Meredith T. Hull

Impaired bacterial clearance and trapping in obstructive jaundice.

Sepsis is a major cause of mortality in patients with common bile duct obstruction. To define possible contributing factors to this phenomenon, this study evaluates the effect of biliary obstruction on the intravascular clearance and organ trapping of viable Escherichia coli using a rat model. Adult male Sprague-Dawley rats were placed in three groups: Group I controls had sham operation, Group II had division and Mgation of common bile duct (CDL), and Group III underwent splenectomy. At 21 days following operation 109 radiolabeled E. coli were injected intravenously. At varying intervals after infusion, blood samples were obtained for clearance study. At 10 minutes, bacterial distribution in the liver, spleen, kidneys, and lungs was determined (expressed as the mean percentage of injected viable E. coli). Intravascular clearance was similar in all groups. There was a significant decrease in the trapping of bacteria by the liver of CDL rats 14.5% ± 4.95 (vs. control = 70.0% ± 13.3) (p < 0.005). A significant increase of bacterial trapping by the lung was observed in the CDL animals: 63.1% ± 7.06 (vs. controls 1.4% ± 0.82) (p < 0.005). There was no significant change in bacterial localization in splenectomized rats. These data suggest that biliary obstruction decreases hepatic phagocytosis and increases pulmonary localization of viable E. coli. As the Kupffer cells of the liver are usually effective in removal of blood borne bacteria, this phagocytic dysfunction may contribute to the increased susceptibility to infection noted in instances of biliary obstruction.

Morphologic features of renal oncocytoma: a light and electron microscopic study.

Five renal oncocytomas were studied by light and electron microscopy. Five glutaraldehyde-fixed blocks from each tumor were examined. Scarce short, blunt microvilli, plasmalemmal interdigitations, basement membrane protuberances, and round or oval mitochondrial profiles were found, suggesting that these neoplasms arise from the epithelium of the distal tubule. Morphologic criteria for the diagnosis of renal oncocytoma, including ultrastructural demonstration of cytoplasmic filling by mitochondria, are presented.

Primitive neuroectodermal tumors arising in testicular germ cell neoplasms

Twenty-nine young men (mean age 29 years) had primitive neuroectodermal tumors (PNETs) arising in germ cell tumors (GCTs). Nine patients had PNETs confined to the testis, eight patients had PNETs in the testis and at metastatic sites, and 12 patients had PNETs identified only at extratesticular sites. Immunohistochemistry was of use in the further classification of these PNETs as neuroblastoma, medulloepithelioma, peripheral neuroepithelioma, or ependymoblastoma. The histologic pattern of PNETs in the testis (neuroblastoma or medulloepithelioma) did not predict which tumors metastasized. PNETs localized to the testis did not affect prognosis. Eight patients with no PNETs outside the testis were free of disease 1 month to 10 years after diagnosis. PNETs in extratesticular sites were an adverse prognostic factor. Nineteen patients with extratesticular PNETs had adequate clinical follow-up. Thirteen are dead of disease from 4 months to 5 1/2 years (mean 26 months) after diagnosis, four are alive with disease 6 months to 2 years after diagnosis, and two have no evidence of disease with short follow-up (6 and 17 months). Mean survival was longer (34 months) for patients whose extratesticular PNET was neuroblastoma than for those with other types of PNETs (13 months). Chemotherapy directed against GCTs was not effective in patients who developed metastatic PNETs of GCT origin. We conclude that extratesticular PNETs in patients with testicular GCTs are usually fatal, but patients with neuroblastomatous metastases may have a more prolonged course.

Superoxide dismutase: A cellular protective enzyme in bowel ischemia

Recent data suggest that the free-radical anion superoxide (O-2), an unstable, cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel injury. This study evaluates the role of superoxide dismutase (SOD), an enzyme specific for enzymatic conversion of O-2 in protecting the bowel from an ischemic insult. At laparotomy, the superior mesenteric artery was occluded for 1 min in 90-g weanling rats (n = 144). Animals were divided into four groups: I, untreated controls (n = 41); II, received aminophylline (AMN) 40 mg/kg ip, a substrate for (O-2) generation (n = 21); III, received superoxide dismutase (SOD) 2.5 mg/kg iv (n = 20); IV, received both AMN and SOD (n = 22). Rats were evaluated for bowel infarction, perforation, and mortality over a 7-day observation period. In 40 additional rats (10 per group) bowel ultrastructure was evaluated by scanning electron microscopy (EM) during occlusive ischemia and at various time intervals following reperfusion. Mortality was 63.4% in controls (26/41) with necrosis noted in 19 and perforation in 7. AMN resulted in a 90% mortality (19/21) (chi 2, P less than 0.05 vs control), with necrosis in 15 and perforation in 4. SOD reduced mortality to 25% (5/20) with necrosis in 4 and perforation in 1 (chi 2, P less than 0.02 vs controls) and, when added to AMN, 45.5% (10/22) (chi 2, P less than 0.01 vs AMN alone). On EM, tissue damage was minimal during occlusive ischemia, worsened by duration of reperfusion, enhanced by AMN, and reduced by SOD. These data suggest that following hypoxia, the injured bowel may be unable to appropriately handle reoxygenation. Tissue damage was related to duration of reperfusion and was worse following AMN, a xanthine derivative that might generate (O-2), a cytotoxic free radical. SOD detoxifies O2-, increases survival, and protects the bowel during reperfusion.

