Onye E. Akwari

Leiomyosarcoma of the small and large bowel

From 1950 through 1974, a total of 108 cases of primary intestinal leiomyosarcoma were seen at the Mayo Clinic. Most of these uncommon tumors occurred in the fifth and sixth decades of life, and more of them in men than in women (2.6:1). There were 73% in the small bowel, 25% in the large bowel, and 2% in the anus. Gastrointestinal bleeding and pain were the two most common signs at presentation, and they led to surgical exploration in all cases where they appeared. By the time surgery was performed, only 48% of the tumors could be resected with hope of cure. Within that group of cases, 50% of the patients survived 5 years, but only 35% survived 10 years, late recurrence being common. The histologic grade of the tumor affected survival strongly. Lack of recognition of the high late recurrence rate probably led to erroneous early optimism in prognosis.

Pylorus-preserving pancreatoduodenectomy: a clinical and physiologic appraisal

Since 1978, 252 patients from different centers in the world have undergone pylorus-preserving pancreatoduodenectomy. Fifty-five per cent of the patients had malignant tumors in the region of the head of the pancreas. The overall operative mortality rate was 2.8%. Anastomotic leakage and fistulae occurred in 19% of the patients. Pancreatic, biliary, and enteric fistulae represented 11%, 4%, and 4%, respectively. Peptic ulcers were subsequently diagnosed in seven patients (3%), two of whom required vagotomy and antrectomy. Delayed recovery of gastric function was the most common complication of this operation, with an overall incidence of 30%. Although the cause of this gastric dysfunction is unknown, its transient nature in most patients makes expectant therapy with gastric tube drainage the best remedy when the problem is encountered. Pylorus-preserving pancreatoduodenectomy decreased the incidence of postgastric surgery syndromes that are commonly associated with the standard Whipple operation. The existing data support the continued use of the operation and the need for future laboratory and clinical investigation of its physiologic impact.

Splenectomy for primary and recurrent immune thrombocytopenic purpura (ITP). Current criteria for patient selection and results.

Of 565 patients with thrombocytopenia admitted to Duke University Hospital between 1975 and 1985, 100 had splenectomy. Ninety-eight patients had failed chronic immunosuppressive therapy and three patients had acute intracranial bleeding or total absence of platelets in the peripheral blood smear, and had urgent splenectomy. At primary splenectomy, accessory spleens were identified and resected in 18% of patients. There was no operative mortality. Fifty-eight patients had an excellent response to splenectomy and their steroids were tapered off within 3 weeks. Thirteen patients had a poor response to primary splenectomy of whom eight remitted spontaneously and five required accessory splenectomy resulting in complete remission in three patients. Twenty-nine patients were considered nonresponders, 25 of whom had radionuclide scanning for accessory spleens. Seven of these patients had accessory spleens identified but only four consented to accessory splenectomy. In three of the four patients, a complete remission was achieved. Neither platelet antibody titers nor measurements of platelet survival or turnover predicted platelet response to splenectomy. However, immune thrombocytopenic purpura (ITP) in older patients was significantly less likely to respond to splencctomy. These data support continuing use of splenectomy in selected patients with ITP and an aggressive search for accessory spleens in patients who relapse since they are easily localized at operation by hand-held isotope detector probe.

Hepatobiliary cystadenoma with mesenchymal stroma.

In a detailed review of cystic hepatobiliary neoplasms, we identified a subset of 50 cases in which tumors were characterized by the presence of a mesenchymal cell layer interposed between an inner epithelial lining and an outer connective tissue layer. We have recently seen three such patients, making a total of 53 patients reported in the English literature. All of the patients were female, 44 of whom, with an average age of 41 years, had benign tumors. The average age of the remaining nine patients was 57 years and these patients had malignant tumors. In seven patients, the malignancy arose from the epithelial layer, but in two patients sarcomatous changes were identified in the mesenchymal tissues. The older age of the patients with malignant tumors with adequate serial biopsies in two cases supported the thesis that malignant transformation may occur in the benign tumors. Moreover the location of the tumor in one of our patients in whom the resected tumor was associated with anomalous right hepatic ducts and portal veins supported the theory that these tumors develop embryologically from nests of primitive hepatobiliary endodermal and mesodermal cells. Although surgical treatment was performed in all patients, 25% of the patients with benign hepatobiliary cystadenoma with mesenchymal stroma (CMS), and 33% of the patients with malignant CMS had tumor recurrence after primary resection. Ninety per cent of these patients had an incomplete resection at the time of their initial operations. Forty-four per cent of the patients with malignant CMS died after a mean follow-up of 17 months. We conclude that CMS (Edmonsons tumor) occurs uniquely in young female patients, develops from nests of primitive embryonal cells, has the potential for malignant transformation, and should be completely resected at primary operation to avoid recurrence.

