Preoperative Muscle Volume Predicts Graft Survival After Pancreas Transplantation: A Retrospective Observational Cohort Study.

BACKGROUND: Several studies have suggested that decreased muscle volume is associated with attenuation of immune function. The recipient's immune system is responsible for rejection of transplanted organs, which is a major cause of graft loss after transplantation. We aimed to determine whether muscle volume is correlated with graft survival after pancreas transplantation (PT). METHODS: Forty-three patients underwent PT for type 1 diabetes mellitus at our institution from August 2001 to May 2016. The quantity of skeletal muscle was evaluated using the psoas muscle mass index (PMI). The correlation between PMI and outcome after PT was assessed. RESULTS: A total of 32 and 11 recipients underwent simultaneous pancreas-kidney transplantation (SPK) and PT alone/pancreas after kidney transplantation, respectively. Patients with a surviving graft showed a significantly lower PMI than those with graft loss (P = .0451). We divided the recipients into two groups according to the PMI cutoff values, which were established using receiver operating characteristic curves. The cumulative graft survival rate was significantly higher in patients with a low PMI (P = .0206). A multivariate Cox regression analysis revealed that a low PMI (P = .0075) is an independent predictive factor for better graft survival. A low PMI was not a significant predictive factor for acute rejection, but was an independent predictive factor for graft survival after the first acute rejection (P = .0025). CONCLUSIONS: Our data suggest that muscle volume could be a predictor of graft survival after PT.

Laparoscopy-Assisted Spleen-Preserving Distal Pancreatectomy for Living-Donor Pancreas Transplantation.

BACKGROUND: Living pancreas transplantation plays an important role in the treatment of patients with severe type 1 diabetes. However, pancreatectomy is very invasive for the donor, and less-invasive surgical procedures are needed. Although some reports have described hand-assisted laparoscopic surgery for distal pancreatectomy in living-donor operations, less-invasive laparoscopy-assisted (LA) procedures are expected to increase the donor pool. We herein report the outcomes of four cases of LA spleen-preserving distal pancreatectomy (Warshaw technique [WT]) in living pancreas donors. PATIENTS AND METHODS: Four living pancreas donors underwent LA-WT at our institution from September 2010 to January 2013. All donors fulfilled the donor criteria established by the Japan Society for Pancreas and Islet Transplantation. RESULTS: The median donor age was 54 years. Two donors underwent left nephrectomy in addition to LA-WT for simultaneous pancreas-kidney transplantation. The median donor operation time for pancreatectomy was 340.5 minutes. The median pancreas warm ischemic time was 3 minutes. The median donor blood loss was 246 g. All recipients immediately achieved insulin independence. One donor required reoperation because of obstructive ileus resulting from a port-site hernia. Another donor developed a pancreatic fistula (International Study Group of Pancreatic Fistula grade B), which was controlled with conservative management. After a maximum follow-up of 73 months, no clinically relevant adverse events had occurred. These results were comparable with those of previous studies concerning living-donor pancreas transplantation. CONCLUSION: The LA-WT is a safe and acceptable operation for living-donor pancreas transplantation.

Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.

Controversy exists regarding the clinical significance of S100A2 in the progression of tumours. In pancreatic cancer, little is known about the role of S100A2. The aim of this study was to clarify the clinical significance of S100A2 expression in pancreatic carcinogenesis. We microdissected invasive ductal carcinoma (IDC) cells from 22 lesions, pancreatic intraepithelial neoplasia (PanIN) cells from five lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 38 lesions, pancreatitis-affected epithelial (PAE) cells from 16 lesions, and normal ductal cells from 18 normal pancreatic tissues. S100A2 expression in 14 pancreatic cancer cell lines, microdissected cells and formalin-fixed paraffin-embedded (FFPE) samples was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Microdissection analyses revealed that IDC cells expressed higher levels of S100A2 than did IPMN, PAE or normal cells (all comparisons, p < 0.007). Cell lines from metastatic sites expressed higher levels of S100A2 than those from primary sites. PanIN cells expressed higher levels of S100A2 than normal cells (p = 0.018). IDC cells associated with poorly differentiated adenocarcinoma expressed higher levels of S100A2 than did IDC cells without poorly differentiated adenocarcinoma (p = 0.006). Analyses of FFPE samples revealed that levels of S100A2 were higher in samples from patients who survived < 1000 days after surgery than in those from patients who survived > 1000 days (p = 0.043). Immunohistochemical analysis was consistent with qRT-PCR. S100A2 may be a marker of tumour progression or prognosis in pancreatic carcinogenesis and pancreatic cancer.