Mucin-hypersecreting intraductal neoplasms of the pancreas: A precursor to cystic pancreatic malignancies

BACKGROUND Muncin-hypersecreting intraductal pancreatic neoplasms were first described in 1982 and have been observed in increasing numbers since. They are observed primarily by endoscopic retrograde cholangiopancreatography (ERCP) and are characterized by an intraductal papillary neoplasm that secretes thick mucin, causing pancreatic duct dilatation and obstructive pancreatitis. METHODS Twenty patients are presented, 14 male and six female, with an average age of 59 +/- 11 years. All patients presented with abdominal pain, and most had nausea and vomiting, weight loss, and documented pancreatitis. Of the preoperative studies, ERCP was positive in all patients. Computed tomography scan, endoscopic ultrasonogram, and cytologic findings were less sensitive. Tumor markers were only positive in one patient. All 20 patients were treated surgically. Nine underwent Whipple procedure, one patient had a total pancreatectomy, and nine had distal pancreatic resections. The first patient in the series did not have a pancreatic resection, and his disease evolved into a lethal cystadenocarcinoma causing his death 99 months later. RESULTS Histopathologic findings were interpreted as borderline malignant in 17 of the 20 patients, and three patients had evidence of invasive adenocarcinoma. Two of these three patients had nodal or distant metastases at the time of diagnosis, and all three died of adenocarcinoma. Seventeen of the patients are alive and well, although two of three with positive pancreatic margins have had recurrent symptoms and have been successfully reresected. CONCLUSIONS The mucin-producing intraductal papillary tumor of the pancreas is a newly described variant of pancreatic cancer. It presents with symptoms of pancreatitis and has a progressive but more indolent course than the more lethal invasive ductal cancers. Patients with unexplained pancreatitis should undergo ERCP investigation, and aggressive surgical therapy should be carried out because the prognosis for this lesion, when appropriately treated, is more favorable than the usual pancreatic cancer.

Glycogen‐rich clear cell carcinoma of the breast: A light and electron microscopic study

A glycogen‐rich clear cell carcinoma arose in the breast of a 49‐year‐old woman. Light microscopic examination of the neoplasm revealed both intraductal papillary growth and stromal invasion. Electron microscopic examination demonstrated neoplastic cells that contained massive quantities of nonmembrane‐bound particulate glycogen and that formed numerous acini. Apically, these cells formed microvilli; laterally they formed tight junctions and desmosomes. Morphologic features of this neoplasm are similar to those of the fetal breast and to some other clear cell carcinomas arising elsewhere in the body.

Familial islet cell tumors in von Hippel‐Lindau's disease

Von Hippel‐Lindaus Disease is an hereditary disorder characterized by the development of hemangioblastomas of the cerebellum and retina and a variety of cystic and neoplastic lesions of other organs such as renal cell carcinoma and pheochromocytoma. In a single generation of a family with Von Hippel‐Lindaus disease, all four siblings developed lesions classically associated with the complex. Additionally, two of the four developed islet cell tumors of the pancreas, one in one patient and five in the other. While a familial incidence of islet cell tumors is known in multiple endocrine adenomatosis, type I and Zollinger‐Ellison syndrome, such a familial occurrence has been heretofore unrecorded in the Von Hippel‐Lindau complex.

Glycogen-rich Clear Cell Carcinomas of the Breast: A Clinicopathologic and Ultrastructural Study

Ten cases of glycogen-rich clear cell carcinoma of the breast are described. Only two previous case reports have been published. These neoplasms are composed of clear cells with abundant glycogen. Ultrastructurally, two cases showed large quantities of non-membrane-bound glycogen and numerous empty glycogen lakes. Neoplastic cells formed tight junctions, immature desmosomes, and occasionally had short microvilli. In nine cases the glycogen-rich carcinoma grew in a solid pattern only, while one case had both solid and papillary patterns. One case was associated with a signet-ring cell carcinoma. Seven of nine patients who underwent axillary dissections had nodal metastases. Five patients died with residual disease, and one is currently alive with local skin recurrence. These data suggest that glycogen-rich clear cell carcinoma is associated with frequent lymph node metastases and mortality.

Villous Adenoma of the Urachus with Mucusuria: A Light and Electron Microscopic Study

After 2 years of mucusuria a villous adenoma of the urachus was resected from a woman by partial cystectomy and excision of the entire urachus. Convalescence was uneventful and the patient was well 12 months later. Urachal adenomas are rare, this being the sixteenth case reported. Generally, they are multilocular cystic tumors lined by columnar epithelium with a population of mucous goblet cells. Often, there is a striking resemblance to gut epithelium. Ultrastructurally, by transmission and scanning electron microscopy, the tissue resembles gut mucosa. Urinary mucus is a common and relatively specific symptom for adenomas of the lower urachus, occurring in 7 of 11 cases. Resection alone is effective therapy but care must be exercised to avoid spilling adenoma cells in the peritoneum.

Neonatal Apnea, Xanthines, and Necrotizing Enterocolitis

This study evaluates the relationship of xanthine treatment of premature apnea and NEC in a bowel ischemia model. The superior mesenteric artery was occluded for 1.0 minute in 82 wheanling rats. Group I (n = 41) were untreated controls. Group II (n = 21) received aminophylline (AMPH) 40 mg/kg I.P., 4 hr and immediately prior to clamping. Animals were evaluated for bowel infarction, perforation, and mortality at 7 days. In 20 additional rats (10 per group) bowel was evaluated by scanning electron microscopy (EM) at timed intervals (5 and 30 min). Ischemic bowel occurred in 25 of 41 (60%) controls (18 (43%) with necrosis; 7 (17%) with perforations) and 19 of 21 (90%) rats with AMPH (15 (70%) had necrosis; 4 (19%) perforations). Mortality was 60% (controls) and 90% (AMPH) respectively (p less than .05). On EM, AMPH enhanced bacterial overgrowth however actual mucosal damage appeared similar. Following ischemia, AMPH has an adverse effect on the bowel. Use of AMPH in prematures at risk for NEC is questioned.