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A man in his 50s was referred to the hospital with fever, right lower abdominal pain, and bloody diarrhea. Based on computed tomography images and characteristic varioliform erosions observed during the colonoscopic examination, the patient was diagnosed with fulminant amebic colitis. Intravenous metronidazole was administered immediately. After symptom improvement, a second colonoscopic examination revealed inflammation localized to the right hemicolon. A right colectomy was performed on the 75th hospital day, and the patient was discharged without further problems. Prompt antiamebic therapy based on early endoscopic diagnosis was effective in quelling colonic inflammation in a life-threatening case of acute fulminant amebic colitis. Moreover, colonoscopic reexamination was useful in determining the extent of inflammation and minimizing colon resection.

Spontaneous regression (SR) has been reported in various malignant tumors. However, SR in colorectal cancer (CRC) is particularly rare and the mechanism remains unclear. We here report three cases of CRCs displaying SR, which were experienced at two institutions. Intriguingly, all of these cases displayed the common endoscopic characteristics; superficial elevated lesion accompanied by a central depression (0-IIa + IIc, in the Paris classification), with a nonpolypoid growth, located in the ascending colon. Furthermore, immunohistology of biopsy specimens revealed the lack of DNA mismatch repair proteins within the CRC lesions, suggesting that these were mismatch repair-deficient (dMMR) CRCs. One of the major features of dMMR cancers is an increase in the number of tumor-infiltrating lymphocytes. Thus, the dMMR phenotype might be associated with SR of CRCs through the activation of anti-tumor host immune responses.

BACKGROUND AND AIM Cholecystitis is a major complication after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement. METHODS Incidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016. RESULTS Cholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow-up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57-137.18; P = 0.001) and 25.26 (95% CI, 4.12-154.98; P < 0.001), respectively. CONCLUSIONS This study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement.

Endoscopic treatments, including endoscopic mucosal resection or endoscopic submucosal dissection, are well accepted as standard treatments for early gastric cancers. However, there are few studies evaluating the safety and efficacy of this approach for early gastric cancers in patients aged over 80 years, and the post-treatment prognosis remains unclear. Here, we retrospectively analyzed the medical records and evaluated the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years (group A) compared with non-elderly patients aged 65-79 years (group B) and under 65 years (group C). In this study, we enrolled 53 patients (mean age, 82 years) in group A, 217 patients (mean age, 73 years) in group B, and 89 patients (mean age, 60 years) in group C who received endoscopic treatment at Kyoto University Hospital between 2001 and 2010. The incidence of treatment-related complications including aspiration pneumonia, bleeding, and perforation was 19% (10/53) in group A, 9.7% (21/217) in group B, and 6.7% (6/89) in group C, respectively. In particular, only the incidence of aspiration pneumonia was significantly higher in group A [11% (6/53) ] than in the other two groups [1.8% (4/217) in group B and 1.1% (1/89) in group C]. There was no significant difference in the curative resection rate and recurrence rate including metachronous lesions among the three groups. In group A, the median survival calculated using the Kaplan-Meier method was 8.0 years, and the 5-year survival rate was 73%. No gastric cancer-related deaths were observed in all groups. In conclusion, endoscopic treatment for early gastric cancers may contribute to an improvement in life expectancy, even among patients aged over 80 years, provided an experienced gastroenterologist selects the appropriate patients based on not only the endoscopic findings for the lesion but also the severity of any comorbidities. However, it is noteworthy that our elderly group aged over 80 years had a high risk of developing aspiration pneumonia.

