Type 1 diabetes mellitus and isolated adrenocorticotropin deficiency manifested by parkinsonism: a case report and literature review.

A 67-year-old woman developed isolated adrenocorticotropin deficiency (IAD), which manifested as lethargy, a 20-kg body weight loss, hypoglycemia, and parkinsonism, and began corticosteroid replacement. Her symptoms resolved rapidly, and her weight returned to normal within six months. However, she then developed slowly progressive type 1 diabetes mellitus (T1D) with co-existing Hashimoto thyroiditis, and commenced insulin therapy. To our knowledge, this is the first reported case of parkinsonism associated with IAD. In addition, because diabetes mellitus, including T1D, could be latent in patients with untreated IAD, careful assessment of glucose metabolism is needed after commencing corticosteroid replacement until weight regain is achieved.

Hyaluronic acid secretion by synoviocytes alters under cyclic compressive load in contracted collagen gels.

Knee osteoarthritis is a degenerative disease of diarthrodial joints. Biomechanical factors are considered as risk factors for the disease, the knee joint being normally subject to pressure. Some studies have examined the biomechanical environment of the knee joint in vitro. The aim of this study was to establish a culture model to mimic the knee joint environment. As a first step, synoviocytes induced contraction of three-dimensional collagen gels. Next, contracted collagen gels containing synoviocytes underwent cyclical compression ranging from 0 to 40 kPa at a frequency of 1.0 Hz for 1.5, 3, 6 and 12 h using the FX-4000C™ Flexercell(®) Compression Plus™ System. RNA in collagen gels was extracted immediately after compression and mRNA expression levels of HAS genes were analyzed by quantitative RT-PCR. Culture medium was collected 48 h after compression and analyzed by agarose gel electrophoresis and cellulose acetate electrophoresis. Synoviocytes in contracted collagen gels were stimulated by cyclic compressive load. Long-term compressive stimulation led to the production of higher molecular weight hyaluronic acid, whereas, short-term, compressive stimulation increased the total amount of hyaluronic acid. Furthermore, mRNA expression levels of both HAS-1 and HAS-2 were significantly higher than without compression. Taken together, using this gel culture system, synoviocytes synthesized higher molecular weight hyaluronic acid and produced large quantities of hyaluronic acid through up-regulation of HAS gene expression. Therefore, the contracted collagen gel model will be a useful in vitro three-dimensional model of the knee joint.

Construction of collagen gel scaffolds for mechanical stress analysis.

We designed a cyclic compression system using readily available six-well culture plates to investigate the influence of mechanical stress on skin-like structures. The effects of cyclic mechanical stress on protein expression by cells were easily examined, and hence, this system should be useful for further analysis of skin responses to mechanical stress.

Effect of strain on human dermal fibroblasts in a three-dimensional collagen sponge.

Our aim was to design a simple compression system and investigate the influence of mechanical stress on skin-like structures. Many mechanical compression studies have employed intricate culture systems, so the relationship between extracellular matrix material and the response of skin cells to mechanical stress remains unknown. Our approach uses only glass vials, 6-well plates and standard laboratory equipment. We examined the influence of mechanical stress on human skin fibroblasts embedded within a collagen sponge. The results show that mechanical compression increases MMP-1 and MMP-2 release by the cells into the the cell culture. Our results suggest that pressure on the skin may affect extracellular matrix degradation through some as yet unidentified pathways and that IL-6 mRNA expression may be involved in this effect. Using our approach, the effects of static mechanical stress on protein expression by cells in the culture medium and in sponges can be easily examined, and therefore this system will be useful for further analyses of skin responses to mechanical stress.

[A patient with middle bile duct cancer who showed rapid obstruction on contrast radiographs 1 week after insertion of a non-covered stent, but this case obtained a long-term stent opening and long survival after re-insertion of a covered stent].