[21-year-old man with squamous cell carcinoma of the lung].

Lung cancer among people in their twenties is rare and accounts for only 0.1-0.4% of all cases. We describe a case of squamous cell carcinoma of the lung in a 21-year-old man. The otherwise healthy patient presented with a 1 month history of cough. Chest radiography showed a well-defined round mass 5 cm in size in the right lower lobe. Computed tomography also showed a 3 cm hilar lymph node. Bronchoscopy revealed a white polypoid mass obstructing the right basal bronchus. Transbronchial biopsy revealed poorly differentiated squamous cell carcinoma of the lung. Clinical diagnosis was T2N1M0, stage IIB lung cancer. Right lower lobectomy with mediastinal lymph node dissection was performed. Lymph node metastases were proven histologically in the pretracheal, subcarinal, hilar, and intrapulmonary regions. Pathological diagnosis was T2N2M0, stage IIIA lung cancer. Endobronchial and mediastinal lymph node metastases were found 2 months after surgery. He received 3 rounds of chemotherapy with cisplatin and docetaxel and irradiation to the right hilum and mediastinum at a total dose of 60 Gy in 30 fractions. He is alive 6 months after surgery.

[Endobronchial neurinoma treated with left lower lobectomy].

Benign endobronchial tumors are rare, and among these endobronchial neurinoma is extremely rare. We describe a case of endobronchial neurinoma successfully treated with left lower lobectomy. A 58-year-old man presented with an 8-month history of cough. During this period he was repeatedly treated with antibiotics for pneumonia of the left lower lobe. Chest X-ray showed atelectasis of the left lower lobe. Computed tomography (CT) of the chest showed a mass in the left main and lower lobe bronchi. Bronchoscopy revealed the mass almost completely obstructing the left main bronchus. Although transbronchial biopsy was inconclusive and yielded necrotic tissue with Aspergillus hyphae, lung cancer was highly suspected based on clinical and radiographic findings. He underwent left lower lobectomy and was discharged 14 days after surgery in good condition. Pathological diagnosis was an endobronchial neurinoma 4 cm in size arising from the left basal bronchus. On immunohistochemical staining, the tumor was positive for S-100 protein and negative for a-smooth muscle actin. He took itraconazole at a daily dose of 200 mg orally for 6 months. He remains well 52 months after surgery without any evidence of recurrence.

[Diffuse malignant pleural mesothelioma].

Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.

Detection of small particles in fluid flow using a self-mixing laser.

We describe a highly sensitive, real-time method of detecting small particles in a fluid flow by self-mixing laser Doppler measurement with a laser-diode-pumped, thin-slice solid-state laser with extremely high optical sensitivity. Asymmetric power spectra of the laser output modulated by the re-injected scattered light from the small particles moving in a dilute sample-flow, through a small-diameter glass pipe, were observed. The observed power spectra are shown to reflect the velocity distribution of the fluid flow, which obeys Poiseuille's law. Quick measurements of flow rate and kinetic viscosities of water-glycerol mixtures were also performed successfully. Measurable low-concentration limits for 262-nm polystyrene latex spheres and 3-mum red blood cells in a fluid flow were below 1 and 10 ppm, respectively, in the present self-mixing laser Doppler velocimeter system.

Endovascular surgery for ruptured aneurysms with vasospasm.

SUMMARY: With the existence of vasospasm, it is recommended that direct clipping surgery for a ruptured aneurysm be delayed until its disappearance, but this may be associated with aneurysmal re-rupture resulting in a poor outcome for the patients. Indications for endovascular coil embolization in such cases are discussed. Since November in 2003, we have applied endovascular coil embolization in 11 consecutive patients with ruptured aneurysms and apparent vasospasm of the parent artery from two to 17 days (average: eight days) after initial subarachnoid hemorrhage. Three patients had aneurysmal re-rupture before treatment, but the other eight had only experienced the one episode of subarachnoid hemorrhage. With one exception, all endovascular procedures could be successfully performed, resulting in complete occlusion of aneurysms and remarkable dilatation of inserted spastic vessels without technical complications or aneurysmal re-rupture. For the one case of failure because of a tortuous artery, direct clipping surgery was performed after disappearance of vasospasm. Cerebral infarction occurred in four, but only one correlated with the distribution of catheterization, and neurological deficits had completely disappeared three months after the onset. This preliminary report concerning a small number of patients suggests that endovascular coil embolization is not contra-indicated for aneurysms with vasospasm requiring catheterization. A large study for confirmation is now warranted.

