Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-specific antigen-based cancer detection

PURPOSE: To examine value of prostate-speci fi c antigen (PSA) adjusted by prostate volume measured using transabdominal ultrasonography in prostate cancer detection among men with elevated PSA. METHODS: 238 men aged 79 years or younger with serum PSA levels of 2.0-20.0 ng/mL and normal digital rectal examination fi ndings were studied in terms of total and free PSA, prostate volumes with transrectal (TRUS) and transabdominal (TAUS) ultrasonography and transition zone volumes with TRUS prior to transrectal 10-core biopsy. In addition to sole PSA values and the free-to-total PSA ratio, volume-adjusted PSA values, PSA densities determined by TRUS (PSAD(TRUS)), and TAUS (PSAD(TAUS)), and PSA transition zone densities (PSATzD) were compared using receiver operating characteristic (ROC) analysis. RESULTS: Prostate cancer was diagnosed in 58 (24.4%) of the 238 men who underwent prostate biopsies. Of the areas under ROC curves (AUC) of studied parameters, PSATzD (AUC 0.751) was the best and signi fi cantly superior to PSAD(TAUS) (AUC 0.664, P = 0.007). However, PSAD(TAUS) exceeded PSA (AUC 0.559, P = 0.004) and showed potential capability of a one-fourth reduction in unnecessary biopsies without spoiling sensitivity (90%). Cancer detection rate was only 4.2% in the 48 patients whose prostate volume in TAUS was > 50 mL and PSAD(TAUS) was < 0.075. CONCLUSIONS: Since PSAD(TRUS) and PSATzD were signi fi cantly superior to PSAD(TAUS), TRUS is feasible as the standard fashion to determine prostate volume in the diagnosis of prostate cancers. However, TAUS is also worthwhile as it can improve the prostate cancer detection using sole PSA, and primary use of TAUS has the potential to reduce the substantial number of unnecessary biopsy safely.     

Selective effector mechanisms for the expulsion of intestinal helminths

In the middle of the era of molecular biology, much less attention is paid to in vivo phenomena. However, carefully designed experimental systems in vivo still can provide valuable information as to the mechanisms underlying the establishment and maintenance of host-parasite relationships. In this review we describe the advantage of using concurrent infections with appropriately chosen combinations of different genera or different maturation stages of parasites to segregate the cellular responses of the host. By means of simple experimental approaches we have found that mucosal mast cells and goblet cells, both of which have long been considered as non-specific effectors, are in fact highly selective and specific effector cells of the host defence mechanisms capable of acting on the establishment and the expulsion of intestinal helminths.     

Mucoid pseudocyst of the obturator nerve

A 71-year-old man visited the outpatients' clinic of National Saitama Hospital, Japan, complaining of pain in the right leg. Magnetic resonance imaging (MRI) revealed a cystic mass adjacent to the right side of the urinary bladder. He underwent the removal of the cystic mass and the pathological diagnosis was a mucoid pseudocyst of the obturator nerve. After tumor resection, the pain was diminished and he has been free of disease for 3 years.     

Prostate gland volume is a strong predictor of biopsy results in men 70 years or older with prostate-specific antigen levels of 2.0–10.0 ng/mL

PURPOSE: The incidence of prostate cancer, benign prostatic enlargement and serum level of prostate-specific antigen (PSA) increase with patient age. Intermediate elevation of PSA in elderly populations is apt to be considered insignificant. We evaluated the impact of PSA and prostate volume on the presence of non-palpable prostate cancer in elderly men with an intermediate level of PSA. MATERIALS AND METHODS: Clinical records of 154 men 70 years or older, with non-cancerous digital rectal examination findings and with serum PSA levels of 2.0-10.0 ng/mL, who underwent initial 6- to 10-core transrectal prostate biopsy, were reviewed for prostate volume, number of biopsy cores, PSA and associated parameters. Stepwise logistic regression and receiver operating characteristic (ROC) models were used to determine the impacts of the parameters on the biopsy results. RESULTS: Overall cancer detection rate was 40/154 or 26.0%. Prostate-specific antigen showed no significant association with the presence of prostate cancer (P = 0.59, Mann-Whitney U-test), while prostate volume did (P < 0.0001). On stepwise logistic regression analysis, prostate volume (P = 0.024, 95% CI 1.008-1.116) and biopsy core density (P = 0.017, 95% CI 4.76-7.12 x 10(6)) were independently associated with a cancer diagnosis, whereas PSA density was not an independent factor for a positive biopsy result. The area under the ROC curve for prostate volume was significantly superior to that of PSA (0.802 vs. 0.529; P = 0.012). CONCLUSIONS: In men 70 years or older with gray zone PSA, prostate cancer patients are equally distributed over any PSA range. Although PSA has less impact on cancer presence than mere prostate volume, prostate cancer would be detected in a substantial proportion of older patients with PSA levels of 2.0-10.0 ng/mL.     

An Evaluation of the Efficacy of Preoperative Therapy for Thoracic Esophageal Carcinoma Using Endoscopic Ultrasonography

Abstract: We performed endoscopic ultrasonography (EUS) to assess the therapeutic efficacy of thoracic esophageal carcinoma treatment and compared this assessment with that of histology. The subjects were 43 patients who underwent surgical resection following preoperative chemotherapy for advanced thoracic esophageal carcinoma. The region of maximal thickness and the cross-sectional area of the tumor were measured, and the percent reduction was taken to be the degree of reduction. Total assessment of metastatic lymph nodes was made on the basis of the degree of reduction in the major axis and cross-sectional area, and the three elements of morphology, border echo and inner echo. The histological findings were classified into Grades 0 through 3 according to criteria for the management of esophageal carcinoma and compared with the EUS findings. The reduction in tumor thickness was 30% or less in 16 patients, 14 (87.5%) of whom had Grades of 0 to 1. The degree of reduction was greater than 50% in 17 patients, 15 (88.2%) of whom had Grades 2 to 3. The degree of reduction was 60% or greater in eight patients, six (75%) of whom had a Grade of 3. Reduction in the cross-sectional area was less than 50% in 19 patients, 16 (84.2%) of whom had Grades of 0 to 1. Of the 19, all who showed a reduction of 30% or less had Grades of 0 to 1. The reduction in cross-sectional area was greater than 50% in 24 patients, 20 (83.3%) of whom had Grades of 2 to 3. A significant difference was noted in the correlation between reduction in thickness and histological assessment between Grades 0 to 1 and Grade 2 (p<0.01) and between of Grades 2 and 3 (p<0.02). The correlation between reduction in cross-sectional area and histological assessment was similar to that for reduction in thickness. None of the methods produced satisfactory results in relation to assessment of metastatic lymph nodes. Assessment of accuracy by down-staging did not prove useful.     

ENDOSCOPIC EVALUATION OF POST-FUNDOPLICATION ANATOMY AND CORRELATION WITH SYMPTOMATOLOGY

​ Open in a separate windowEndoscopic aspect of fundoplication anatomy: Normal aspect of Nissen fundoplication