Intensity-modulated radiation therapy administered to a previously irradiated spine is effective and well-tolerated.

PURPOSE: This study sought to discern the clinical outcomes of intensity-modulated radiation therapy (IMRT) administered to the spine in patients who had undergone previous radiotherapy. METHODS: A total of 81 sites of 74 patients who underwent previous radiotherapy administered to the spine or peri-spine and subsequently received IMRT for the spine were analyzed in this study. The prescribed dose of 80 Gy in a biologically effective dose (BED) of α/ß = 10 (BED10) was set as the planning target volume. The constraint for the spinal cord and cauda equine was D0.1 cc ≤ 100 Gy and ≤ 150 Gy of BED for re-irradiation alone and the total irradiation dose, respectively. RESULTS: The median follow-up period was 10.1 (0.9-92.1) months after re-irradiation, while the median interval from the last day of the previous radiotherapy to the time of re-irradiation was 15.6 (0.4-210.1) months. Separately, the median prescript dose of re-irradiation was 78.0 (28.0-104.9) of BED10. The median survival time in this study was 13.9 months, with 1-, 3-, and 5-year overall survival rates of 53.7%, 29.3%, and 26.6%, respectively. The 1-, 3-, and 5-year local control rates were 90.8%, 84.0%, and 84.0%, respectively. Neurotoxicity was observed in two of 72 treatments (2.8%) assessed after re-irradiation. CONCLUSION: Re-irradiation for the spine using IMRT seems well-tolerated. Definitive re-irradiation can be a feasible treatment option in patients with the potential for a good prognosis.

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients.

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

Relationship between Eustachian tube dysfunction and otitis media with effusion in radiotherapy patients.

OBJECTIVE: This study evaluated the relationship between radiation and Eustachian tube dysfunction, and examined the radiation dose required to induce otitis media with effusion. METHODS: The function of 36 Eustachian tubes in 18 patients with head and neck cancer were examined sonotubometrically before, during, and 1, 2 and 3 months after, intensity-modulated radiotherapy. Patients with an increase of 5 dB or less in sound pressure level (dB) during swallowing were categorised as being in the dysfunction group. Additionally, radiation dose distributions were assessed in all Eustachian tubes using three dose-volume histogram parameters. RESULTS: Twenty-two of 25 normally functioning Eustachian tubes before radiotherapy (88.0 per cent) shifted to the dysfunction group after therapy. All ears that developed otitis media with effusion belonged to the dysfunction group. The radiation dose threshold evaluation revealed that ears with otitis media with effusion received significantly higher doses to the Eustachian tubes. CONCLUSION: The results indicate a relationship between radiation dose and Eustachian tube dysfunction and otitis media with effusion.

Diurnal and circadian oscillations in expression of kisspeptin, kisspeptin receptor and gonadotrophin-releasing hormone 2 genes in the grass puffer, a semilunar-synchronised spawner.

In seasonally breeding animals, the circadian and photoperiodic regulation of neuroendocrine system is important for precisely-timed reproduction. Kisspeptin, encoded by the Kiss1 gene, acts as a principal positive regulator of the reproductive axis by stimulating gonadotrophin-releasing hormone (GnRH) neurone activity in vertebrates. However, the precise mechanisms underlying the cyclic regulation of the kisspeptin neuroendocrine system remain largely unknown. The grass puffer, Takifugu niphobles, exhibits a unique spawning rhythm: spawning occurs 1.5-2 h before high tide on the day of spring tide every 2 weeks, and the spawning rhythm is connected to circadian and lunar-/tide-related clock mechanisms. The grass puffer has only one kisspeptin gene (kiss2), which is expressed in a single neural population in the preoptic area (POA), and has one kisspeptin receptor gene (kiss2r), which is expressed in the POA and the nucleus dorsomedialis thalami. Both kiss2 and kiss2r show diurnal variations in expression levels, with a peak at Zeitgeber time (ZT) 6 (middle of day time) under the light/dark conditions. They also show circadian expression with a peak at circadian time 15 (beginning of subjective night-time) under constant darkness. The synchronous and diurnal oscillations of kiss2 and kiss2r expression suggest that the action of Kiss2 in the diencephalon is highly dependent on time. Moreover, midbrain GnRH2 gene (gnrh2) but not GnRH1 or GnRH3 genes show a unique semidiurnal oscillation with two peaks at ZT6 and ZT18 within a day. The cyclic expression of kiss2, kiss2r and gnrh2 may be important in the control of the precisely-timed diurnal and semilunar spawning rhythm of the grass puffer, possibly through the circadian clock and melatonin, which may transmit the photoperiodic information of daylight and moonlight to the reproductive neuroendocrine centre in the hypothalamus.