[Long-term survival following multimodality treatment of metachronous metastases (parotid gland, adrenal gland, brain and mediastinal lymph node) after resection of non-small cell lung cancer; report of a case].

We describe a case of long-term survival following multimodality treatment of metachronous metastases (parotid gland, adrenal gland, brain and mediastinal lymph node) after resection of non-small cell lung cancer. A 72-year-old man had a past history of right upper lobectomy for pT3N0M0 tubular adenocarcinoma of the lung 12 years ago and left lower lobectomy for pT3N1M0 papillary adenocarcinoma of the lung 42 months ago, and left parotidectomy and irradiation to the neck for parotid metastasis 20 months ago. A progressive increase in serum CEA level during the follow-up period revealed a 5 cm left adrenal mass and small (1 cm or less) multiple brain metastases, and a 2 cm mediastinal lymph node. He underwent adrenalectomy and gamma knife surgery and received irradiation to the mediastinum, and was administered gefitinib as first-line chemotherapy for about a year. Brain metastases recurred despite 4 more rounds of gamma knife surgery and 4 cycles of docetaxel hydrate as second-line chemotherapy, and 1 cycle of vinorelbine ditartrate as third-line chemotherapy. He died of multiple brain metastases 65 months postoperatively. We confirm the possibility of long-term survival following multimodality treatment even though multiple organ metastases were found after resection of non-small cell lung cancer.

Successful coil embolization for a "three-hump" internal carotid artery anterior wall aneurysm: a case report.

SUMMARY: We describe an unusually shaped aneurysm arising from the anterior wall of the internal carotid artery (ICA) that was treated successfully with Guglielmi detachable coils (GDCs). A 38-year-old woman presented with sudden onset of headache and was transferred to our hospital. Computed tomography revealed thin subarachnoid hemorrhage in the basal cisterns. Three-dimensional rotational angiography clearly showed a "three-hump" anterior wall aneurysm of the ICA. The two distal humps of the aneurysm were successfully obliterated with GDCs, but the proximal hump was too small to treat by coil embolization. The patient was discharged without neurological deficit. Anterior wall (blisterlike) aneurysms of the ICA have a high risk of rupture due to fragility of the wall. These aneurysms are considered difficult to manage by traditional surgical approaches. Our experience suggests that endovascular GDC embolization is a good alternative treatment modality for patients with such an aneurysm.

Application of the liquid coil as an embolic material for arteriovenous malformations.

SUMMARY: The purpose of this paper is to clarify advantages and disadvantages of platinum liquid coils as an embolic material for AVMs. During the last eight years, 50 endovascular procedures using liquid coils were conducted in our institute for 19 cases with AVMs, 15 of which were located in the eloquent area. All but one presented with haemorrhage, the exception demonstrating repeated ischemic symptoms. Only liquid coils were used as the embolic material to obliterate the nidus and feeders. In ten of the 15 patients with AVMs located in the eloquent area and one case rejecting surgery, liquid coil embolization was applied one to 11 times (average 3.5 times) to achieve decrease in size and this was then followed by radiosurgery. The remaining eight AVM patients underwent total removal after liquid coil embolization. No complications were encountered during the peri-embolization period. In all cases, the purpose of embolization was to diminish the size to facilitate radiosurgery and decrease bleeding during surgery. The liquid coil has advantages as a material for embolization of AVMs; it is non-toxic and bioinart material; it seldom occludes normal minute vascular channels; when it used in a nidus, it seldom to migrates in the venous direction, and it has good radio-opacity and offers good marking for surgery. Appropriate applications include preoperative embolization or pre-radiosurgical embolization of AVMs, especially when staged embolizations are performed to reduce risk of perfusion pressure breakthrough in patients which are large or located in the eloquent area.

Differential gene-expression profiles associated with gastric adenoma.

