Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy.

BACKGROUND: Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients. This controlled randomized trial was designed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury. PATIENTS AND METHODS: Twenty-two cadaver liver transplant recipients were randomized to receive either thymoglobulin (1.5 mg/kg per dose) during the anhepatic period and two doses every other day or no thymoglobulin. No differences in recipient or donor demographics were present. Maintenance immunosupression consisted of tacrolimus (or cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage, and 1 hour after revascularization. Postoperative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary nonfunction, and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft nonfunction and no need for retransplantation. The incidence of acute rejection was similar between the two groups. Although donor livers randomized to thymoglobulin had less optimal preimplantation biopsies, these recipients had significant decreases in ALT at day 1 compared to the control group (P = .02), near significant decreases of total bilirubin at day 5, and shorter length of hospitalization. CONCLUSION: Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function.

Allopurinol-induced granulomatous hepatitis with cholangitis and a sarcoid-like reaction.

A 36-year-old man had pain in both knees and an elevated uric acid concentration; his liver function was normal. Allopurinol therapy was started, 100 mg twice daily. After one month fever, lethargy, and severe polyarthralgia developed. On admission to our hospital liver function was abnormal, and a liver biopsy specimen showed granulomas with cholangitis and pericholangitis. He also had lymphopenia with a reduced number of T cells and granulomas in the bone marrow. One month after discontinuation of allopurinol therapy the patient was clinically well with normal liver function and a normal lymphocyte count. A repeated liver biopsy specimen showed normal liver tissue with no granulomas. The onset of the symptoms and findings shortly after the initiation of allopurinol therapy, and their disappearance after the discontinuation of therapy suggest a drug-induced hypersensitivity.

Neuroendocrine carcinomas of the colon. Ultrastructural and biochemical evidence of their secretory function.

Four cases of malignant colonic tumors diagnosed by light microscopy as "small cell undifferentiated carcinomas" were shown by electron microscopy to have neurosecretory-type granules. Biochemical analysis of tumor tissue extracts disclosed the presence of considerable levels of VMA and catecholamines in all tumors; 5-HIAA was present in one tumor. Clinically, there had been no signs or symptoms attributable to those or related substances. Similar observations have been reported in a variety of neuroendocrine neoplasms; for example, the demonstration of neurosecretory-type granules and determination of amine or peptide materials in tumor tissue or body fluids may not be necessarily reflected in clinical hormonal syndromes or obvious metabolic abnormalities. Our structural and biochemical observations indicate that, regardless of clinically evident hormonal activity or lack thereof, some small cell "undifferentiated" colonic cancers derive from APUD elements, and therefore they should be classified within the group of neuroendocrine carcinomas. The evident secretory capabilities of these carcinomas suggest obvious diagnostic possibilities and could conceivably lead to a reappraisal of current therapy.

Synaptophysin. A new marker for pancreatic neuroendocrine tumors.

Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux. AIM: To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus. METHODS: An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2-4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8. RESULTS: The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups. CONCLUSION: In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.

Ultrastructural and biochemical analysis of "undifferentiated" pulmonary carcinomas.

Seven cases of "undifferentiated" pulmonary carcinoma were studied ultrastructurally; five were of the typical oat cell variety and the remaining two consisted of larger cells. In three of the former and both of the latter cases neurosecretory-like granules were demonstrated. Biochemical analysis of tumor tissue extracts revealed 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in all instances. No hormonal syndrome or metabolic abnormality was detected in any of the patients. The concomitant morphologic demonstration of neurosecretory-like granules and the presence of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamines in neoplastic tissue would provide further evidence that these tumors may indeed arise from bronchial endocrine cells and could therefore be classified within the group of neuroendocrine carcinomas. Also it seems apparent that these neuroendocrine bronchial carcinomas may include tumors consisting of cells somewhat larger than the typical oat cell. The observation of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in two oat cell carcinomas in which neurosecretory granules could not be demonstrated poses an interesting problem whose solution may only derive from further studies.