Exome sequencing in a family with an X-linked lethal malformation syndrome: clinical consequences of hemizygous truncating OFD1 mutations in male patients.

Oral-facial-digital syndrome type 1 (OFD1; OMIM #311200) is an X-linked dominant disorder, caused by heterozygous mutations in the OFD1 gene and characterized by facial anomalies, abnormalities in oral tissues, digits, brain, and kidney; and male lethality in the first or second trimester pregnancy. We encountered a family with three affected male neonates having an 'unclassified' X-linked lethal congenital malformation syndrome. Exome sequencing of entire transcripts of the whole X chromosome has identified a novel splicing mutation (c.2388+1G > C) in intron 17 of OFD1, resulting in a premature stop codon at amino acid position 796. The affected males manifested severe multisystem complications in addition to the cardinal features of OFD1 and the carrier female showed only subtle features of OFD1. The present patients and the previously reported male patients from four families (clinical OFD1; Simpson-Golabi-Behmel syndrome, type 2 with an OFD1 mutation; Joubert syndrome-10 with OFD1 mutations) would belong to a single syndrome spectrum caused by truncating OFD1 mutations, presenting with craniofacial features (macrocephaly, depressed or broad nasal bridge, and lip abnormalities), postaxial polydactyly, respiratory insufficiency with recurrent respiratory tract infections in survivors, severe mental or developmental retardation, and brain malformations (hypoplasia or agenesis of corpus callosum and/or cerebellar vermis and posterior fossa abnormalities).

Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors.

Interferon-alpha (IFN-α) has strong antitumor effects, and IFN-α gene therapy has been used clinically against some cancers. In this study, we evaluated the efficacy of the combination of IFN-α-transduced tumor cell vaccines and programmed cell death 1 (PD-1) blockade, and investigated the mechanisms of the antitumor effects of the combined therapy. A poorly immunogenic murine colorectal cancer cell line, MC38, was transduced to overexpress IFN-α. In a therapeutic model, parental tumor-bearing mice were inoculated with MC38-IFNα cells and an anti-PD-1 antagonistic antibody. Analyses of immunohistochemistry and tumor-specific lysis were performed. The outgrowth of the established tumors was significantly reduced in mice treated with the combination of IFN-α and anti-PD-1. Immunohistochemical analyses of the therapeutic model showed marked infiltration of CD4(+) cells and CD8(+) cells in the established MC38 tumors of mice treated with both IFN-α and anti-PD-1. Significant tumor-specific cytolysis was detected when splenocytes of mice that were treated with both IFN-α and anti-PD-1 were used as effector cells. These results suggest that blockade of the PD-1 PD-ligand enhanced the Th1-type antitumor immune responses induced by IFN-α. The combination of IFN-α gene-transduced tumor cell vaccines and PD-1 blockade may be a possible candidate for a cancer vaccine for clinical trials.

Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease.

