received no antibiotic therapy and had their preceding antibiotics terminated. Twelve (10.5%) patients had documented relapses, and all had an immunocompromising condition. There was no statistically significant difference in relapse rates between the vancomycin and metronidazole-treated patients. We conclude that metronidazole, with its significantly lower cost, should be used as first-line therapy in immunocompromised patients.

Flexible endoscopy as an adjunct to laparoscopic surgery.

The combination of flexible endoscopy and laparoscopy has allowed a creative approach to management of both benign and malignant gastrointestinal diseases. Historically, attempts to incorporate intraluminal endoscopy with laparoscopy were made early in the historical development of laparoscopy, especially as an aid to stage gastric cancer. The most common modern application is that of flexible choledochoscopy by laparoscopic cholecystectomy. Other innovative uses include localization of tumors, control of upper gastrointestinal bleeding, gastric tumor excision and biliary decompression, and bowel resection. With imagination guided by sound surgical principles, the combined use of laparoscopy and intraluminal endoscopy should expand the boundaries of general surgery.

Laparoscopic liver biopsy to evaluate hepatic dysfunction in patients with hematologic malignancies: a useful tool to effect changes in management.

Hepatic dysfunction is common in patients who receive intensive chemotherapy and it is important to determine the etiology in order to institute appropriate therapy. The role of laparoscopic liver biopsy in patients with neutropenia, thrombocytopenia, or both was evaluated as a mean of making treatment decisions and as a determinant of clinical outcome. Laparoscopic liver biopsy was performed in 29 subjects who were receiving intensive cytotoxic therapy with or without bone marrow transplantation. One to three direct-vision laparoscopic liver biopsies were performed in each patient using a Tru-cut needle during general anesthesia. Platelet concentrate transfusions were usually given before, during, and immediately after biopsy. Bleeding was controlled with spatula electrocautery. Thirty-two biopsies were obtained in 29 patients. At the time of liver biopsy, white blood cell and platelet counts ranged from 0 to 14,300/microliters (median: 2500/microliters), and 1000 to 47,000/microliters (median: 20,000/microliters), respectively. Bleeding at the liver biopsy site was readily controlled during the procedure without clinical evidence of significant bleeding; no procedure-related complications were noted and no patients required re-exploration. All biopsies were informative and the lesions observed in 32 biopsies revealed graft-versus-host disease (n = 5), hepatic candidiasis (n =1), hepatic veno-occlusive disease (n = 3), cholestasis (n = 19), hemosiderosis (n = 26), toxic injury (n = 8), hepatic steatosis (n = 4), granuloma (n = 1), viral infection (n =1), and malignancy (n = 1). Laparoscopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients who were thrombocytopenic and immunosuppressed. The diagnosis obtained at laparoscopic liver biopsy altered therapy in nine of 29 (31%) patients.