A 73-year-old female with jaundice was referred to our department and admitted. Blood examination on admission showed an abnormal liver function and an increase in CA19-9. Ultrasonography of the abdomen revealed a well-delineated round mass in the middle bile duct. After admission, PTBD was performed, and a complete obstruction was observed in the middle bile duct. Cytological examination of the bile demonstrated adenocarcinoma. Based on these findings, a diagnosis of middle bile duct cancer was made. Because of delirium and frequent wandering during the night due to dementia, a radical operation was abandoned, and a non-covered stent was placed. However, since 1 week after insertion of a non-covered stent, contrast radiography showed tumor protrusion (rapid obstruction) in the stent, and a covered stent was placed in the stent. The stent was open for 486 days after stent re-insertion. PTBD was performed for re-obstruction, but she died 596 days after admission. In patients for whom surgery is impossible for reasons other than tumor factors, internal fistula construction using a metallic stent, which neither impairs QOL nor shorten survival, can be indicated.

Carcinoid tumor of the Vater's papilla presenting with chronic pancreatitis--a case report--.

Carcinoid tumors are common in the duodenum except for in the Vater's papilla [1-9]. We report here a case of carcinoid tumor arising in the Vater's papilla with repeated episods of pancreatitis. The patient is a 28 year-old-woman who had repeated abdominal pain with elevated serum amylase and had been treated as chronic pancreatitis. Computed tomography (CT) revealed a slight dilatation of the main pancreatic duct from the pancreatic head to the tail, and mild swelling of the pancreas. A submucosal tumor measuring 1.3 cm in diameter was detected in the ampulla of Vater by esophagogastroduodenscopy (EGD), and total papillectomy was performed under the suspicious of carcinoid tumor. The tumor was not encapsulated, 1.0 cm in diameter, undefined, and whitish in color. Histologically monomorphic tumor cells with lightly eosinophlic cytoplasm and round nuclei proliferate in trabecular and solid patterns. Immunohistochemically tumor cells were positive for neuron-specific enolase, chromogranin A and synaptophysin, and the tumor was diagnosed as carcinoid tumor. It should be noted that carcinoid tumor in the ampulla may occur with initial signs of acute or chronic pancreatitis.

A case of pulmonary embolism after abdominal angiography.

The patient was a 72-year-old woman who had been diagnosed with cholecystolithiasis and had undergone laparoscopic cholecystectomy. Since the postoperative pathologic diagnosis was a gallbladder cancer with a depth of wall penetration of subserosa, she was admitted to Kurume University Hospital for a second-look operation. After admission, abdominal angiography was performed with a right femoral arterial puncture. After the release of inguinal compression with a belt, chest pain and difficulty in breathing appeared. Despite her normal blood pressure, arterial blood gas analysis showed a PO2 of 74.7 mmHg and a PCO2 of 41.5 mmHg, representing a slight decrease in PO2. Chest X-rays showed an increased cardiothoracic ratio and decreased lucency in the left upper lung field. The electrocardiogram revealed atrial premature contraction. Cardiac ultrasound did not show expansion of the right heart and blood vessels or abnormal structures in the main pulmonary artery. Since lung perfusion scintigraphy revealed perfusion defects in the left upper to middle and right upper lung fields, acute pulmonary embolism was diagnosed, and oxygen inhalation, thrombolytic, and anticoagulant therapy were instituted immediately. The symptoms improved the following day, but 240,000 u/day of urokinase was administered for 5 days, and 1,500 u/day of heparin for 10 days. On lung perfusion scintigrams 6 days later, the defects had disappeared. Moreover, no definite abnormal shadows were noted on chest X-rays. Radical surgery for gallbladder cancer was performed 3 weeks later. Considering the possible development of pulmonary embolism, we felt the need for careful management if the patient is released from bed rest after abdominal angiography.

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma.

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.

Evaluation of resection of the papilla of Vater for the treatment of cancer in the papilla of Vater.

