Postoperative recurrence detection using individualized circulating tumor DNA in upper tract urothelial carcinoma.

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0-202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence.

Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer.

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50 or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 versus 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.

Frequent post-operative monitoring of colorectal cancer using individualised ctDNA validated by multiregional molecular profiling.

BACKGROUND: Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. METHODS: We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. RESULTS: "Founder" mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, "truncal" mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than "non-founder" and "branch" mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. CONCLUSIONS: A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.

Efficacy of enhanced prehabilitation for patients with esophageal cancer undergoing esophagectomy.

BACKGROUND: Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. METHODS: We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). RESULTS: The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p < 0.001) and postoperative (EP group vs. control group, 431.5 ± 80 vs. 378 ± 68.7 m, p < 0.001) 6-min walk distance was significantly higher in the EP group than in the control group. The respiratory complications rate was significantly lower in the EP group (4.3%) than in the control group (36%) (p = 0.007). The incidence of atelectasis was particularly significantly lower in the EP group (0%) than in the control group (24%) (p = 0.012). CONCLUSIONS: EP was performed safely for patients before esophagectomy. EP improved the exercise tolerance of the patients before esophagectomy and might be useful in preventing respiratory complications.

Feasibility of totally laparoscopic pylorus-preserving gastrectomy with intracorporeal gastro-gastrostomy for early gastric cancer: a retrospective cohort study.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving surgery for the treatment of early gastric cancer in East Asian countries. Therefore, this study aimed to evaluate the feasibility and safety of totally laparoscopic PPG (TLPPG) with intracorporeal anastomosis. METHODS: A total of 43 patients with early gastric cancer underwent laparoscopy-assisted PPG (LAPPG) with extracorporeal anastomosis between May 2006 and November 2012. The operative outcomes of 22 patients who underwent TLPPG between November 2012 and February 2019 were evaluated, and data were compared with that of the LAPPG group. RESULTS: No significant difference in the operative time was observed between the two groups. Blood loss was lower in the TLPPG group (18.5 mL) than in the LAPPG group (30.7 mL, p = 0.008), and the length of abdominal incision was shorter in the TLPPG group (3.8 cm) than in the LAPPG group (4.7 cm, p < 0.001). No significant difference in the complication rate was observed between the two groups (13.6% in the TLPPG vs. 9.3% in the LAPPG group, p = 0.594). No anastomosis-related complications occurred in either group. No significant between-group difference was observed in the delayed gastric emptying (TLPPG, 9.1 vs. LAPPG, 7%, p = 0.762). The initiation of postoperative fluid (TLPPG, 1.0 day vs. LAPPG, 3.0 days, p < 0.001) and meal (TLPPG, 3.0 days vs. LAPPG, 4.0 days, p < 0.001) intake was earlier in the TLPPG group than in the LAPPG group. No significant between-group difference was observed in the postoperative hospital stay. CONCLUSIONS: The findings of this study suggest that TLPPG with intracorporeal reconstruction not only is as feasible and safe as LAPPG for the treatment of patients with early gastric cancer but also provides certain advantages such as reduced blood loss and wound size.

Rare strangulated intenal hernia following extraperitoneal colostomy for rectal cancer operation: A case report.

INTRODUCTION: Few cases of intestinal obstruction after colostomy are caused by internal hernia. Some institutions perform stomas through the extraperitoneal route because some patients experience an internal hernia outside the stoma performed through the intraperitoneal route. PRESENTATION OF CASE: A 72-year-old woman presented with a history of laparoscopic abdominoperineal resection (APR). A sigmoid colostomy was performed via the extraperitoneal route during APR. One month after APR, the patient presented to the emergency department of our hospital with abdominal pain and vomiting. Computed tomography revealed that the small intestine had passed through the extraperitoneal tunnel, resulting in strangulated intestinal obstruction, and emergency laparotomy was performed. During surgery, the ileum passed behind the elevated sigmoid colon in a caudal-to-cranial direction and formed an unusual closed loop. The strangulated part of the small intestine showed ischemic change; however, the intestine quickly normalized soon after strangulation was released, and the operation was completed without resection of the intestine. DISCUSSION: The major cause of intestinal obstruction after colostomy is intraperitoneal adhesion. Looseness of the elevated sigmoid colon can cause internal hernia, if under pneumoperitoneum, when a colostomy is created through the extraperitoneal route in laparoscopic APR. Furthermore, the patient had lost more than 5 kg of body weight after the surgery, which may have led to the looseness of the elevated sigmoid colon. CONCLUSION: Releasing the pneumoperitoneum during the elevation of the sigmoid colon is necessary to prevent internal hernia, even with a colostomy performed through the extraperitoneal route.1.