Malignant gastric neuroendogrinomas. Ultrastructural and biochemical characterization of their secretory activity.

In two cases of malignant gastric tumors originally diagnosed as undifferentiated carcinomas electron microscopy revealed a neurosecretory type of granule. Subsequently tumor extracts were tested by biochemical methods and shown to have vanillylmandelic acid and 5-hydroxy-3-indoleacetic acid activity. Neither patient had signs or symptoms referable to the presence of these or related substances. These observations parallel those made in a variety of neuroendocrine tumors in which demonstration of neurosecretory granules or isolation of amine or peptide materials or their metabolites has not necessarily been reflected in clinical hormonal syndromes. Our findings indicate that regardless of clinically apparent hormonal activity or lack thereof, some undifferentiated gastric carcinomas may in fact derive from neuroendocrine APUD elements.

"Myeloma lung"--a previously unreported complication of multiple myeloma.

A 52-year-old man with known lambda light-chain multiple myeloma developed chronic renal failure, which was proven by renal biopsy to be the result of "myeloma kidney." Terminally, disseminated pulmonary infiltrates developed. Postmortem examination showed the infiltrates to consist of neoplastic plasma cells with crystalline casts, strikingly similar to those found in the kidneys. The term "myeloma lung" is proposed to describe this unusual and heretofore unreported complication of multiple myeloma.

Clinical features of duodenal somatostatinomas.

BACKGROUND: Duodenal somatostatinomas are rare tumors that are often asymptomatic or present with local symptoms rather than with evidence of excess somatostatin production. To characterize the clinical presentation and management of these neoplasms we reviewed the course of four patients. METHODS: The records of three men and one woman with duodenal somatostatinomas, who were treated between 1988 and 1992, are reviewed. RESULTS: Three of the patients presented with vague gastrointestinal complaints, and one was free of symptoms. No patient had symptoms of somatostatinoma syndrome, nor did any have associated neurofibromatosis. Three patients were diagnosed after biopsy of a submucosal mass during upper endoscopy. Three patients with tumors that measured less than 2 x 2 cm underwent local resection. One patient with a large tumor and liver metastases underwent a Whipple's operation and resection of the liver lesions. Immunohistochemically all tumors predominantly contained somatostatin, although each had traces of other neuropeptides. All tumors contained psammoma bodies. Follow-up periods ranged from 1 to 4 years. CONCLUSIONS: Duodenal somatostatinomas often appear with only local symptoms or are completely asymptomatic. Small tumors may be locally excised. Intraarterial methylene blue injection may help localize very small tumors during operation. Larger tumors, including those with localized metastases, should also be resected when possible.

Plasma calcitonin gene-related peptide and atrial natriuretic peptide levels during resection of pheochromocytoma.

Calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) are potent hypotensive agents. To determine if they play a counterregulatory role in catecholamine excess in patients with pheochromocytoma, plasma levels were measured in four patients undergoing resection of sporadically occurring tumors. Each patient was prepared with phenoxybenzamine hydrochloride (Dibenzyline); two patients also received propranolol. Blood was obtained for plasma levels of epinephrine, norepinephrine, CGRP, and ANP at induction of anesthesia, skin incision, tumor manipulation, tumor removal, and 24 hours after operation. Baseline plasma norepinephrine and epinephrine levels were markedly elevated and increased significantly with tumor manipulation and decreased significantly 24 hours after operation. CGRP and ANP levels were slightly elevated throughout but did not change significantly with tumor manipulation or early after tumor resection. Circulating CGRP and ANP do not appear to have an acute counterregulatory role in catecholamine excess in patients with pheochromocytoma but may exert some influence on postoperative hypotension after tumor removal.

Parathyroid carcinoma: biochemical and pathologic response to DTIC.

