High-dose intraoperative radiotherapy for unresectable pancreatic cancer

PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.     

Cytoreductive surgery and sandwich therapy with chemohyperthermic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer

Cytoreductive resection (RST), chemohyperthermic peritoneal perfusion (CHPP) and/or intra-aortic chemotherapy (IA-chemo) were performed for peritoneal dissemination in gastric cancer. Ninety-six patients with peritoneal dissemination were grouped into tubercular (TB), 40; nodular (ND), 31; diffuse (DF) type, 19; and others, 6, respectively, by the gross findings. Sixty-three patients underwent RST. Fifty-nine patients received CHPP by 10-liter heated saline. Thirty patients underwent intra-aortic catheterization for the IA-chemo. The 1-year and 2-year survival rate (1-ysr and 2-ysr) of the RST(+) group were 47% and 10% significantly greater than the 9% and 0% of the RST(-) group (p<0.001). The 1-ysr and 2-ysr of the CHPP(+) group were 37% and 11% significantly greater than the 27% and 0% of the CHPP(-) group (p=0.04). In the TB type the 1-ysr and 2-ysr of the former was 43% and 8% significantly greater than the 15% and 0% of the latter (p=0.04). But there was no significant difference in survival time between the CHPP(+) and the CHPP(-) group in the ND type (p=0.22) or in the DF type (p=0.42). The 1-ysr and 2-ysr of the IA-chemo(+) group were 49% and 19% significantly greater than the 27% and 2% of the IA-chemo(-) group (p<0.01). In the DF type the 1-ysr and 2-ysr of the former was 50% and 33% significantly greater than the 8% and 0% of the latter (p=0.02). However, there was no significant difference in survival time between the IA-chemo(+) and the IA-chemo(-) group in the TB type (p=0.06) or in the ND type (p=0.50). Moreover, the effect of the combination therapy of CHPP and IA-chemo (the sandwich therapy, SDW) were examined. The 1-ysr and 2-ysr of the SDW(+) group were 49% and 22% significantly greater than the 24% and 0% of the SDW(-) group (p=0.002). The sandwich therapy should be performed in addition to cytoreductive surgery for improvement of prognosis in the patient with intractable peritoneal dissemination.     

A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation

The authors report a patient carrying a missense mutation in exon 10 of tau that causes a substitution at codon 301 (P301S). Although the patient shares the rapidly progressive frontotemporal dementia of the other reported pedigrees with P301S, the clinical phenotype is unique in that parkinsonism was a major symptom in the early stage and because behavioral symptoms with dementia became prominent 2 years after the onset of the disease. This study substantiates the notion that tau mutations at codon 301 can show various phenotypes.     

Artificial ventilation-induced diffuse alveolar damage in rabbits: preliminary study of early detection on expiratory high-resolution computed tomography

RATIONALE AND OBJECTIVES: To investigate whether expiratory high-resolution computed tomography (HRCT) is more useful than inspiratory HRCT for the detection of early-phase diffuse alveolar damage. METHODS: Eleven anesthetized rabbits were scanned with both inspiratory and expiratory HRCT every 30 minutes during mechanical ventilation. Ten rabbits were killed after the detection of pulmonary abnormalities on both inspiratory and expiratory HRCT. The remaining rabbit was killed when the pulmonary abnormalities appeared only on expiratory HRCT. RESULTS: In four cases (36%), the abnormal findings were detected earlier on expiratory HRCT than on inspiratory HRCT. In seven cases (64%), the abnormalities appeared simultaneously on inspiratory and expiratory HRCT. In all 11 cases, the histopathological changes of areas with abnormal CT findings corresponded to the exudative or proliferative phase of diffuse alveolar damage. CONCLUSIONS: Expiratory HRCT has the potential to detect the abnormalities of diffuse alveolar damage earlier than inspiratory HRCT.     

Systemic inflammatory response syndrome and acute renal failure associated with Hemophilus influenzae septic meningitis

Sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis.     

Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays.

We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray.     

Comparison of two-year and five-year tamoxifen use in Japanese post-menopausal women

AIM: Large multicenter, randomized trials have revealed the advantages of using tamoxifen for 5 years vs 2 years in breast cancer patients. The aim of this report is to confirm the optimal duration of tamoxifen administration in a study of Japanese breast cancer patients. METHODS: Japanese post-menopausal estrogen receptor-positive breast cancer patients treated with mastectomy were randomly assigned to either a 5-year or 2-year course of tamoxifen. The primary endpoint was disease-free survival, with secondary endpoints of overall survival and a reduction in the development of metachronous contra-lateral breast cancer. RESULTS: A total of 256 breast cancer patients were randomized to a 5-year or 2-year tamoxifen administration group. After a median follow-up time of 81 months, there were no significant differences seen in terms of disease-free or overall survival (p=0.65 and 0.56, respectively). Furthermore, the impact of the 5-year use of tamoxifen on the development of contra-lateral breast cancer did not reach statistical significance (p=0.0511). However, 5-year tamoxifen use was closely associated with gynaecological complications (p=0.0081). CONCLUSION: We could not show a beneficial effect of using tamoxifen for 5 years over 2 years in Japanese estrogen receptor-positive patients. This is likely due to the small number of patients enrolled in our study; however, racial disparity may influence this result. A reevaluation is necessary to study the advantages of the 5-year use of tamoxifen in the Japanese racial subgroup.