Clinical Results of a Trifocal Toric Intraocular Lens Using the Holladay Total Surgically Induced Astigmatism Formula for Correcting Low Corneal Astigmatism in Japanese Patients.

Purpose: To evaluate the effectiveness and safety of the AcrySof IQ PanOptix toric intraocular lens (IOL) with cylinder power of 1.0 D (TFNT20) in a Japanese population with low corneal astigmatism and compare with historical control data for nontoric IOLs. Setting: Tokyo Dental College Suidobashi Hospital, Tokyo, Japan. Design: Prospective, single-center study. Methods: Patients ≥20 years old received TFNT20 IOL in at least 1 eye based on Alcon Toric calculator (Holladay Total surgically induced astigmatism). Effectiveness endpoints included the percentage of eyes with refractive cylinder ≤0.25 D at 30-60 days after surgery, which was compared with a historical control threshold rate of 29.2% for nontoric IOLs and refractive cylinder ≤0.50 D. Monocular uncorrected distance visual acuity (UDVA; 5 m), uncorrected intermediate visual acuity (UIVA; 60 cm), uncorrected near visual acuity (UNVA; 40 cm), and adverse events were evaluated. Results: Of 41 eyes implanted with TFNT20 IOLs, 37 eyes (90%) achieved refractive cylinder ≤0.25 D at 30-60 days after surgery, demonstrating the superiority of TFNT20 compared with historical data (P<0.0001). Refractive cylinder of ≤0.50 D was achieved by 41 eyes (100%). At 30-60 days, mean ± SD monocular CDVA was -0.15 ± 0.07 logMAR, UDVA was -0.09 ± 0.09 logMAR, UIVA was -0.00 ± 0.07 logMAR, and UNVA was 0.03 ± 0.07 logMAR. Six eyes (15%) had elevated postoperative intraocular pressure, which returned to normal and was not device-related. Conclusion: TFNT20 IOLs successfully reduced postoperative refractive cylinder and provided good distance, intermediate, and near uncorrected VAs in Japanese patients with low corneal astigmatism.

Incarcerated Larrey hernia with small bowel obstruction: A case report.

INTRODUCTION AND IMPORTANCE: Morgagni-Larrey hernias (MLHs) are rare diaphragmatic hernias that can cause incarceration or strangulation of the hernia contents in some cases. Here we report a case of incarcerated Larrey hernia with small bowel obstruction, which was successfully treated with emergent laparoscopic surgery. CASE PRESENTATION: An 87-year-old woman presented to our hospital with abdominal pain and nausea. Computed tomography scan revealed an MLH comprising an obstructed intestinal loop. The patient underwent emergency laparoscopic surgery. Surgical findings showed incarceration of the small bowel on the left side of the falciform ligament. The small bowel was laparoscopically reduced and does not show signs of intestinal ischemia or perforation. The hernia orifice, which was approximately 15 mm in diameter, was closed with a surgical suture without the need for sac excision. The patient was discharged on postoperative day 7 without postoperative complications. CLINICAL DISCUSSION: There are no established surgical techniques for the treatment of MLH due to its rarity. Our experience in the present case suggests that the laparoscopic approach might be considered as a feasible method even for incarcerated MLH. CONCLUSION: Surgical techniques for MLH should be selected on a case-by-case basis.

One-year multicenter evaluation of a new hydrophobic acrylic intraocular lens with hydroxyethyl methacrylate in an automated preloaded delivery system.

