Rectovaginal fistulography: a technique for the identification of recurrent elusive fistulas

Introduction and hypothesis  The purpose of this study is to review our experience with a technique for diagnosing small rectovaginal fistulas that occasionally permit passage of air or mucus. Methods  During an in-office visit suspicious areas of the vagina were probed with a cone-tip catheter and injected with a contrast dye to visualize the suspected fistula tract communicating to the rectum under fluoroscopic guidance. The fistulous tracts were further isolated using a flexi-tip glide wire. Results  Five out of nine patients were found to have fistulas not diagnosed by other means. Three patients had recurrent rectovaginal fistula after a vaginal delivery, one patient was identified with a high rectovaginal fistula due to diverticular disease, and one patient had a rectovaginal fistula due to prior hemorrhoidectomy. One patient had a negative test, and the fistula that was diagnosed intraoperatively was due to underlying Crohn’s disease. Conclusion  Direct fistulography is a useful technique to visualize otherwise elusive symptomatic rectovaginal fistula tracts.     

Roux-en-Y reconstruction using staplers during pancreaticoduodenectomy: Results of a prospective preliminary study

Purpose  The aim of this study was to reveal the utility of alimentary reconstruction using staplers during pancreaticoduodenectomy (PD), focusing on the occurrence of delayed gastric emptying. Methods  Between 2003 and 2007, 72 PDs with alimentary reconstruction were performed by a single surgeon. Since August 2006, the new Roux-en-Y reconstruction methods using staplers were applied in 26 of the patients. We compared their clinical outcomes with those of the 46 patients who underwent PD using the conventional hand-sewn reconstruction methods. Results  The results of upper gastrointestinal study showed improvement within 10 postoperative days (PODs; P = 0.03): the patients resumed eating their regular diet sooner (13 vs 6 days, P < 0.001), and both the incidence of delayed gastric emptying (43% vs 19%, P = 0.04) and the hospital stay (27 vs 21 days, P = 0.008) were reduced significantly in patients with stapled reconstruction. Despite the fact that operative costs were significantly higher for patients with stapled reconstruction (P = 0.009), hospital costs were significantly lower (P = 0.049) for those who underwent the conventional method. Conclusions  Our retrospective analysis shows that stapled reconstructions might reduce the incidence of delayed gastric emptying; however, further study will be necessary to evaluate the utility of this new method.     

Prognostic Factors After Resection of Pancreatic Cancer

Objectives  The purpose of this study was to identify important prognostic factors related to the status of a pancreatic tumor, its treatment, and the patient’s general condition. Methods  Between April 1992 and December 2006, 140 patients underwent a pancreatic resection for invasive ductal carcinoma. Prognostic factors were defined by univariate and multivariate analyses. Results  The study included 103 tumors in the head of the pancreas and 37 tumors in the body or tail. The median survival time and the actuarial 5-year survival rate for all patients were 14.5 months and 12.3%, respectively. Using the significant prognostic factors identified by univariate analysis, multivariate analysis revealed that a preoperative serum CA19-9 concentration >100 U/ml (HR = 1.84, p = 0.0074), a tumor size >3 cm (HR = 1.74, p = 0.0235), venous involvement (HR = 2.39, p = 0.0006), a transfusion requirement of ≥1000 ml (HR = 2.23, p = 0.0006), and a serum albumin concentration on 1 postoperative month (1POM) < 3 g/dl (HR = 2.40, p = 0.0009) were significant adverse prognostic factors. The presence of hypoalbuminemia on 1POM significantly correlated with a longer surgical procedure (p = 0.0041), extended nerve plexus resection around the superior mesenteric artery (p = 0.0456), and a longer postoperative hospital stay (p = 0.0063). Conclusion  To improve long-term survival, preserving the patient’s general condition by performing a curative resection with a short operation time and minimal blood loss should be the most important principle in the surgical treatment of pancreatic cancer.     

Enterovirus Infection, CXC Chemokine Ligand 10 (CXCL10), and CXCR3 Circuit: A Mechanism of Accelerated ��-Cell Failure in Fulminant Type 1 Diabetes

OBJECTIVE

Fulminant type 1 diabetes is characterized by the rapid onset of severe hyperglycemia and ketoacidosis, with subsequent poor prognosis of diabetes complications. Causative mechanisms for accelerated β-cell failure are unclear.

