Free vascularized fibula grafting for reconstruction of the wrist following wide tumor excision

Free vascularized fibula transfer is an established method for reconstruction of the wrist following tumor resection. In cases of resection of the radial articular surface, three reconstructive options are possible: fibular head transfer along with the shaft to replace the radial joint surface, fixation of the fibula to the scaphoid and lunate, or a complete wrist fusion. Three patients with a tumor involving the distal end of the radius were treated with wide resection, and subsequent wrist reconstruction was performed, using the above-mentioned procedures. Although our experience included only a small number of patients, both radio-carpal hemiarthroplasty and fibulo-scapho-lunate fusion similarly provided successful wrist stability and functional range of motion in these cases. Even when the wrist was totally fused with the fibula, its function was still acceptable.     

Change of components of the metabolic syndrome in a workers' health checkup after five years--relation with elevated liver enzymes, gene polymorphisms for ALDH 2, beta3-AR and lifestyle

We previously reported that the prevalence of elevated alanine aminotransferase (ALT) increases with accumulation of metabolic syndrome components, and a greater degree of involvement of aldehyde dehydrogenase 2 (ALDH2) than beta3-adrenergic receptor gene (beta3-AR) polymorphisms. The present study was designed to clarify the effect of aging, lifestyle and the two gene polymorphisms on the relationship between 4 components of the metabolic syndrome (obesity, hypertension, dyslipidemia and impaired glucose tolerance) and elevated ALT values in a subset of 73 out of 148 male workers who were 35 years of age in the baseline study and 40 years old in the present study. Study subjects completed questionnaires about drinking and smoking habits, and underwent urinalysis, physical examination and peripheral blood tests, blood chemistry, electrocardiogram and chest X-rays each year as required by Japanese law. Information from the questionnaires and physical examinations, including liver function tests, were compared with previously reported ALDH2 and beta3-AR genotypes for the 73 workers. Of the 73 workers studied, 14 (19%) demonstrated decrease in metabolic syndrome components, 39 (53%) demonstrated no change, and 20 (27%) demonstrated an increase. Ten workers (14%) showed liver dysfunction at age 35 and 20 workers (27%) at age 40. Fourteen workers were newly diagnosed as having liver dysfunction at their 40-year checkup, thus being associated with the BMI and an active ALDH2 genotype. Accumulation of components of the metabolic syndrome were associated with the presence of liver dysfunction at 35 years. In conclusion, these findings indicate that ALDH2 genotyping as well as lifestyle habits may be important factors in causing metabolic syndrome with liver dysfunction.     

A five-year review of patients admitted with the diagnosis of bacterial endophthalmitis

We conducted a retrospective, hospital-based study of patients who were diagnosed with bacterial endophthalmitis on admission to the Department of Ophthalmology, Hiroshima University Hospital, between January 1999 and December 2003. Thirty eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an endogenous source. All of the patients underwent immediate three-port pars plana vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly higher incidence of positive bacterial culture. Diabetic vitreous appeared to be a good medium for culture. Visual acuity of hand motion or less at the latest follow-up visit was associated with the presence of diabetes. Prompt treatment with vitrectomy and intra-vitreal antibiotics is crucial for patients with bacterial endophthalmitis, especially if they are diabetic.     

Gastrectomy Performed with Noninvasive Positive Pressure Ventilation for a Patient with Severe Chronic Obstructive Pulmonary Disease: Report of a Case

We report the case of a patient with severe chronic obstructive pulmonary disease (COPD) for whom gastrectomy was successfully performed with the use of noninvasive positive pressure ventilation (NPPV). A 63-year-old man who had been suffering from chronic pulmonary emphysema for 12 years and receiving home oxygen therapy (HOT) for 9 years was diagnosed with gastric carcinoma. The patient required supplemental oxygen via nasal cannulae even at rest, and had labored breathing through pursed lips after a short conversation. The forced expiratory volume in 1 s was 400 ml. He underwent conventional gastrectomy under general anesthesia, and was extubated 90 min after surgery and given NPPV support. He was successfully weaned from NPPV on postoperative day (POD) 10 and discharged from our hospital on POD 28. Noninvasive positive pressure ventilation is useful for the perioperative management of patients with severe COPD and for extending the possibilities of surgery for patients on HOT.     

Locally advanced adenocarcinoma of the endometrium: results of irradiation with and without subsequent hysterectomy

From 1965 through 1977, 54 patients with locally advanced adenocarcinoma of the endometrium were treated at the Medical College of Wisconsin Affiliated Hospitals. According to the FIGO-AJC staging system, 39 had Stage II and 15 Stage III disease. Stage II was subdivided into II A-microscopic (28 patients) and II B-clinical (11 patients) involvement of the cervix. Patterns of failure were evaluated, viz. central pelvic, lateral pelvic, and distant. The results confirm an association of increasing grade with increasing stage. Disease-free survival rates at five years are better for Stage II (78%) than Stage III (34%), but are no different for Stages II A (77%) and II B (81%). Pattern of failure and disease-free survival data support the combined irradiation-surgical approach over irradiation alone. Central pelvic failures are reduced by subsequent hysterectomy (6% vs. 20%). Lateral pelvic failures are less frequent when the dose of external pelvic irradiation is 5000+ rads/5-6 weeks compared to less than 5000 rads (4% vs. 20%). In Stage II (corpus et collum) the prognosis is better with preoperative irradiation and abdominal hysterectomy than with irradiation alone (89% vs. 63%). Whenever possible, patients with Stage III disease should be offered irradiation and hysterectomy.     

Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation

The problem of brain metastasis from small cell carcinoma (SCC) of the lung has been appreciated for many years, but the magnitude of the problem has been underestimated. Recent studies have shown that the risk of brain metastasis increase as survival is prolonged. Although prophylactic cranial irradiation (PCI) has reduced the frequency of brain metastases, the effect on risk estimates of differences in the periods of observation was not evaluated. From 1974 through 1979, 131 patients with SCC of the lung who had no evidence of brain metastasis by radionuclide or computerized tomographic scan were treated in the Division of Therapeutic Radiology at the Medical College of Wisconsin Affiliated Hospitals. PCI was started in 1977; 57 patients received it and 74 did not. To correct for the differing periods of observation for the two groups, an actuarial calculation of the probability of brain metastasis was used. The calculated rate of clinical failure in the brain for patients who did not receive PCI was 28% at 12 months and 58% at 24 months. The calculated failure rate of the brain for patients who received PCI was 11% at 12 and 24 months. The difference in the probability of brain metastasis between the patients who did or did not receive PCI is highly significant (P less than 0.01). The true benefit of PCI becomes apparent only when the risk of intracranial metastasis is evaluated by methods that correct for incomplete followup. PCI eliminates the progressive increase in the risk of brain metastasis that accompanies increased survival and is important to maximize the probability for cure of patients with SCC.     

Transplantation of neural cells derived from retinoic acid-treated cynomolgus monkey embryonic stem cells successfully improved motor function of hemiplegic mice with experimental brain injury

We induced neural cells by treating cynomolgus monkey embryonic stem (ES) cells with retinoic acid. The treated cells mainly expressed betaIIItubulin. They further differentiated into neurons expressing neurofilament middle chain (NFM) in elongated axons. Half of the cells differentiated into Islet1+ motoneurons in vitro. The monkey ES-derived neural cells were transplanted to hemiplegic mice with experimental brain injury mimicking stroke. The neural cells that had grafted into periventricular area of the mice distributed extensively over the injured cortex. Some of the transplanted cells expressed the neural stem/progenitor marker nestin 2 days after transplantation. The cells expressed markers characteristic of mature motoneurons 28 days after transplantation. Mice with the neural cell graft gradually recovered motor function, whereas control animals remained hemiplegic. This is the first demonstration that neural cells derived from nonhuman primate ES cells have the ability to restore motor function in an animal model of brain injury.     

Preoperative induction of CPT-11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction

BACKGROUND: Patients with localized esophageal carcinoma often develop locoregional and distant disease recurrence. The current study investigated the outcome of a new chemotherapy combination as induction therapy before chemoradiotherapy. METHODS: Forty-three patients with resectable carcinoma of the esophagus or gastroesophageal junction were enrolled. Most of the tumors were endoscopic ultrasonography (EUS) (EUS)T3 (84%) and (EUS)N1 (63%). The patients received < or = 2 6-week cycles of CPT-11 and cisplatin followed by chemoradiotherapy (45 grays with 5-fluorouracil and paclitaxel). Five to six weeks after chemoradiotherapy, the patients underwent staging and surgery. The feasibility, curative resection rates, overall and disease-free survival rates, rate of significant pathologic response, and patterns of disease recurrence were assessed. RESULTS: Of the 43 patients, 39 (91%) underwent an R0 resection. Two patients (5%) died after surgery. A pathologic complete response (pathCR) was observed in 11 (28%) of the 39 patients (or 26% of the 43 patients). In addition, 16 patients (41% of 39 patients or 37% of 43 patients) had < 10% viable tumor in the surgical specimen (pathPR). A comparison of endoscopic ultrasonograpy T and N classifications with surgical T and N classifications demonstrated significant down-staging (P < 0.01). The median survival period of all 43 patients was 22.1 months. Patients who had achieved a pathCR or pathPR had a longer median survival (25.6 months) than those who achieved less than a pathPR (18.5 months; P = 0.52). None of the clinical parameters examined were found to correlate with survival or pathologic response. CONCLUSIONS: CPT-11-based induction chemotherapy resulted in substantial pathCR and pathPR rates, both of which lead to a favorable survival outcome. The three-step strategy needs to be developed further, with the investigation of targeted therapies with chemotherapy and radiotherapy.     

Cullin 3 promotes proteasomal degradation of the topoisomerase I-DNA covalent complex

DNA topoisomerase I (TOP1)-DNA covalent complexes are the initial lesions produced by antitumor camptothecins (CPTs). The TOP1-directed drugs stimulate degradation of TOP1 via the ubiquitin-proteasome pathway. We found that proteasome inhibition prevents degradation of DNA-bound TOP1 and sustains high levels of covalent complexes, thus enhancing CPT-induced cell death. Consistent with this, increased degradation of TOP1-DNA covalent complexes was seen in acquired CPT-resistant cells. We found that the resistant cells showed elevated expressions of Cul3, a member of the cullin family of E3 ubiquitin ligases. The reduction in Cul3 expression by small interfering RNA decreased degradation of TOP1-DNA covalent complexes. Conversely, Cul3 overexpression by stable transfection promoted covalent complex degradation and reduced CPT-induced cell death without affecting basal TOP1 expression levels. These results indicate that Cul3, by promoting proteasomal degradation of TOP1-DNA covalent complexes, becomes an important regulator for cellular CPT sensitivity.