PURPOSE: To assess a single-piece monofocal hydrophobic acrylic intraocular lens (IOL) with hydroxyethyl methacrylate (HEMA) (Clareon) contained in automated preloaded delivery system (AutonoMe). SETTING: 18 surgical sites in Japan. DESIGN: Observational study. METHODS: In patients undergoing phacoemulsification and IOL implantation of a new hydrophobic acrylic IOL using an automated injector, clinical data were collected preoperatively and at 1 day, 1 week, and 1 month, 6 months, and 12 months postoperatively. The degree of glistenings was graded on a 4-point scale. The surgeons rated usability and performance of the IOL delivery system on a 5-point scale. RESULTS: The study enrolled 384 eyes of 384 patients, ranging in age from 41 to 93 (73.8 ± 8.2, mean ± SD) years. The percentage of eyes with corrected distance visual acuity of 20/25 or better at 1 day, 1 week, and 1 month, 6 months, and 12 months postoperatively was 82.6%, 91.9%, 92.8%, 96.6%, and 95.2%, respectively. Refractive error was within 1.0 diopter in approximately 90% of cases. No glistenings were found in all cases throughout the study period. The rate of Nd:YAG laser posterior capsulotomy was 0.9% at 1 year. The IOL delivery system received high ratings on its usability and performance by the surgeons. CONCLUSIONS: The new hydrophobic acrylic IOL with HEMA showed excellent visual and refractive outcomes without developing glistenings throughout the 1-year study period. The surgeons gave high marks for usability and performance of the automated preloaded delivery system.

Experimental Study on Delivery Performance of an Automated Preloaded Intraocular Lens Injector System for Corneal and Sclerocorneal Incisions.

PURPOSE: To evaluate delivery performance of an automated preloaded intraocular lens (IOL) injector systems (AutonoMe) in the porcine eyes. METHODS: In the freshly excised porcine eyes, lens removal and IOL implantation were performed. There were 4 groups (10 eyes per group) with different incision site and size: 2.2-mm and 2.4-mm corneal incisions and 2.2-mm and 2.4-mm sclerocorneal incisions. Delivery performance and wound enlargement of AutonoMe were analyzed and compared with those of iTec and iSert from a previous study. RESULTS: There were a few minor troubles associated with AutonoMe, such as overriding plunger within cartridge and trapped trailing haptic during IOL insertion, but the incidence was low. Other interactions were not observed, such as IOL adherence to plunger, sudden ejection of IOL, intrawound lens manipulation, IOL behavior, and gross damage to IOL. AutonoMe caused significantly less wound enlargement for both corneal and sclerocorneal incisions than other injector devices. Wound enlargement by using AutonoMe was significantly smaller with 2.4-mm corneal incision than with 2.2-mm corneal incision, but the final incision size was still smaller with 2.2-mm corneal incision. For sclerocorneal incisions, the amount of wound stretch was not different between 2.2 and 2.4 mm incisions. CONCLUSION: The wound enlargement caused by the automated preloaded insertion system, AutonoMe, was smaller than that of other preloaded injectors for both corneal and sclerocorneal incisions. There were a few minor technical events during IOL insertion, but the overall incidence was low.

Comparison of Femtosecond Laser-Assisted Cataract Surgery and Conventional Phacoemulsification on Endothelial Cell Density When Using Torsional Modality.

PURPOSE: To compare the effects of femtosecond laser assisted cataract surgery (FLACS) and manual phacoemulsification on cumulative dissipated energy (CDE), torsional amplitude, and endothelial cell density (ECD). PATIENTS AND METHODS: This prospective, randomized study was conducted at Oka Eye Clinic (Fukuoka, Japan). Surgeries were performed using FLACS (with LenSx) or conventional technique in adults ≥20 years with grade 2-4 cataracts. Visits included preoperative, surgery day, and 5 postoperative visits (days 1, 4-10, 20-40, 60-120, and 150-210). Primary endpoint was CDE. Secondary endpoints included ECD percent change at day 150-210 versus preoperative visit and average torsional amplitude on surgery day. Exploratory endpoints included central corneal thickness and corrected distance visual acuity (CDVA). Superiority of FLACS to conventional technique was evaluated using t-tests based on a mixed model for repeated measures. RESULTS: Full analysis set included 53 eyes per group. Mean cataract grade was 2.92±0.58 in FLACS and 2.94±0.57 in conventional group. FLACS versus conventional method had significantly lower mean CDE (0.213±0.334 versus 1.718±0.898%-seconds, respectively; P<0.0001), demonstrating superiority of FLACS. Low endothelial cell loss (ECL) was achieved with both FLACS and conventional methods (1.5±5.6% and 2.7±5.2%; P=0.260). Torsional amplitude was significantly lower for FLACS versus conventional method (19.6±16.0% versus 31.1±6.6%; P<0.0001). Central corneal thickness was comparable for both methods at all visits except day 1; CDVA was comparable for both methods at all postoperative visits. CONCLUSION: FLACS achieved significantly lower CDE compared with the conventional surgical method (P<0.0001). Low ECL was achieved with both FLACS (1.5%) and conventional (2.7%) methods.

