Long-term clinical and virological outcomes of chronic hepatitis C after successful interferon therapy

Clinical relevance of occult hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection(s) remains uncertain years after interferon (IFN) therapy for chronic hepatitis C. By 1993, 38 sustained virological responders (SVRs) showing HCV RNA clearance at 6 months post-treatment and 37 biochemical responders (BRs) with end-of-treatment alanine aminotransferase (ALT) normalization and subsequent 6-month stabilization within 2 x the upper limit of normal (ULN) were enrolled. They were monitored for 4.4-12 years (median 6.8), then 15 SVRs and 15 BRs underwent paired liver biopsies. Biopsy samples were tested for positive and negative HCV RNA strands, and HBV DNA surface and X sequences. All SVRs showed sustained serum HCV RNA clearance during follow-up, but hepatocellular carcinoma (HCC) developed in 4 (11%) SVRs. On paired liver biopsies, histological improvement was significant, but mild inflammation persisted in 87% of SVRs. Nonetheless, no HCV RNA sequence was amplified from liver tissues, and HBV DNA sequences were found in only one SVR. As for BRs, biochemical flare-up of >2 x ULN occurred at a 5-year risk of 41% (95% CI 24.7-56.4). The event was unpredictable but controllable by retreatment in 70%. Liver tissues after follow-up contained positive and negative HCV RNA strands, but no HBV DNA sequence was amplified. These results suggest that SVRs, albeit free of occult HCV and/or HBV infection(s) over a decade, retain mild liver inflammation and the risk of HCC. Occult HBV was also shown uninvolved in flare-up during follow-up of BRs.     

Primary somatosensory evoked magnetic fields elicited by sacral surface electrical stimulation

To explore the brain response to sacral surface therapeutic electrical stimulation (SSTES) for the treatment of refractory urinary incontinence and frequent micturition, evoked magnetic fields were measured in six healthy males. Electrical stimuli were applied between bilateral surface electrodes over the second through fourth posterior sacral foramens with intensity just below the pain threshold. Somatosensory evoked magnetic fields (SEFs) for the bilateral median (MN) and posterior tibial nerves (PTN) were also measured for the comparison. Sources of the early SEF peaks were superimposed on individual magnetic resonance images. The first peak latency for sacral stimuli, M30, occurred at 30.2 ± 0.8 ms (mean ± standard deviation, N = 6), with shorter latency than those for PTN stimulus (39.3 ± 1.4 ms, N = 12) and longer latency than those for MN stimulus (21.0 ± 0.9 ms, N = 12). The second peak latency for sacral stimuli, M50, occurred at 47.2 ± 2.9 ms (N = 6). Both M30 and M50 peaks showed a single dipole pattern over the vertex in the isofield maps. The equivalent current dipoles of M30 and M50 were both estimated near the medial end of the central sulcus with approximately posterior current direction. These results suggest that the sacral M30 and M50 are responses from the primary somatosensory cortex. The relatively long time lag between the onset and peak of M30 suggests that SSTES directly affects both the cauda equina and cutaneous nerve of the sacral surface.     

Analysis by comparative genomic hybridization of gastric cancer with peritoneal dissemination and/or positive peritoneal cytology

Peritoneal metastasis is an important prognostic factor in cases of gastric cancer. Although studies on comparative genomic hybridization (CGH) in gastric cancer have been reported, there are few reports on the peritoneal metastasis (P) and peritoneal cytology (CY) factors in this cancer. In this study, we analyzed the chromosomal changes in the primary tumor with a combination of laser microdissection analysis and CGH in an attempt to detect the unknown abnormal chromosomal regions. We analyzed 34 primary tumors, including 13 primary tumors with peritoneal metastasis (P1) and/or positive peritoneal cytology (CY1) using a combination of laser microdissection and CGH. The minimal overlapping regions in gains were assigned to 5p14 (46.2%), 7q21.3 (61.5%), 7q31 (46.2%), 7q36 (46.2%), 8q23 (53.8%), 15q26 (46.2%), 20q12 (61.5%), 20q13.1 (53.8%), and 20q13.2 (53.8%) in primary tumors with P1 and/or CY1. The minimal regions of losses that occurred most frequently were 4q34-q35 (23.1%) and 22q11.2 (23.1%). There were significant differences in the minimal regions of 5p14 (P=0.033), 7q21.3 (P < 0.0001), 7q31 (P=0.013), 7q36 (P=0.033), and 22q11.2 (P=0.048) between primary tumors with and without P1 and/or CY1. In this study, gain/amplification of 5p14, 7q21.3, 7q31, and 7q36, and loss of 22q11.2 were significant in gastric cancer cases with peritoneal dissemination and/or positive peritoneal cytology.     

Epigallocatechin gallate attenuates adhesion and migration of CD8+ T cells by binding to CD11b

BACKGROUND: Although green tea polyphenol catechin has been reported to have antiallergic and anti-inflammatory activities, the precise mechanisms of its effect on the immune system have been poorly investigated. OBJECTIVE: In this study, we aimed to elucidate the mechanisms of the anti-inflammatory effect of catechin. For this purpose, we studied the effect of 2 kinds of catechin, epigallocatechin gallate (EGCG) and epicatechin gallate, on peripheral blood CD8+ T cells, which play the key role in immune responses. METHODS: Isolated peripheral blood mononuclear cells or CD8+ T cells were incubated without or with catechin, and the changes in the surface expression of integrin molecules were investigated by flow cytometry and the direct binding of catechin to CD11b molecule by competitive ELISA. Also, the effect of catechin on the ability of CD8+ T cells to bind intracellular adhesion molecule 1 and to migrate in response to chemokines was evaluated by using the adhesion and migration assays. RESULTS: The 2 catechins directly bound to CD11b expressed on CD8+ T cells, which caused a consequent decrease of flow-cytometric CD11b expression. The effect was more prominent with EGCG than epicatechin gallate, and the impaired expression of CD11b induced by EGCG resulted in decreased ability of CD8+ T cells to adhere intercellular adhesion molecule 1, and consequently decreased migration in response to chemokines. CONCLUSION: We concluded that catechin, especially EGCG, by downregulating CD11b expression on CD8+ T cells and, in consequence, inhibiting infiltration of these cells into the sites of inflammation, is a promising new potent anti-inflammatory agent.     