The multidiameter balloon catheter is used widely for severe esophageal stricture dilation. However, the relationships between inflation pressure, balloon size, and radial dilation force at the stricture site have not been examined fully. We performed an experiment using phantom models to investigate the relationships between inflation pressure, balloon size, and radial dilation force. The balloon dilation procedure was performed for each stricture model using three sizes of balloon: 10–11–12, 12–13.5–15, and 15–16.5–18 mm. A positive association between inflation pressure and dilation force was observed for each balloon size. In balloons inflated by targeting the same diameter, the dilation force was higher for smaller balloons than for larger balloons. An inverse association between stricture size and dilation force was observed in the 12–13.5–15 mm balloon (3 vs 5 mm, P = .002; 5 vs 7 mm, P

Narrow band imaging (NBI) combined with magnifying endoscopy enables us to detect superficial laryngo-pharyngeal cancers, which are difficult to detect by standard endoscopy. Endoscopic laryngo-pharyngeal surgery (ELPS) is a technique developed to treat such lesions and the purpose of this study is to evaluate the usefulness of ELPS for superficial laryngo-pharyngeal cancer. Seventy five consecutive patients with 104 fresh superficial laryngo-pharyngeal cancers are included in this study. Under general anesthesia, a specially-designed curved laryngoscope was inserted to create a working space in the pharyngeal lumen. A magnifying endoscope was inserted transorally to visualize the field and a head & neck surgeon dissected the lesion using the combination of the orally-inserted curved grasping forceps and electrosurgical needle knife in both hands. The safely, functional outcomes, and oncologic outcomes of ELPS were evaluated retrospectively. Median operation time per lesion was 35 min. Post-operative bleeding occurred in 3 cases and temporal subcutaneous emphysema occurred in 10 cases. No vocal fold impairment occurred after surgery. The median fasting period was 2 days and all patients except one have a normal diet with no limitations. Local recurrence occurred in 1 case, and the 3-year overall survival rate and the 3-year disease specific survival rate was 90 % and 100 %, respectively. ELPS is a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, and enjoys the merit of both procedures. ELPS makes it possible to perform minimally-invasive surgery, preserving both the swallowing and phonation functions.

Diffuse cavernous hemangioma of the rectum (DCHR) is a relatively rare disease. A 40-year-old man presented with long-standing lower abdominal discomfort and hematuria. At the time of hospitalization, his vital signs and hemoglobin level were normal. Colonoscopy showed markedly dilated blood vessels in the sigmoid mucosa, which was confirmed on magnetic resonance imaging and computed tomography as cavernous hemangioma. Without surgery, there have been no signs of progression of DCHR during a 3-year follow-up period.

A randomized Phase II/III trial commenced in May 2014. Endoscopic balloon dilation with steroid injection is the current standard treatment for patients with refractory anastomotic stricture after esophagectomy. The purpose of this study is to confirm the superiority of radial incision and cutting with steroid injection in terms of both restricture-free survival and number of dilations within 24 weeks compared with endoscopic balloon dilation with steroid injection for these patients. A total of 130 patients will be accrued from 30 Japanese institutions over 3 years. The primary endpoint in the Phase II part is proportion of Grade 3/4 intraoperative hemorrhages, post-operative esophageal perforations, esophageal hemorrhages, pneumothorax, lung or mediastinum infections or other unexpected adverse events. Co-primary endpoints in the Phase III part are restricture-free survival and number of dilations within 24 weeks after treatment. Secondary endpoints are proportion of patients with anastomotic diameter >10 mm at 8 weeks after treatment, proportion of adverse events, proportion of patients experiencing improvement of dysphagia score at 2, 4, 8 and 24 weeks after treatment and proportion of patients with dysphagia score ≤1 at 24 weeks after treatment. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000014017 [http://www.umin.ac.jp/ctr/index.htm].

Objectives/Hypothesis To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME-NBI) is useful in predicting pathological depth of tumor invasion in laryngo-pharyngeal cancer. Study Design Retrospective study. Methods Preoperative endoscopy reports and postoperative pathological reports on 139 laryngo-pharyngeal cancer lesions were retrospectively reviewed, and the association between macroscopic findings in the lesions and the depth of tumor invasion was analyzed statistically. Results The ratios of lesions macroscopically classified as 0-I (superficial and protruding), 0-IIa (slightly elevated), 0-IIb (true flat), 0-IIc (slightly depressed), and 0-III (superficial and excavated) in the preoperative endoscopy reports were 3%, 25%, 71%, 1%, and 0%, respectively. Regarding the depth of tumor invasion in the postoperative pathological reports, the ratios of lesions classified as EP (carcinoma in situ), SEP (tumor invades subepithelial layer), and MP (tumor invades muscularis propria) were 73%, 26%, and 1%, respectively. The ratios of subepithelial invasion or muscular invasion in 0-I, 0-IIa, and 0-IIb were 100%, 54%, and 14%, respectively, and showed significant difference (P

