The significance of gastric and duodenal histological ischemia reported on endoscopic biopsy.

Although frequently reported, it is unknown whether pathological reports of ischemia obtained from gastroduodenal biopsies suggest a diagnosis, prognosis or a requirement for additional evaluation. The aim of this study was to review the natural history, clinical presentation, endoscopic appearance, treatments, and major clinical outcomes of patients with gastroduodenal ischemia. A case series of 14 patients with variable etiologies (seven gastric and seven duodenal) was obtained from a search of our endoscopic pathological database for reports of histological ischemia. The results were as follows. The most common presentation was upper gastrointestinal bleeding (71 %). Half of the endoscopic lesions appeared very severe (large or circumferential lesions, exudative, pseudomembranous, black or pale mucosa). There were six cases of rebleeding (43 %) and four deaths (29 %). Computed tomography scanning was frequently used (12 cases, 86 %), but led to an underlying diagnosis in only three cases. In our series, patients with underlying vascular pathology have substantial 6-month mortality (29 %).

Spinal hematoma after total knee arthroplasty: a case report.

Spinal anesthesia is a common procedure performed in orthopedic surgery, and it is regarded as secure and safe. Although puncture-related complication of spinal anesthesia has a very low incidence, it would lead to dramatic neurological damage (tetra- or paraplegia). Early diagnosis and surgical decompression are mandatory to promote a better outcome. We present a case of acute spinal hematoma from T11 to L3, triggered by laborious anesthesia puncture after total knee arthroplasty. A prompt surgical decompression within few hours after diagnosis allowed rapid functional recovery and avoided permanent paraplegia.

Successful implantation of a cochlear implant in a four-yr-old boy after kidney transplantation: a case report.

Sensorineural hearing loss is common in children with chronic renal insufficiency. The implantation of a CI is performed routinely in children with profound sensorineural hearing loss. A feared complication is a local infection with subsequent meningitis. Because of this risk, a successful implantation of a CI in children under immunosuppression after kidney transplantation has yet to be described. A four-yr-old boy with congenital renal dysplasia and posterior urethral valves, who was successfully transplanted with a kidney from his father at the age of two and a half yr, is presented. The boy had profound bilateral hearing loss before transplantation, most likely due to ototoxic antibiotic medication and long-term furosemide use. A hearing aid was insufficient; therefore, a CI was performed 20 months after the transplantation and no complications occurred in the 24 months of follow-up. This is the first report of a successful CI in a child after kidney transplantation.

A retrospective clinical study of the treatment of high-grade anal dysplasia by infrared coagulation in a population of HIV-positive men who have sex with men.

HIV-positive men who have sex with men (MSM) are at high risk of developing human papillomavirus-associated anal squamous cell cancer. Similar to the management of cervical dysplasia, clinicians are treating high-grade anal dysplasia to prevent progression to cancer. Initial treatments such as cold scalpel excision and electrofulguration have shown limited efficacy in a HIV-positive population. Infrared coagulation (IRC) is an outpatient treatment for high-grade anal dysplasia. This retrospective clinical study reports on 68 HIV-positive MSM with 78 biopsy proven high-grade anal lesions. Each lesion was treated with the IRC with re-biopsy of the treatment site a mean of 140 days later. Of the 74 evaluable lesions; 39 had anal intraepithelial neoplasia (AIN) 1, 20 had AIN 2, seven had AIN 3, and eight had normal epithelium. The IRC showed 64% efficacy per treated lesion and shows promise as a treatment modality for high-grade anal dysplasia in this population.

The prevalence, and predictive value, of abnormal anal cytology to diagnose anal dysplasia in a population of HIV-positive men who have sex with men.