Delayed Arterial Hemorrhage After Pancreaticoduodenectomy

Delayed arterial hemorrhage is a rare complication of pancreaticoduodenectomy that is associated with a high mortality and has no standard management. Between 2000 and 2011, 204 pancreaticoduodenectomies were performed, and there were 3 cases of delayed arterial hemorrhage. We reviewed the role of endoscopy, laparotomy, and interventional radiology the management of delayed hemorrhage. One patient presented with intraluminal bleeding and upper gastrointestinal endoscopy failed to identify the bleeding site. Two patients presented with bleeding from the drain tube. Laparotomy was performed in the patient with intraluminal bleeding and interventional radiology was employed for the other 2 patients. There was no hemorrhage-related mortality or rebleeding, but the patient who underwent laparotomy developed sepsis. Endoscopy may have no role in the initial management of delayed arterial hemorrhage after pancreaticoduodenectomy. Interventional radiology is less invasive compared with laparotomy, and may be considered as the first-line treatment for delayed arterial hemorrhage in pancreaticoduodenectomy patients.Key words: Pancreaticoduodenectomy, Postoperative hemorrhage, Interventional radiologyThe mortality rate of patients undergoing pancreaticoduodenectomy (PD) has decreased in recent decades, but complications still occur at a high rate of 30% to 50%.^1–5 Common complications of PD include pancreatic leakage, delayed gastric emptying, and intra-abdominal abscess. Hemorrhage only has an incidence of 2%–4%, but this complication is associated with a high mortality rate of 11% to 54%.^1–3 Because delayed hemorrhage is uncommon after PD, its management remains unclear. Here we present our experience with this complication and review the available therapeutic strategies.     

Effects of Collateral Vessel Occlusion on Oral Glucose Tolerance Test in Liver Cirrhosis

Alterations in carbohydrate metabolism associated with liver cirrhosis are characterized by a high serum insulin level and prolonged hyperglycemia on oral glucose tolerance test (OGTT). We measured plasma glucose, immunoreactive insulin (IRI), and C-peptide immunoreactivity (CPR) levels during a 75-g OGTT before and after varices obliteration in 10 cirrhotic patients with gastric varices. After obliteration, the indocyanine green retention rate was decreased and the portal flow velocity was increased. A significant decline in plasma glucose and IRI levels was also noted on OGTT. Moreover, the plasma glucose and IRI levels declined at 90 and 120 min in OGTT while they increased progressively by 120 min before obliteration. The levels of CPR were similar before and after treatment. These results indicate that decreased portal flow due to extrahepatic shunt and consequent impairment of insulin metabolism play a role in glucose intolerance observed in cirrhotic patients and that shunt occlusion improves glucose metabolism.     

Role of perfusion-weighted imaging at 3T in the histopathological differentiation between astrocytic and oligodendroglial tumors

Objective

The differentiation of oligodendroglial tumors from astrocytic tumors is important clinically, because oligodendroglial tumors are more chemosensitive than astrocytic tumors. This study was designed to clarify the usefulness of 3 T MR perfusion imaging (PWI) in the histopathological differentiation between astrocytic and oligodendroglial tumors. This is because there is a growing interest in the diagnostic performance of 3 T MR imaging, which has the advantages of a higher signal-to-noise ratio (SNR) and greater spatial and temporal resolution.

Materials and methods

This study retrospectively included 24 consecutive patients with supratentorial, WHO grade II and III astrocytic and oligodendroglial tumors (7 astrocytic, 10 oligoastrocytic, and 7 oligodendroglial tumors) that were newly diagnosed and resected between November 2006 and December 2009 at Hiroshima University Hospital. These patients underwent dynamic susceptibility contrast-enhanced (DSC) PWI relative cerebral blood volume (rCBV) measurements before treatment. Astrocytic tumors were designated as the astrocytic group, and oligoastrocytic and oligodendroglial tumors as the oligodendroglial group. The regions of interest with the maximum rCBV values within the tumors were normalized relative to the contra-lateral white matter (rCBVmax).

Results

The average rCBVmax of astrocytic tumors (2.01 ± 0.68) was significantly lower than that of the oligoastrocytic (4.60 ± 1.05) and oligodendroglial tumors (6.17 ± 0.867) (P < 0.0001). A cut-off value of 3.0 allowed to differentiate the oligodendroglial group from the astrocytic group at 100% sensitivity and 87.5% specificity.

Conclusion

The rCBVmax values obtained from 3 T MR PWI may be useful as an adjunct to the postoperative histopathological diagnosis of glioma patients.     

Proton beam therapy combined with chemotherapy for advanced cancer

Radiotherapy combined with chemotherapy(chemoradiotherapy)has been standard therapy for advanced cancer. The rationality of chemoradiotherapy is summarized in three points: 1)control of distant metastasis, 2)additional effect on tumor in irradiated field, and 3)diminution of adverse effects of radiation therapy by decreasing radiation dose. Though reports of proton therapy combined with chemotherapy are limited, this therapy will have a very important role in treating many advanced cancers.