Although chemoradiotherapy (CRT) is one curative treatment option for patients with esophageal squamous cell carcinoma (ESCC), local failure after CRT remains a major problem for patients’ curability. The aim of this study was to evaluate the efficacy and safety of photodynamic therapy (PDT) as a salvage treatment for local failure. From August 2007 to March 2012, 193 consecutive ESCC patients were treated with definitive CRT in Kyoto University Hospital. Eighteen of the patients with T2 or earlier T-stage local failure after CRT underwent salvage PDT. After the salvage PDT, 11 patients (61.1%) achieved a complete response at the primary site. Over a median follow-up period of 28.3 months, the 1-year survival and progression-free survival rates were 77.8% and 38.9%, respectively; and the 2-year survival and progression-free survival rates were 60.6% and 33.3%, respectively. Adverse events were mild esophageal stricture in seven (38.9%), esophageal obstruction because of necrotic tissue in nine (50.0%), and photosensitivity in three (16.7%) patients. There were no severe complications or treatment-related deaths. Salvage PDT may be a promising treatment option for the patients with a local residual or recurrent tumor after CRT for ESCC when the lesion is suspected to be in T2 or earlier.

Objectives: Acetaldehyde, the first metabolite of ethanol, is a definite carcinogen for the esophagus, head, and neck; and aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that catalyzes the metabolism of acetaldehyde. The ALDH2 genotype exists as ALDH2*1/*1 (active ALDH2), ALDH2*1/*2 (heterozygous inactive ALDH2), and ALDH2*2/*2 (homozygous inactive ALDH2). Many epidemiological studies have reported that ALDH2*2 carriers are at high risk for esophageal or head and neck squamous cell carcinomas by habitual drinking. Therefore, identification of ALDH2*2 carriers would be helpful for the prevention of those cancers, but there have been no methods suitable for mass screening to identify these individuals. Methods: One hundred and eleven healthy volunteers (ALDH2*1/*1 carriers: 53; ALDH2*1/*2 carriers: 48; and ALDH2*2/*2 carriers: 10) were recruited. Breath samples were collected after drinking 100 ml of 0.5% ethanol using specially designed gas bags, and breath ethanol and acetaldehyde levels were measured by semiconductor gas chromatography. Results: The median (range) breath acetaldehyde levels at 1 min after alcohol ingestion were 96.1 (18.1–399.0) parts per billion (p.p.b.) for the ALDH2*1/*1 genotype, 333.5 (78.4–1218.4) p.p.b. for the ALDH2*1/*2 genotype, and 537.1 (213.2–1353.8) p.p.b. for the ALDH2*2/*2 genotype. The breath acetaldehyde levels in ALDH2*2 carriers were significantly higher than for the ALDH2*1/*1 genotype. Notably, the ratio of breath acetaldehyde level-to-breath ethanol level could identify carriers of the ALDH2*2 allele very accurately (whole accuracy; 96.4%). Conclusions: Our novel breath test is a useful tool for identifying ALDH2*2 carriers, who are at high risk for esophageal and head and neck cancers.

