Pathophysiology and management of intracranial arterial stenosis around the circle of Willis associated with hyperthyroidism: case reports and literature review

Cases of moyamoya disease or intracranial arterial stenosis around the circle of Willis (M/IAS) associated with hyperthyroidism have been reported. However, most of these previous reports were of the ischemic form of M/IAS and primary hyperthyroidism. To the best of our knowledge, no studies have documented therapy for M/IAS associated with hyperthyroidism. We discuss four previously unreported cases, including those involving the intracerebral hemorrhage form and thyroid-stimulating hormone (TSH) secretion from a pituitary adenoma (secondary hyperthyroidism). We analyzed data from 52 previously reported cases, including the 4 cases presented here, and discuss M/IAS associated with hyperthyroidism, treatment options, pathophysiology, the ischemic and hemorrhagic forms, secondary hyperthyroidism, and the relevant literature. Hyperthyroidism results in thyrotoxicosis and the stimulation of the superior cervical ganglion by TSH antibodies and f-T3/f-T4. Consequently, hypercoagulability and stenosis of the cerebral artery can occur. There are many reports of ischemic M/IAS associated with hyperthyroidism. A conservative approach to treatment is important in such cases; for example, antithyroid therapy should be the first choice to treat ischemic M/IAS. There have been only a limited number of reports on hemorrhagic M/IAS. We presume that hemorrhagic M/IAS tears the weakened vasculature in a manner similar to that of normal M/IAS (with no complicating hyperthyroidism). The authors also reported M/IAS associated with secondary hyperthyroidism due to pituitary thyroid secreting hormone secreting adenoma.     

Esophagogastric tube reconstruction with stapled pseudo-fornix in laparoscopic proximal gastrectomy: a novel technique proposed for Siewert type II tumors

Purpose

The incidence of adenocarcinoma of the esophagogastric junction is increasing, but laparoscopic proximal gastrectomy is not widely accepted due to the absence of a standardized technique of reconstruction. This report describes a novel technique of esophagogastric tube reconstruction in laparoscopic proximal gastrectomy for Siewert type II tumors.

Methods

Laparoscopic proximal gastrectomy, sometimes with transhiatal distal esophagectomy, was performed. After a perigastric, suprapancreatic, and lower thoracic paraesophageal lymphadenectomy, a gastric tube of 35-mm width was prepared. An esophagogastric tube anastomosis with pseudo-fornix was made with a no-knife linear stapler to prevent postoperative reflux esophagitis.

Results

Fifteen patients with Siewert type II tumors underwent this operation. They included six patients with early-stage cancer, six at high risk for transhiatal total gastrectomy due to several comorbidities, and three who needed palliative tumor resection. The mean operation time was 315 min. One postoperative anastomotic leak was treated conservatively, and three anastomotic stenoses were resolved with endoscopic balloon dilatation. Postoperative 1-year follow-up endoscopy revealed four cases of reflux esophagitis that were well controlled by medication.

Conclusions

This new technique of reconstruction was feasible. With the advantage of a gastric tube, a tension-free anastomosis was possible even for bulky tumors that needed lower esophagectomy. Although long-term follow-up and a larger number of patients are required to evaluate long-term functional outcomes and oncological adequacy, our procedure has the potential of becoming a treatment of choice for early-stage Siewert type II tumors and/or for some selected high-risk patients who need tumor resection.     

Prognostic significance of pleural or pericardial effusion and the implication of optimal treatment in primary mediastinal large B-cell lymphoma: a multicenter retrospective study in Japan

The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow up of 48 months, the overall survival at four years for patients treated with R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2^nd- or 3^rd-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher International Prognostic Index score and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy (IPI: hazard ratio 4.23, 95% confidence interval 1.48–12.13, P=0.007; effusion: hazard ratio 4.93, 95% confidence interval 1.37–17.69, P=0.015). Combined with the International Prognostic Index score and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower International Prognostic Index score and the absence of effusion comprised approximately one-half of these patients and could be identified as curable patients (95% overall survival at 4 years). The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of International Prognostic Index score and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment.     

Case report: The operation for the lumbar disk herniation just after cesarean delivery in the third trimester of pregnancy

INTRODUCTION

Low back pain is common during pregnancy. However, the incidence of symptomatic lumbar disc herniation during pregnancy is very rare. We report a case of lumbar disc herniation underwent discectomy just after cesarean delivery in the third trimester of pregnancy.

