Long-Term Outcomes of Self-Expandable Metallic Stents as a Bridge to Surgery for Obstructive and Symptomatic Primary Tumors of Stage IV Colorectal Cancer: A Propensity-Score Analysis.

Background: Self-expandable metallic stent (SEMS) was introduced for the treatment of obstructive colorectal cancer (CRC) a few decades ago. However, its long-term outcomes remain controversial, especially for stage IV CRC. The aim of this study was to clarify the outcomes of SEMS as a "bridge to surgery" (BTS) for obstructive and symptomatic primary tumors in stage IV CRC by one-to-one propensity-score matching. Materials and Methods: This retrospective cohort study was conducted at a single center from January 2007 to December 2017. Patients with obstructive and symptomatic primary tumors of stage IV CRC underwent primary resection (PR) or placement of a SEMS as a BTS. They were divided into SEMS and PR groups, and their short- and long-term outcomes were compared. Results: In total, 52 patients were reviewed (SEMS group, 21; PR group, 31). Sixteen patients in both groups were matched using propensity scores. Patients in the SEMS group more frequently underwent laparoscopic surgery than those in the PR group (75% versus 19%, P = .004). The two groups showed no significant differences in perioperative and pathological outcomes. The 5-year overall survival was not significantly different between groups (29% versus 20%, P = .53). Conclusions: As a BTS, the use of SEMS for obstructive and symptomatic primary tumors in CRC stage IV can be a comparable option to PR in terms of short- and long-term outcomes, and would be less invasive with respect to surgical procedures.

Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial).

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD. METHODS: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study. DISCUSSION: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures. TRIAL REGISTRATION: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

Changes in Coding and Efficiency through Modular Modifications to a One Pot PURE System for In Vitro Transcription and Translation.

The incorporation of unnatural amino acids is an attractive method for improving or bringing new and novel functions in peptides and proteins. Cell-free protein synthesis using the Protein Synthesis Using Recombinant Elements (PURE) system is an attractive platform for efficient unnatural amino acid incorporation. In this work, we further adapted and modified the One Pot PURE to obtain a robust and modular system for enzymatic single-site-specific incorporation of an unnatural amino acid. We demonstrated the flexibility of this system through the introduction of two different orthogonal aminoacyl tRNA synthetase:tRNA pairs that suppressed two distinctive stop codons in separate reaction mixtures.

How do magnetic resonance cholangiopancreatography findings predict conversion from laparoscopic cholecystectomy for acute cholecystitis to bailout procedures?

BACKGROUND: Acute cholecystitis is one of the most prevalent surgical abdominal conditions. The Tokyo Guidelines describe the management of acute cholecystitis and recommend bailout procedures for "difficult" cholecystitis cases. This study aimed to identify risk factors for conversion from laparoscopic cholecystectomy to bailout procedures in patients with acute cholecystitis. METHODS: This retrospective cohort study was conducted at a single center between January 2017 and December 2021. Patients who underwent laparoscopic cholecystectomy for acute cholecystitis were enrolled and classified into bailout and non-bailout groups. The patients' characteristics and perioperative data were compared between the 2 groups. RESULTS: In total, 161 patients who underwent laparoscopic cholecystectomy for acute cholecystitis were reviewed. Fourteen were excluded because of a lack of preoperative magnetic resonance cholangiopancreatography; thus, 147 patients were enrolled (bailout group, 21; non-bailout group, 126). Age (74 vs 67 years old; P = .048), days from onset to surgery (3 vs 2 days; P = .02), or defect of cystic duct in magnetic resonance cholangiopancreatography (57% vs 29%; P = .02) were significantly associated with conversion to bailout procedures. In the logistic regression analysis, a defect of the cystic duct in magnetic resonance cholangiopancreatography was an independent predictor for bailout procedures (odds ratio, 2.793; P = .04). CONCLUSION: In this study, defect of the cystic duct in the magnetic resonance cholangiopancreatography can predict conversion to bailout procedures. To the best of our knowledge, this is the first report to describe magnetic resonance cholangiopancreatography finding of the cystic duct as a predictor of surgical difficulty in patients with acute cholecystitis.

Safety and Efficacy of Sedation During Emergency Endoscopy for Upper Gastrointestinal Bleeding: A Propensity Score Matching Analysis.