Objective: Fluorouracil, cisplatin, and taxane are widely used in the standard chemotherapy regimens for esophageal squamous cell carcinoma (ESCC). Although S-1 is expected to demonstrate considerable efficacy for ESCC, there is any clinical data. The purpose of this retrospective study was to evaluate the efficacy and safety of S-1 as salvage chemotherapy for ESCC. Methods: From 2007 to 2014, fifteen patients with ESCC refractory or refusal to the standard chemotherapy were treated with S-1 as salvage treatment at the Kyoto University Hospital and their clinical records were reviewed retrospectively. Results: The median age was 70 years old (range: 63-77). A complete response (CR) was achieved in 1 case (7%). A stable disease (SD) and progressive disease (PD) were seen in 9 (60%) and 5 (33%) cases, respectively. After a follow-up duration of 13.9 months, median progression free survival and overall survival was 6.2 and 10.0 months, respectively. One-year survival rate was 33.3%. Toxicities greater than CTCAE grade 3 were observed in 3 of 15 patients (20%). Two patients had grade 3 neutropenia and one patient had grade 3 diarrhea. There was no treatment related death. Conclusions: S-1 salvage chemotherapy could be expected to be an effective and safe treatment option to improve the prognosis of patients with ESCC refractory to the standard chemotherapy.

Paraneoplastic neurological syndromes (PNSs) are rare nervous system dysfunctions in cancer patients, which are primarily observed with small-cell lung cancer, gynecological cancer, and thymoma. We herein present an uncommon case of PNS in an anti-Hu antibody-positive patient with human epidermal growth factor receptor (HER)-2-positive gastric cancer (GC), who developed limbic encephalitis and a worsening cognitive function. Trastuzumab-combined chemotherapy was initiated and appeared to be partially effective for controlling the neurological symptoms and tumor volume. Chemotherapy failure eventually led to uncontrollable neurological symptoms. This is the first case demonstrating that trastuzumab-combined chemotherapy may be effective for controlling neurological symptoms of PNS in HER2-positive GC patients.

Distant metastasis (DM) after definitive chemoradiotherapy has not been a focus of research in esophageal carcinoma. At present, local–regional control is improving following advances in salvage treatments after definitive chemoradiotherapy. There is a need to focus on suppressing the development of DM. The aim of this study was to identify pre-treatment factors associated with DM after definitive chemoradiotherapy. This study included 144 patients with thoracic esophageal squamous cell carcinoma (Stage I/II/III/IV; 35/17/69/23) (TNM 7th) who underwent definitive chemoradiotherapy; >50 Gy was prescribed to all gross tumors with concurrent administration of 5-fluorouracil ± platinum. Pre-treatment factors included age, gender, performance status, tumor location, T/N/M status, tumor length, size of metastatic lymph nodes (LN size), and the presence of intramural metastasis or multiple primary tumors. The effects of pre-treatment factors on overall survival (OS) and DM were evaluated. The median follow-up period was 48 months. DM occurred as an initial progression in 21 % of patients, and LN size correlated with DM development (hazard ratio [HR] = 5.12; p = 0.0013) and poor OS (HR = 2.20; p = 0.0076) in univariate and multivariate analyses. LN size is a quantitative pre-treatment prognostic factor that should be assessed prior to definitive chemoradiotherapy. Patients with large metastatic lymph nodes are at high risk of DM and should be monitored.

A randomized Phase III trial commenced in Japan in September 2014. Endoscopic local steroid injection has been commonly used and considered acceptable as the current standard treatment for the prevention of esophageal stricture after endoscopic submucosal dissection for superficial esophageal cancer. The purpose of this study is to confirm the superiority of prophylactic oral steroid administration following endoscopic submucosal dissection in terms of stricture-free survival over endoscopic local steroid injection for patients with superficial esophageal cancer. A total of 360 patients will be accrued from 35 Japanese institutions within 2.5 years. The primary endpoint is stricture-free survival, and the secondary endpoints are the number of endoscopic balloon dilations for 12 weeks after endoscopic submucosal dissection, adverse events, serious adverse events and the proportion of patients with dysphagia score ≤1 at 12 weeks after endoscopic submucosal dissection. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015064 (http://www.umin.ac.jp/ctr/index.htm).

