Nonfunctioning islet cell carcinoma of the pancreas associated with massive intra-abdominal hemorrhage.

Pancreatic islet cell tumors are rarely associated with intra-abdominal hemorrhage. We report herein a rare case of nonfunctioning islet cell carcinoma associated with massive hemorrhage into the abdominal cavity caused by spontaneous rupture of the tumor. A 44-year-old man presenting with sudden upper abdominal pain was admitted to his local hospital on April 18, 1994. On April 19, a laparotomy was performed with the diagnosis of peritonitis. Massive hemorrhage of unknown origin occurred, and he was transferred to our hospital in a state of hypovolemic shock. Imaging findings revealed massive hematoma in the abdominal cavity and a hypervascular tumor arising from the body of the pancreas. Because the hemorrhage was life-threatening, an emergent re-laparotomy was performed on April 20. Apart from the massive hemorrhage, a pancreatic tumor (60 x 35 x 30 mm in size) with spontaneous rupture was noted. Distal pancreatectomy, combined with splenectomy and removal of the hematoma, was performed. Histological findings revealed an islet cell carcinoma of the pancreas with venous invasion. Peritoneal dissemination, liver metastasis, and lymph node metastasis were not observed. The patient is alive without recurrence 6 years and 5 months after the operation.

A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome.

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.

Malignant melanoma in the thymus.

A case of malignant melanoma in the thymus is reported. Diagnostic imaging demonstrated a left anterior mediastinal mass in a patient with giant pigmented nevus without malignant change. Histologic and cytologic specimens obtained from the tumor revealed that the tumor was malignant melanoma. Surgery revealed malignant melanoma in the left lobe of the thymus. Many cell nests of pigmented nevi were observed throughout the thymus. The malignant melanoma was thought to have originated from the nevocellular nevus in the thymus. This is the first report of malignant melanoma in the thymus.

Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C.

BACKGROUND/AIMS: To confirm the immune reaction of hosts in chronic hepatitis C, we examined the association of human leukocyte antigen (HLA) DR with the histopathological outcome including bile duct damage and steatosis, which are characteristic of hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-five patients with chronic HCV infection were examined. The pathological appearance of liver biopsy specimens was evaluated by both Knodell's histological activity index and examination of bile duct damage and steatosis. HLA DRB1 was determined by the polymerase chain reaction sequence-specific oligonucleotide probe method. RESULTS: HLA DRB1 1302 was found with significantly higher frequency in patients without than with bile duct damage (34.8% vs. 4.7%, p=0.0001, p corrected by Bonferroni's inequality method=0.002). It was also found more frequently in patients without marked portal lymphocyte infiltration (28.6% vs. 7.7%, p=0.0015, p corrected by Bonferroni's method=0.03). HLA DRB1 1101 was found more frequently in patients without than with piecemeal necrosis (p=0.004). In contrast, the frequency of HLA DRB1 1502 tended to be higher in patients with than without piecemeal necrosis and marked portal lymphocyte infiltration (p=0.015 and p=0.03, respectively). HLA DRB1 1201 and 0802 were seen more frequently in bile duct damage-negative (p=0.02) and piecemeal necrosis-negative patients (p=0.03), respectively. Interestingly, serum HCV levels of HLA DRB1 1302-positive patients were significantly higher than those of 1302-negative patients (mean: 7.7 Meq/ml vs. 3.1 Meq/ml, p=0.0007). CONCLUSION: These findings suggest that some histopathological changes in chronically HCV-infected livers could be caused by the host's immune reaction regulated by HLA DR.

[Antitumor effect of 5'-DFUR and PyNPase activity in colorectal cancer].

Following preoperative administration of 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with colorectal cancer, histologic antitumor effects as well as pyrimidine nucleoside phosphorylase (PyNPase) activities in cancerous tissues were examined. Fifty-five patients were randomly divided into two groups: Twenty-five patients received 5'-DFUR orally at a daily dose of 800 mg for 3 weeks before operation (Group A) and twenty-nine received no medication (Group B). PyNPase activities in cancerous tissues obtained from resected specimens in Group A and B were 49.7 +/- 21.6 and 66.6 +/- 40.0 U/mg prot, respectively, which were significantly higher than 25.5 +/- 14.1 and 22.1 +/- 11.2 U/mg prot in normal colorectal tissues. No significant difference was observed in PyNPase activities in cancerous tissues between Group A and B. PyNPase activities in cancerous tissues in Group A were no different either from 59.2 +/- 40.0 U/mg prot in biopsy specimens before administration of 5'-DFUR. Histologic anti-tumor effects were as follows: Grade 2, 1 case Grade 1b, 5; Grade 1a, 10; and Grade 0, 9. Although no correlation was observed between antitumor effects and PyNPase activities in cancerous tissues, antitumor effects of 2 cases in which PyNPase activities in cancerous tissues before administration of 5'-DFUR showed more than 100 U/mg prot were Grade 2 and 1b, respectively.

Phlebosclerosis of the colon with positive anti-centromere antibody.