BACKGROUND AND AIM: This study aimed to compare patients with and without sedation during emergency endoscopy for upper gastrointestinal bleeding (UGIB) and to clarify the safety and efficacy of sedation in emergency endoscopy. METHODS: We retrospectively collected 389 patients who underwent emergency endoscopy for UGIB at Ureshino Medical Center from 2016 to 2021. Patients were divided into two groups: sedation group during emergency endoscopy and nonsedation group. Clinical characteristics, patient status on admission, and UGIB etiology were evaluated. Treatment outcomes and adverse events were evaluated using propensity score matching (PSM), and risk factors for mortality from UGIB were investigated using Cox multivariate analysis. RESULTS: The sedation group was significantly younger, composed of a higher proportion of males, and had chronic liver disease. Blood pressure and hemoglobin level on admission were significantly higher in the sedation group. The main cause of bleeding was peptic ulcer, which was significantly higher in the nonsedation group. PSM created 133 matched pairs. The success rate of endoscopic hemostasis was similar in both groups, and procedure time was significantly shorter in the sedation group than in the nonsedation group (17.6 ± 10.0 versus 20.2 ± 10.2 min, P = 0.04). There were no significant differences in adverse events between groups. Cox multivariate analyses revealed that red blood cell transfusion [hazard ratio (HR) 4.45, P < 0.02] and rebleeding (HR 3.30, P = 0.03) were associated with increased risk of 30-day mortality from UGIB. CONCLUSIONS: Sedation reduced the procedure time during emergency endoscopy for UGIB. Sedation during emergency endoscopy for UGIB is acceptable for safe endoscopic procedures.

Inner residues of macrothiolactone in autoinducer peptides I/IV circumvent spontaneous S-to-O acyl transfer to the upstream serine residue.

Autoinducing peptides I and IV (AIP-I/IV) are naturally occurring cyclic thiodepsipeptides (CTPs) bearing a Ser-Thr-Cys-Asp/Tyr (STC[D/Y]) tetrapeptide motif, where the Cys thiol (HSC) in the side-chain is linked to the Met C-terminal carboxylic acid (MCOOH) to form 5-residue macrothiolactones,-SC(D/Y)FIMCO-. We have recently reported that CTPs containing SX1CX2 motifs spontaneously undergo macrolactonization to yield cyclic depsipeptides (CDPs) by an unprecedented rapid S-to-O acyl transfer to the upstream Ser hydroxyl group. Interestingly, even though the STC[D/Y] motif in AIP-I/IV is a member of the SX1CX2 motif family, it maintains the CTP form. This suggests that AIP-I/IV have a structural or chemical motive for avoiding such an S-to-O acyl transfer, thus retaining the CTP form intact. Here we have used genetic code reprogramming to ribosomally synthesize various AIP-I analogs and studied what the determinant is to control the formation of CTP vs. CDP products. The study revealed that a Gly substitution of the inner Asp/Tyr or Met residues in the thiolactone drastically alters the resistance to the promotion of the S-to-O acyl transfer, giving the corresponding CDP product. This suggests that the steric hindrances originating from the α-substituted sidechain in these two amino acids in the AIP-I/IV thiolactone likely play a critical role in controlling the resistance against macrolactone rearrangement to the upstream Ser residue.

A Method for Evaluating Coastal Underground Barrier Wall Using Groundwater Tidal Response.

Tidal response methods are usually used to estimate the hydraulic parameters of coastal aquifers. In this study an analytical model for aquifer tidal response was used. An existing analytical solution for tidal response of groundwater levels was extended to evaluate a subsurface barrier wall to prevent saltwater penetration in a coastal aquifer. A field feasibility study was conducted at the Komesu Dam, Japan. Groundwater levels were observed at pairs of sites on the seaward and reservoir sides of the wall. Groundwater-level time series data collected from a reservoir-side site near a horizontal hollow pipe penetrating the wall contained a visible sinusoidal tidal component, whereas data from another reservoir-side site did not. Analysis of these observations on the groundwater tidal response derived hydraulic parameters of the barrier wall between the paired observation sites. Although the parameters derived by the used simple formulas seem only approximate or apparent, the difference of the results for the two pairs indicated that the extended tidal response method can be useful for evaluation of the barrier function of the wall.

The safety and feasibility of laparoscopic gastrectomy for gastric cancer in very elderly patients: short-and long-term outcomes.

PURPOSE: It remains unclear whether laparoscopic gastrectomy (LG) for gastric cancer is a suitable treatment for very elderly (VE) patients. We aimed to assess the safety and feasibility of LG for gastric cancer in VE patients. METHODS: We reviewed 226 consecutive patients who underwent LG between January 2010 and December 2016. We compared VE patients (age ≥ 80, n = 38) with non-elderly patients (age ≤ 79, n = 188). RESULTS: An ASA-PS score ≥ 2 was more common in VE group (86.8 vs. 48.9%; P < 0.01). There were no significant differences in the operating time, blood loss, postoperative hospital stay, or postoperative morbidity between the groups. The 3-year survival rate and 3-year disease-specific survival rate were lower in the VE group (53.7 vs. 85.6%; P < 0.0001, 78.5 vs. 92.4%; P = 0.0116). A univariate analysis showed that PS scores ≥ 2, Charlson comorbidity index ≥ 4, and pN stage were independent predictors of decreased overall survival rates in the VE group. A multivariate analysis showed total gastrectomy, a Charlson comorbidity index ≥ 4, and the pN stage to be independent predictors in the VE group. CONCLUSION: LG for gastric cancer is, thus, considered to be safe for patients aged 80 years or older. Total gastrectomy, a Charlson comorbidity index ≥ 4, and the pN stage were independent risk factors for a poor prognosis in these patients.