OBJECTIVE: RNF213 was recently reported as a susceptibility gene for moyamoya disease (MMD). Our aim was to clarify the correlation between the RNF213 genotype and MMD phenotype. METHODS: The entire coding region of the RNF213 gene was sequenced in 204 patients with MMD, and corresponding variants were checked in 62 pairs of parents, 13 mothers and 4 fathers of the patients, and 283 normal controls. Clinical information was collected. Genotype-phenotype correlations were statistically analyzed. RESULTS: The c.14576G>A variant was identified in 95.1% of patients with familial MMD, 79.2% of patients with sporadic MMD, and 1.8% of controls, thus confirming its association with MMD, with an odds ratio of 259 and p < 0.001 for either heterozygotes or homozygotes. Homozygous c.14576G>A was observed in 15 patients but not in the controls and unaffected parents. The incidence rate for homozygotes was calculated to be >78%. Homozygotes had a significantly earlier age at onset compared with heterozygotes or wild types (median age at onset 3, 7, and 8 years, respectively). Of homozygotes, 60% were diagnosed with MMD before age 4, and all had infarctions as the first symptom. Infarctions at initial presentation and involvement of posterior cerebral arteries, both known as poor prognostic factors for MMD, were of significantly higher frequency in homozygotes than in heterozygotes and wild types. Variants other than c.14576G>A were not associated with clinical phenotypes. CONCLUSIONS: The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for predicting the severe type of MMD, for which early medical/surgical intervention is recommended, and may provide a better monitoring and prevention strategy.

LKB1, TP16, EGFR, and KRAS somatic mutations in lung adenocarcinomas from a Chiba Prefecture, Japan cohort.

The discovery of somatic mutations in cancer-related genes has been applied to understand the genetic basis of cancer. Here we report somatic mutations of two tumor suppressor genes: LKB1 (exons 1, 4, and 8) and TP16 (CDKN2A) (exons 1 and 2); and two oncogenes: epidermal growth factor receptor EGFR (exons 18-21) and KRAS (exon 2) in 97 lung adenocarcinoma tissues in a cohort from the Kujukuri coast area of Chiba, Japan. In the LKB1 gene, only F354L substitutions were observed in 14 of the 97 tissue samples (14.4%). In the TP16 gene, only two deletions were observed in contrast to previous reports. On the other hand, the EGFR gene was highly mutated (38.1%) and mainly L858R substitutions occurred (23.7%) as well as insertions and deletions. In the KRAS gene, 10 substitutions at codon 12 were observed (10.3%). Co-occurrence of EGFR and KRAS somatic mutations was identified in one patient, those of EGFR and LKB1 were in three patients, and those of KRAS and LKB1 were in four patients. The lower rates of LKB1, TP16, and KRAS somatic mutations in lung adenocarcinomas are characteristic of the Kujukuri cohort as compared to Caucasians.

Exonic deletion of CASP10 in a patient presenting with systemic juvenile idiopathic arthritis, but not with autoimmune lymphoproliferative syndrome type IIa.

Systemic juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly defined. To detect copy number variations, we performed single nucleotide polymorphism (SNP) array analysis in 50 patients with s-JIA. We found a 13-kb intragenic deletion of CASP10 in one patient. RT-PCR of the mRNA extracted from the patient's lymphoblastoid cells revealed that CASP10 mRNA was truncated. Sequencing the mRNA revealed that this deletion resulted in a frame shift with an early stop codon. CASP10 is known as a causative gene for autoimmune lymphoproliferative syndrome (ALPS) type IIa, another childhood syndrome of lymphadenopathy and splenomegaly associated with autoimmune haemolytic anaemia and thrombocytopenia. TCR αß(+) CD4/CD8 double-negative T cells in the peripheral blood as a diagnostic marker of ALPS were not high in this patient and lymphocyte apoptosis induced by anti-Fas antibody was normal, denying ALPS in the patient. The father and a sister of the patient showing no symptoms of ALPS or s-JIA, also had the same deletion. Furthermore, we found no other mutations of CASP10 in the other 49 s-JIA patients. These data suggest that the pathogenic significance of CASP10 mutations should be carefully evaluated in s-JIA or even ALPS type IIa in further studies.

Glutamate exocrine dynamics augmented by plasma glutamine and the distribution of amino acid transporters of the rat pancreas.