PRESENTATION OF CASE

A 33-year-old woman presented at 32 weeks gestation. She had a low back pain and the left-sided leg pain below the knee. At 34 weeks gestation, she had severe weakness of the left extension halluces longus, left ankle dorsiflexion. MRI showed a large disc herniation at L4/5 expanded to the spinal canal more. The cesarean delivery was performed in the supine position. The patient was then turned to a prone position, and a left L4/5 discectomy was performed. But the day after surgery, she had a severe low back pain and the right leg pain below the knee. MRI showed a disc herniation at L4/5 on the right side of the spinal canal. At 6 days after the first surgery, a right L4/5 discectomy was performed. In the immediate postoperative period, the patient experienced complete relief of the right leg pain.

DISCUSSION

It is necessary to cooperate with a pediatrician, an obstetrician, and an anethesiologists. For obtaining the best outcome on mother and child, it is important to discuss in advance to be able to respond quickly for changeable situation.

CONCLUSION

It is necessary to conduct the operation under pregnancy in consideration of the great influence on mother and child.     

Early gastric cancer combined with multiple metachronous osteosclerotic bone and bone marrow metastases that responded to chemoradiotherapy

We report a 75-year-old woman who suffered multiple metachronous osteosclerotic bone metastases 4 years after a distal gastrectomy for early gastric cancer (EGC). The primary tumor was a poorly differentiated adenocarcinoma, which had invaded the submucosal layer, and only one lymph node metastasis was noted. To the best of our knowledge, cases of EGC combined with metachronous osteosclerotic multiple bone and bone marrow metastases that respond to chemoradiotherapy are very rare. In this case, the multiple bone metastases were diagnosed 4 years after surgery. The patient’s metastatic tumor was successfully treated using S-1, paclitaxel, and camptothecin, with subsequent irradiation. The patient survived for 24 months after the treatment, without having any major symptoms.     

Determinants of Bronchodilator Responsiveness in Patients with Controlled Asthma

Short-term bronchodilator responsiveness to an inhaled β 2 adrenergic agonist was assessed by changes in forced expiratory volume in 1 second (FEV₁) in nonsmoking adults with controlled asthma (mild disease, 20 patients; moderate disease, 20 patients; severe disease, 18 patients). Responsiveness correlated significantly with age and with percent of predicted FEV₁ (%FEV₁) except in patients with severe asthma, who showed significantly less responsiveness than others. Thus, responsiveness is closely associated with degree of airflow limitation in patients with controlled asthma and is significantly influenced by severity of disease and by aging.     

Structural determination of a new mutagenic heterocydic amine, 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMeIgQx), present in beef extract

We previously found two new mutagens, compounds I and II, inbacteriological-grade beef extract by monitoring the mutagenicityto a new Salmonella strain, YG1024; compound I was identifiedas 2-amino-4-hydroxymethyl-3,8-dimethyli-midazo[4,5-f]quinoxaline(4-CH₂OH-8-MeIQX) In the present study, we isolated compoundII from the beef extract, which accounted for 2% of the totalmutagenicity of materials adsorbed on blue cotton. Further,we found that a large quantity of compound II was produced byheating a mixture of creatine, threonine and glucose (1:1:0.5)at 200^°C for 5 h, the level being 860-fold of that in thebeef extract. The structure of this compound was determinedto be 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMeIgQx)by X-ray crystallography. The amount of 7,9-DiMeIgQx in bacteriological-gradebeef extract was estimated to be 53 ng/g. This compound induced13 800 and 670 revertants of S.typhimurium YG1024 and TA98 respectively,per µg in the presence of S9 mix.     

CPT-11: Population Pharmacokinetic Model and Estimation of Pharmacokinetics Using the Bayesian Method in Patients with Lung Cancer