We evaluated the resection of the papilla of Vater performed in patients with cancer in the papilla of Vater. The subjects were 6 patients who underwent resection of the papilla of Vater between January 1969 and December 2001. The patients aged 57-87 years consisted of 3 males and 3 females. The maximal diameter of the tumors was 0.5 cm in 1 patient, 1.5 cm in 3 patients, and 2.0 cm in 2 patients. Macroscopically, the tumors were of the protruded type (exposed) in 3 patients, of the mixed type (predominant protruded type) in 2 patients, and of the ulcerative type in 1 patient. The histological depth of the tumors was up to the mucosa in 1 patient, up to the oddi in 1 patient, up to the panc0, du1 in 1 patient, up to the panc1, du2 in 1 patient, and unknown in 2 patients. Histologically, the tumors were papillotubular adenocarcinoma (pap-tub) in 4 patients and tubular adenocarcinoma of the well-differentiated type (tub1) in 2 patients. Resection of the papilla of Vater was chosen because of high risk factors such as advanced age in 2 patients, complicated severe cirrhosis and confinement to bed due to poor systemic conditions after intracerebral hemorrhage in 3 patients, and hepatic metastasis observed during surgery in 1 patient. Residual cancer cells around the excised region were positive in 4 patients and unknown in the remaining 2 patients. Of the 6 patients, 5 died within 2 years after surgery, but 1 is alive without symptoms of recurrence 7 years after surgery. The death causes were the primary disease in 3 of the 5 patients. From the viewpoint of radical treatment, resection of the papilla of Vater cannot be chosen as a reduced surgery for cancer in the papilla of Vater. However, resection of the papilla of Vater can be applied to very elderly patients and patients under poor systemic conditions, for whom pancreatoduodenectomy (PD) is considered excessively invasive due to a small diameter of tumor.

Two cases of acute cholecystitis in which percutaneous transhepatic gallbladder aspiration (PTGBA) was useful.

We report 2 patients with acute cholecystitis for which percutaneous transhepatic gallbladder aspiration (PTGBA) was useful. In Case 1, the patient was a 75-year-old woman who experienced a sudden onset of back pain and upper abdominal pain at night. Abdominal ultrasound (US) showed enlargement of the gallbladder with thickening of the wall, a sonolucent layer, and a stone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance imaging (MRI) demonstrated thickening of the gallbladder wall and 2 areas of low-intensity signal. The pain and fever persisted, for which we performed PTGBA, aspirating about 113 ml of infected bile. Subsequently, the pain and fever subsided, and abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the eighth day after PTGBA, open abdominal cholecystectomy was performed. In Case 2, the patient was a 56-year-old woman who had right hypochondriac pain after supper. The pain gradually increased in severity. Abdominal US showed enlargement of the gallbladder with a thickened wall, a sonolucent layer, and a gallstone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance cholangiopancreatography (MRCP) showed enlargement of the gallbladder with no abnormalities in the common bile duct. After admission to hospital, the pain and fever persisted, for which we performed PTGBA, aspirating about 50 ml of infected bile. Subsequently, the pain and fever vanished. Abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the seventh day after PTGBA, laparoscopic cholecystectomy was performed. PTGBA seems useful for early alleviation of the symptoms of acute cholecystitis because of low invasiveness and ease of performance.

[Intra-arterial chemotherapy with gemcitabine (GEM) for unresectable pancreatic cancer].

PURPOSE: Most patients with pancreatic cancer are unresectable because of local invasion and liver metastasis at the time of diagnosis. To date, no treatment has had a significant impact on this disease. To deliver a high concentration of drug to the cancer, intra-arterial chemotherapy with GEM was performed in two patients with unresectable advanced cancer. PATIENTS AND METHODS: One patient, a 70-year-old man with liver metastasis, was treated with arterial infusion of GEM 1,000 mg/body. Another patient, a 55-year-old woman with local invasion and distant metastatic lymphadenopathy, was given intra-arterial infusion of GEM 400 mg and intra-venous infusion of GEM 1,000 mg/body. The patients were given GEM weekly for 3 weeks followed by a week of rest. RESULTS: In the first patient, the pain went away and CEA was decreased for 6 months. After that, the patient died due to intra-abdominal dissemination within 4 months. In the other patient, the pain went away. Tumor markers, such as CEA and CA19-9, were normalized and primary pancreatic cancer was reduced locally. The patient currently has a metastatic liver tumor, but she has had a significant improvement in performance status. CONCLUSION: Intra-arterial chemotherapy with GEM may be tolerated in patients with unresectable pancreatic cancer.