Results of a clinical evaluation of a trifocal intraocular lens in Japan.

PURPOSE: To evaluate the effectiveness and safety of a new trifocal intraocular lens (IOL) after cataract removal in patients living in Japan. STUDY DESIGN: Prospective multicenter clinical study. METHODS: One hundred and thirty-five eyes of 68 patients (19 men, 49 women; mean age, 66.3 ± 7.4 years) were followed for 6 months. Trifocal IOLs with focal points at near, intermediate, and distance were implanted bilaterally in eyes with less than 1 diopter of corneal astigmatism. The visual acuity (VA) at distance, 60 and 40 centimeters (cm), and contrast sensitivities were measured. Patients completed quality-of-life questionnaires preoperatively and postoperatively. RESULTS: The mean bilateral logarithm of the minimum angle of resolution VA at 5 meters (m), 60 cm, and 40 cm were, respectively: uncorrected, - 0.104 ± 0.095, - 0.065 ± 0.111, and - 0.042 ± 0.105; and distance-corrected, - 0.197 ± 0.076, - 0.112 ± 0.111, and - 0.073 ± 0.111. The contrast sensitivities at distance and near were within the normal range at all spatial frequencies under photopic conditions. Patients reported complete spectacle independence in 75.0% of cases. Total use of spectacles was reported by 1.5% and partial by 20.6%; the purpose of spectacle use was primarily for near visual tasks. Mild-to-moderate glare was reported by 65.7% of patients and halos by 70.1%; only 1.5% of subjects reported severe glare and halos. CONCLUSIONS: This new trifocal IOL provides equally good uncorrected VAs at distance, intermediate, and near, and decreases spectacle dependence in daily life. Patients frequently report mild-to-moderate glare and halos, and patients should be informed about these before implantation.

Primary esophageal malignant melanoma successfully treated with anti-PD-1 antibody for retroperitoneal recurrence after esophagectomy: A case report.

INTRODUCTION: Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. Here, we report a case of retroperitoneal recurrence of PMME successfully treated with the anti-programmed cell death 1 antibody, nivolumab. PRESENTATION OF CASE: A 70-year-old male with dysphagia was referred to our hospital. Esophagogastroscopy showed an elevated tumor in the lower thoracic esophagus. A histopathological examination of the biopsy revealed poorly differentiated squamous cell carcinoma. The patient was diagnosed with clinical T3N1M0 stage III esophageal squamous cell carcinoma and was treated with neoadjuvant chemotherapy followed by radical esophagectomy. A postoperative histopathological examination revealed that atypical cells with a brown pigment were scattered in the tumor. Immunohistochemical staining demonstrated positive expression of human melanoma black 45, melan A, and S100. A pathological diagnosis of PMME was confirmed. Sixteen months after surgery, abdominal computed tomography revealed solitary retroperitoneal recurrence in the lateral portion of the ascending colon. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) showed hypermetabolic accumulation with a maximum standardized uptake value of 5.8. The patient was treated with nivolumab (240 mg) every two weeks. After eight courses of nivolumab, abnormal accumulation of the retroperitoneal mass disappeared on PET, and this therapeutic effect continued for 20 months. CONCLUSIONS: Nivolumab was effective for recurrence of PMME in our case. There are few reports of treatment with nivolumab for PMME. Further studies are necessary to establish the usefulness of nivolumab for PMME in the future.

Esophageal carcinosarcoma in which the sarcomatous element has sloughed off: A case report.

INTRODUCTION: Most esophageal carcinosarcoma (ECS) tumors present as a polypoid tumor that is continuous with the superficial lesion and suspended by a pedicle. Here, we report a case of ECS in which a polypoid lesion sloughed off before surgery. PRESENTATION OF CASE: A 76-year-old man with dysphagia was admitted to our hospital. Esophagogastroscopy revealed a 20-mm polypoid tumor continuous with a superficial lesion and attached to the lesion by a thin pedicle in the mid-thoracic esophagus. Histopathological examination of the endoscopic biopsy showed that the superficial lesion was a moderately differentiated squamous cell carcinoma and that the polypoid tumor contained a sarcomatous element. He was diagnosed with ECS and underwent radical esophagectomy with three-field lymph node dissection. In the resected specimen, no polypoid tumor was found, and only a superficial lesion was observed. The histopathological findings revealed only squamous cell carcinoma, and the pathological diagnosis was esophageal squamous cell carcinoma, pT1bN0M0, pathological stage I. The patient was discharged from the hospital 22 days after surgery and did not experience any complications. He is currently alive and remained cancer-free for three years since surgery was performed. DISCUSSION: Due to the distinctive configuration in which the polypoid lesion was connected to the superficial cancerous lesion by a very thin pedicle, researchers suggested that the polypoid tumor, which consisted of a sarcomatous element, was sloughed off before surgery. CONCLUSION: We encountered a rare case of ECS in which the sarcomatous element sloughed off prior to surgical resection.