Gastric adenomas may eventually progress to adenocarcinomas at varying rates. The purpose of the present study was to identify gene-expression profiles linked to the heterogeneous nature of gastric adenoma as compared to adenocarcinoma. Suppression subtractive hybridisation analysis was performed to extract relevant genes from two cases of low- and high-grade gastric adenomas. The identified genes were quantified by RT-PCR in 14 low-grade adenoma, nine high-grade adenoma and nine adenocarcinoma samples, followed by hierarchical clustering analysis to separate tumours into groups according to their gene-expression profiles. Nine genes previously implicated in carcinogenesis in a variety of organs, including three genes related to gastric adenocarcinoma, were identified. The overexpression of these genes in gastric adenoma has not been reported previously. The clustering analysis of these nine genes across 32 cases identified three groups, one of which consisted primarily of adenocarcinomas, whereas the other two groups consisted of adenomas. One group of adenomas, characterised by larger tumour size, exhibited gene-expression profiles of an intestinal cell lineage implicated in the pathogenesis of an intestinal-type gastric adenocarcinoma. Another adenoma group consisting of low-grade adenomas with smaller tumour size exhibited a unique expression profile. In conclusion, clustering analysis of expression profiles using a limited number of genes may serve as molecular markers for gastric adenoma with different biological properties. Although the prognostic values of these gene-expression profiles need to be evaluated in further follow-up study of adenoma cases, these findings add new insights to (a) our understanding of the pathogenesis of gastric tumours, (b) the development of specific tumour markers for clinical practice, and (c) the design of novel therapeutic targets.

Multiple arteriovenous malformations with hemorrhage.

BACKGROUND: A rare case of a left temporal arteriovenous malformation (AVM) with bleeding 10 days after removal of another hemorrhagic AVM in the frontal lobe is reported. METHOD: A 47-year-old man had an attack of headache and vomiting and was admitted to our hospital. On admission, a CT scan showed subcortical hemorrhage in the left frontal lobe. Left carotid angiography revealed four AVMs and a vertebro-basilar angiogram demonstrated a vascular malformation. FINDINGS: First, a hemorrhagic AVM was removed with a hematoma. Following the operation, left carotid angiograms continued to show, AVMs, particularly a temporal AVM with increased blood flow, and after 10 days this hemorrhaged. This was surgically resected and the remaining small AVMs were treated by stereotactic radiosurgery. INTERPRETATION: The patient had a high risk of hemorrhage. Adding hemodynamic stress to this situation, hemorrhage would have been expected to occur at an early time after the initial intervention for hemorrhagic AVM. Considering the risk of hemorrhage, other AVMs should undergo surgery as soon as possible after resection of hemorrhagic AVM.

Superselective arterial chemotherapy for inoperable metastases in the dura mater and cranium.

SUMMARY: Diffuse metastases to the cranium and dura mater of the bilateral hemisphere do not allow surgical intervention. We describe an excellent case which was treated by intra-arterial chemotherapy using Epirubicine (Farumorbicine). A 58-year-old woman treated for breast cancer ten years ago was admitted to our hospital with headache and frontal mass lesions.Magnetic resonance (MR) imaging on admission revealed a remarkable enhanced lesion of the bilateral dura mater and cranium, and bilateral brain edema in the frontal lobe. Angiography disclosed a vascular rich tumour supplied by bilateral external carotid artery branches.We successfully treated the lesion using superselective intra-arterial chemotherapy with a minimal dose of Epirubicine followed by embolization of bilateral external carotid artery branches. Followup MR imaging two years after the endovascular treatment showed disappearance of the enhanced lesion and remodeling of the skull bone. The patient is neurologically free of symptoms.

Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan.

OBJECTIVES: We sought to study the prevalence and mortality of subjects exhibiting the Brugada-type electrocardiogram (ECG) in a community-based population in Japan. BACKGROUND: The Brugada syndrome has been associated with sudden death in subjects without structural heart disease. Hospital-based studies showed 11% to 38% annual fatal arrhythmic events in patients with the Brugada syndrome. METHODS: Prevalence and mortality of the Brugada-type ECG were studied in subjects who had ECGs during a health examination in Moriguchi, Osaka, Japan. Information about death and relocation from Moriguchi city was obtained prospectively. RESULTS: The Brugada-type ECG was found in 98 of 13,929 study subjects (0.70%, 95% confidence interval [CI]: 0.57% to 0.86%). The typical coved-type with an rsR' pattern in V(1) lead ("typical" Brugada-type) was found in 0.12% of subjects (95% CI: 0.07% to 0.20%). The prevalence for male subjects with the Brugada-type ECG (81%) was significantly higher than it was for those without (26%, p < 0.0001). In male subjects, the Brugada-type ECG was found in 2.14% (95% CI: 1.70% to 2.66%), and the "typical" Brugada-type was found in 0.38% (95% CI: 0.21% to 0.64%). After 2.6 +/- 0.3 years of follow-up, there was 1 death (1.0%, 95% CI: 0.03% to 5.6%) of a subject with the Brugada-type ECG, whereas there were 139 deaths (1.0%, 95% CI: 0.85% to 1.2%) of those without the Brugada-type ECG (p = 0.9943, log-rank test). CONCLUSIONS: A substantial number of the Brugada-type ECG were observed in subjects in a community-based population in Japan, especially in men. The total mortality of subjects with the Brugada-type ECG did not differ from the mortality of those without the Brugada-type ECG in a community-based population.