The nutritional and physiological roles of amino acid (AA)s have been investigated for individual organs. In the current study, we focused on the dynamics of glutamate and transport systems in the pancreas. We employed original procedures to obtain rat pancreatic juice (PJ) subjected to intravenous administration of alanyl-glutamine (AG) for AA analysis. The pancreatic expressions of the transporters were evaluated by immunohistochemistry. We found that glutamate was secreted into the PJ in the basal state. The intravenous administration of AG increased the concentration and total amount of glutamate excreted into the PJ. In terms of the transport systems, L-type AA transporter (LAT1) was identified exclusively in the islet cells. Glutamate transporter 1 (GLT1), glutamate-aspartate transporter (GLAST), vesicular glutamate transporter 1 (VGUT1) and cystine/glutamic acid transporter (xCT) were found in the islet cells. xCT was identified in the duct cells as well, but was not accompanied by the expression of 4F2 heavy chain (4F2hc) staining in the islets and the acinar cells, similar to neutral AA transporter (ASCT2) or b0,+-type AA transporter 1(BAT1). Excitatory AA transporter (EAAC) was identified only in the acinar cells. Glutamate was exclusively found in the acinar cells. We revealed the novel dynamics of glutamate in the rat PJ. The glutamate secretion into the PJ was augmented by plasma glutamine, indicating the de novo metabolisms of glutamate, together with the local expression of the related transporters.

[Surgical treatment for infective endocarditis].

OBJECTIVE: Surgery for infective endocarditis (IE) is technically demanding, especially the one for active IE. METHODS: Operations were performed in 21 patients with a mean age of 52.2 +/- 18.8 years. Fifteen patients were male, and 6 were female. There were 15 patients with active IE and 6 patients with healed IE. Isolated pathogens were Streptococcus in 8 cases, Staphylococcus in 3, and Enterococcus in 2. Two patients had prosthetic valve endocarditis. When the lesions affected the aortic valve, aortic valve replacement (AVR) was performed. When the lesions affected the mitral or tricuspid valves, valve repair was the treatment of choice. RESULTS: Six patients underwent AVR and 15 patients underwent a mitral valve operation (mitral valve repair in 13, replacement in 2). In 2 patients, mitral valve repair was changed to replacement, judged by intraoperative transesophageal echocardiogram. One patient underwent isolated tricuspid valve repair. Total survival and survival free of reoperation at 45 months was 95.2%. The grade of mitral regurgitation (MR) decreased from 3.7 +/- 0.1 to 0.2 +/- 0.1, and that of tricuspid valve regurgitation (TR) recovered from 3.5 +/- 0.5 to 1.0 +/- 1.0 at 21 +/- 15 months after the operation. CONCLUSIONS: Valve repair operations were useful in the mitral and tricuspid valve positions, even in the presence of active IE. Both mechanical valve and bioprosthesis showed good results after AVR for IE.

Effect of heat treatment on transformation temperatures and bending properties of nickel-titanium endodontic instruments.

AIM: To investigate the effect of heat treatment on the bending properties of nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Nickel-titanium super-elastic alloy wire (1.00 mm Ø) was processed into a conical shape with a 0.30 mm diameter tip and 0.06 taper. The heat treatment temperature was set at 440 or 500 degrees C for a period of 10 or 30 min. Nonheat-treated specimens were used as controls. The phase transformation behaviour was examined using differential scanning calorimetry. A cantilever-bending test was used to evaluate the bending properties of the specimens. Data were analyzed by ANOVA and the Tukey-Kramer test (P = 0.05). RESULTS: The transformation temperature was higher for each heat treatment condition compared with the control. Two clear thermal peaks were observed for the heat treatment at 440 degrees C. The specimen heated at 440 degrees C for 30 min exhibited the highest temperatures for M(s) and A(f), with subsequently lower temperatures observed for specimens heated at 440 degrees C for 10 min, 500 degrees C for 30 min, 500 degrees C for 10 min, and control specimens. The sample heated at 440 degrees C for 30 min had the lowest bending load values (P < 0.05), both in the elastic range (0.5 mm deflection) and in the super-elastic range (2.0 mm deflection). The influence of heat treatment time was less than that of heat treatment temperature. CONCLUSIONS: Change in the transformation behaviour by heat treatment may be effective in increasing the flexibility of nickel-titanium endodontic instruments.

Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints.