In this study, we aimed to develop a population pharmacokinetic model for CPT-11 and to use the Bayesian method to estimate CPT-11 pharmacokinetic parameters in each of 43 patients who received combined therapy consisting of CPT-11 and etoposide. The group was divided into first and second data sets of 30 and 13 patients, respectively. We developed a population pharmacokinetic model of CPT-11 based on the first data set. The individual pharmacokinetic parameters [area under the concentration curve (AUC) and clearance (CD] were subsequently estimated by using the Bayesian method on the second data set. Plasma CPT-11 concentrations were measured by high-performance liquid chromatography, and compartmental pharmacokinetic models were fitted by the Bayesian method. The population pharmacokinetic model was developed by using the nonlinear mixed effect model. We selected the volume of the central compartment (Vc), CL, and distribution rate constants (K12, K21) as population pharmacokinetic parameters. The population mean values (CV%) of Vc, CL, K12, and K21 were, respectively, 31.8 (15.7%) liter/m²,14.1 (27.8%) liter/h/m²,1.1 (8.4%)/h, and 0.41 (30.3%)/h. Residual intraindivirtual variability was 22.9%. The optimal sampling regime for estimation of the AUC and CL in using the Bayesian method was the two time points of 1 and 8 h post infusion. The mean predictive error, the mean absolute predictive error, and the root mean squared error were -3.3, 9.4, 3.2% (AUC) and 6.3, 10.0, 3.5% (CL), respectively. We concluded that the AUC and CL of CPT-11 could be estimated from plasma concentrations at two times by using the Bayesian method.     

Intensive Chemotherapy with Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and Granulocyte Colony-stimulating Factor for Advanced Thymona or Thymic Cancer: Preliminary Results

A study was conducted to evaluate the impact of cisplatin, doxorubicin,cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulatingfactor (G-CSF) on advanced thymoma or thymic cancer. BetweenAugust 1989 and December 1994, 14 patients with invasive, metastaticor recurrent thymoma or thymic cancer were treated with cisplatin(80 mg/m², on day 1), doxorubicin (45 mg/m², on day 1), cyclophosphamide(800 mg/m², on day 1) and etoposide (80 mg/m², on day 1–3)with G-CSF (90 mg/m², on day 5–18) at the National CancerCenter Hospital, Tokyo. Courses were repeated every 3 or 4 weeksfor a maximum of 4 cycles. Twelve patients were treated with2 or more courses of PACE. Two patients were treated with onlyone course, one refused and another required emergency thoracicradiotherapy after one course of PACE. Six patients had partialresponses (3 thymomas and 3 thymic cancers) but there were nocomplete remissions (response rates, 42.9%; 95% confidence interval,17.7% to 71.1%). Moderate hematological toxicities were observed:grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopeniain 10, 13, 8 and 6 patients, respectively. Six patients developedinfections that required antibiotics. Surgical resection orthoracic radiotherapy after PACE treatment was performed in2 and 7 patients, respectively. The overall median survivaltime was 14.7 months (range, 5.9 to 59.7 months). For 9 patientswho had received no prior treatment before chemotherapy, themedian survival time was 8.9 months, and one patient survivedfor 4 years and is still alive. In conclusion, PACE with G-CSFfrequently produces objective remissions in patients with advancedthymoma or thymic cancer. A large-scale intergroup study isnecessary to determine the impact of this regimen on advancedthymoma and thymic cancer.     

Prospective Evaluation of the Feasibility of Cisplatin-based Chemotherapy for Elderly Lung Cancer Patients with Normal Organ Functions

A study was conducted to examine the feasibility of cisplatin-based chemotherapy in elderly patients (75 years old) with advanced non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Thirty-four patients were enrolled between September 1993 and December 1994. Patients with normal organ function and good performance status (PS) received cisplatin-based chemotherapy (cisplatin 80 mg/m² on day 1 and vindesine 3 mg/m² on days 2 and 8 for NSCLC, or cisplatin 80 mg/ m² on day 1 and etoposide 100 mg/m² on days 2 to 4 for SCLC). Ten patients (29%) were eligible for this study, 7 with NSCLC and 3 with SCLC. Reasons for exclusion were ischemic heart disease in 14, poor PS (2) in 11, reduced creatinine clearance (Ccr) in 10, abnormal electrocardiogram without ischemia in 9 and noncompliance with the protocol in 2 patients. Eight patients had two or more reasons. Nine of the 10 eligible patients were able to tolerate 2 or more courses of chemotherapy. All 3 patients with SCLC responded (1 complete response and 2 partial response), but only 1 of the patients with NSCLC achieved partial response. Toxicity was evaluated according to Japan Clinical Oncology Group criteria. All but one patient experienced grade 4 neutropenia, and 6 patients had infectious episodes requiring antibiotics. Grade 3 anemia and thrombocytopenia were observed in 1 and 2 patients, respectively. Non-hematological toxicities were mild. Only 10 of 34 patients (29%) satisfied our eligibility criteria and they experienced severe myelotoxicity. We conclude that chemotherapy should be given carefully to elderly patients even if they appear to have normal organ function.