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Cure results from successful en bloc resection. However, because of its rarity, the malignant nature may not be appreciated at the initial operative procedure and as a result, definitive resection may not be accomplished. However, even with extensive en bloc resections, local recurrences do occur and patients die of metabolic derangements associated with hypercalcemia. Thus in addition to operative intervention, palliative chemotherapy may be required to control the hypercalcemia. Radiotherapy has been unsuccessful. A single case of nonfunctioning parathyroid carcinoma responding to treatment with methotrexate, Adriamycin, cyclophosphamide, and CCNU has been reported. We report a case of recurrent functioning parathyroid carcinoma treated with dacarbazine (DTIC) in which biochemical and pathologic evidence of at least a partial response was seen. The patient, a 33-year-old woman, had undergone five previous neck explorations during a 26-month period for aggressive locally recurrent disease. Before DTIC therapy the intact parathyroid hormone (PTH) level was 1032 pg Eq/ml (normal 163 to 347 pg Eq/ml) and the serum calcium level was 16.8 mg/dl (normal 8.8 to 10.0 mg/dl). After a course of DTIC there was a marked improvement in her clinical status and biochemical parameters (intact PTH 545 pg Eq/ml; serum calcium 11.8 mg/dl). For 2 months her condition stabilized, with PTH levels between 700 and 760 pg Eq/ml and serum calcium levels between 10.2 and 16.0 mg/dl. With a slowly progressive rise in biochemical parameters a second course of DTIC was initiated and a marked drop in serum calcium levels (5.7 mg/dl) occurred, but PTH levels remained unchanged. A progressive course of septicemia, malnutrition, and disseminated intravascular clotting ultimately lead to her death 4 weeks later. At autopsy examination the tumor was confined to the neck. Grossly and microscopically there was extensive central as well as peripheral necrosis of the tumor, which was thought to be the result of the cytotoxic effect of DTIC. From this experience and because of the grim prognosis in patients with recurring parathyroid carcinoma, it may be that aggressive use of chemotherapy with DTIC early in the course of treatment should be considered.

Fecal occult blood testing: a false sense of security?

BACKGROUND: Recent screening studies with fecal occult blood testing (FOBT) report that one of three patients with colorectal cancer (CRC) can be cured of the disease; minimal attention has been given to the two of three patients who despite repeated screening go on to die of silent CRC. We report the known "miss rate" (known false negatives) of our 14-year ongoing program of FOBT that was organized in 1979 to detect early CRC. METHODS: From October 1979 through December 1993, 36,034 FOBT kits were distributed to patients who were without gastrointestinal complaints at Hines Veterans Affairs Hospital. The test was considered positive if at least one result of the six tests was positive and negative if the test result was equivocal. Patients with negative FOBT received a new test kit each year by mail. A positive test was followed by full colonoscopy or an air contrast barium enema if a full colonoscopy was not possible. RESULTS: The overall return rate was 47.8%. CRC was detected in 115 patients: 94 had a favorable and 21 had an unfavorable Duke's C or D or lymphoma prognosis. Of 21 patients 13 (62%) had initially tested FOBT negative (missed lesion). Of the 21 cases of advanced CRC 15 (71.43%) were in the descending, sigmoid, or rectosigmoid colon or rectum. CONCLUSIONS: (1) The majority (82%) of all CRC detected by FOBT screening are diagnosed at a favorable stage. (2) The majority of known advanced CRC (62%) escape early detection with FOBT. (3) Five (62.5%) of eight of the advanced CRC cases discovered on initial FOBT and 10 (76.9%) of 13 of advanced CRC cases missed on initial FOBT but detected in subsequent years were in the left colon and most likely in the range of the flexible sigmoidoscope. (4) FOBT as a sole screening test may provide a false sense of security, especially in patients with advanced left-side CRC.

Effects of radiation on parafollicular C cells of the thyroid gland.