Analysis of mutational and proteomic heterogeneity of gastric cancer suggests an effective pipeline to monitor post-treatment tumor burden using circulating tumor DNA.

Circulating tumor DNA (ctDNA) is released from tumor cells into blood in advanced cancer patients. Although gene mutations in individual tumors can be diverse and heterogenous, ctDNA has the potential to provide comprehensive biomarker information. Here, we performed multi-region sampling (three sites) per resected specimen from 10 gastric cancer patients followed by targeted sequencing and proteomic profiling using reverse-phase protein arrays. A total of 126 non-synonymous mutations were identified from 30 samples from 10 tumors. Of these, 16 (12.7%) were present in all three regions and were designated as founder mutations. Variant allele frequencies (VAFs) of founder mutations were significantly higher than those of non-founder mutations. Phylogenetic analysis also demonstrated a good concordance between founder and truncal mutations, defined as mutations shared by all simulated clones at the trunk of the tumor phylogenetic tree. These findings led us to prioritize founder mutations for quantitative ctDNA monitoring by digital PCR with individually-designed primer/probe sets. In preoperative plasma, the average ctDNA VAF of founder mutations was significantly higher than that of non-founder mutations (p = 0.039). Proteomic heterogeneity was present across the tumor regions both within and between patients independent of mutational status. Our results suggest that, in practice, mutations having high VAF identified without multi-regional sequencing may be immediately useful for quantitative ctDNA monitoring but do not provide sufficient information to predict the proteomic composition of tumors.

Short term outcomes of helical tomotherapy during concurrent chemoradiotherapy for advanced cervical cancer.

The aim of the present study was to clarify the feasibility and efficacy of helical tomotherapy during concurrent chemoradiotherapy for treating cervical cancer. The medical records of 13 patients who underwent oncurrent chemoradiotherapy using helical tomotherapy for cervical cancer at Wakayama Medical University Hospital between 2013 and 2015 were retrospectively reviewed. A total of 15 patients who underwent oncurrent chemoradiotherapy using conventional radiotherapy (CRT) between 2008 and 2013 at our institution were also examined for comparison. The median age of patients treated with helical tomotherapy was 60 (range, 35-71), and the median age of patients treated with CRT was 57 (range, 43-77). The median follow-up period was 27 months (range, 3-46) in the tomotherapy group and 35 months (range, 7-88) in the CRT group. The frequency of G3/4 thrombocytopenia in the tomotherapy group was significantly higher than that in the CRT group (P=0.049). However, the platelet count spontaneously recovered without transfusion. There were no significant differences between the groups in terms of frequency of G3/4 neutropenia, diarrhea or late intestine injury. The rate of complete response in the tomotherapy group and the CRT group was 84.6 and 73.3%, respectively, and there was no significant difference in the response rate between the groups. There were no significant differences in the progression-free survival or progression-free rate in the irradiation field between the groups. Adverse events from concurrent chemoradiotherapy using helical tomotherapy were acceptable and clinically controllable. The present results suggest that helical tomotherapy is efficient during concurrent chemoradiotherapy for treatment of advanced cervical cancer.

Twelve-month efficacy and safety of glaucoma filtration device for surgery in patients with normal-tension glaucoma.