Cancer of the bile ducts associated with ulcerative colitis.

Thirteen patients with bile duct cancer (excluding gallbladder) and associated chronic ulcerative colitis (CUC) were seen at the Mayo Clinic from 1935 through 1973. Most patients had initial symptoms of severe diarrhea and bleeding, followed by a pattern of mild-to-moderate disease with exacerbations and remissions. Three patients had especially severe symptoms and underwent total colectomy (1 patient) or proctocolectomy (2 patients) an average of 15.7 years from onset of CUC symptoms. Anorexia, followed rapidly by the development of progressive jaundice (or a sudden deterioration when liver disease was already present), marked the onset of symptoms of bile duct cancer in the 13 patients. The overall mean duration from onset of CUC to development of symptoms of bile duct cancer was 19 years. The patients in whom colitis was managed by proctocolectomy or total abdominal colectomy developed symptoms of bile duct cancer an average of 9.4 years after colectomy. When cancer was diagnosed, the tumor had spread beyond the bile ducts in 10 patients. The tumors were difficult to identify and often infiltrated the hepatic hilus. The present series and review of the literature suggest that the relationship between CUC and bile duct cancer is more than a chance occurrence. The carcinoma has an onset approximately 3 decades earlier than does carcinoma of the bile ducts without CUC. Surgical removal of the diseased colon and mode of medical management of the unresected colon have no relationship to the subsequent development of carcinoma of the bile ducts; neither does the extent or severity of the colonic disease. The prognosis of carcinoma of the bile ducts unfortunately continues to be dismal.

Defective Glucose-Stimulated Insulin Release from Perifused Islets of C57BL/6J Mice

Previous work has shown that the C57BL/6J (BL/6) mouse strain develops type 2 diabetes after being fed a high-fat, high-simple carbohydrate (HFHSC) diet. In contrast, the AJ mouse strain does not. The aim of the present study was to determine if differences in the insulin secretory characteristics of isolated perifused islets of these animals could help explain why the BL/6 mouse develops diet-induced diabetes. Insulin secretion was assessed as mean integrated area under the curve during 20 min of stimulation with 27.7 mM glucose or 5 mM lauric acid. We found that both glucose- and laurate-stimulated insulin secretions were significantly less in euglycemic BL/6 mice than in the euglycemic AJ mice. The defect in insulin response to glucose, but not laurate, in islets from the BL/6 mouse was exacerbated when the animals were fed the HFHSC diet. These data suggest that the BL/6 mouse has a defective insulin response to glucose, which is exacerbated by a diabetogenic diet.

Effect of l-glutamine supplementation on impaired glucose regulation during intravenous lipid administration

In contrast to L-glutamine, lipid emulsions are routinely administered to patients receiving nutritional support. The provision of fat during intravenous feeding is essential, but the potentially toxic byproducts of fatty acid oxidation may have adverse metabolic consequences. In the present study, we have examined the effect of L-glutamine, an inhibitor of fatty acid oxidation, on the development of defective blood glucose regulation caused by a 48-hour infusion of 10% intralipid in rats. Male Sprague-Dawley rats (200-290 g) were anesthetized with sodium pentobarbital, the right femoral vein cannulated, and baseline blood samples were taken. Each rat was placed in a metabolic cage with access to water, in the presence or absence of rodent chow. Two hours after waking, the rats were infused with 10% intralipid with either saline (control), 2% L-glutamine, or 2% L-alanine. After 48 hours, all animals were sacrificed and blood samples were again obtained. The mean +/- SEM plasma glucose levels before and after lipid infusion at the rate of 1 mL/hr in control rats fed ad libitum, were 125 +/- 13 and 170 +/- 5 mg/dL (p < 0.01, n = 7). Similarly, plasma free fatty acids (FFA) in these animals rose from 0.74 +/- 0.11 to 1.34 +/- 0.32 mmol/L (p < 0.05). Plasma insulin levels also increased from 337 +/- 44 to 1278 +/- 88 pg/mL (p < 0.01). Reduction of intralipid dose infusion did not prevent insulin resistance characterized by hyperglycemia and hyperinsulinemia. However, addition of L-glutamine to the high-dose lipid infusion with chow feeding prevented changes in plasma glucose, insulin levels, and FFA but not triglyceride levels. Also, glutamine but not alanine supplementation in intralipid infused rats without chow feeding prevented changes in plasma glucose, insulin, and malondialdehyde levels. In conclusion, these data show that glutamine supplementation during intravenous lipid administration in rats prevents the development of impaired glucose regulation associated with hyperlipidemia.

