Mari S. Oba

A prospective, multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911

BACKGROUND Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene. METHODS Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d. RESULTS Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes. CONCLUSION The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.

Evaluation of the efficacy of daikenchuto (TJ -100) for the prevention of paralytic ileus after pancreaticoduodenectomy: A multicenter, double-blind, randomized, placebo-controlled trial

BACKGROUND We assessed the efficacy of TJ-100 taken perioperatively to recovery among patients with periampullary tumor or tumor of the head of the pancreas who underwent pancreaticoduodenectomy (PD). PATIENTS AND METHODS In this multicenter, randomized, double-blinded, placebo-controlled, phase II trial (JAPAN-PD Study), patients were assigned randomly in a 1:1 ratio to receive TJ-100 or placebo. The coprimary endpoints were (1) incidence of postoperative paralytic ileus lasting >72 hours after surgery and (2) time to occurrence of postoperative paralytic ileus. This trial is registered at the UMIN Clinical Trials Registry (000007975) and at ClinicalTrials.gov (NCT01607307). RESULTS From August 2012 through July 2013, we assessed 273 patients for eligibility, and 224 underwent randomization; 112 patients received TJ-100, and 112 patients received placebo. The population for analysis consisted of 104 patients who received TJ-100 and 103 who received placebo. Paralytic ileus occurred 35 (33.7%) in the TJ-100 group and 38 (36.9%) in the placebo group (P = .626). Time to first flatus was 2.25 (2.00-2.50) days in the TJ-100 group and 2.50 (1.50-2.50) days in the placebo group (P = .343). Among 23 patients who underwent a pylorus ring-preserving PD, time to first flatus was lower in the TJ-100 group than in the placebo group: 0.50 (0.50-1.00) days versus 1.50 (0.50-3.00) days (P = .034). CONCLUSION Our findings suggest that use of TJ-100 did not improve recovery from paralytic ileus after PD, and may preclude the routine use of TJ-100 in clinical practice after PD operation.

Effect of Umbilical Cord Entanglement and Position on Pregnancy Outcomes.

Introduction. To investigate the effect of complex umbilical cord entanglement primarily around the trunk on pregnancy outcomes. Methods. We studied 6307 pregnant women with singleton pregnancies who underwent vaginal delivery of an infant at ≥37 weeks of gestation. Cases were classified into no cord, nuchal cord, and body cord groups and defined as cases without umbilical cord entanglement, one or more loops of the umbilical cord around the neck only, and umbilical cord around the trunk only, respectively. Pregnancy outcomes were compared among these three groups. Results. The no cord, nuchal cord, and body cord group included 4733, 1451, and 123 pregnancies, respectively. Although delivery mode was not significantly different among the three groups, 1-minute Apgar scores <7 and umbilical artery (UA) pH <7.10 were significantly more common in the umbilical cord entanglement groups than in the no cord group. In particular, the frequency of 5-minute Apgar scores <7 was significantly higher (P = 0.004), whereas that of UA pH <7.10 tended to be higher (P = 0.057) in the body cord group than in the nuchal cord group. Conclusion. Compared to nuchal cord, umbilical cord entanglement around the trunk was associated with a higher risk of low Apgar scores and low UA pH.

Relationship Between Short Umbilical Cord Length and Adverse Pregnancy Outcomes

Abstract To investigate how umbilical cord length relates to pregnancy outcomes, we retrospectively analyzed data from 89,042 deliveries recorded in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System. We included term deliveries in which vaginal birth was attempted. Umbilical cord length was categorized into four groups: less than the first percentile, from the first percentile to less than the 10th percentile, from the 10th percentile to less than 25th percentile, and from the 25th percentile to less than the 75th percentile, which constituted the control group. Cord lengths of 33, 43, 48, 63 cm corresponded to the first, 10th, 25th, and 75th percentile values of the cord length distribution, respectively. Statistically significant differences were observed in the rate of unplanned cesarean delivery for all three short cord groups compared to control. There was a higher odds ratio for unplanned cesarean delivery as the umbilical cord became shorter.

Prognostic factors in stage IB gastric cancer.

AIM To identify the subset of patients with stage IB gastric cancer with an unfavorable prognosis. METHODS Overall survival (OS) rates were examined in 103 patients with stage IB (T1N1M0 and T2N0M0) gastric cancer between January 2000 and December 2011. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. RESULTS The OS rates of patients with T1N1 and T2N0 cancer were 89.2% and 94.1% at 5-years, respectively. Both univariate and multivariate analyses demonstrated that tumor location was the only significant prognostic factor. The OS rate was 81.8% at 5-years when the tumor was located in the upper third of the stomach and was 95.5% at 5-years when the tumor was located in the middle or lower third of the stomach (P = 0.0093). CONCLUSION These data may suggest that tumor location is associated with survival in patients with stage IB gastric cancer.

