A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma.

Background: There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities. Results: Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%-59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%-87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3-12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. Conclusion: This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. Clinical Trial Registration: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Intra-arterial chemoradiation therapy with weekly low-dose cisplatin for squamous cell carcinoma of the maxillary sinus.

A new intra-arterial chemoradiation regimen that involves infusing low-dose cisplatin in combination with definitive irradiation was used in 36 patients diagnosed with squamous cell carcinoma of the maxillary sinus. The safety and therapeutic efficacy of this regimen were reviewed retrospectively. An intra-arterial catheter was inserted in a retrograde manner into the target artery via the superficial temporal artery or occipital artery. Intra-arterial infusion was performed using cisplatin at a dose of 20-50mg/m(2) per week for 6-8 weeks. At the same time, sodium thiosulphate was infused as a neutralizing agent. Irradiation was performed at 60Gy in 30 fractions. All 36 patients completed treatment. Grade 3 adverse events occurred in only seven patients (19.4%) and no grade 4 events were noted. As a primary therapy, the complete response rate was 83.3%, the partial response rate was 16.7%, and the overall response rate was 100%. The 2-year local control rate was 63.0%, and the 2-year overall survival rate was 75.5%. The 2-year preservation rate of the hard palate was 97.1%, that of the eyeball was 97.2%, and that of visual function was 94.4%. This treatment regimen can contribute to improving the quality of life of patients without reducing the curability of the therapy.

Postoperative chylothorax in congenital diaphragmatic hernia.

INTRODUCTION: The mechanisms responsible for postoperative chylothorax in Congenital Diaphragmatic Hernia (CDH) patients remain unclear. The aim of the present study was to examine the clinical features of CDH that may contribute to an association with postoperative chylothorax. MATERIAL AND METHODS: 198 neonates with CDH, in whom surgical repair of a diaphragmatic defect was performed between 1981 and 2008, were retrospectively studied. The patients were divided into 2 groups; patients with postoperative chylothorax (group I, n=11) and patients without postoperative chylothorax (group II, n=187). The clinical findings were compared between group I and group II to investigate potential predictive parameters for an association with chylothorax. Moreover, the clinical findings and treatments were evaluated in patients with chylothorax. RESULTS: 11 of the 198 infants (5.5%) developed a chylothorax. Although the incidence of a prenatal diagnosis was slightly higher in group I, no relationship with other clinical features was found which would indicate the severity of CDH or the occurrence of postoperative chylothorax. Treatment for chylothorax was drainage alone in 2 cases, total parenteral nutrition with drainage in 8 infants and additional intrathoracic OK-432 infusion in 1 patient. No patients required surgical intervention for chylothorax. No recurrences were observed in this patient series. CONCLUSIONS: It was concluded that postoperative chylothorax is not rare in infants after CDH repair. However, no statistically significant predictive parameters for chylothorax were identified, except for the presence of a prenatal diagnosis.

[Pacemaker implantation in a patient with sick sinus syndrome, complicated with persistent left superior vena cava and absent right superior vena cava; report of a case].

A 78-year-old man was referred to our hospital with syncope and palpitation. A Holter electrocardiography (ECG) revealed sick sinus syndrome (SSS), and an enhanced chest computed tomography (CT) scan showed persistent left superior vena cava (PLSVC) and absent right superior vena cava. Myocardial leads and a pacemaker implantation were peformed through left anterior thoracotomy approach. There were only 10 reports of pacemaker implantation in a patient with SSS complicated with PLSVC and absent right superior vena cava in Japan. Open thoracotomy approach was thought to be usuful for these patients.

Expression and localization of ATP binding cassette (ABC) family of drug transporters in gastric hepatoid adenocarcinomas.

