Predictors of response to anamorelin in gastrointestinal cancer patients with cachexia: a retrospective study.

PURPOSE: Anamorelin, a ghrelin receptor agonist, has recently been approved for gastric, pancreatic, and colorectal cancer patients with cachexia in Japan. However, only few studies have investigated the predictors of response to anamorelin in clinical settings. Thus, our study aimed to investigate the predictors of the response, in addition to its efficacy and safety. METHODS: The clinical outcomes of 20 patients were evaluated during administration. They were divided into two groups based on lean body mass, responders and non-responders, and their clinical characteristics were compared. RESULTS: The mean ± standard error (SE) variations at 12 weeks in lean body mass and handgrip strength were 2.63 ± 0.79 kg and - 1.53 ± 1.20 kg, respectively. The mean ± SE variations at 8 weeks in fasting blood glucose and hemoglobin A1c were 32.88 ± 13.77 mg/dL and 0.90 ± 0.18%, respectively. Total protein, albumin, transferrin, and prognostic nutritional index at baseline were significantly higher in responders (n = 8) than in non-responders (n = 12), whereas the neutrophil/lymphocyte and C-reactive protein/albumin ratios at baseline were significantly higher in non-responders than in responders. CONCLUSION: The study confirmed the efficacy and safety of anamorelin and identified nutritional or systemic inflammatory markers as predictors of anamorelin response in advanced gastrointestinal cancer patients.

Rectal administration of low-dose diclofenac does not reduce post-endoscopic retrograde cholangiopancreatography pancreatitis: a propensity score matching analysis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching. METHODS: This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30 min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50 kg were administered a 50 mg dose, while those weighing < 50 kg were administered a 25 mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis. RESULTS: Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52). CONCLUSIONS: The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP.

[A Case of Duodenal Tumor Accompanied by Liver and Lymph Node Metastases after Ten Years of Observation].

A 67-year-old woman presented with a history of upper abdominal pain and weight loss. Physical examination revealed a lump in the right lower quadrant. She had undergone esophagogastroduodenoscopy at another hospital ten years ago, which showed a 15-mm elevated lesion in the duodenal bulb. The patient had not undergone further examinations or received treatment during the 10 years. Esophagogastroduodenoscopy conducted in our hospital revealed an enlarged tumor that was difficult to assess on the whole image. The tumor was diagnosed as a well-differentiated adenocarcinoma based on a biopsy specimen. Enhanced computed tomography revealed a hypervascular duodenal tumor with liver and lymph node metastases. The patient was treated with capecitabine plus oxaliplatin for the duodenal cancer. Lymph node metastases increased markedly after 2 courses of chemotherapy. The patient died 3 months after the initiation of chemotherapy. The natural history of sporadic non-ampullary duodenal epithelial tumors remains to be fully elucidated due to the low incidence rate. This case suggests that sporadic non-ampullary duodenal epithelial tumors have a biological potential for invasive malignancy.

Different survival strategies involve carbon translocation rather than de novo C assimilation under complete submergence in rice plant.

This study investigated the effect of transient submergence on the recovery of photosynthetic activity and translocation of photosynthate in IR67520 (Sub1A genotype) and IR72442 (non-Sub1A genotype) using 13C-labeled tracer, coupled with some photosynthetic physiological assessments. Plant growth, photosynthetic capacity, and photosynthetic recovery were studied by treating the two rice genotypes without or completely submerged for 7 days in transparent acrylic tanks filled with water to a depth of 80 cm, followed by 7 days of reaeration. Results revealed that the IR67520 was able to obtain new carbon source for assimilation during at 7 days of recovery periods. The IR72442 genotype partitioned 13C to the newly developed upper leaves more than the IR67520 genotype did. This was due to its inability to obtain CO2 from other source during post submergence. Recovery of chlorophyll content, ability to retain higher biomass, and ability to grow faster at 7 days of recovery periods also indicated the ability of Sub1A genotype to reactivate its photosynthetic capacity.

Microbiological analysis of patients with first and recurrent episodes of acute cholangitis in a middle-sized hospital: A single-center retrospective study in rural North Kyoto, Japan.