Due to the increasing incidence of anal cancer in HIV-positive men who have sex with men, and the potential to detect and treat high-grade anal dysplasia--the putative anal cancer precursor--we have introduced an anal cytology screening service. Patients with abnormal anal cytology have follow-up high-resolution anoscopy (HRA) with biopsy of lesions clinically suspicious for high-grade dysplasia. In total, 244 men were screened and 235 (96%) of the samples were adequate for cytological interpretation using the Bethesda 2001 system. One hundred and sixty-four (67%) men had abnormal anal cytology, and 93 of them had follow-up HRA and anal biopsy. The positive predictive value for any anal cytological abnormality to predict any degree of anal dysplasia was 95.7+/-2.1%, and for any anal cytological abnormality to predict high-grade anal dysplasia was 55.9+/-5.1%. Abnormal anal cytology was highly predicative of anal dysplasia on biopsy.

Predicting allosteric mutants that increase activity of a major antibiotic resistance enzyme.

The CTX-M family of beta lactamases mediate broad-spectrum antibiotic resistance and are present in the majority of drug-resistant Gram-negative bacterial infections worldwide. Allosteric mutations that increase catalytic rates of these drug resistance enzymes have been identified in clinical isolates but are challenging to predict prospectively. We have used molecular dynamics simulations to predict allosteric mutants increasing CTX-M9 drug resistance, experimentally testing top mutants using multiple antibiotics. Purified enzymes show an increase in catalytic rate and efficiency, while mutant crystal structures show no detectable changes from wild-type CTX-M9. We hypothesize that increased drug resistance results from changes in the conformational ensemble of an acyl intermediate in hydrolysis. Machine-learning analyses on the three top mutants identify changes to the binding-pocket conformational ensemble by which these allosteric mutations transmit their effect. These findings show how molecular simulation can predict how allosteric mutations alter active-site conformational equilibria to increase catalytic rates and thus resistance against common clinically used antibiotics.

Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel.

Diaphragm disease (DD) is a radiographically subtle cause of small bowel obstruction and is part of the spectrum of diseases associated with nonsteroidal anti-inflammatory drug injury. The neuromuscular and vascular hamartoma (NMVH) is a nonepithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. The authors report two patients in whom the clinical setting and gross pathology are that of DD, but the histologic characterization is identical to that described for NMVH. It is probable that in some patients the two diseases overlap so that some patients readily fit the criteria for both entities.

Outcome after intestinal transplantation: results from one center's 9-year experience; discussion 1031-2.

HYPOTHESIS: Outcomes after intestinal transplantation have improved during the past decade with refinements in surgical techniques as well as advances in immunosuppression and antimicrobial therapy. DESIGN: Retrospective analysis. SETTING: Tertiary care medical center, August 1991 through December 2000. PATIENTS: Adult (5) and pediatric (12) patients with intestinal failure. All developed complications from long-term total parenteral nutrition therapy. Median age was 8.6 years and median weight was 22 kg. INTERVENTIONS: Primary intestinal transplantation with (n = 14) or without (n = 3) the liver. MAIN OUTCOME MEASURES: Patient and graft survival, viral infections, rejection, and nutritional autonomy. RESULTS: Twenty-one intestinal grafts were transplanted into the 17 recipients. All donors were cadaveric and were matched by ABO blood group and size. Patient survival at 1 and 3 years was 63% and 55%, respectively. Death-censored graft survival at 1 and 3 years was 73% and 55%, respectively. There were 1.5 acute cellular rejection episodes per graft and 3 grafts were lost to rejection. Incidences of infection with the Epstein-Barr virus and cytomegalovirus were negligible with aggressive prophylaxis and preemptive therapy. Nutritional autonomy was achieved in 69% of grafts surviving more than 30 days after intestinal transplantation. CONCLUSIONS: Intestinal transplantation is now the standard of therapy for patients with intestinal failure and complications resulting from total parenteral nutrition. Outcomes have markedly improved since initiation of the program. Aggressive immunosuppression as well as prophylaxis and preemptive antiviral therapy have led to low incidences of acute cellular rejection, Epstein-Barr virus, and cytomegalovirus. Finally, nutritional autonomy can be achieved after successful intestinal transplantation.

An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats.

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.

Functional and morphologic changes of the ileal mucosa after ileoanal pouch procedure.