AIMS: Hepatoid adenocarcinomas are clinically chemoresistant; however, data concerning the mechanisms of chemoresistance are lacking. ATP-binding cassette (ABC) transporters play a role in the ATP-dependent outward efflux of drugs, and their function renders tumour cells multidrug resistant. We assumed that the expression of ABC transporters may be accompanied by hepatic differentiation because most ABC transporters are dominantly expressed in hepatocytes. The aim of this study was to investigate the expression of ABC transporters in hepatoid adenocarcinomas. METHODS AND RESULTS: The expression of P-glycoprotein, multidrug resistant-associated protein (MRP) 1, MRP2, MRP3 and MRP6 was investigated using immunohistochemistry in 13 cases of gastric hepatoid adenocarcinoma and 32 cases of control adenocarcinoma. P-glycoprotein was expressed in all cases examined. The positive rates of MRP1 (84.6% versus 21.9%), MRP2 (100% versus 43.8%) and MRP6 (61.5% versus 15.6%) were significantly higher in hepatoid than in control adenocarcinoma. MRP3 was negative in all hepatoid adenocarcinomas. Immunohistochemistry by polyclonal anti-carcinoembryonic antigen antibody, which detects bile canaliculi, suggested that MRP2 and MRP6 are located on bile canalicular-like structures in sheet or trabecular nests. CONCLUSIONS: These results support the hypothesis that ABC transporters participate in the mechanisms of multidrug resistance in hepatoid adenocarcinomas.

Metastasis in para-aortic lymph nodes in patients with advanced gastric cancer, treated with extended lymphadenectomy.

BACKGROUND/AIMS: Lymph node dissection is an essential component of curative resection for advanced gastric cancer. To improve the survival of N2 patients, Asian surgeons have been performing D2+para-aortic lymph node dissection. The current study presents the results of lymph node status from multicenter trial of D2 and D2 + para-aortic nodal (No.16) dissection (D4 dissection). METHODOLOGY: Patients enrolled in the study had potentially curable gastric adenocarcinoma in an advanced stage, T2, T3 or T4/N1 or N2. Patients were randomized to undergo either D2 or D4 gastrectomy. RESULTS: Two hundred and seventy patients were registered and 136 and 134 patients were allocated into the D2 or D4 group, respectively. The average nodal yield of No.16 in D4 group was 18.4 +/- 14.1, ranging from 2 to 84. No.16 metastasis was detected in 12 (9.0%) of 134 D4 patients. One, 9 and 2 patients had simultaneous involvement in N1, N2, and N3 (No.8p, 12, 13 or 14). Namely, in 39 patients who were diagnosed as N2 from the lymph node status in N1 and N2 levels, nine (23.0%) patients had No.16 metastasis. The stage migration by D4 was found in 10 (7.5%). Logistic regression analysis revealed that the stations of No.7 and No.8 were the significant predictors of No.16 involvement. CONCLUSIONS: The present study may strongly suggest that prophylactic D4 dissection may be indicated for patients with N2 involvement, and that No.7 and No.8 are the junctional nodes for D4 dissection.

Prevention of Salmonella cross-contamination in an oilmeal manufacturing plant.

AIMS: The mechanisms of Salmonella contamination in an oilmeal plant were investigated and the basic data were collected in order to achieve control of Salmonella in oilmeal. METHODS AND RESULTS: Salmonella was detected in all contamination vectors and environmental factors investigated, namely: operators, processing floor, dust in the air and rodents. In particular, high concentrations of Salmonella were detected on the processing floor of the manufacturing area, which has high oil content. Steam was the most effective disinfection method used for the processing floor, as the effects of heat sterilization and disinfection may work in tandem. In addition, restricting the movement of operators of the production chain remarkably reduced Salmonella contamination, even in areas of otherwise high contamination. CONCLUSIONS: Within the oilmeal plant, high Salmonella contamination rates for the processing floor represent the greatest risk of contamination of oilmeal via operators, dust in the air and rodents. Therefore, control of the processing floor is the most important means for reducing the oilmeal contamination rate. SIGNIFICANCE AND IMPACT OF THE STUDY: Specific Salmonella control methods for oilmeal plants have been established.