While radiation has well-recognized effects on follicular cells of the thyroid gland, those on parafollicular C cells are not yet established. Low-dose radiation that has been proved to be nonablative and carcinogenic to follicular cells was administered to 8-week-old Long-Evans rats to study the changes in C cell number and function. Circulating calcitonin levels were significantly reduced in animals that had undergone radiation at age 24 months. Mean calcitonin values were 0.66 (+/- 0.20) ng/ml and 1.64 (+/- 0.59) ng/ml for control males and females compared with 0.14 (+/- 0.06) ng/ml and 0.11 (+/- 0.01) ng/ml for males (P less than 0.05) and females (P less than 0.001) that had undergone radiation, respectively. These levels correlated well with C cell population density in thyroid glands in the control group and in the group that had undergone radiation as evidenced by light microscopy. Routine hematoxylin and eosin staining showed C cell hyperplasia in 77% of control animals of both sexes compared with 4% in animals that had undergone radiation (P less than 0.005). Immunoperoxidase staining with an anticalcitonin antibody showed virtual absence of C cells in most animals that had undergone radiation compared with diffusely scattered cells in animals in the control group. Medullary carcinomas occurred in 14% of animals in the control group compared with 3% of animals that had undergone radiation (P less than 0.05). These data indicate that the radiation dosage that is carcinogenic to the follicular epithelium causes lethal injury to C cells and thus suggest that C cells are more sensitive to radiation than are follicular cells. This increased sensitivity could explain the virtual absence of C cells, decrease in calcitonin levels, and reduced numbers of medullary carcinomas in the animals that had undergone radiation.

Node-positive duodenal carcinoma is curable.

OBJECTIVES: To document our experience with duodenal carcinoma during the past 15 years to ascertain optimal treatment. DESIGN: A retrospective case series. SETTING: A tertiary care referral center. PATIENTS: A consecutive sample of 24 patients, 17 men and 7 women, with duodenal carcinoma was evaluated during the 15 years ending in December 1992. Ages ranged from 44 to 81 years. All patients were available for follow-up for a minimum of 20 months. INTERVENTIONS: Therapy included 15 radical pancreaticoduodenectomies (Whipple procedures), 7 bypass operations, and 2 segmental resections. MAIN OUTCOME MEASURES: Tumor staging and survival. RESULTS: Segmental resections were performed in 2 patients, bypass operations in 7, and Whipple procedures in 15. One patient in each of the bypass and Whipple groups died postoperatively. All other patients who underwent bypass and segmental resection died of cancer. Of 14 patients surviving a Whipple procedure, 9 continue to survive with an average follow-up of 77 months. Four of these patients had lymph nodes involved with cancer and have survived for longer than 5 years. CONCLUSIONS: Adenocarcinoma of the duodenum gives rise to nonspecific gastrointestinal tract symptoms, and diagnosis is often delayed. Despite this delay, the Whipple procedure may still be curative for patients with positive lymph nodes, a fact poorly appreciated in the surgical literature. The role of segmental resection for distal duodenal tumors is unclear.

Bombesin in human neuroendocrine (NE) neoplasms.

Bombesin is a 14 amino acid peptide isolated from amphibian skin which was found to have stimulatory effects upon gastric and pancreatic secretions, release of gastrointestinal hormones, gallbladder contraction and bronchoconstriction. It is present in amphibian gastric endocrine cells, avian proventriculus endocrine cells and avian brain. In mammals it is present mainly in nerve cells and fibers. The only mammalian endocrine cell shown to date to have bombesin is the P-cell in fetal lung. Bombesin is also found in mammalian brain, with its highest concentration in the hypothalamus. We examined several groups of human neuroendocrine neoplasms for the presence of bombesin by immunohistochemistry. Our findings indicate that bombesin is present 68% of bronchial carcinoids, 65% of pulmonary neuroendocrine carcinomas, 62% of neuroendocrine carcinomas of the skin, 5-10% of pheochromocytomas and extraadrenal paragangliomas and 35% of gastrointestinal carcinoids and neuroendocrine carcinomas. Parallel studies in a wide variety of non neuroendocrine neoplasms failed to reveal the presence of bombesin. We conclude that bombesin is a highly specific marker of neuroendocrine differentiation and thus a valuable tumor marker. Furthermore, its specificity compares favorably with another neuroendocrine marker, neuron specific enolase, an enzyme thought to be present only in neural tissues and neuroendocrine cells but recently found in non neural human tissues and non neuroendocrine neoplasms.