BACKGROUND: Restorative proctocolectomy is used widely for treatment of ulcerative colitis and familial polyposis coli. Limited information is available regarding the morphologic and functional adaptation of the mucosa in a functioning ileoanal pouch. STUDY DESIGN: Ileal pouch specimens from patients who underwent pouch reconstruction (mean 7.5 years postcolectomy, n = 12) were compared with normal ileum (n = 15) and normal colon (n = 5). Amino-oligopeptidase (AOP) and maltase activity were measured as parameters of normal ileal function. Histologic samples were examined for the presence of neutrophils and plasma cells, the villus to crypt height ratio, and the degree of crypt hyperplasia, villus blunting, and goblet cell mass. Data were analyzed by analysis of variance. RESULTS: The AOP activity in the normal ileum was 73 +/- 32 units of enzymatic activity per gram of mucosal protein; the AOP activities of the pouch and colon were 21 +/- 22 and 16 +/- 10, respectively. The maltase activity of the normal ileum measured 254 +/- 116 units of enzymatic activity per gram of mucosal protein, and the maltase activities of the pouch and colon were 57 +/- 71 units and 29 +/- 25 units, respectively. The ileal pouch mucosa demonstrated little acute inflammation and varying degrees of chronic inflammation. Morphologically, the ileal pouch mucosa demonstrated a range of adaptations, including villus blunting and crypt hyperplasia. Several specimens contained immature epithelial cells. CONCLUSIONS: The AOP and maltase activities in mucosa from ileoanal pouches and colon were significantly lower than those in normal ileal mucosa. Ileoanal pouch mucosa from humans undergoes adaptive changes to resemble colonic mucosa both morphologically and functionally.

Molecular and immunologic pathology for the endoscopist. Special techniques.

Special techniques for the endoscopic biopsy include both immunologic (IHC) and molecular approaches (ISH, PCR). Both approaches have been adapted to foster additional diagnostic power with little or no additional work by the endoscopist. The techniques take advantage of tissue-specific antigens, unique markers in infectious diseases, and unique nucleic acid sequences present in some malignancies. From these advantages, benign conditions may be more easily distinguished from malignant ones, the causes of some infectious diseases can be confirmed, and clinically relevant classification of malignancies can be made. Some special techniques have added difficulties, such as fastidious requirements for some IHC or Southern blotting. At UCLA, approaches with the least technical challenges are those in practice for endoscopic biopsy. Lastly, the information gleaned from special techniques requires endoscopic and histopathologic context for accurate interpretation.

Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure.

Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP. All nine patients were female with a mean age of 32 years (range 16-66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years. SPENP is considered to be a low-grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure.

Porcelain gallbladder is not associated with gallbladder carcinoma.

The surgical management of porcelain gallbladder is based on studies performed in 1931 and 1962, which indicated a correlation between porcelain gallbladder and carcinoma. We sought to evaluate the characteristics of patients with porcelain gallbladder and the risk for gallbladder carcinoma. The medical records of 10,741 cholecystectomies performed between 1955 and 1998 were reviewed and recorded. The pathology slides were evaluated for evidence of calcification and gallbladder carcinoma. Fifteen (0.14%) of 10,741 specimens were porcelain gallbladders. Ten patients (67%) had symptoms suggestive of biliary colic or cholecystitis. Five (33%) were asymptomatic and diagnosed incidentally. All specimens demonstrated chronic cholecystitis and partial calcification of the gallbladder wall. Nine (60%) had cholelithiasis. None had gallbladder carcinoma by recent review of pathologic material. During this same period 88 (0.82%) patients had gallbladder carcinoma, none of which showed calcification of the wall. This report represents the largest modern review of porcelain gallbladders. No carcinoma was identified among patients with porcelain gallbladder. In addition no patient with gallbladder carcinoma had calcified gallbladder. With a better understanding of the natural history of the porcelain gallbladder the current management of these patients may change.

Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium.

Acute cellular rejection remains a serious and frequent complication during the posttransplant course of small bowel allograft recipients. Currently, small bowel biopsies are the optimal method to identify this form of rejection. The morphological criteria for this diagnosis have been known for some time; however, no consensus study has classified these changes. To address issues in bowel transplant pathology, several pathologists experienced in this particular subdiscipline participated in a Pathology Workshop preceding the VIIIth International Small Bowel Transplant Symposium in Miami, Florida. Among the results of this workshop was the development a standardized grading scheme for acute cellular rejection in small bowel transplants.