PURPOSE: To assess the efficacy and safety of filtration surgery using the EX-PRESS glaucoma filtration device in patients with normal-tension glaucoma (NTG). STUDY DESIGN: Prospective, single-arm, multicenter interventional case series. METHODS: Eyes with NTG underwent EX-PRESS implantation with or without cataract surgery. The efficacy and safety were assessed at 1 day; 1 and 2 weeks; and 1, 3, 6, and 12 months after surgery. The main outcome measure was reduction in intraocular pressure (IOP) from baseline at 3, 6, and 12 months after surgery. Safety assessments included adverse event incidence, postoperative inflammation, and corneal endothelial cell density. RESULTS: Thirty-two Japanese patients (37 eyes) with NTG were enrolled. The mean IOP decreased from 14.8 ± 2.3 mmHg at baseline to 10.0 ± 3.1 mmHg at 12 months after surgery (mean reduction 4.9 ± 4.2 mmHg [31.1%]; P < .0001). IOP-lowering medication use decreased from a mean of 3.3 medications per eye before surgery to 0.1 medications per eye at 12 months after surgery. IOP reductions > 20% were achieved by 61.5% of the eyes at 12 months. Adverse events were typical for filtration procedures, and none was deemed device-related. Postoperative inflammation was mild and self-limiting. The mean corneal endothelial cell density had decreased by 3.3% at 12 months after surgery. CONCLUSION: The EX-PRESS glaucoma filtration device is safe and effective for filtration surgery in patients with NTG, providing mean IOP reduction consistent with recommendations based on the Collaborative NTG Study.

Influence of surface light scattering and glistenings of intraocular lenses on visual function 15 to 20 years after surgery.

PURPOSE: To assess the long-term influence of surface light scattering and glistenings of hydrophobic acrylic (Acrysof), silicone, and poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) on visual function. SETTING: Eleven surgical sites, Japan. DESIGN: Retrospective case series. METHODS: Patients who had cataract surgery with implantation of a hydrophobic acrylic, silicone, or PMMA IOL from 1994 to 2000 were examined. Silicone and PMMA IOLs were not restricted to specific manufacturers or models. Patients were included if their corrected distance visual acuity (CDVA) within 3 months postoperatively (baseline CDVA) was 20/25 or better. The CDVA, contrast sensitivity, degree of surface light scattering measured with Pentacam densitometry, and glistening grades were recorded at the patient's latest visit. RESULTS: Of the eyes, 31 had a hydrophobic acrylic IOL, 37 a silicone IOL, and 30 a PMMA IOL. Surface light scattering and glistenings were significantly greater with the hydrophobic acrylic IOL than with silicone and PMMA IOLs (P < .0001). The CDVA at the latest visit as well as the changes in CDVA from the baseline to the latest visit did not differ between the IOLs and was unaffected by surface light scattering and glistenings, as was the contrast sensitivity. CONCLUSIONS: The hydrophobic acrylic IOL was associated with a significantly greater level of surface light scattering and glistenings than the silicone IOLs and PMMA IOLs 15 to 20 years postoperatively. However, the optical phenomena within the optics of the hydrophobic acrylic IOL did not influence the patients' visual function.

Additive effects and safety of fixed combination therapy with 1% brinzolamide and 0.5% timolol versus 1% dorzolamide and 0.5% timolol in prostaglandin-treated glaucoma patients.

PURPOSE: To compare the additive effects and safety of 1% brinzolamide/0.5% timolol fixed combination (BTFC) versus the low-dose regimen of 1% dorzolamide/0.5% timolol fixed combination (DTFC) in patients with open-angle glaucoma and ocular hypertension (OAG/OH) following treatment with prostaglandin analogues (PGAs). METHODS: A prospective, randomized, double-masked, multicentre, parallel-group and active-controlled study included 201 Japanese OAG/OH patients who had been treated with PGA. Efficacy was assessed as the change in intra-ocular pressure (IOP) from baseline after weeks 4 and 8. Safety was assessed with adverse event rates, ocular discomfort score, blur scale, blood pressure and heart rates, best-corrected visual acuity (BCVA) and slit lamp examinations. RESULTS: Intra-ocular pressure (IOP) change from baseline at 9 AM/11 AM pooled over the 8 weeks was -3.3/-3.3 mmHg in the BTFC group and -2.9/-3.4 mmHg in the DTFC group, demonstrating non-inferiority of BTFC to DTFC. Ocular irritation was frequently seen in DTFC group. Although blurred vision was frequently seen in BTFC group, it was transient and blurring became the equivalent 3 min after instillation between two groups. No noteworthy issue was observed in other safety outcome. CONCLUSION: Non-inferiority of BTFC to DTFC in IOP reduction was demonstrated after adding onto PGA therapy in Japanese OAG/OH patients. Although the score of blurred vision was transiently higher in BTFC than DTFC, treatment difference decreased and disappeared with time. Thus, BTFC can be considered as a safe and effective agent for glaucoma treatment.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

OBJECTIVE: To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. RESULTS: The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. CONCLUSION: Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. CLINICAL TRIAL REGISTRATION: NCT02081599.