Cystic glucagonoma: A rare variant of an uncommon neuroendocrine pancreas tumor.

Glucagon-producing neuroendocrine tumors typically present with a characteristic constellation of symptoms including necrolytic migratory erythema, non-insulin-dependent diabetes, weight loss, anemia, glossitis, and an increased thrombotic tendency. Most glucagonomas are solid and arise in the body or tail of the pancreas. We report two cases of cystic glucagonoma, one found incidentally in an asymptomatic patient and one in a patient with weight loss and diabetes but no rash. In the first patient, distal pancreatectomy and splenectomy were curative, whereas the second patient continued to exhibit elevated serum glucagon levels and symptoms of glucose intolerance in the absence of demonstrable metastases. Cystic glucagonoma is a unique variant of classic glucagonoma and should be considered in the differential diagnosis of cystic pancreatic neoplasms.

Neuroendocrine tumors of the gastrointestinal tract.

Neoplastic proliferations of neuroendocrine cells (NE) may occur throughout the entire GI tract but affect particularly appendix and ileum ("midgut carcinoids"), rectum ("hindgut carcinoids"), as well as stomach and the duodenum ("foregut carcinoids"). Only more exceptionally, they arise in the esophagus, jejunum and colon. The NE tumors encompass a heterogeneous gross and microscopic structural spectrum, ranging from inconspicuous microproliferations ("mucous membrane nevi") to bulky tumor masses. Their growth patterns are usually characteristic and easily recognized. In doubtful cases their NE differentiation becomes established by a characteristic silver affinity, by the ultrastructurally observed presence of characteristic "endocrine" secretion granules, and by immunohistochemically detectable occurrence of "pan-NE markers" (neuron-specific enolase, chromogranins, and synaptophysin), biogenic amines (mainly serotonin), and neurohormonal peptides. Foregut carcinoids usually contain serotonin, gastrin, and somatostatin, midgut carcinoids often only serotonin and tachykinins, whereas the hindgut carcinoids as a rule are multihormonal with a wide spectrum of hormonal peptides, including even insulin. Most GI NE tumors are found in the appendix (50%) and the ileum (30%). Practically all (98%) of the appendiceal NE tumors are benign. They have recently been proposed as arising from apparently Schwann-cell-related NE cells in the submucosa, whereas the ileal--and probably also all the other non-appendiceal NE tumors--are derived from the totipotential cells in epithelial crypts of the mucosa. Among the ileal NE neoplasms a large number can metastasize and result in a fatal outcome. The ability to metastasize is related to the size and to the multiplicity of the primary tumors at the time of initial diagnosis and, to some extent, to their histopathologic growth pattern. Now, some relationship between the prognosis and the cytochemically assessed nuclear DNA content of the NE tumor cells has also been established; not less than about 1/4 to 1/3 seem to be aneuploid. Almost 90% of the rectal carcinoids are benign. Exceptionally, a highly malignant NE neoplasms can arise from the colon/rectum--as well as from the esophagus--composed of NE cells of small and intermediate size. The NE tumors of the stomach are often composed of ECL (enterochromaffin-cell-like) cells; such ECL cell carcinoids are related to atrophic gastritis with pernicious anemia; experimentally, they can be induced by hypergastrinemia in rats. Duodenal carcinoids often contain psammoma bodies and can be associated with neurofibromatosis.

Islet cell carcinoma of the pancreas.