RESEARCH DESIGN AND METHODS

Subjects comprised three autopsied patients who died from diabetic ketoacidosis within 2–5 days after onset of fulminant type 1 diabetes. We examined islet cell status, including the presence of enterovirus and chemokine/cytokine/major histocompatibility complex (MHC) expressions in the pancreata using immunohistochemical analyses and RT-PCR.

RESULTS

Immunohistochemical analysis revealed the presence of enterovirus-capsid protein in all three affected pancreata. Extensive infiltration of CXCR3 receptor–bearing T-cells and macrophages into islets was observed. Dendritic cells were stained in and around the islets. Specifically, interferon-γ and CXC chemokine ligand 10 (CXCL10) were strongly coexpressed in all subtypes of islet cells, including β-cells and α-cells. No CXCL10 was expressed in exocrine pancreas. Serum levels of CXCL10 were increased. Expression of MHC class II and hyperexpression of MHC class I was observed in some islet cells.

CONCLUSIONS

These results strongly suggest the presence of a circuit for the destruction of β-cells in fulminant type 1 diabetes. Enterovirus infection of the pancreas initiates coexpression of interferon-γ and CXCL10 in β-cells. CXCL10 secreted from β-cells activates and attracts autoreactive T-cells and macrophages to the islets via CXCR3. These infiltrating autoreactive T-cells and macrophages release inflammatory cytokines including interferon-γ in the islets, not only damaging β-cells but also accelerating CXCL10 generation in residual β-cells and thus further activating cell-mediated autoimmunity until all β-cells have been destroyed.Fulminant type 1 diabetes is characterized by abrupt onset of severe hyperglycemia and ketoacidosis preceded by flu-like symptoms including fever, abdominal pain, and headache (1–3). Due to the rushed clinical course in most cases, patients with fulminant type 1 diabetes are sometimes untreated until becoming comatose and/or entering a critical, life-threatening state (4). Endogenous insulin secretion is completely abolished over time and diabetic microangiopathies develop over a short duration (5,6). The mechanisms underlying the aggressive and rapid destruction of β-cells have remained one of the major questions regarding this subtype of type 1 diabetes. However, in situ human data on affected islets and pancreas and possible mechanisms have been completely lacking for fulminant type 1 diabetes.Viral infection with subsequent immunological mechanisms represents one of the leading candidates for destruction of β-cells in fulminant type 1 diabetes (3,7). Some studies on the mouse model of lymphocytic choriomeningitis virus–induced type 1 diabetes have demonstrated that islet β-cells can be destroyed as follows: within 1 day after virus infection, CXC chemokine ligand 10 (CXCL10) (8), a key chemoattractant for activated T-cells and macrophages, is produced in β-cells and secreted from islets (9). Activated T-cells bearing the receptor for CXCL10, named CXCR3 (8), infiltrate and accumulate in islets secreting CXCL10 (10). Accumulated T-cells at the islets then destroy β-cells through cell-mediated mechanisms (11). With this mechanism, CXCL10 is necessary and sufficient for accelerated T-cell response with complete β-cell destruction and resulting type 1 diabetes (10,12,13). We have recently found that serum CXCL10 levels are increased at the onset of fulminant type 1 diabetes, suggesting a crucial role of the CXCL10-CXCR3 axis in the aggressive β-cell destruction in this syndrome (14). We therefore examined in situ status with regard to enterovirus infection, CXCL10-CXCR3 axis, major histocompatibility complex (MHC) molecule expression, and islet dysfunction in pancreata from patients with fulminant type 1 diabetes who died due to diabetic ketoacidosis within 2–5 days after outset of flu-like symptoms. Our in situ findings for affected pancreata provide new insights into understanding the pathogenesis of and developing interventional strategies against human type 1 diabetes.     

Relation of stiffness parameter β to carotid arteriosclerosis and silent cerebral infarction in patients on chronic hemodialysis

