Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: long-term results of KDOG1001 trial.

PURPOSE: The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years. METHODS: Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed. RESULTS: From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1-87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8-76.0%). CONCLUSION: Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer.

Strengthening retina eye care services in Nepal: retina eye care of Nepal project.

BACKGROUND: Retinal diseases are very difficult to treat. So, early diagnoses and preventions are very important. But, few eye doctors can treat patients with retinal diseases in Nepal. Retina Eye Care of Nepal (RECON) project was designed to strengthen retina eye care services in Nepal. METHODS: RECON was implemented from May 2016 to February 2019 in Nepal. Four Master Eye Doctors (MED) received Training of Trainers (TOT) from Tokushima University, Japan. MEDs developed training materials for different cadres of ophthalmic human resources, enhanced retina eye care facilities, and conducted retina-screening camp in Nepal. RESULTS: Twenty ophthalmologists, 16 optometrists, 48 ophthalmic assistants and 17 ophthalmic nurses, 76 physicians and 28 health workers were trained in retina care. Eight outreach retina camps were conducted. CONCLUSIONS: The project was a novel approach to strengthen retina services in Nepal. The aim of the project was accomplished with the ultimate benefits to the needy retina patients who otherwise were going to miss the retina services.

[Conversion Surgery for Locally Advanced Unresectable Pancreatic Cancer Treated with FOLFIRINOX Therapy and Proton Beam Therapy Combined with S-1 Chemotherapy-A Case Report].

We report a case of locally advanced unresectable(UR-LA)pancreatic cancer in a patient who underwent conversion surgery after FOLFIRINOX and proton beam therapy(PBT)combined with S-1. A 68-year-old woman was referred to our hospital for a pancreatic tumor. The abdominal CT scan revealed a 40mm pancreatic body tumor with an abutment(>180°) of the celiac artery and the superior mesenteric artery. Moreover, the tumor was classified as UR-LA with a contact to the abdominal aorta. The tumor was histologically diagnosed as adenocarcinoma via an endoscopic ultrasound-guided fine-nee- dle aspiration. After 2 courses of FOLFIRINOX, PBT(50 GyE/25 Fr)combined with S-1 were administered. The tumor shrunk to 30mm at the CT scan. After 5 courses of FOLFIRINOX, the tumor reduced to 20 mm. No distant metastasis or malignant cells in abdominal washing cytology was detected using staging laparoscopy. Then, distal pancreatectomy with celiac axis resection(DP-CAR)was performed. According to the General Rules for the Study of Pancreatic Cancer(7th edition)from Japan Pancreas Society, the histological findings were suggestive of ypT3, ypN0, R0, and Grade 3 histological effect. The patient had a Grade A delayed gastric emptying post-operation. He was discharged 35 days after the surgery and has been alive without recurrence on imaging for 11 months post-operation.

Secondary neuroendocrine tumor after allogeneic bone marrow transplantation.

Here we report a case of aggressive neuroendocrine tumor (NET), which is an extremely rare secondary solid tumor that occurs after allogeneic hematopoietic cell transplantation (allo-HSCT). A patient with chronic active Epstein-Barr virus infection received allo-HSCT from an HLA-DR two allele-mismatched unrelated donor. Four years later, he developed NET with multiple metastases. He received thoraco-abdominal irradiation as a conditioning regimen, and developed repeated episodes of intestinal graft-versus-host disease, for which he received long-term immunosuppressive therapy. Although these factors may be potential contributing factors to the development of secondary NET, the exact pathogenesis remains unclear.

Achromobacter buckle infection diagnosed by a 16S rDNA clone library analysis: a case report.