OBJECTIVE: To investigate the in vitro and in vivo effects of interleukin (IL)-4 on mechanical stress-induced nitric oxide (NO) expression by chondrocytes, and destruction of cartilage and NO production in an instability-induced osteoarthritis (OA) model in rat knee joints, respectively. MATERIALS AND METHODS: Cyclic tensile stress (CTS; 0.5Hz and 7% elongation) was applied to cultured normal rat chondrocytes with or without pre-incubation with recombinant rat IL-4 (rrIL-4). Inducible NO synthase (iNOS) mRNA expression and NO production were examined with real-time polymerase chain reaction and the Griess reaction, respectively. OA was induced in rat knee joints by transection of the anterior cruciate and medial collateral ligaments and resection of the medial meniscus. rrIL-4 (10, 50, and 100 ng/joint/day) was injected intra-articularly, and knee joint samples were collected 2, 4, and 6 weeks after surgery. Cartilage destruction was evaluated by the modified Mankin score and Osteoarthritis Research Society International scoring system on paraffin-embedded sections stained with safranin O. Cleavage of aggrecan and NO production were examined by immunohistochemistry for aggrecan neoepitope (NITEGE) and of nitrotyrosine (NT), respectively. RESULTS: rrIL-4 down-regulated CTS-induced iNOS mRNA expression and NO production by chondrocytes. The intra-articular injection of rrIL-4 gave rise to a limited, but significant amelioration of cartilage destruction, prevention of loss of aggrecan, and decrease in the number of NT-positive chondrocytes, an effect that was not dose-dependent. CONCLUSION: The present study suggests that IL-4 may exert chondroprotective properties against mechanical stress-induced cartilage destruction, at least in part, by inhibiting NO production by chondrocytes.

Phase transformation behaviour and bending properties of hybrid nickel-titanium rotary endodontic instruments.

AIM: To investigate the bending properties of hybrid rotary nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Four types of nickel-titanium rotary endodontic instruments with different cross-sectional shapes (triangular-based and rectangular-based) and different heat treatment conditions (super-elastic type and hybrid type with shape memory effect) were selected to investigate bending properties and phase transformation behaviour. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 3.0 mm. A commercial rotary instrument, ProFile (PF; Dentsply Maillefer, Ballaigues, Switzerland) was used as a reference for the bending test. Phase transformation temperatures were calculated from the diagrams obtained from differential scanning calorimetry. Data were analysed by anova and Scheffe's test. RESULTS: The bending load values of the hybrid type that had undergone additional heat treatment at the tip were significantly lower (P < 0.05) than those of the super-elastic type with no additional heat treatment. The bending load values of rectangular-based cross-sectional shaped instruments were significantly lower (P < 0.05) than those of triangular-based cross-sectional shaped instruments. Phase transformation temperatures (M(s) and A(f) points) of the hybrid type were significantly higher (P < 0.05) than the super-elastic type. The M(f) and A(s) points of the tip part were significantly higher (P < 0.05) than those of the whole part of the hybrid instrument. CONCLUSIONS: Additional heat treatment of hybrid nickel-titanium instruments may be effective in increasing the flexibility of nickel-titanium rotary instruments.

Electrogene therapy using endostatin, with or without suicide gene therapy, suppresses murine mammary tumor growth and metastasis.

Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of a plasmid vector containing either endostatin (pEndo) with or without a suicide gene (pHSVtk), pHSVtk alone or control vector once a week for 8 weeks. We applied electrogene transfer to the tumors after each injection and administered ganciclovir (GCV) to pHSVtk-transfected mice using an osmotic minipump. Anticancer efficacy was monitored using a variety of parameters, namely tumor volume, intratumoral microvessel density and DNA synthesis, number of mice with metastasis, and number of sites of metastasis per mouse. Tumor volume was significantly lower in all therapeutic groups, with the most effective growth suppression in the pEndo+pHSVtk/GCV group. Lymph node metastasis was significantly less frequent in all therapeutic groups, whereas the multiplicity of lung metastases was significantly lower only in the pEndo and pEndo+pHSVtk/GCV groups. All therapeutic groups showed significantly lower intratumor microvessel density and DNA synthesis. The pEndo and pEndo+pHSVtk/GCV groups also showed a significant reduction in the numbers of dilated lymphatic vessels containing intralumenal tumor cells. Our data suggest that endostatin electrogene therapy alone or in combination with pHSVtk/GCV suicide gene therapy is more beneficial than suicide gene therapy alone. The observed antimetastatic activity of endostatin may be of high clinical significance in the treatment of metastatic breast cancer.