Surgical treatment for chronic pancreatitis: results of pancreatic duct drainage operation and pancreatic resection.

Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically treated at the Surgical Department of Kurume University Hospital. Of these patients, 30 were treated by pancreatic duct drainage operation (drainage operation), while 40 were treated by pancreatic resection, and the results were compared between the two groups. In patients who underwent drainage operation, pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%. In patients who underwent pancreatic resection, pain disappeared in 73.4%, slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no significant difference in the pain-relieving effect between the two groups. However, the pain-relieving effect was poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. In addition, all patients who showed poor results for pain relief had alcoholic pancreatitis. Endocrine and exocrine functions of the pancreas were improved in 6, maintained in 2, and exacerbated in 4 patients who underwent drainage operation. In patients who underwent pancreatic resection, endocrine and exocrine function of the pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore, endocrine and exocrine function of the pancreas were poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. Distant results in patients who underwent drainage operation were good in 75.0%, fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection, distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore, favorable distant results were obtained in both groups. These findings suggest that surgical techniques that preserve functions of the pancreas should be selected during surgical treatment for chronic pancreatitis. We consider that the presence or absence of main pancreatic duct dilation and the site of pancreatic lesions are important indices for selecting surgical techniques. Therefore, drainage operation consisting of pancreaticojejunostomy should be indicated for patients with main pancreatic duct dilation, while pancreatic resection should be indicated for those without main pancreatic duct dilation, those with localized pancreatic lesions, and those with suspected pancreatic cancer.

A case of gallbladder cancer associated with pancreaticobiliary maljunction.

We report a case of gallbladder cancer associated with pancreaticobiliary maljunction. The patient was a 60-year-old woman who consulted a local doctor because of discomfort in the right hypochondriac region. Abdominal ultrasonography (US) showed a gallbladder abnormality, and she was referred to Kurume University Hospital, where she was hospitalized for further study and surgery. Abdominal US revealed a sessile tumor with an irregular surface in the fundus of the gallbladder. The internal echo of the tumor was nonhomogeneous, and the structure of the gallbladder wall was partly torn. The common bile duct and the left intrahepatic bile duct were dilated. Abdominal computed tomography (CT) showed an elevated lesion with the same degree of imaging effect as that of the liver on the peritoneal side of the fundus of the gallbladder. The structure of the gallbladder was preserved, and the gallbladder was well demarcated from the surrounding tissue. No hepatic or lymph node metastases were noted. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the pancreaticobiliary maljunction where the pancreatic duct joined the bile duct, entering an approximately 2-cm-long common channel. Dilatation of the common bile duct and intrahepatic bile ducts was observed and diagnosed as the IV-A type according to the Toya classification. Abdominal angiography in the arterial phase showed dilatation of the cystic artery and hyperplasia of vessels but no apparent encasement. In the venous phase, a deep-staining tumor was observed. From the above findings, we made a diagnosis of gallbladder cancer complicating pancreaticobiliary maljunction, and performed an operation. Since intraoperative US showed that the outermost layer of the gallbladder was in part ill-demarcated, we diagnosed the depth of penetration as ss, and performed cholecystectomy and bile duct resection and hepatic resection (S4a and S5), and lymphnode dissection (D2; dissection of groups 1 and 2 lymphnodes). The resected specimen grossly showed a papillomatous lesion with a cauliflower-like surface. The histopathologic diagnosis was papillary adenocarcinoma, depth ss, stage II. Tumor cells proliferated in a papillomatous pattern and were mostly confined to the muscular coat but partly infiltrated into the subserosal coat. In the diagnosis of pancreaticobiliary maljunction, it is crucial to consider complicating gallbladder cancer.