Overexpression of interferon gamma-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization.

OBJECTIVE: To clarify gene expression profiles in the liver may elucidate the pathogenesis of type I autoimmune hepatitis (AIH). Using suppression subtractive hybridization (SSH), we identified genes overexpressed in the liver of AIH. METHODS: A small liver biopsy sample from a patient with definite AIH was available to be analyzed in our system. By mixing cDNA synthesized from this sample as a 'tester' and cDNA from a normal liver as a 'driver,' we subtracted cDNA to enrich genes overexpressed in AIH. After polymerase chain reaction (PCR) amplification and subcloning, we identified subtracted genes by sequencing 50 randomly selected clones. RESULTS: Only one cDNA fragment, which is identical to interferon inducible protein 10 (IP-10), was overexpressed by > 10 times in the liver of AIH, as compared with control. We confirmed IP-10 overexpression in all eight patients with AIH by reverse transcription PCR. Immunohistochemical analysis demonstrated increased IP-10 expression in hepatocytes in the liver of AIH. Reverse transcription PCR analysis of 63 liver biopsy samples with various liver diseases revealed that IP-10 expression was significantly higher in AIH (p = 0.025) and chronic hepatitis C (p = 0.0043) than in other liver diseases. Interestingly, the amount of IP-10 mRNA expression was correlated with serum ALT values in AIH (p = 0.0006), but not in chronic hepatitis C (p = 0.43). CONCLUSION: These results indicate the IP-10 expression in the liver might be used as a preferential marker of AIH, and that IP-10 has some pathophysiological roles in the liver damage of AIH.

Analysis of differentially expressed genes in human hepatocellular carcinoma using suppression subtractive hybridization.

The genetic basis of hepatocellular carcinoma (HCC) has not yet been fully understood. Although various methods have been developed to detect differentially expressed genes in malignant diseases, efficient analysis from clinical specimens is generally difficult to perform due to the requirement of a large amount of samples. In the present study, we analysed differentially expressed genes with a small amount of human HCC samples using suppression subtractive hybridization (SSH). Total RNA were obtained from the hepatitis C virus-associated HCC and adjacent non-HCC liver tissues. cDNA was synthesized using modified RT-PCR, and then tester cDNA was ligated with 2 different kinds of adaptors and hybridized with an excess amount of driver cDNA. Tester specific cDNA was obtained by suppression PCR and the final PCR product was subcloned and sequenced. We identified 7 known genes (focal adhesion kinase, deleted in colon cancer, guanine binding inhibitory protein alpha, glutamine synthetase, ornithine aminotransferase, M130, and pepsinogen C) and 2 previously unknown genes as being overexpressed in HCC, and 1 gene (decorin) as suppressed in HCC. Quantitative analysis of gene expression using quantitative RT-PCR demonstrated the differential expression of these genes in the original and other HCC samples. These findings demonstrated that it is possible to identify the previously unknown, differential gene expression from a small amount of clinical samples. Information about such alterations in gene expression could be useful for elucidating the genetic events in HCC pathogenesis, developing the new diagnostic markers, or determining novel therapeutic targets.

Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement.

AIM: The aim of this study was to examine the effectiveness and toxicity of radiation therapy in combination with transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with extensive portal vein tumor thrombus (PVTT). METHODS: The combined therapy was performed in 24 HCC patients with extensive PVTT. External radiation targeted for PVTT (50 Gy in 2 Gy fractions) was performed in combination with repetitive TACE for intralobar lesions using 30-60 mg epirubicin every 3 months, and associations of the following variables with the survival rate were evaluated: gender, age, viral etiology, Child's class, performance status, extrahepatic metastasis, size and number of HCC, and location of PVTT. RESULTS: The local response confined to PVTT was complete response (CR) in four patients, partial response (PR) in eight patients, no change (NC) in eight patients, and progressive disease (PD) in four patients. By using the stepwise Cox's regression analysis, only Child's class was associated with the survival rate. The survival rates after 1 and 2 years were 73 and 21% in Child's A, 10 and 0% in Child B or C, and 61 and 21% in patients in whom the local response was CR or PR, and 19 and 9% in those in whom the local response was NC or PD, respectively. By using the multiple logistic regression analysis, Child's class was the only factor associated with the local response (P = 0.006). CONCLUSIONS: The combined therapy is feasible and may be useful to reverse PVTT in patients with good hepatic function reserve.