BACKGROUND: In clinical settings, bacterial infections are usually diagnosed by isolation of colonies after laboratory cultivation followed by species identification with biochemical tests. However, biochemical tests result in misidentification due to similar phenotypes of closely related species. In such cases, 16S rDNA sequence analysis is useful. Herein, we report the first case of an Achromobacter-associated buckle infection that was diagnosed by 16S rDNA sequence analysis. This report highlights the significance of Achromobacter spp. in device-related ophthalmic infections. CASE PRESENTATION: A 56-year-old woman, who had received buckling surgery using a silicone solid tire for retinal detachment eighteen years prior to this study, presented purulent eye discharge and conjunctival hyperemia in her right eye. Buckle infection was suspected and the buckle material was removed. Isolates from cultures of preoperative discharge and from deposits on the operatively removed buckle material were initially identified as Alcaligenes and Corynebacterium species. However, sequence analysis of a 16S rDNA clone library using the DNA extracted from the deposits on the buckle material demonstrated that all of the 16S rDNA sequences most closely matched those of Achromobacter spp. We concluded that the initial misdiagnosis of this case as an Alcaligenes buckle infection was due to the unreliability of the biochemical test in discriminating Achromobacter and Alcaligenes species due to their close taxonomic positions and similar phenotypes. Corynebacterium species were found to be contaminants from the ocular surface. CONCLUSIONS: Achromobacter spp. should be recognized as causative agents for device-related ophthalmic infections. Molecular species identification by 16S rDNA sequence analysis should be combined with conventional cultivation techniques to investigate the significance of Achromobacter spp. in ophthalmic infections.

[A case of advanced gallbladder cancer with mediastinum lymph node metastasis successfully treated with multimodality therapy].

A 69 -year-old female with advanced gallbladder cancer underwent cholecystectomy, S4a/S5 segmentectomy of the liver, and resection of the extra-hepatic bile duct in October 2005. Adjuvant chemotherapy consisted of gemcitabine (GEM) and tegafururacil (UFT) administered consecutively. Four years after surgery, computed tomography revealed a single enlarged lymph node in the mediastinum, along with ¹8F-fluorodeoxyglucose accumulation and increased carcinoembryonic antigen (CEA) levels. Therefore, the mediastinal lymph node was considered to be a metastasis and GEM was readministered. Although the patient was treated with GEM for 1 year, the accumulation of 18F-fluorodeoxyglucose in the lymph node remained elevated. No other distant metastases were detected. Abronchoscopic biopsy histologically confirmed mucinous adenocarcinoma in the lymph node. Thus, the mediastinal lymph node was resected. Post-surgery, there was no evidence of recurrence during the 30-month follow up period without chemotherapy. Herein, we report a successful case of surgical treatment for solitary mediastinal lymph node metastasis of gallbladder cancer and review the relevant literature.

[A case report of complete pathological response of a locally advanced rectal cancer after long term chemotherapy].

A-39-year-old man presented to a nearby clinic owing to long-term diarrhea and painful defecation. He was diagnosed with a well-differentiated tubular adenocarcinoma of the rectosigmoid and underwent a laparotomy at another hospital. At surgery, the tumor was seen to deeply invade into the urinary bladder with the presence of intra-abdominal abscess. Loop sigmoid colostomy was performed due to possible invasion into the pelvic wall and peritoneal dissemination. The patient was referred to the our hospital for systemic chemotherapy. After 32 courses of FOLFIRI, 10 courses of CapeOX + Bmab, and 34 courses of LV5FU2 + Bmab, radiographic examination revealed complete response (CR) of the rectal tumor, and low anterior resection of the rectum was carried out. Since pathological examination showed no viable cancer cells in any specimen, the patient was considered to have achieved a CR from a pathological standpoint.

[A case of pancreatic cancer with local recurrence and liver metastases eight years after surgery].

Here we report a rare case of late recurrence of pancreatic cancer 8 years after surgery. A woman in her mid-fifties was hospitalized for examination of epigastralgia. Computed tomography (CT) revealed a 4 cm nodule at the pancreatic head with suspected invasion of the superior mesenteric vein. She underwent pancreaticoduodenectomy with wedge resection of superior mesenteric vein and intraoperative radiation therapy. Pathological findings showed moderately differentiated tubular adenocarcinoma and T3N1M0, Stage IIB according to The Union for International Cancer Control (UICC) TNM classification. As adjuvant chemotherapy, 56 courses of gemcitabine (GEM) were administered in 3.5 years. Because of long-term use of GEM, common terminology criteria for adverse events (CTCAE) Grade 3 anemia occurred, and chemotherapy was discontinued. Tumor markers were evaluated every month and CT scans were taken every 6 months for 5 years. Subsequently, CT was performed annually. The patient was hospitalized for high-grade fever, 8.5 years after surgery. CT, magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) detected local recurrence with liver metastases. GEM was administered again, but was ineffective. The patient died 9 years after surgery. In conclusion, even if long-term survival is achieved in pancreatic cancer, follow-ups should not be stopped.