Induction therapy with interleukin-2 receptor antagonist after intestinal transplantation is associated with reduced acute cellular rejection and improved renal function.

PURPOSE: To determine the effectiveness of induction immunotherapy with interleukin-2 receptor antagonists (IL2RA) after intestinal transplantation (IT). METHODS: A single-center, retrospective study was undertaken of all patients undergoing IT using existing medical records and database. Immunotherapy was either triple (standard maintenance triple therapy [SMTT]) or IL2RA [induction IL2RA plus SMTTx] or OKT3 [induction antilymphocyte preparations plus SMTTx]). Data was collected for the first 175 postoperative days. Outcomes included pretransplant renal function, posttransplant serum creatinine normalized to age (nl-sCR), rejection (ACR), and survival. Standard statistical analysis was undertaken. RESULTS: There were no significant differences in the groups: triple (n = 10, median age 3.5 years, cGFR 106 +/- 44 mL/min), IL2RA (n = 13, median age 3.2 years, cGFR 101 +/- 61 mL/min), OKT3 (n = 4, median age 7.7 years, cGFR 104 +/- 27 mL/min). nl-sCR was significantly (P <.01) lower in IL2RA at most postoperative weeks. IL2RA had significantly fewer rejection and infectious episodes than the other two groups. Three-year patient survival was 92% in IL2RA versus 50% triple and OKT3. CONCLUSIONS: IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls. Furthermore, IL2RA therapy resulted in a lower incidence of rejection and improved survival. IL2RA should be considered in select patients undergoing IT.

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

AIM: To review the incidence, timing, and outcome of infectious enteritis after intestinal transplantation (IT). METHOD: A retrospective review of all patients undergoing IT at a single institution between 1991 and 2003 was analyze with standard statistical tools. RESULTS: Among 33 IT recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of infectious enteritis. The recipient demographics were 77% men and median age 2.6 years. Infections were diagnosed at a median of 76 days (32 to 1800) after IT. There were 14 viral (CMV one, rotavirus eight, adenovirus four, EBV one, three bacterial (Clostridium difficile), and three other infections (Giardia lamblia one, cryptosporidium two). Complete resolution was achieved in 17 (94%) infectious after appropriate antimicrobial or conservative therapy. Interestingly, there were six rejection episodes following infectious enteritis. Grafts were lost to rejection after rotaviral enteritis (n = 1) and adenoviral enteritis misdiagnosed as rejection (n = 1). Patient and graft survival were not adversely affected by infections. CONCLUSIONS: Infectious enteritis occurs frequently after IT. Viral agents are the cause in two-thirds of cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection by histopathology can be difficult.

Improved outcome after intestinal transplantation at a single institution over 12 years.

PURPOSE: To evaluate the outcomes of patients undergoing intestinal transplantation (IT). METHODS: Retrospective review was undertaken using existing medical records and database. RESULTS: Between November 1991 and May 2003, 114 patients were referred for consideration for IT, of which 33 patients received 37 intestinal allografts. All patients had intestinal failure and all patients had significant complications from total parenteral nutrition (TPN). TPN was the predominant cause of liver failure (63%). Combined liver intestinal grafts were used in the majority of patients. Overall 1- and 3-year patient survival is 77% and 52% with patients transplanted since 1999 having a 1- and 3-year survival of 94% and 73%, respectively. The most common cause of death was sepsis. No graft or patient was lost to cytomegalovirus or Epstein-Barr virus disease. Twenty-seven percent of allografts were lost to rejection. Long-term TPN independence is 82% for grafts more than 30 days after IT. Statistical analysis revealed several important factors impacting outcome. CONCLUSIONS: Successful IT defined as prolonged patient and graft survival and TPN independence can be readily achieved in select patients with IF and complications related to TPN therapy. Outcomes have improved with experience gained and control of viral infections and rejection.