Objective   Aortic stiffness measured by pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality in hemodialysis (HD) patients. However, there is a lack of information on stiffness parameter β, another index of arterial stiffness, in HD patients. The aim of the present study was to investigate the clinical usefulness of stiffness parameter β in HD patients. Materials and methods   We compared the relation of stiffness parameter β to carotid intima-media thickness (IMT) and plaque score estimated by carotid ultrasound and investigated the relationship between stiffness parameter β and silent cerebral infarction (SCI) in 64 HD patients. Results   Stiffness parameter β was positively correlated with mean IMT (r = 0.318, P = 0.0113) and plaque score (r = 0.672, P < 0.0001). Stepwise regression analysis revealed that pulse pressure and age were found to be independent determinants of stiffness parameter β (partial correlation coefficients: β = 0.501 and P < 0.0001 for pulse pressure, β = 0.488 and P < 0.0001 for age). In addition, stiffness parameter β in patients with SCI (12.2 ± 3.9) was significantly higher than those (8.0 ± 2.4) in patients without SCI. However, there was no significant difference in mean IMT and plaque score in both groups. Conclusion   These results suggest that arteriosclerosis assessed by stiffness parameter β is associated with atherosclerotic changes of carotid arteries and with the presence of SCI in HD patients.     

Rosai–Dorfman disease presenting as a solitary mediastinal mass

Rosai–Dorfman disease (RDD) involving an extranodal site is a diagnostic challenge. Reported herein is the case of a 67-year-old man who presented with a solitary superior mediastinal mass. The lesion was clinically suspected of malignancy including lymphoma because of its high uptake during a ⁶⁷Ga-scintigram and ¹⁸F-fluorodeoxyglucose–positron emission tomography. There was no evidence of spread of the disease. Histology of thoracoscopic biopsy specimens indicated granulomatous lesion with infiltration of lymphocytes, plasma cells, and histiocytes with lymphocytes engulfed in their cytoplasm. The lesion did not contain lymph node or thymic elements. On immunohistochemistry the histiocytes were positive for S-100 protein, CD68, and CD163 but were negative for CD1a. These findings suggested a diagnosis of RDD. Despite lack of intervention, the lesion remained almost the same size for 3 years. To the best of the authors' knowledge this is the first case of RDD presenting as a solitary mediastinal mass.     

Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low–intermediate in 86% of CNS DLBCL patients and high or high–intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.     

Genome-wide histone methylation profile for heart failure

Epigenetic alterations are implicated in the development of cardiac hypertrophy and heart failure, but little is known of which epigenetic changes in which regions of the genome play such a role. We now show that trimethylation of histone H3 on lysine-4 (K4TM) or lysine-9 (K9TM) is markedly affected in cardiomyocytes in association with the development of heart failure in a rat disease model. High-throughput pyrosequencing performed with ChIP products for K4TM or K9TM prepared from human left ventricular tissue with retained or damaged function also revealed that protein-coding genes located in the vicinity of K4TM marks differ between functional and disabled myocytes, yet both sets of genes encode proteins that function in the same signal transduction pathways for cardiac function, indicative of differential K4TM marking during the development of heart failure. However, K9TM mark-profile was less dependent on the disease status compared to that of K4TM. Our data collectively reveal global epigenetic changes in cardiac myocytes associated with heart failure.     

Bone Mineral Density Measurement at Both Spine and Hip for Diagnosing Osteoporosis in Japanese Patients

In Japan, spinal dual-energy X-ray absorptiometry (DXA) has been commonly performed for diagnosing osteoporosis but scanning the proximal femur is not done widely. The latest Japanese guidelines for prevention and treatment of osteoporosis, revised in 2006, recommend bone mineral density (BMD) measurement at both spine and hip for diagnosing osteoporosis, although there have been no reports that proved the necessity of those measurements. One thousand forty-one women and 485 men with clinical suspicion of osteoporosis were enrolled in this study, and DXA was performed at both spine and hip. The proportions of the patients who had inconsistency between diagnosis of osteoporosis from spinal DXA and that of hip were estimated. As a result, 22% of women and 15% of men had an inconsistency with the diagnosis of osteoporosis using DXA at each measurement site. There was inconsistency in diagnosing osteoporosis using DXA at the spine and proximal femur measurement sites. Because spine and femoral DXA measurements complement each other in the diagnosis of osteoporosis, BMD measurement at both spine and hip should be performed for all Japanese patients who are suspected osteoporosis, regardless of age and sex.     

Treatment for colorectal liver metastases: a review

Introduction  

Over the past decade, the emergence of surgical adjuncts such as portal vein embolization, two-stage hepatectomy, and ablative therapies not only decreases mortality and morbidity after an extended hepatectomy but also broadens the indication for surgical treatment of liver metastasis from colorectal cancer. Combination chemotherapeutic regimens, namely 5-fluorouracil/folinic acid with irinotecan or oxaliplatin, and targeted monochromal antibodies can downsize the tumor burden to the extent that formerly unresectable metastases can sometimes be excised.