[Two cases of advanced gastric cancer achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose CDDP].

We report 2 cases of resectable advanced gastric cancer who achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose cisplatin (CDDP). S-1 (80 mg/m²)was administered consecutively for 21 days followed by 14 days' rest, with CDDP (25mg/m²) injected on days 1, 8, and 21. Case 1: A man in his 70s diagnosed with cStage III gastric cancer with lymph node metastases received 2 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph node dissection. Case 2: A man in his 60s diagnosed with cStage III gastric cancer with lymph node metastases received 4 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph-node dissection. In both cases, postoperative pathological examination revealed no cancer cells in the resected stomach and lymph nodes. The therapeutic effect of preoperative chemotherapy was assessed as Grade 3. With this regimen, we accomplished preoperative chemotherapy successfully without inpatient care. This regimen can be a promising option as preoperative chemotherapy for advanced gastric cancer.

A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats.

The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1(IIIB) and HIV-1(BaL) as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1(IIIB) activity, whereas fusion inhibitors showed both anti-HIV-1(IIIB) and anti-HIV-1(BaL) activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, "phenotypic drug evaluation", may be applicable for the evaluation of various antiviral drugs in vivo.

Quantitative analysis of cystoid macular edema using scanning laser ophthalmoscope in modified dark-field imaging.

PURPOSE: To quantitatively analyze cystoid macular edema (CME) using scanning laser ophthalmoscope in the modified dark-field imaging. METHODS: We studied 37 eyes with CME associated with different diseases before and after treatment. The CME area was measured with the modified dark-field imaging and fluorescein angiography. The best-corrected visual acuity, mean deviation and macular sensitivity measured by Humphrey automated perimetry, and foveal thickness and macular volume determined by optical coherence tomography were investigated. RESULTS: The CME area could be clearly outlined in 50% with the fluorescein angiography and in 100% with the modified dark-field imaging (P < 0.0001). The CME area calculated using the modified dark-field imaging was significantly correlated with that using the fluorescein angiography (P = 0.0001). Before treatment, the CME area calculated using the modified dark-field imaging was significantly correlated with only the macular volume (P = 0.0230). Three months after treatment, decrease in the CME area was significantly correlated with improvement in the best-corrected visual acuity, mean deviation, macular sensitivity, foveal thickness, and macular volume (P < 0.05 for all). CONCLUSION: Our findings indicate that scanning laser ophthalmoscope in the modified dark-field imaging can measure the CME area and is useful in analyzing CME quantitatively. The findings can also be used to evaluate the effectiveness of treatment.

[A 5-year survival case of locally advanced cancer of the pancreatic body treated by distal pancreatectomy with en bloc celiac axis resection after neoadjuvant chemoradiation therapy].

A 59-year-old man was diagnosed with locally advanced cancer of the pancreatic body, involving the nerve plexus around the celiac axis, the common hepatic artery, and the splenic artery. He was treated with a combination of irradiation (2 Gy/day, total 24 Gy) and 600 mg/m2 of gemcitabine(GEM)biweekly. The tumor size and the involved plexus area were not diminished, but CA19-9 was reduced by half. Distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histological findings indicated extensive invasion into the nerve plexus, including that adjacent to the stump of the pancreas, and thus the R classification was R1. After surgery, 1,000 mg/m2 of GEM was administered biweekly. The chemotherapy has been performed for 5 years to prevent local and systemic recurrence. No recurrence has been found 5 years after surgery. Multidisciplinary treatment, combined with neoadjuvant chemoradiation therapy, curative-intent resection, and postoperative chemotherapy is important for effective treatment of locally advanced pancreatic cancer.

Early visual impacts of optical coherence tomographic parameters in patients with age-related macular degeneration following the first versus repeated ranibizumab injection.