BACKGROUND: Knowledge of the bacterial spectrum involved in acute cholangitis is essential for adequate empiric antibiotic treatment. There is a lack of published data comparative data between patients with first and recurrent episodes of acute cholangitis. This study aimed to analyze the microbial spectrum in patients with first and second episodes of acute cholangitis. METHODS: We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020. RESULTS: At the first episode of acute cholangitis, the predominant strains belonged to Escherichia coli (17.9%), followed by Klebsiella spp. (15.5%), Enterobacter spp. (6.4%), and Enterococcus spp. (5.6%). During follow-up, acute cholangitis recurred in 109 patients; at the second episode, the predominant strains belonged to Enterococcus spp. (35.8%), followed by Klebsiella spp. (27.5%), Enterobacter spp. (22.9%), and Escherichia coli (15.6%). Enterococcus spp. were the most common pathogen in patients with second episode of acute cholangitis, regardless of whether the cholangitis was caused by a malignant tumor or a benign disease. CONCLUSIONS: Unlike in patients with a first episode of acute cholangitis, clinicians should consider empirical treatment with anti-enterococcal antibiotics in patients with recurrent episodes of acute cholangitis.

Efficacy and limitations of the histological diagnosis of type 1 autoimmune pancreatitis with endoscopic ultrasound-guided fine needle biopsy with large tissue amounts.

OBJECTIVES: We examined the efficacy and limitations of acquiring large specimens by endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for diagnosing type 1 autoimmune pancreatitis (AIP). METHODS: Patients from 12 institutions with non-neoplastic diseases or pancreatic ductal adenocarcinoma (PDAC) with large EUS-FNB specimens were investigated. Slides stained with hematoxylin-eosin, elastic, IgG4, and IgG stains were evaluated. The IgG4- and IgG-positive cell numbers were counted in three foci. The diagnoses were based on the Japan Pancreas Society 2011 (JPS 2011) criteria and the International Consensus Diagnostic Criteria (ICDC). RESULTS: We analyzed 85 non-neoplastic (definite type 1 AIP in 73/85 based on the ICDC) cases and 64 PDAC cases. IgG4-positive cells were numerous (>10 in 85.9%), and the IgG4/IgG ratios were high (>40% in 81.2%). Plasma cell crushing by an artifact caused unsuccessful immunostaining, notably in smaller samples. Tissue lengths were an important factor for the presence of storiform fibrosis and obliterative phlebitis, but storiform fibrosis was equivocal even in large tissues. A definite or possible histological diagnosis was achieved in 45.9% (39/85) and 41.2% (35/85), respectively, and contributed to the definite final diagnosis of type 1 AIP in 33.3% (ICDC) and 55.6% (JPS 2011) in cases with segmental/focal lesions. In the PDAC group, >10 IgG4-positive cells was rare (2/58), but elastic stains revealed fibrous venous occlusions in 10.3% (6/58). CONCLUSIONS: EUS-FNB with large tissue amounts was useful for diagnosing type 1 AIP, notably by facilitating successful IgG4 immunostaining, but definite diagnosis may not be achieved even in cases with large specimens.

Guidance for diagnosing autoimmune pancreatitis with biopsy tissues.

The biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.

High-resolution mapping and characterization of xa42, a resistance gene against multiple Xanthomonas oryzae pv. oryzae races in rice (Oryza sativa L.).

Improvement of resistance against rice bacterial blight (BB) disease is an important breeding strategy in breeding programs across the world, especially in Africa and southern Asia where BB is more prevalent. This report describes a high-resolution map and characterization of xa42 at XA42 locus, a rice BB resistance gene in XM14, a mutant line originating from IR24. The candidate gene region was narrowed down from 582 kb, which had been obtained in our previous study, to 57 kb. XM14 shows brown spots in its leaves like lesion mimic mutants. This line also shows a shorter stature than the original cultivar IR24. In XA42 gene segregating populations, homozygotes of xa42 allele were consistently resistant to the six Japanese Xanthomonas oryzae pv. oryzae races used for this study. They also showed brown spots and markedly short stature compared with the other genotypes, suggesting that xa42 gene exhibits pleiotropic effects.

Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis.

OBJECTIVE: Corticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP. DESIGN: We conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5-7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis. RESULTS: Between April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed. CONCLUSIONS: Maintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks. TRIAL REGISTRATION NUMBER: UMIN000001818; Results.

Identification and linkage analysis of a new rice bacterial blight resistance gene from XM14, a mutant line from IR24.

Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is a chief factor limiting rice productivity worldwide. XM14, a rice mutant line resistant to Xoo, has been obtained by treating IR24, which is susceptible to six Philippine Xoo races and six Japanese Xoo races, with N-methyl-N-nitrosourea. XM14 showed resistance to six Japanese Xoo races. The F2 population from XM14 × IR24 clearly showed 1 resistant : 3 susceptible segregation, suggesting control of resistance by a recessive gene. The approximate chromosomal location of the resistance gene was determined using 10 plants with shortest lesion length in the F2 population from XM14 × Koshihikari, which is susceptible to Japanese Xoo races. DNA marker-assisted analysis revealed that the gene was located on chromosome 3. IAS16 line carries IR24 genetic background with a Japonica cultivar Asominori segment of chromosome 3, on which the resistance gene locus was thought to be located. The F2 population from IAS16 × XM14 showed a discrete distribution. Linkage analysis indicated that the gene is located around the centromeric region. The resistance gene in XM14 was a new gene, named XA42. This gene is expected to be useful for resistance breeding programs and for genetic analysis of Xoo resistance.

[Outcome and Problems of Nab-Paclitaxel Therapy for Gastric Cancer in Clinical Practice].

Nanoparticle albumin-bound paclitaxel(nab-PTX)was approved for the treatment of gastric cancer without a large-scale clinical trial in Japan. Its safety and efficacy should be validated in clinical practice. We retrospectively investigated prognostic factors related to time to treatment failure(TTF)in 11 patients with unresectable or recurrent gastric cancer treated with nab- PTX in our hospital. In univariate analysis, Onodera's prognostic nutritional index(PNI)and the time from the start of first-line chemotherapy to the start of nab-PTX were related to TTF. In multivariate analysis, Onodera's PNI was identified as an independent predictive factor for TTF (hazard ratio 0.056, p=0.022). PNI could contribute to adequate patient selection and the improvement of nab-PTX therapy efficacy ingastric cancer.

Prognostic value of moderate or massive ascites in patients with advanced gastric cancer.

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer.

Halopriming in the submergence-tolerant rice variety improved the resilience to salinity and combined salinity-submergence at the seedling stage.

The role of halopriming in alleviating the detrimental effects of salinity and combined salinity-submergence was evaluated using two rice genotypes, "IR06F148" (anaerobic germination + submergence tolerant [Sub1]) and "Salt-star" (salt tolerant) with contrasting levels of tolerance. Nonprimed seeds and those primed with 1% calcium chloride (CaCl2) were germinated, and the seedlings were exposed to salinity (50 or 100 mM sodium chloride [NaCl]) and submergence (nonsaline or saline water). Salinity substantially inhibited plant height, shoot/root dry mass, and leaf area. Priming improved the resilience to 50 mM NaCl by increasing the chlorophyll content and lowering hydrogen peroxide (H2O2) production; and to 100 mM NaCl by increasing the total soluble sugars. However, apparent differences in the responses of primed "Salt-star", such as an increase in the Na+, K+, and Ca2+ levels, indicated that halopriming differentially affected the response to salt based on the salinity tolerance of the variety. Submergence reduced the shoot biomass, chlorophyll, and photosynthetic efficiency to a greater extent in "Salt-star" than in "IR06F148". Priming, especially in "Salt-star", caused a lesser reduction in the chlorophyll (Chl) and maximum quantum yield of photosystem II (Fv/Fm) but increased the total soluble sugars post-submergence, indicating a boost in the photosynthetic efficiency. The responses of the two varieties to submergence depended on their tolerance, and halopriming affected each variety differently. The metabolic and molecular changes induced by halopriming in submergence-tolerant rice may be explored further to understand the underlying mechanisms of improved resilience.

Prediction of pancreatic anastomotic failure after pancreatoduodenectomy: the use of preoperative, quantitative computed tomography to measure remnant pancreatic volume and body composition.