One of the greatest needs in the clinical bone field is a bioactive agent to stimulate bone formation. We previously reported that fibroblast growth factor-2 (FGF-2) exhibited strong anabolic actions on bone formation in models of rodents and dogs. Aiming at a clinical application, this study was undertaken to clarify the effect of a single local application of recombinant human FGF-2 on fracture healing in nonhuman primates. After a fracture was created at the midshaft of the right ulna of animals and stabilized with an intramedullary nail, gelatin hydrogel alone (n = 10) or gelatin hydrogel containing 200 microg FGF-2 (n = 10) was injected into the fracture site. Although 4 of 10 animals treated with the vehicle alone remained in a nonunion state even after 10 weeks, bone union was complete at 6 weeks in all 10 animals treated with FGF-2. Significant differences in bone mineral content and density at the fracture site between the vehicle and FGF-2 groups were seen at 6 weeks and thereafter. FGF-2 also increased the mechanical property of the fracture site. We conclude that FGF-2 accelerates fracture healing and prevents nonunion in primates, and therefore propose that it is a potent bone anabolic agent for clinical use.

This study is a trial to promote repairing of the rabbit skull bone gap between an autologous bone flap and the intact bone with biodegradable gelatin microspheres containing transforming growth factor-beta1 (TGF-beta1). A 10-mm diameter bone defect was prepared in rabbit skulls by drilling out a bone flap of 6 mm in diameter. After a surrounding gap defect of 2 mm was created and treated with 0.5 microg of free TGF-beta1 and gelatin microspheres containing 0.5 microg of free TGF-beta1, the circular autologous bone flap was placed in the center. Significant bone healing at the gap defect was observed 3 weeks after implantation of the TGF-beta1-containing gelatin microspheres. The bone mineral density (BMD) was significantly higher than that of other experimental groups. On the contrary, when applied with free TGF-beta1, a fibrous tissue initially infiltrated into the gap defect, resulting in impairing bone healing. The tissue response was similar to that at the defect implanted with empty gelatin microspheres and TGF-beta1-free phosphate-buffered saline solution alone. There was more space in the gap-filling bone in the 16-week view than the 3-week view. It is possible that this was an intermediate step along the way toward normal healing and formation of cancellous bone. We conclude that gelatin microspheres containing TGF-beta1 show promise as an agent to promote bone regeneration of subcritical size defects between surgically positioned autologous bone flaps and surrounding host bone.

The effect on intraosseous bone formation of a single local injection of recombinant human basic fibroblast growth factor into the distal femur was examined in normal and ovariectomized rabbits. In normal rabbits, basic fibroblast growth factor increased bone mineral density around the injected site in a dose-dependent manner at 4 weeks, with significant effects at concentrations of 400 micrograms and greater. Doses of 400 and 1,600 micrograms of basic fibroblast growth factor increased bone mineral density by 8 and 9%, respectively, compared with the opposite control femur. Histological examination showed that basic fibroblast growth factor (400 micrograms) induced the proliferation or recruitment of undifferentiated mesenchymal cells around the existing trabeculae at 3 days after the injection. For the first 2 weeks, osteoid formation was strongly stimulated, and this was followed by mineral apposition for another 2 weeks, at which time the femurs were harvested. Consequently, basic fibroblast growth factor stimulated intraosseous bone formation at 4 weeks. We speculate that the direct action of basic fibroblast growth factor on bone formation may be to stimulate proliferation or recruitment of minimally differentiated mesenchymal cells and to initiate the cascade of events in later stages of bone formation. In ovariectomized rabbits, basic fibroblast growth factor (400 micrograms) also increased bone mineral density, histomorphometrical bone formation markers, and trabecular connectivity to levels similar to those in rabbits who had received sham operations.

Background There is no effective treatment for gastroesophageal anastomotic strictures that are refractory to repeated endoscopic balloon dilation (EBD). However, EBD is still selected worldwide to manage such refractory strictures. To relieve the symptoms of dysphagia and keep a wide lumen, we developed a new incisional treatment, radial incision and cutting (RIC). Objective To evaluate the efficacy and safety of the RIC method for the treatment of refractory anastomotic strictures. Design Retrospective cohort study. Setting National Cancer Center and University Hospital. Patients This study involved 54 consecutive patients with refractory anastomotic stricture after esophagogastric surgery. Intervention RIC. Main Outcome Measurements The safety and clinical success of RIC and the long-term patency after RIC compared with those of continued EBD. Results The median procedure time of RIC was 14 minutes (range, 4–40 minutes). No serious adverse events associated with RIC were observed. Immediately after RIC, 81.3% (26/32) of patients were able to eat solid food without symptoms of dysphagia. As a short-term effect, the dysphagia improved after RIC in 93.8% (30/32) of the patients. As a long-term effect, 63% (17/27) and 62% (13/21) of patients were able to eat solid food 6 and 12 months after RIC, respectively. The 6-month and 12-month patency rates were significantly different between the RIC group and the continued EBD group (65.3% vs 19.8%, P P Limitations Nonrandomized retrospective study. Conclusions RIC is an effective and safe method. The demonstration of the validity of this method may place RIC as a new medical treatment for patients with refractory stricture after surgical resection for esophagogastric diseases.