BACKGROUND: The aim of this study is to evaluate the early visual impacts of various optical coherence tomographic (OCT) parameters after the first versus repeated intravitreal ranibizumab injection in patients with exudative age-related macular degeneration (AMD). METHODS: A retrospective comparative case series study was conducted on 20 eyes of 18 consecutive patients who received intravitreal ranibizumab injection for exudative AMD either for the first time (group 1; n = 8) with no prior anti-vascular endothelial growth factor (anti-VEGF) injection in the same or fellow eye, or for repeated times during the course of monthly injected ranibizumab (group 2; n = 12 eyes). The following baseline and 1 month post-injection data was collected for both groups and compared: best-corrected visual acuity (BCVA), qualitative and quantitative OCT parameters including: foveal thickness, foveal volume (central 1-mm circle), retinal volume at 3- and 5-mm central circles, retinal pigment epithelium (RPE) elevation, type of fluid collections, and type of AMD lesion. The size of the fluid and fibrovascular lesion (FVL) areas were measured using manual delineation and automatic calculation of the device. We made correlations between the post-injection visual acuity (VA) and each of post-injection OCT parameters in both groups and these were the main outcome measures. RESULTS: In group 1, there was a strong correlation between post-injection logarithm of minimum angle of resolution (logMAR) BCVA and each of the following: FVL size, foveal thickness, retinal volume at 3- and 5-mm central circles, RPE elevation, the size of the fluid area, and age of the patient (r > 0.70, p < 0.05), whereas in group 2; logMAR BCVA was strongly correlated only with foveal volume (r = 0.74, p = 0.01). Multivariate analysis showed that post-injection FVL size (r (2) = 0.69) and foveal volume (r (2) = 0.55) were the most important factors for VA 1 month following the initial and repeated ranibizumab injection, respectively. CONCLUSIONS: The size of FVL and foveal volume showed a significant correlation with VA in AMD patients shortly after the first and repeated ranibizumab injection, respectively. Further studies with larger sample sizes are needed in order to support these results.

Outcomes of 25-gauge vitrectomy for proliferative diabetic retinopathy.

BACKGROUND: To evaluate the efficacy and safety of 25-gauge transconjunctival sutureless vitrectomy (25-G TSV) in the management of vitreoretinal complications of proliferative diabetic retinopathy (PDR). METHODS: A retrospective review of a noncomparative interventional case series including 200 eyes of 164 consecutive patients who underwent 25-G TSV for the management of PDR was performed. The main outcome measures were preoperative and postoperative visual acuity and intraocular pressure (IOP), the surgical success rate, and intraoperative and postoperative complications. All cases had a follow-up period of at least 6 months. RESULTS: The mean logarithm of the minimum angle of resolution (LogMAR) visual acuity was significantly improved from 1.55 preoperatively to 0.72 at the final visit. No intraoperative complications related to the 25-G TSV procedure were recorded. Transient hypotony was recorded in 18 eyes (9%) on postoperative day 1 and 15 eyes (7.5%) on postoperative day 5. Two of these eyes (1%) had choroidal detachment on postoperative day 5. One case showed bacterial endophthalmitis after the second surgery. The single operation and final surgical success rates were 81.5% and 98% respectively. CONCLUSION: These outcomes of 25-G TSV showed its safety and efficacy in the management of PDR.

[A case of distal cholangiocarcinoma with high sensitivity to neoadjuvant chemoradiation therapy].

We hypothesized that neoadjuvant chemoradiation therapy for cholangiocarcinoma (NACRAC) using gemcitabine would improve the prognosis of resected cases. Phase II trial of NACRAC is ongoing. We report a very effective case to NACRAC for distal cholangiocarcinoma, which markedly reduced the size and levels of the tumor markers. The patient was a 50- year-old man who presented jaundice. Serum tumor markers were clearly elevated, and abdominal CT scan revealed an enhanced mass in the lower bile duct, a dilatation of the intrahepatic to the middle bile duct and a swollen regional lymph node. After NACRAC, the tumor markers were decreased within a normal range. Also on CT scan, the main tumor was slightly detectable and the swollen node was reduced more than 30% in short diameter. Therefore, the effect of NACRAC was considered PR in RECIST guidelines (ver.1 .1). Pancreaticoduodenectomy was performed 2 weeks after NACRAC. No perioperative complications occurred. Pathological examination showed a good response, Grade 2b on Oboshi-Shimosato's classification. In this case, NACRAC had a good effect in imaging and pathological findings as well as in the tumor markers. Therefore, the neoadjuvant chemoradiation therapy has a potential to improve the prognosis for cholangiocarcinoma.