Influence of phase transformation on the torsional and bending properties of nickel-titanium rotary endodontic instruments.

AIM: To investigate the relationship between the functional properties and the phase transformation of nickel-titanium endodontic instruments. METHODOLOGY: Five types of rotary nickel-titanium endodontic instruments with a 0.30 mm diameter tip (EndoWave, HERO 642, K3, ProFile.06, and ProTaper) were selected to investigate torsional and bending properties, and phase transformation behaviour. A torsional test was performed according to ISO publication 3630-1, and maximum torque and angular deflection at fracture were measured. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 4.0 mm. A stainless steel K-file was used for reference. Phase transformation behaviour was measured by differential scanning calorimetry (DSC). From the DSC curve, transformation temperatures were calculated. Data were analysed by anova and the Tukey-Kramer's test. RESULTS: The maximum torsional torque values of HERO, K3 and ProTaper were significantly higher (P < 0.05) than those of EndoWave, ProFile and K-file. The K-files had the lowest torque value. Angular deflection at fracture was significantly higher (P < 0.05) for K-files than that for any nickel-titanium instrument. The bending load values of HERO and K3 were significantly higher (P < 0.05) than those of EndoWave, ProFile, ProTaper and K-file. The K-files had the lowest load value, although residual deflection remained. The transformation temperatures of HERO and K3 were significantly lower (P < 0.05) than those of EndoWave, ProFile and ProTaper. CONCLUSIONS: The functional properties of nickel-titanium endodontic instruments, especially their flexible bending load level, were closely related to the transformation behaviour of the alloys.

[Successful implantation of a metal coronary angioplasty stent for bronchomalacia of the right tracheal bronchus associated with right isomerism complex in an early infant].

One-month-old boy had severe emphysema of the right upper lobe due to the stenotic tracheal bronchus compressed between the distorted right patent ductus arteriosus (PDA) and the right aortic arch associated with right isomerism complex. He underwent a left modified Blalock-Taussig shunt and a division of the PDA on cardiopulmonary bypass. Extracorporeal lung support (ECLS) was introduced because of severe hypoxemia caused by remaining bronchomalacia of the tracheal bronchus. On postoperative day 3, a metal coronary angioplasty stent was implanted at the stenotic lesion under fluoroscopic and bronchoscopic guidance. He was successfully weaned from ECLS and then respirator after the implantation. This simple stenting procedure might be an effective alternate in the treatment of bronchomalacia or bronchial stenosis in early infancy.

Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study.

BACKGROUND AND AIMS: Helicobacter pylori infection and gastric atrophy are both risk factors for gastric cancer. We aimed to elucidate the natural history of gastric cancer development according to H pylori infection and gastric atrophy status. SUBJECTS AND METHODS: A total of 9293 participants in a mass health appraisal programme were candidates for inclusion in the present prospective cohort study: 6983 subjects revisited the follow up programme. Subjects were classified into four groups according to serological status at initial endoscopy. Group A (n = 3324) had "normal" pepsinogen and were negative for H pylori antibody; group B (n = 2134) had "normal" pepsinogen and were positive for H pylori antibody; group C (n = 1082) had "atrophic" pepsinogen and were positive for H pylori antibody; and group D (n = 443) had "atrophic" pepsinogen and were negative for H pylori antibody. Incidence of gastric cancer was determined by annual endoscopic examination. RESULTS: Mean duration of follow up was 4.7 years and the average number of endoscopic examinations was 5.1. The annual incidence of gastric cancer was 0.04% (95% confidence interval (CI) 0.02-0.09), 0.06% (0.03-0.13), 0.35% (0.23-0.57), and 0.60% (0.34-1.05) in groups A, B, C, and D, respectively. Hazard ratios compared with group A were 1.1 (95% CI 0.4-3.4), 6.0 (2.4-14.5), and 8.2 (3.2-21.5) in groups B, C, and D, respectively. Age, sex, and "group" significantly served as independent valuables by multivariate analysis. CONCLUSIONS: The combination of serum pepsinogen and anti-H pylori antibody provides a good predictive marker for the development of gastric cancer.