Congenital atresia of the left coronary ostium: Diagnosis and surgical treatment

Summary An 11-year-old girl with congenital atresia of the left coronary ostium underwent coronary artery bypass grafting using the internal mammary artery. Before surgery, the patient complained of syncope on exertion. Exercise electrocardiogram (ECG), two-dimensional echocardiogram, and²⁰¹Tl myocardial scintigram were useful in establishing the diagnosis. Selective coronary angiograms showed typical findings. Postoperative recovery was uneventful; exercise ECG and stress²⁰¹Tl myocardial scintigram demonstrated improvement. Internal mammary artery graft is probably better than a saphenous vein graft as a coronary artery bypass graft in childhood and adolescence because of the long-term patency of this type of graft.     

A Randomized Cross-over Study of High-dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High-dose Cisplatin

We carried out a randomized, single-blind, cross-over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty-four patients with primary or metastatic lung cancer, given single-dose cisplatin (> 80 mg/m²) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively ( P =0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively ( P = 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty-four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group ( P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed.     

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.     

Fetal diaphragmatic hernia: prenatal evaluation of lung hypoplasia and effects of immediate operation

The outcome of fetuses with diaphragmatic hernia (CDH) has been reported to be related to the severity of lung hypoplasia. As an index of pulmonary hypoplasia, we attempted to measure the lung-thorax transverse area ratio (L/T) using ultrasonic echography in eight fetuses with left-sided CDH. Two cases with L/T more than 0.28 (controls: 0.52±0.04) were transported postnatally and recovered after early operation without episodes of persistent fetal circulation. Elective surgical repair was performed in six infants immediately after cesarean delivery at 35–37 weeks' gestation. In three cases with L/T between 0.21 and 0.24 who recovered with no complications, surgical reduction of the abdominal organs improved arterial blood gases and high-frequency oscillation ventilation (HFOV) was fully effective for respiratory management. In three with L/T between 0.11 and 0.17, extracorporeal membrane oxygenation (ECMO) was required from the 1st to the 12th postoperative day despite HFOV. Although two infants died of combined cardiovascular anomalies and airway bleeding caused by prolonged HFOV, respectively, one infant with minimal L/T survived. Measurement of L/T may help to predict the outcome of fetuses with CDH and to determine the indications for various treatments including immediate operation after cesarean delivery, HFOV, and ECMO. Offprint requests to: S. Kamata     

The Measles Outbreak in Chikuhou District, Fukuoka, Japan, 1990: Correlation between Herd Immunity Level and Outbreak Size

A measles outbreak occurred in the Chikuhou district of Fukuoka, Japan from May to October 1990, during which 71 patients were cared for at the Itoda Public Hospital. Hospital records revealed a large outbreak in the adjacent town of Kanada. In order to characterize the outbreak, questionnaires were sent to all preschool-age children in Itoda (73% effective response) and in Kanada (76% effective response) requesting information about their vaccination and/or history of measles. The number of patients was 22 (4%) in Itoda and 63 (14%) in Kanada, most of these being preschoolers, while the vaccination rate was 61% and 44%, respectively. The herd immunity levels in age-specific groups were compared between the two towns. Before the epidemic, the immunity level of 1 year old children in Kanada, who showed the higher attack rate, was lower (18%) than that in Itoda (39%), while after the epidemic it rose above 60% in both towns. When we studied the correlation between the attack rate and the vaccination rate, or the number of children susceptible to measles (susceptibility rate) in each preschool, the attack rate correlated negatively with the vaccination rate (correlation coefficient [CC] = - 0.818; P < 0.01), and positively with the susceptibility rate (CC 0.860; P < 0.01). The regressed equation on the correlation indicated that the immunity level should be more than 70% to keep the attack rate under 5% in preschoois. After the epidemic, the immunity levels of all preschoolers reached above 70%. Early vaccination should be given to at least 70% of young preschoolers in order to prevent a large outbreak of measles under the present vaccination program in Japan.     

Frequency of a 22q11 deletion in patients with conotruncal cardiac malformations: A prospective study

Recent molecular studies have revealed that a 22q11 deletion is frequently detected in DiGeorge syndrome (DGS), velo-cardio-facial syndrome (VCFS), and conotruncal anomaly face syndrome (CTAFS). As one of the major clinical manifestations in these three syndromes is conotruncal cardiac malformation, we prospectively studied the frequency of a 22q11 deletion in a group of patients with conotruncal cardiac malformation. Fluorescence in situ hybridization (FISH) analyses using N25 (D22S75) DiGeorge Chromosome Region probe were performed on 64 patients with conotruncal cardiac malformation, who visited our clinic from October 1993 to January 1994. Of the 64 patients studied, a 22q11 deletion was detected in 5 patients (7.8%): 3 out of 30 patients with tetralogy of Fallot, one of three with interruption of the aortic arch, and one hemitruncus patient. No deletion was found in 16 patients with complete transposition of the great arteries, 8 with double outlet right ventricle and 2 with aortopulmonary window. In these five patients with 22q11 deletion, patient 1 was clinically diagnosed as having DGS, patients 2 and 3 had CTAFS, and patient 4 had VCFS. Patient 5 could not be dysmorphologically evaluated. It was noteworthy that all patients with a 22q11 deletion, except a non-evaluated patient, had some symptoms of syndromes DGS, CTAFS or VCFS, and that we failed to identify a non-syndromic 22q11 deletion positive patients in the present series of 64 patients.Conclusion This study suggests that it is advisable to bear 22q11 deletion in mind when a patient with conotruncal cardiac anomalies has some other features of DGS, VCFS or CTAFS.     

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.     

Frequent Genetic Instability in Small Intestinal Carcinomas

To determine whether genetic instability plays a part in the development of digestive tract carcinomas, we analyzed 3 microsatellite loci isolated from tumors and surrounding normal tissue samples obtained during surgery. The polymerase chain reaction (PCR) technique was used to assess differences between tumor and matched normal DNAs. Replication errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%) esophageal carcinoma cases showed any RER, but 5 of the 11 cases of small intestinal carcinoma (45%) had RERs, a significantly frequent finding. These results suggest that genetic instability plays an important role in the pathogenesis of small intestinal carcinomas.