Operative morbidity and mortality after D2 and D4 extended dissection for advanced gastric cancer: a prospective randomized trial conducted by Asian surgeons.

BACKGROUND/AIMS: A randomized study was performed to evaluate morbidity and mortality after D2 (level 1 and 2 lymphadenectomy) and D4 (D2 plus lymphadenectomy of para-aortic lymph nodes) dissection for advanced gastric cancer. METHODOLOGY: Two hundred and fifty-six patients with advanced gastric adenocarcinoma were enrolled (128 to each group). Patients were randomly allocated into D2 (N = 128) or D4 (N = 128) group. The first and second tiers of lymph nodes are removed in D2 dissection. In D4 gastrectomy, the paraaortic lymph nodes were additionally removed. RESULTS: There was no indication of significant distribution bias with regard to age, sex, T-grade, and N-grade between the two groups. Operation time of D4 gastrectomy (369 +/- 120 min) was significantly longer than that of D2 gastrectomy (273 +/- 1103 min), and blood loss of the D4 group (872 +/- 683 mL) was significantly greater than that of the D2 group 571 +/- 527 mL (P < 0.001). Five (4%) and two (2%) medical complications developed in the D2 and D4 groups, respectively. Surgical complications developed in 28 (22%) and 48 patients (38%) after D2 and D4 gastrectomy. The most common complications were anastomotic leakage, pancreatic fistula, and abdominal abscess. Pancreatic fistula developed in 6 (19%) of 32 patients after D4 plus pancreatosplenectomy, but the incidence of pancreatic fistula after D2 gastrectomy plus pancreatosplenectomy was low (6%, 1/16). Two patients died within 30 days of operation (0.8%, 2/256), and each patient belonged to the D2 and D4 group. CONCLUSIONS: Although there is a significantly higher surgical complication rate in D4 dissection, D4 dissection can be done safely as D2 dissection when performed by well-trained surgeons.

[Experience of off-pump coronary artery bypass grafting with starfish heart positioner].

Recent advances in off-pump coronary artery bypass (OPCAB) technique have demonstrated that multivessel coronary revascularization can be safely performed in selected patient without cardiopulmonary bypass. Numerous positioning technique and devices have been developed to assist access to coronary vessels during OPCAB, such as deep pericardial suture, surgical pads, and cardiac positioning device and stabilizers. We used new cardiac positioning device Starfish heart positioner (Medtronic Corporation) for 2 case of OPCAB. Starfish heart positioner was very useful to successfully perform multivessel coronary bypass on all walls of the beating heart. Starfish heart positioner will facilitate and expand the ability to easily and consistently perform OPCAB.

Prenatal ultrasonographic appearance of type IIId (uncorrectable type with cystic dilatation) biliary atresia.

Although prenatal ultrasonographic (US) diagnosis has been reported in biliary atresia (BA), most cases are type I (correctable with cystic dilatation). We report three prenatal cases of type IIId BA (uncorrectable with cystic dilatation). Routine fetal US at 22 to 24 weeks of gestation showed two communicating cystic lesions 12 to 16 mm in diameter. On color Doppler US, the lesions were separate from the portal vein or hepatic artery. The size did not change during the prenatal period in any case. Choledochal cyst (CC) was considered the most likely diagnosis, although BA with cystic lesions was also considered. After birth, the patients developed acholic stools and prolonged neonatal jaundice. Hepatobiliary scintigraphy showed negative passage. Duodenal fluid showed a negative or slightly positive Gmelin test. The neonates underwent laparotomy at the age of 36, 46, and 32 days, respectively. Intraoperative cholangiography showed the gallbladder and slightly-dilated common-bile duct without entering the proximal or distal bile ducts in all cases. They were classified as type IIId BA and underwent excision of the cystic lesions and dissection of the portal bile-duct remnants, followed by hepatic portoenterostomy. Case 1 showed persistent jaundice and finally underwent liver transplantation (LTx), case 2 became anicteric. Case 3 remained jaundiced and is to undergo LTx. In conclusion, type IIId BA may be one of the differential diagnoses when a cystic lesion is detected under the hepatic hilum by fetal US. However, prenatal diagnosis of BA is still difficult with respect to differentiation from a CC or type I BA. Early postnatal diagnosis followed by immediate treatment is important, especially in type IIId BA.