To define the course of malignant pancreatic islet cell tumors, 20 patients seen over 14 years with these neoplasms were reviewed. The 12 men and 8 women ranged in age from 22 to 76 years, with a mean of 52. Seven functional tumors included three insulinomas, two glucagonomas, one gastrinoma, and one somatostatinoma. One insulinoma was associated with a multiple endocrine neoplasia type I (MEN-I) syndrome. The 13 patients with nonfunctioning tumors had abdominal pain (3), jaundice (2), and steatorrhea (2). Seven had a palpable abdominal mass. Diagnosis of malignancy was based on local invasion (4), distant metastases (15), or both (1). One patient had percutaneous biopsy of a hepatic metastasis. All others had laparotomy for diagnosis and/or treatment. Each patient had a single tumor except the patient with MEN-I syndromes, who had multiple tumors throughout the pancreas. The head was involved in seven patients, the body in seven, and the tail in five. Operations included six curative and three palliative resections, five biliary diversions (two with concomitant enteric bypass), and five biopsies. Palliative resections were done for hormonal or local symptoms such as gastrointestinal (GI) bleeding and pain. Multiple chemotherapeutic agents were used, but the best results were obtained with DTIC (50% response). Four patients had radiation for liver, brain, or bone metastasis, with some improvement. Of five patients who had curative resections, four are alive 15 to 144 months, with a mean of 75 months. One died six years after diagnosis. Of the remaining 15 patients who had liver metastasis, seven patients are alive 8 to 168 months later, with a mean of 87 months.(ABSTRACT TRUNCATED AT 250 WORDS)

"Nonfunctioning" islet cell carcinoma of the pancreas.

Although most pancreatic islet cell tumors are associated with clinically evident hormone hypersecretion, a small group have no obvious signs or symptoms of excess endocrine activity and are termed "nonfunctioning." The clinical course of eight patients with "nonfunctioning" islet cell carcinoma seen during an eight-year period was reviewed. The six men and two women ranged in age from 36 to 68 years (mean--52). The initial complaint in six was a palpable abdominal mass associated with pain, steatorrhea, or jaundice. Two patients presented with abdominal pain that was initially thought to be of biliary tract origin, and the tumor was discovered at operation. Two patients underwent radical distal pancreatectomy and have no gross evidence of residual or recurrent tumor one and two years later. Five had a biopsy and biliary diversion; three of these also had a gastrojejunostomy. Five were given postoperative 5-fluorouracil and streptozotocin chemotherapy. One developed renal dysfunction and was switched to dimethyltriazenoimidazole carboxamide (DTIC) chemotherapy. Three patients are alive four, six, and eight years, respectively, after diagnosis. Two expired two and a half and three years after diagnosis. One patient had only biopsy of peripancreatic nodes, and he expired in one year. "Nonfunctioning" islet cell carcinoma presents with symptoms related to the mass effects of the tumor. An aggressive therapeutic approach utilizing surgery and chemotherapy is advocated for these slow growing neoplasms.

Adult nesidioblastosis. An unusual cause of fasting hypoglycemia.

Laidlaw coined the term nesidioblastosis in 1938 to characterize the neodifferentiation of the islet cells of Langerhans from pancreatic duct epithelium. It is well recognized in the pediatric population as a frequent cause of persistent neonatal hypoglycemia. However, its occurrence in adults is presumed to be rare and, therefore, it is not appreciated as a cause of hyperinsulinism. Three women, aged 29, 42, and 63, with adult onset hyperinsulinism secondary to nesidioblastosis are reported. All three patients required near-total pancreatectomy. The preoperative findings were consistent with hyperinsulinemic hypoglycemia as with insulinomas. Results of pancreatic imaging studies were normal in two patients and one patient had a pancreatic examination by computerized tomography and magnetic resonance imaging, with false-positive results. Two of the three patients had previously undergone a 50 per cent distal pancreatectomy in which the resected specimens were interpreted as normal in one patient and consistent with nesidioblastosis in the second. Both patients subsequently developed recurrent symptomatic hyperinsulinemic hypoglycemia that persisted despite dosage adjustments in diazoxide therapy. The oldest patient underwent a 95 per cent pancreatectomy at the initial surgical exploration because an insulinoma could not be identified. The other patients underwent a completion 95 per cent pancreatectomy. In both, histochemical examination of each specimen disclosed nesidioblastosis, characterized by clusters of islet cells interspersed throughout the exocrine tissue.