OBJECTIVE: To determine whether remnant pancreatic volume (RPV), subcutaneous/visceral adipose tissue(SAT/VAT) area, and skeletal muscle (SM) area calculated from preoperative computed tomography (CT) can predict the occurrence of pancreatic anastomotic failure (PAF) after pancreatoduodenectomy (PD). BACKGROUND: Increased body mass index, small main pancreatic duct, and soft pancreatic texture are well-established predictors of PAF after PD. The impact on PAF of anthropomorphic measurements, such as RPV and body composition, is unknown. METHODS: In 173 patients undergoing PD from 2004 to 2009, cross sections of SAT/VAT/SM area were quantitated volumetrically, respectively, from preoperative CT. RPV was calculated from the CT as the sum of pancreatic tissue area to the left of the presumed pancreatic transection site. The predictive ability for multiple models using combinations of body mass index, RPV, SAT/VAT area, SM area, main pancreatic duct size, and pancreatic gland texture was described using a concordance index (c-index). RESULTS: Clinically relevant PAF occurred in 22 patients (13%). Multivariate logistic regression analysis identified RPV (P = 0.0012), VAT area (P = 0.0003), and SM area (P = 0.0006) as independent predictors of PAF. Using previously identified risk factors, the best 2-predictor model (body mass index and pancreatic duct size) resulted in a c-index of 0.748. Using anthropomorphic factors, however, the 2-predictor model using VAT and SM areas revealed a superior c-index of 0.959. CONCLUSIONS: Our 2-predictor model using VAT area and SM area based on volumetric quantification using preoperative CT may offer clinical benefit as an objective prognostic measure to predict clinically relevant PAF after PD.

Spatial O2 Profile in Coix lacryma-jobi and Sorghum bicolor along the Gas Diffusion Pathway under Waterlogging Conditions.

While internal aeration in plants is critical for adaptation to waterlogging, there is a gap in understanding the differences in oxygen diffusion gradients from shoots to roots between hypoxia-tolerant and -sensitive species. This study aims to elucidate the differences in tissue oxygen concentration at various locations on the shoot and root between a hypoxia-tolerant species and a -sensitive species using a microneedle sensor that allows for spatial oxygen profiling. Job's tears, a hypoxia-tolerant species, and sorghum, a hypoxia-susceptible species, were tested. Plants aged 10 days were acclimated to a hypoxic agar solution for 12 days. Oxygen was profiled near the root tip, root base, root shoot junction, stem, and leaf. An anatomical analysis was also performed on the roots used for the O2 profile. The oxygen partial pressure (pO2) values at the root base and tip of sorghum were significantly lower than that of the root of Job's tears. At the base of the root of Job's tears, pO2 rapidly decreased from the root cortex to the surface, indicating a function to inhibit oxygen leakage. No significant differences in pO2 between the species were identified in the shoot part. The root cortex to stele ratio was significantly higher from the root tip to the base in Job's tears compared to sorghum. The pO2 gradient began to differ greatly at the root shoot junction and root base longitudinally, and between the cortex and stele radially, between Job's tears and sorghum. Differences in the root oxygen retention capacity and the cortex to stele ratio are considered to be related to differences in pO2.

Autopsy of a Patient with Primary Pancreatic Lymphoma with Findings Resembling Severe Acute Pancreatitis.

Primary pancreatic lymphoma is a rare pancreatic malignancy, reportedly accounting for only 0.2-0.7% of all primary pancreatic tumors. Primary pancreatic lymphoma is often difficult to distinguish from other diseases, such as acute pancreatitis. We herein report the autopsy of a patient with primary pancreatic lymphoma with imaging findings resembling those of severe acute pancreatitis, with a focus on the gross and histological features.

Spontaneous regression in solid pseudopapillary neoplasm of pancreas.

A solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of spontaneous regression in SPN of the pancreas. A 48-years-old female was found to have a mass in the head of the pancreas on examination for her back pain and referred to our hospital in 20XX. Laboratory data showed no abnormalities in serum levels of pancreatic enzymes and tumor markers. A contrast CT scan of upper abdomen showed a slightly enhanced lesion (23 × 19 mm in diameter) without cystic component or fibrous capsule in the head of the pancreas. An MRI scan showed the mass as low-intensity in T1-WI and high-intensity in T2-WI. She admitted to our hospital for further examination of a pancreatic mass by EUS-FNA in 20XX + 4. EUS showed a slightly hypoechoic mass (30 × 19 mm in diameter) compared with the neighboring normal pancreas. Tumor margin was relatively clear and the internal echo image was homogenous. Histological findings revealed a solid and pseudopapillary proliferation of eosinophilic polygonal cells with oval nuclei. The tumor cells were positive for vimentin and CD10 in the cytoplasm and ß-catenin in the nuclei, which led to the diagnosis of SPN. We recommended this patient to undergo surgical resection, however, the patient chose follow-up examinations. Follow-up study after 1 year using MRI scan showed spontaneous regression, which was coincided with her menopause. These findings suggest that the natural regression of SPN may occur and female sex hormone changes may regulate the growth of SPN.