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.     

Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

Melatonin treatment for rhythm disorder

Abstract We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome, who did not respond to treatments by vitamin B₁₂, bright light therapy, or hypnotics. In one patient, melatonin 5–10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep-wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from free-running pattern to delayed sleep phase pattern. However, melatonin re-administration after a 4-month drug-free interval failed to improve his free-running sleep-wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.     

Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development

The roles of IgE and mast cells on expulsion of adult Hymenolepis nana from the intestine were examined in mice. IgE-dependency was determined by comparing congenitally IgE-deficient SJA/9 and IgE-producing SJL/J mice infected with 50 H. nana eggs. Anti-H. nana IgE antibody was detected at three weeks post infection (p.i.) in SJL but not in SJA mice. The number of adult worms in the intestines of SJA and of SJL mice were similar at two weeks, but significantly more were found in SJA mice at three weeks p.i. Treatment of mice with anti-ɛ antibody also resulted in an increased worm burden at three weeks, suggesting participation of IgE in expulsion of H. nana. Intestinal mastocytosis was induced by infection regardless of the IgE status of the mice. Mast cell-dependency was tested in mast cell-deficient W/W^u and in normal littermate +/+ mice infected with 100 H. nana eggs. Anti-H. nana antibody was detected in both groups of mice at three weeks p.i. Worm expulsion seemed to be mast cell dependent because expulsion was less complete in W/W^u mice at three weeks p.i. Peripheral blood eosinophilia was comparable at three weeks p.i. in both IgE and mast cell sufficient and deficient mice. These results suggest that IgE and mast cells participate in the expulsion of H. nana adults from intestine in mice.     

Multiple primary malignancies in Japanese patients with renal cell carcinoma

AIM: To evaluate the incidence, nature and prognosis of multiple primary malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975 and 1998, 319 patients underwent an operation for RCC at Hokkaido University, Sapporo, Japan. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. Follow-up was obtained by thorough chart review or telephone interview, and ranged from 0 to 276 months (median 49.0 months). To analyze the influence of other primary malignancies on prognosis, overall and cause-specific survival rates of the patients with an antecedent or synchronous malignancy were compared to the remaining patients. RESULTS: Of the 319 patients there was at least one other malignancy in 38 patients (12%). Four patients had two other malignancies. The other malignancies were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty-two patients had gastrointestinal cancer. In cases of antecedent or synchronous diagnosis of other primary malignancies, RCC was commonly incidental, small or low-stage. Multivariate analysis using Cox's proportional hazards model showed that, for overall survival, the presence of other antecedent or synchronous malignancies was the second most significant prognostic factor, following the pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the incidence of other primary malignancies was not uncommon and these malignancies contributed to the prognosis of these patients. Therefore, the malignant potential of individual tumors should be paid careful attention in the management of these patients.     

A Ro/SS-A auto-antibody positive mother's infant revealed congenital complete atrioventricular block,followed by insulin dependent diabetes mellitus and multiple organ failure

We experienced a congenital complete atrioventricular block infant who was born from a Ro/SS-A antibody positive mother. Ro/SS-A antibody was also found in this baby which was presumed to be mediated by the maternal placenta. Temporary cardiac pacing was required at birth and pacemaker implantation was performed at 9 months. At 11 months of age, the baby fell into shock and experienced multiple organ failure because of diabetes mellitus-induced coma. The association between congenital complete heart block and the Ro/SS-A antibody is well known. However, the accompaniment of insulin-dependent diabetes mellitus has not been reported previously. As the Ro/SS-A antigen appears in the cytoplasm of many tissues, the possibility of an association between Ro/SS-A antibody and diabetes mellitus is difficult to deny. We report this rare case to draw attention to the possibility that babies who are born from an Ro/SS-A antibody positive mother may develop diabetes mellitus as well as congenital complete heart block.