Sessile serrated adenoma is a subtype of serrated colorectal polyps that can potentially give rise to colorectal carcinoma. We aimed to characterize the endoscopic features of sessile serrated adenoma as compared to those of other subtypes of serrated colorectal polyps.A total of 202 serrated colorectal polyps were retrospectively collected and pathologically subclassified as sessile serrated adenoma, hyperplastic polyp, or traditional serrated adenoma. The patients' demographics and endoscopic findings were reviewed, and comparisons were made between groups.We found 57 sessile serrated adenomas, 104 hyperplastic polyps, and 41 traditional serrated adenomas. Sessile serrated adenomas were larger in size, and they had more granular or nodular surface and more irregular or vague margin than hyperplastic polyps; however, these two subgroups were similar in terms of their sessile configuration and white coloring. Sessile serrated adenomas could be distinguished from traditional serrated adenomas based on the pedunculated configuration and red coloring unique to the traditional serrated adenomas. Nine sessile serrated adenomas were of note due to coverage with abundant mucus, which was rarely seen in other subgroups.We characterize the endoscopic features of sessile serrated adenoma as compared to those of hyperplastic polyp and traditional serrated adenoma.

A 70-year-old woman who underwent proximal gastrectomy for gastric cancer (poorly-differentiated adenocarcinoma) of Stage IIIB at age 46 visited our hospital April 2004 because of exacerbated pain by movement in the buttocks since November 2003. She showed multiple bone metastasis by CT (computerized tomography). Pancreas cancer or gallbladder cancer was suspected by CT, and a high tumor marker score (CA19-9 18,625 U/mL, DUPAN-II 15,000 U/ mL elevations were acknowledged). Although her symptoms were severe with performance status (PS) 4, she was administered combination chemotherapy with gemcitabine and cisplatin. After 2 cycle therapy, her PS was improved to 2, but the tumor markers had elevated. So we changed the chemotherapy menu to S-1 and gemcitabine. Her tumor markers lowered and PS was improved to 1. There was a remarkable response to this chemotherapy, and the result of CT and bone scintigraphy suggested that her bone metastasis was improved. Because of hematologic relapse due to DIC at 1 year after the first treatment, she was readmitted to our hospital and later died. The autopsical result revealed recurrence of gastric cancer 23 years post-operatively.