Is Routine Prophylactic Cholecystectomy Necessary During Gastrectomy for Gastric Cancer? Reply

Background Performing routine prophylactic cholecystectomy during gastrectomy in gastric cancer patients has been controversial. The frequency of cholelithiasis, cholecystitis, and cholangitis after gastrectomy has not been reported for large patient populations, so we carried out this retrospective study to aid the assessment of the necessity for prophylactic cholecystectomy.

Significance of oligohydramnios in preterm small-for-gestational-age infants for outcome at 18 months of age

The aim of this study was to evaluate the association between oligohydramnios and other perinatal factors in preterm small‐for‐gestational‐age (SGA) infants who had cerebral palsy at 18 months of age or who had died before this age.

Gonadal function, fertility, and reproductive medicine in childhood and adolescent cancer patients: a national survey of Japanese pediatric endocrinologists.

Abstract. An increasing number of pediatric cancer patients survive, and treatment-related infertility represents one of the most important issues for these patients. While official guidelines in Japan recommend long-term follow-up of childhood cancer survivors (CCSs), their gonadal function and fertility have not been clarified. To address this issue, we organized a working panel to compile evidence from long-term survivors who received treatments for cancer during childhood or adolescence. In collaboration with members of the CCS Committee of the Japanese Society for Pediatric Endocrinology (JSPE), we conducted a questionnaire survey regarding reproductive function in pediatric cancer patients. A cross-sectional survey was sent to 178 JSPE-certified councilors who were asked to self-evaluate the medical examinations they had performed. A total of 151 responses were obtained, revealing that 143 endocrinologists were involved in the care of CCSs. A quarter of the respondents reported having experienced issues during gonadal or reproductive examinations. Several survivors did not remember or fully understand the explanation regarding gonadal damage, and faced physical and psychological distress when discussing the risk of becoming infertile. Pediatric endocrinologists had anxieties regarding their patients’ infertility and the risk of miscarriage, premature birth, and delivery problems. Only a limited number of endocrinologists had experience with managing childbirth and fertility preservation. Many councilors mentioned the necessity for inter-disciplinary communication among healthcare providers. Both endocrinologists and oncologists should set and follow a uniform clinical guideline that includes management of fertility of CCSs.

Extraction of the subpleural lung region from computed tomography images to detect interstitial lung disease

PurposeTo quantify lesions in the subpleural lung region (SubPL) on computed tomography (CT) images and to evaluate whether they are useful for detecting interstitial lung disease (ILD).Materials and methodsThe subjects were 40 patients with idiopathic pulmonary fibrosis (IPF) diagnosed by multidisciplinary methods and 35 age-matched patients without ILDs. The lungs and SubPL were extracted from CT images using a Gaussian histogram normalized correlation system and evaluated for the mean CT attenuation value (CTmean) and the percentage of high attenuation area (%HAA), exceeding −700 Hounsfield units. The H pattern was defined as a honeycomb appearance and/or fibrosis with traction bronchiectasis, and the H-pattern volume ratios for the whole lung and the 2-mm-wide SubPL were measured. The utility of the SubPL for detecting ILD was evaluated by receiver operating characteristic (ROC) analysis.ResultsThe areas under the ROC curves (AUCs) of CTmean and %HAA for the SubPL were greater than those for the whole lung. The AUCs for the whole lung and the SubPL were 0.990 and 0.994, respectively, for H-pattern volume; 0.875 and 0.994, respectively, for CTmean; and 0.965 and 0.991, respectively, for %HAA.ConclusionThe SubPL extraction method may be helpful for distinguishing patients with ILD from those without ILD.

Childbirth and fertility preservation in childhood and adolescent cancer patients: a second national survey of Japanese pediatric endocrinologists

Abstract. Although existing guidelines recommend long-term follow-up of childhood cancer survivors (CCSs), their fertility has not been fully investigated in Japan. To address this issue, we organized a working panel consisting of medical specialists in foundation hospitals. We conducted questionnaire surveys targeting pediatric endocrinologists regarding reproduction in pediatric and adolescent cancer patients in collaboration with the CCS committee of the Japanese Society for Pediatric Endocrinology (JSPE). The first questionnaire was sent to 178 directors or councilors of the JSPE, and the second was sent to those who had provided answers on their experience with childbirth or fertility preservation. A total of 151 responses (84.8%) were obtained in the first survey. In the second survey, the response rate was 100% (39 respondents). There were 27 answers describing experiences with childbirth (16 from partners of male CCSs, 22 from female CCSs). A few cases of premature birth and low birth weight were reported. There were 25 answers describing experiences with fertility preservation; 21 were from male and 17 from female CCSs. It was mainly physicians who recommended fertility preservation. This nationwide questionnaire survey revealed that a limited number of Japanese pediatric endocrinologists had experience with childbirth and fertility preservation in CCSs. A further long-term follow-up study of their fertility is needed.