The Gastrointestinal Tract in Chemotherapy-induced Emesis

SummaryThe objective of this paper is to summarize current knowledge of gastrointestinal motility and to describe those alterations which emetic agents induce, or may induce, which result in vomiting.The proximal stomach (fundus and orad corpus) acts as a reservoir, regulates intragastric pressure and controls gastric emptying of liquids. On the other hand, distal gastric motility is regulated by a myogenous pacemaker located along the greater curvature in the proximal corpus. The electrical activity controls the rate, strength, and direction of gastric peristalsis. The proximal and distal stomach differ in their responses to ingested substances according to the texture of the ingesta. Therefore, ‘baseline contractile activity’ is a function of the nature of ingesta (solid or liquid).The electrical pattern of the small bowel is controlled by a pacemaker located in the first centimetre of the duodenum. As pacesetter potentials spread from the duodenum to the distal small bowel, they phase the onset and direction of contractions in the bowel.Apomorphine and morphine at emetic doses decrease the amplitude of pacesetter potentials and cause retrograde propagation of action potentials resulting in jejuno-duodenogastric reflux and vomiting. After a characteristic latency period, cisplatin administration results in similar disorganisation of gastrointestinal motility and vomiting. Emetic episodes can be predicted as they are associated with orad sequences of action potentials which are propagated from the small bowel, through the duodenum, and then well into the proximal corpus.Metoclopramide effectively blocks cisplatin emesis while it induces brisk bursts of action potentials in the stomach which are propagated distally into the terminal antrum. Antroduodenal electrical bursts are coordinated by metoclopramide. It appears that the most potent dopamine antagonists, domperidone and metoclopramide, are the most effective antiemetics. Both drugs increase the frequency of action potentials in the distal stomach and duodenum and appear to improve gastrointestinal coordination, thus improving gastric emptying and aboral transit.The ‘central’ effects of chemotherapeutic drugs may be projected on the gastrointestinal tract by direct or indirect neural and/or humoral pathways. Indeed it is likely that there are direct motility pathways to the gastrointestinal tract from multiple central areas. The roles of gastrointestinal hormones, endogenous opiates, and dopamine as potential neurotransmitters influencing gut motility are being studied. Their relationship to emesis is currently only conjectural. However, it is evident that simple mechanical relationships between intrathoracic and intra-abdominal pressure do not explain all the phenomena observed during nausea and vomiting. It is likely that the rhythmic contractions of the muscles of respiration and the other phenomena associated with emesis occur in parallel with the gastrointestinal alterations. The coordination of these phenomena is so exquisite that the retching and other movements of the respiratory muscles may facilitate emetic expulsion. To the point of expulsion, gastrointestinal retroperistalsis appears to be the final common pathway to all emesis.

Anterior resection for adenocarcinoma of the distal large bowel

Among 400 patients with adenocarcinoma of the distal large bowel, anterior resection resulted in more anastomotic leaks, postoperative urinary retention and diarrhea when used for lesions of the mid-rectum than when used for lesions of the proximal rectum or sigmoid colon. However, the operative mortality, long-term morbidity and 2 year survival were similar among patients with lesions at all three locations.

Enhancement of endocrine pancreatic secretions by essential fatty acids.

Recent studies have suggested the beneficial effects of essential fatty acids in postoperative patients receiving total parenteral nutrition. While there is abundant information on the role of glucose and amino acids on insulin release, the effect of essential fatty acids on endocrine pancreatic secretions is not clear. Since linoleic and linolenic acids are constituents of TPN solutions as well as dietary fat, our aim was to examine their effect on the endocrine pancreatic function, using isolated islets. In each experiment, six islets microdissected from three mice were preperifused at the rate of 1 ml/min with Krebs-Ringer bicarbonate (KRB) buffer pH 7.4 containing 2% bovine albumin and 5.5 mM glucose (basal) with continuous supply of 95%/5%, O2/CO2 for 1 hr, after which basal samples were collected on ice every minute. The perifusion was continued for 20 min after the addition of a mixture of 10 mM linoleic acid and 5 mM linolenic acid to the KRB. During each perifusion phase, effluent samples were also collected for insulin and glucagon assay. The mean integrated area under the curve/20 min showed an increase in both insulin and glucagon secretions with the addition of fatty acids. Hence insulin increased from a basal 3154.8 +/- 953.7 to 8393.0 +/- 2073.1 pg (P less than 0.025, n = 6) and glucagon increased from 193.7 +/- 46.9 to 1566.1 +/- 411.2 pg (P less than 0.0025, n = 5). The fatty-acid-induced insulin but not glucagon secretion was blocked by the addition of 2 mM palmoxirate an inhibitor of fatty acid oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)