Continuous flow hydrogenation using polysilane-supported palladium/alumina hybrid catalysts.

Continuous flow systems for hydrogenation using polysilane-supported palladium/alumina (Pd/(PSi-Al(2)O(3))) hybrid catalysts were developed. Our original Pd/(PSi-Al(2)O(3)) catalysts were used successfully in these systems and the hydrogenation of unsaturated C-C bonds and a nitro group, deprotection of a carbobenzyloxy (Cbz) group, and a dehalogenation reaction proceeded smoothly. The catalyst retained high activity for at least 8 h under neat conditions.

Validation and standardization of DNA extraction and library construction methods for metagenomics-based human fecal microbiome measurements.

BACKGROUND: Validation and standardization of methodologies for microbial community measurements by high-throughput sequencing are needed to support human microbiome research and its industrialization. This study set out to establish standards-based solutions to improve the accuracy and reproducibility of metagenomics-based microbiome profiling of human fecal samples. RESULTS: In the first phase, we performed a head-to-head comparison of a wide range of protocols for DNA extraction and sequencing library construction using defined mock communities, to identify performant protocols and pinpoint sources of inaccuracy in quantification. In the second phase, we validated performant protocols with respect to their variability of measurement results within a single laboratory (that is, intermediate precision) as well as interlaboratory transferability and reproducibility through an industry-based collaborative study. We further ascertained the performance of our recommended protocols in the context of a community-wide interlaboratory study (that is, the MOSAIC Standards Challenge). Finally, we defined performance metrics to provide best practice guidance for improving measurement consistency across methods and laboratories. CONCLUSIONS: The validated protocols and methodological guidance for DNA extraction and library construction provided in this study expand current best practices for metagenomic analyses of human fecal microbiota. Uptake of our protocols and guidelines will improve the accuracy and comparability of metagenomics-based studies of the human microbiome, thereby facilitating development and commercialization of human microbiome-based products. Video Abstract.

Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres.

A set of cyclic peptide analogues of a selective CXCR4 antagonist FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] were synthesized and bioevaluated. Using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres for Arg-Arg and Arg-Nal substructures, indispensable or the partial contribution of the two peptide bonds to the CXCR4 antagonism and anti-HIV activity was demonstrated. FC131 and the analogues were shown to selectively inhibit SDF-1 binding to CXCR4, whereas no inhibition of binding of SDF-1 to CXCR7 was observed.

A Unique Experience of Retinal Diseases Screening in Nepal.

BACKGROUND: Recently, the number of retinal patients is increasing in Nepal. The retinal problems are the second common cause of blindness in Nepal. Retinal diseases are challenging to manage due to the lack of simple and cost-effective screening methods, limited human resources, poverty, and lack of awareness in Nepal. Hospital for Children, Eye, ENT & Rehabilitation Services (CHEERS), Nepal conducted retina screening camps and education in communities through Retina Eye Care of Nepal project (RECON) in the years 2017 and 2018. MATERIALS AND METHODS: We screened retinal patients with an indirect ophthalmoscope coupled with plus 20 Dioptre lens and portable fundus camera. We referred the patients needing interventions to the base hospital (CHEERS) using a screening algorithm, where they received retinal laser and surgery. Besides, we also provided on-site educational programs for retinal disease awareness to the community. RESULTS: Retinal problems found from two static outreach clinics (SORC) and a day screening and treatment service (DSTS) were 18.3%, 20%, and 20%, respectively, while from a remote rural health camp (RRHC) was 2.61%. Likewise, patients referred to CHEERS for retinal laser or other retinal interventions were 15%, 16.6%, 16%, and 1.96% from 2 SORCs, 1 DSTS, and 1 RRHC, respectively. CONCLUSION: Retina camp is a cost-effective approach to early detection and referral for retinal-related vision impairment patients. It is also one opportunity to educate the community. The purpose of the project was to provide retina care to the community who otherwise could not afford it. We recommend a similar screening model on a large scale in a low-resource setting for the maximum benefits to the rural community.