18 Background: Alcohol drinking increases the risk of upper aerodigestive tract cancer, and acetaldehyde (a metabolite of alcohol) is a definite carcinogen for this type of cancer. Acetaldehyde is formed mainly by the oxidation of ethanol by alcohol dehydrogenase 1B (ADH1B) and is eliminated by aldehyde dehydrogenase 2 (ALDH2) in the liver. About 50% of Asian people have the ALDH2*2 variant allele, which encodes an inactive enzyme. Those with the ALDH2*2 allele and an alcohol drinking habit are at definite risk of esophageal and head and neck cancers. Genetic testing is the most reliable method for identifying the ALDH2 genotype, but it is not practical for mass screening because of the cost and time. Therefore, we have established a simple method to identify the ALDH2 genotype by analyzing breath samples. Methods: One hundred seven consecutive healthy Japanese volunteers participated in this study. After providing informed consent, participants drank 100 ml of 0.5% ethanol in a single gulp. Breath samples were collected with originally developed simple gasbags before the alcohol was consumed, and 1, 2, and 5 minutes later. The concentrations of acetaldehyde and ethanol in the bag were measured by high-sensitivity gas chromatography. The ALDH2 and ADH1B genotypes of all participants were confirmed using blood DNA. The relationships between acetaldehyde level and genotypes were determined. Results: The frequencies of ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2 were 46.7%, 43.9%, and 9.3%, respectively. The breath acetaldehyde levels at 1 minute after alcohol ingestion were 89.2 (18.1–399.0) ppb in those with ALDH2*1/*1, 346.3 (78.4–1218.4) ppb in those with ALDH2*1/*2, and 537.1 (213.2–1353.8) ppb in those with ALDH2*2/*2. The breath acetaldehyde level was significantly higher in the ALDH2*2 carrier group regardless of the ADH1B genotype (P–3 to include ALDH2*2 carriers yielded an accuracy for the detection of ALDH2*2 carriers of 96.3% (95% CI: 91.5–96.9%), sensitivity of 100%, and specificity of 92%. Conclusions: Our breath test may be a convenient screening tool for identifying those at high risk of upper aerodigestive tract cancer.

The objective of this study is to enhance the bone induction activity of basic fibroblast growth factor (bFGF) for reconstruction of skull bone defects which has been clinically recognized as almost impossible. For this purpose, we prepared biodegradable hydrogels from gelatin with an isoelectric point of 4.9 which is capable of polyionic complexing with basic bFGF. When implanted in rabbit skull defects of 6 mm in diameter (6 defects per experimental group), the gelatin hydrogels incorporating 100 microg of bFGF promoted bone regeneration at the defect in marked contrast to free bFGF of the same dose, finally closing the bone defects after 12 weeks of implantation as is apparent from histological examination. In dual energy X-ray absorptometry analysis, the bone mineral density at the skull defects enhanced by the hydrogels was significantly higher than that by free bFGF at doses ranging from 2 to 200 microg/defect (P < 0.05). The extent of bone regeneration induced by gelatin hydrogels incorporating 100 microg of bFGF increased with a decrease in their water content. Histological examination indicated that more slowly degrading hydrogels of lower water content prolonged the retention period of osteoblasts in the bone defects. This led to enhanced bone regeneration compared with faster degrading hydrogels of higher water content. It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone.

Background and aims Docetaxel (DOC) is a key drug in second-line chemotherapy after the failure of chemoradiotherapy (CRT) for esophageal cancer. Interstitial pulmonary disorder (IPD) is one of the fatal adverse effects of DOC, but its frequency and risk factors have not been clarified. The aim of this study was to determine the frequency of and risk factors for IPD in patients with esophageal squamous cell carcinoma (ESCC), who were treated with DOC after the failure of CRT. Patients and methods We retrospectively reviewed the clinical data for 115 patients with ESCC who had been treated with CRT at Kyoto University Hospital from April 2007 to March 2011. Thirty-seven of these patients had been treated with DOC after CRT (D group) and 78 had not been treated with DOC (non-D group). We compared the incidence of IPD in the two groups and also identified the risk factors for IPD. Results The incidence of grade 3/4 IPD in the D and non-D groups was 10.8% (4/37) and 1.3% (1/78), respectively (P = 0.035). A median of 4 cycles of DOC was administered (range, 2–7). The median total radiation dose was 60 Gy. The mean value for V20 (% total lung volume receiving ≥20Gy) in patients with grade 3/4 IPD was greater than that in patients without IPD (20.0% vs 12.3%, respectively; P = 0.012). The V20 value was greater than 20% in 80% (4/5) of patients with grade 3/4 IPD. The mean lung dose (MLD) in patients with grade 3/4 IPD was also greater than that in patients without IPD (11.1 Gy vs 6.6 Gy, respectively; P Conclusion The incidence of grade 3/4 IPD was 10.8% in patients who received DOC after CRT. IPD must be considered when DOC is administered to patients who have already received radiotherapy with high V20 and MLD in their first-line CRT. Disclosure All authors have declared no conflicts of interest.