A 56-year-old woman with symptoms of chronic bowel disease presented a peculiar calcification of the mesenteric vein of the ascending to transverse colon on barium enema study. The resected colon was hard and black. Histo-pathologic examinations demonstrated fibrous change of the colon with a calcified and hyaline-deposited mesenteric vein. No cell infiltration was observed. These findings were compatible with phlebosclerosis and also with systemic sclerosis. Positive anti-centromere antibody and Raynaud's phenomenon, hallmarks of a variant systemic sclerosis, the CREST syndrome were observed. We therefore speculated that the pathogenesis of the phlebosclerosis of the colon is related to the CREST syndrome.

Why couldn't an accurate diagnosis be made? An analysis of 1044 consecutive autopsy cases.

The protocols of 1044 consecutive patients autopsied between 1983 and 1997 at Sumitomo Hospital (Osaka, Japan) were retrospectively analyzed and the findings were compared with clinical diagnoses. In 73 cases, the clinical diagnosis apparently differed from the autopsy findings, and in six cases the origin of a malignant neoplasm remained unsolved even at autopsy. Of the 73 discrepant cases, 24 were a result of clinician misjudgment and a neglect to conduct further examinations. Missed diagnosis due to an erroneous pathological report, technical error of endoscopy, and misleading results obtained by new non-invasive technologies accounted for seven, nine, and 11 cases, respectively. Twenty-two cases were missed because the clinician could not carry out precise examination. It is concluded that advances in diagnostic technology and medical knowledge have not reduced the value of an autopsy.

Intradural spinal hibernoma: case report.

BACKGROUND: Hibernoma is a rare, benign tumor arising from vestigial remnants of brown adipose tissue. It usually affects muscle and subcutaneous tissue and is asymptomatic and slow growing. METHODS: A review of the worldwide literature contains about 110 cases of hibernomas. However, only two cases (including our case) of hibernoma located in the intradural spine have been reported. We present an extremely rare case of intradural extramedullary spinal hibernoma and summarize the magnetic resonance imaging (MRI) findings of the lesion. CASE DESCRIPTION: A 35-year-old woman suffered from motor weakness and numbness of the left upper extremity. Cervical spinal MRI revealed an intradural extramedullary mass at C7. She underwent surgery via the posterior approach and the lesion was completely removed. Histopathologic examination showed multivacuolated cells with centrally placed nuclei, and the diagnosis of hibernoma was made. CONCLUSIONS: Because the CT and MRI findings of hibernoma are almost same as those of other lipomatous tumors, a surgical specimen of this tumor is necessary to establish the correct diagnosis. Early diagnosis and total resection are necessary as some cases showed malignant features or rapid growth. Etiologically, the tumor may have developed by the ectopic growth or migration of adipose tissue.

Ectopic thymoma mimicking diffuse pleural mesothelioma: a case report.

A case of ectopic thymoma of the pleura with a particular growth pattern mimicking diffuse pleural mesothelioma is reported. Diagnostic imaging showed that the pleural tumor encased the entire left lung. The specimen biopsied from the tumor was composed of lymphocytes and epithelial cells, consistent with the mixed type of thymoma. The autopsy found no evidence of a mediastinal tumor. An involuted thymus was found in the parietal pleural tissue adhered to the apex of the left lung. The thymoma was thought to originate from the ectopic thymic tissue in the parietal pleura, as a lesion independent from the primary mediastinal thymoma, and spread along the pleura like diffuse mesothelioma.

Peripheral vascular reactions to smoking--profound vasoconstriction by atherosclerosis.

Analyses of direct effects of smoking on peripheral arteries were done using thermography, blood fluorometry and echography on 97 habitual smoker-diabetics without triopathy. There were found to be four types of thermographic changes following smoking, which varied according to the degree of atherosclerosis of the artery. The smoking-stimulated thermographic pattern in the control group of healthy volunteers was a small wavy pattern, fluctuating along the base line every few minutes within a temperature range of 1.0-1.5 degrees C (N type). In diabetics, four types of thermographic patterns were produced: normal (N) type as control, increasing (I) type (increasing in skin temperature), decreasing (D) type (decreasing in temperature), and F type (no changes in temperature). The most significant finding was the decreasing pattern which closely connected to clinical and echographic aspects of macroangiopathic changes. The increasing type was characterized by a paradoxical increase in temperature after smoking in order diabetics with good blood glucose control and who were less atherosclerotic. Blood flow was correlated to the skin temperature at the base state and changes after smoking. Moreover, blood flow changes measured by fluorometry suggest that vasoconstriction or vasodilatation following smoking took place. These results suggest that this smoking test might be a good tool for diagnosing for the degree of atherosclerosis and for its following up.

Multiple intramedullary spinal sarcoidosis: case report.