Reoperative minimally invasive axillocoronary artery bypass to the obtuse marginal branch.

A 73-year-old man was admitted with unstable angina, having severe coronary artery disease involving 3 vessels. He had undergone coronary artery bypass grafting to the left anterior descending artery and the obtuse marginal branch using saphenous vein grafts in 1979. Computed tomography showed severe calcium deposition and atherosclerosis in the ascending and descending aorta. We conducted axillocoronary artery bypass to the obtuse marginal branch and left internal thoracic artery as an in situ graft to the left anterior descending artery without cardiopulmonary bypass. Grafts were satisfactory and clinical results good.

Pectus excavatum repair using a costal cartilage graft for patients with tracheobronchomalacia.

BACKGROUND: Pectus excavatum is sometimes associated with tracheobronchomalacia, which usually manifests left mediastinal shift, atelectasis of the left lung, and recurrent pulmonary infection. Standard repair of pectus excavatum alone usually failed to improve symptoms. METHODS: Pexis of the great vessels and pericardium combined with the support of the lower sternum, using a contralateral costal cartilage graft following the standard Ravitch's repair of pectus excavatum, has been used in 6 children during the past 5 years. In addition to respiratory symptoms, diagnosis of tracheobronchomalacia was made by bronchoscopy using an ultrathin fiberscope. RESULTS: Using the described operative technique, an excellent cosmetic and functional result was obtained in 5 of 6 children. However, atelectasis of the left lower lobe and the narrowing of the left mainstem bronchus continued postoperatively in one patient, which required the insertion of the Palmaz stent in the left mainstem bronchus. CONCLUSION: This technique may help improve tracheobronchomalacia in patients with pectus excavatum and should be tried before the insertion of an internal stent.

Surgical results of skull base surgery for the treatment of head and neck malignancies involving skull base: multi-institutional studies on 143 cases in Japan.

We analyzed 143 cases of skull base surgery collected from the eight institutions of the Study Group supported by the Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan. Histologically, the most common type was squamous cell carcinoma (n = 78), which was followed by olfactory neuroblastoma (n = 16) and adenoid cystic carcinoma (n = 16). The most frequent surgical approach was frontal craniotomy (n = 66), followed by front-temporal craniotomy (n = 54) and infratemporal fossa approach (n = 8). For repair of dura matter, fascia lata was used in 37 cases. galeopericranial flap in 35 and temporal muscle fascia in 16. The 5-year survival rate by Kaplan-Meier method of nose and paranasal sinus carcinoma (n = 119) was 48%. As for histological classification, the survival rates were both 65%) in adenoid cystic carcinoma (n = 12) and bone soft tissue malignancy (n = 10), 62% in olfactory neuroblastoma (n = 16), 46% in squamous cell carcinoma (n = 62) and 33% in adenocarcinoma (n = 11). All the three cases of malignant melanoma died within 1 year, so we considered skull base surgery to be contraindicated for this disease. Complications were observed in 62 out of the 143 cases (43%); local infection was most frequent in 29 cases. liquorrhea in 18, abscess in 16, necrosis of the flap and meningitis in ten cases, DIC in four, rupture of the internal carotid artery in two and cerebral thrombosis in one. Death caused directly by surgery was in ten cases (7%). It is important that a multi-center registry be maintained to have a large enough database for comparison of results, and prognosis for each histological entity and further define the role of multidisciplinary treatment.