BACKGROUND: According to past reported cases, spinal intramedullary sarcoidosis has the radiologic characteristics of a single enhanced lesion with cord swelling. However, it is difficult to make a diagnosis using only radiologic examinations. Including our case, 20 cases have been reported of intramedullary spinal sarcoidosis. Only six cases were diagnosed as primary spinal sarcoidosis. We present a rare case of multiple spinal intramedullary sarcoidosis without cord swelling. CASE DESCRIPTION: This 63 year-old man was afflicted with progressive paraparesis and numbness of the lower extremities. Magnetic resonance imaging showed intramedullary lesions without cord swelling. The patient underwent biopsy for diagnosis and the specimen showed a noncaseating granuloma mainly composed of epitheloid cells. Postoperative corticosteroid therapy was effective and the lesion disappeared 1 month after the operation. CONCLUSIONS: Biopsy is a less invasive method and is useful for early diagnosis. Early diagnosis is important for spinal sarcoidosis so that high-dose corticosteroid therapy can be commenced while the lesion still has a good chance of being successfully treated.

Abnormal vasoreaction of peripheral arteries to cold stimulus of both hands in diabetics.

Abnormal vasoreactions of peripheral arteries to cold stimulus of both hands were studied in controls and NIDDM patients by measuring changes of toe skin temperatures using thermography, and compared with thickness and calcification of wall and inner diameters of popliteal and dorsal pedal arteries using B mode ultrasonic imaging. Cold stimulated vasoreactions were divided into four patterns: (1) normal type (skin temperature going up and down within 1 degree C on the basal line), (2) increasing type (temperature going up), (3) decreasing type (temperature going down) and (4) flat type (no change of temperature). The difference in patterns was suggested to be related to the degree of atherosclerotic changes of the dorsal pedal artery obtained from the ultrasonic studies. The mechanism of abnormal vasoreactions of arteries with atherosclerosis is not clear, but cold stimulated thermography may be a useful tool in evaluating the state of peripheral atherosclerosis.

Sclerosis of lytic metastatic bone lesions during treatment with pamidronate in a patient with adenocarcinoma of unknown primary site.

Pamidronate disodium is a second-generation biphosphonate, a group of compounds that are being used increasingly to inhibit bone resorption in disorders that are characterized by excessive bone loss such, as hypercalcemia of malignancy, osteoporosis, and Paget's disease. The precise mechanisms whereby bisphosphonates inhibit bone resorption are still not completely understood. Pamidronate has previously been reported to induce sclerosis of lytic bone metastases in patients with breast cancer. We have had a similar experience in a patient with multiple bone metastases due to adenocarcinoma of unknown primary site who developed massive consolidation of lytic bone lesions after therapeutic infusions of pamidronate, leading to a satisfactory quality of life.

Histologic changes in small cell lung carcinoma after treatment.

BACKGROUND: Small cell lung carcinoma (SCLC) has been divided into three subtypes: pure SCLC, mixed small cell/large cell carcinoma (mixed SC/LC), and combined SCLC. Patients with mixed SC/LC show a worse prognosis than those with pure SCLC. METHODS: Persistence of histologic subtype in SCLC in the primary sites during the course of treatment or in the different organs at autopsy was examined. For this purpose, biopsy or cytologic specimens before chemotherapy, and autopsy specimens from 175 patients with SCLC were reviewed. They included 147 (84%) men and 28 (16%) women with an age range of 29-83 (median, 65) years. RESULTS: The frequency of mixed SC/LC in the primary sites was statistically higher in autopsy (14.3%) than that in biopsy or cytology specimens (8.6%) (P < 0.05). At autopsy, involved organs were categorized into two groups according to frequency of appearance of mixed SC/LC, i.e., a higher frequency group, including the liver (31 of 85; 36.4%), adrenal gland (15 of 56; 26.8%), brain (6 of 9; 66.7%), and extrathoracic lymph nodes (17 of 59; 28.8%) and a lower frequency group, including the lung (metastatic sites) (12 of 102; 11.8%), pleura (8 of 74; 10.8%), and intrathoracic lymph nodes (12 of 94; 12.8%). The difference in frequency between these two groups was statistically significant (P < 0.05). CONCLUSIONS: These findings suggest that primary pure SCLC can progress to mixed SC/LC with an increased potential for distant metastasis.

[Chronic daily oral low-dose etoposide therapy for an aged patient with aggressive lymphoma: a successful case report].

A 72-year-old female from Fukuoka Prefecture was admitted to our hospital complaining of puffy face and general malaise in April, 1992. Physical examinations revealed generalized lymphadenopathy and hepatosplenomegaly complicated with superior vena cava syndrome. A histological diagnosis of diffuse large cell-type malignant lymphoma was made by cervical lymph node biopsy according to the Working Formulation. Immunohistochemical staining showed the lymphoma cells were of T cell lineage (CD43+). Though anti-human T lymphotropic virus type I (HTLV-I) antibody was positive, southern blot analysis of the cells did not reveal monoclonal integration of HTLV-I proviral DNA. Her liver and renal function were almost normal but there was slight elevation of LDH. Considering her age, oral administration of low-dose etoposide (25 mg/day) was started. In 4 days, her lymph nodes decreased in size with subjective improvements. Ten weeks later, examinations of the hand, ultrasonogram and CT scan showed lymphadenopathy and hepatosplenomegaly had disappeared completely. The neutrophil count was consistently above 1,500/microliters, with no remarkable adverse effects and only a moderate degree of alopecia. Thus, low-dose etoposide therapy was considered to be very useful in such a case of malignant lymphoma in the elderly.

Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat.

This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)