Telepsychiatry: assessment of televideo psychiatric interview reliability with present- and next-generation internet infrastructures.

OBJECTIVE: We assessed the reliability of remote video psychiatric interviews conducted via the internet using narrow and broad bandwidths. METHOD: Televideo psychiatric interviews conducted with 42 in-patients with chronic schizophrenia using two bandwidths (narrow, 128 kilobits/s; broad, 2 megabits/s) were assessed in terms of agreement with face-to-face interviews in a test-retest fashion. As a control, agreement was assessed between face-to-face interviews. Psychiatric symptoms were rated using the Oxford version of the Brief Psychiatric Rating Scale (BPRS), and agreement between interviews was estimated as the intraclass correlation coefficient (ICC). RESULTS: The ICC was significantly lower in the narrow bandwidth than in the broad bandwidth and the control for both positive symptoms score and total score. CONCLUSION: While reliability of televideo psychiatric interviews is insufficient using the present narrow-band internet infrastructure, the next generation of infrastructure (broad-band) may permit reliable diagnostic interviews.

Changes in activities of enzymes related to malate-aspartate shuttle in leukocytes from dogs given a herb supplement.

Changes in activities of enzymes related to the malate-aspartate shuttle were measured in leukocytes (WBC) from dogs given food supplemented with 2 mg/kg of herb powder, Echevaria glauca, every day for 4 weeks. There were no significant differences in plasma concentrations of glucose, immunoreactive insulin, free fatty acids and triglyceride between dogs given food with or without the herb supplementation. Activities of malate dehydrogenase (MDH) and aspartate aminotransferase (AST) in the malate-aspartate shuttle increased remarkably in mitochondria of WBC from dogs fed the herb supplementation. It is suggested that Echevaria glauca herb supplementation might activate NADH shuttle systems and mitochondrial energy metabolism in dogs.

Bilateral diaphragmatic hernia followed by fetal ultrasonography. A report of two cases.

Two cases of bilateral congenital diaphragmatic hernia (CDH) followed by fetal ultrasonography were described. Although many cases of CDH are diagnosed by fetal ultrasonography, it is difficult to diagnose bilateral CDH in utero, which is a relatively rare and fatal condition. Two fetuses were diagnosed as having left CDH associated with severe anomalies. However, a retrospective review of fetal ultrasonography indicated elevation of the liver in the right posterior chest. Both patients died shortly after surgical repair for left CDH despite the use of extracorporeal membrane oxygenation. Diagnosis of bilateral CDH by fetal ultrasonography and the evaluation of its prognosis were discussed.

Operative management for sacrococcygeal teratoma diagnosed in utero.

BACKGROUND/PURPOSE: Sacrococcygeal teratomas (SCT) diagnosed in utero have been reported to be large and associated with high perinatal mortality rate. However, operative management including timing of operation after birth, combined abdominal approach for devascularization, and the position of the patients during resection is not well established. METHODS: A retrospective review of 14 patients with SCT between 1978 and 1999 was performed. To prevent massive bleeding during surgery, the authors used an abdominoperineal resection in the supine position after devascularization. The patients' clinical and sonographic characteristics, prenatal outcome, operative management, and postnatal outcomes were examined. RESULTS: One fetus died in utero. Two patients died within a week, but no late death and no malignant degeneration were noted. A staged operation with devascularization was performed in 2 patients, and 1 death occurred. Surgical management was analyzed between survivors without massive bleeding at surgery (n = 9) and others (n = 4). A significant difference was observed in the subgroup of tumor resection with devascularization or supine position and that of early resection with devascularization or supine position. CONCLUSIONS: Early resection using the abdominoperineal approach supported by close antenatal sonography may be preferable for a favorable outcome. Resection in the supine position after devascularization may have advantages of respiratory management, cardiac resuscitation, and bleeding prevention. J Pediatr Surg 36:545-548.