Diaphragm disease associated with nonsteroidal anti-inflammatory drugs mimicking intestinal tumor: A case report.

INTRODUCTION: Diaphragm disease is rare and caused by intestinal obstruction due to nonsteroidal anti-inflammatory drugs (NSAIDs). Given the availability of video capsule endoscopy (VCE) and balloon enteroscopy (BE) this disease will be diagnosed more often. PRESENTATION OF CASE: A 73-year-old man was presented to our hospital for persistent nausea and vomiting. Abdominal ultrasound and computed tomography revealed small-bowel thickening, stricture in the terminal ileum, and dilation of the proximal small intestine. Differential diagnosis included ileal lymphoma and multiple ileal adenocarcinomas, and a diagnostic laparoscopy was performed. Twenty-centimeter of ileum was resected by primary ileo-ileal anastomosis. On pathological examination, fibrosis of the submucosa was identified, and erosions and numerous inflammatory cells reaching the submucosa were also identified from the specimen. DISCUSSION: The preoperative diagnosis of diaphragm disease is sometimes challenging due to its uncharacteristic symptoms; moreover, radiological findings are usually indefinite and distinctive. Currently, the main treatment for diaphragm disease is surgery. CONCLUSION: We have documented a case of intestinal obstruction by NSAIDs. However, it is desirable to determine the course of treatment based on small bowel endoscopic dilatation cases in the future.

A novel technique of laparoscopic reduction of incarcerated internal supravesical hernia via peritoneal incision: A case report.

INTRODUCTION: Laparoscopic reduction techniques for internal supravesical hernia have not been discussed much in literature. CASE PRESENTATION: A 90-year old woman was admitted for symptoms of intestinal obstruction. She was diagnosed with small bowel strangulation by CT scan and laparoscopy was performed. Laparoscopy revealed a mass medial to the medial inguinal fold with tightly incarcerated small bowel. The bowel could not be reduced by traction or external compression, and required incision of the hernia ring. The tight incarceration posed a risk of bowel injury and so we performed peritoneal incision in a similar manner to the TAPP approach for loosening and precise incision of the hernia ring. The bowel was successfully reduced and the hernia was repaired by partial sac resection. DISCUSSION: Surgical methods as well as reduction technique were reviewed from previous literature. Procedures with open laparotomy, laparoscopy and anterior approach have been described, but details of reduction were not seen in many of these reports. Various methods have been described for bowel reduction in other hernias, but none involving peritoneal incision. This is the first report describing bowel reduction via the peritoneal incision technique. CONCLUSION: Internal supravesical hernia may pose difficulty in bowel reduction, but the peritoneal incision technique allows safe incision of the hernia ring under laparoscopic situations.

Laparoscopic duodenojejunostomy requiring a side-to-side jejunojejunostomy in malignant stenosis of the gastrojejunal anastomosis in jejunal cancer: A case report.

INTRODUCTION: Laparoscopic duodenojejunostomy is a common surgical treatment for SMA syndrome. Although there are successful cases of laparoscopic duodenojejunostomies on malignant conditions, cancer patients with opioid-induced bowel dysfunction could struggle in maintaining an oral diet despite surgical treatment of the mechanical obstruction. CASE PRESENTATION: A 66 year-old woman with a chemotherapy history of 18 months for Stage 4 jejunal cancer near the ligament of Treiz presented with vomiting and dehydration. She had a gastrojejunostomy constructed prior to the induction of chemotherapy. CT scan and endoscopic studies confirmed the stricture of this anastomosis due to tumor invasion. Laparoscopic duodenojejunostomy was performed, but tolerable food intake was not achieved, likely due to limited bowel movements caused by opioid use and tumor invasion of the celiac plexus. A side-to-side jejunojejunostomy was constructed, since accumulation of food in her jejunal loop was thought to be a significant cause of her limited food intake and vomiting. She was able to tolerate oral intake after the second intervention and was discharged home. DISCUSSION: Successful cases of laparoscopic duodenojejunostomy in malignant strictures of the duodenum have been reported. In this case, the outcome was not so well due to limited bowel movements caused by opioid use. Literature review of laparoscopic duodenojejunostomy on SMA syndrome revealed some cases to be unsuccessful in enabling oral feeding or resolving nausea, and methods to treat such cases could be discussed further. CONCLUSION: Laparoscopic duodenojejunostomy is an option for malignant strictures of the duodenum, but a favorable outcome could not be achieved in our case. A side to side anastomosis of the jejunal loop and the efferent jejunum may help in improving the outcome.

An aminoacylation ribozyme evolved from a natural tRNA-sensing T-box riboswitch.

When the primitive translation system first emerged in the hypothetical RNA world, ribozymes could have been responsible for aminoacylation. Given that naturally occurring T-box riboswitches selectively sense the aminoacylation status of cognate tRNAs, we introduced a domain of random sequence into a T-box-tRNA conjugate and isolated ribozymes that were self-aminoacylating on the 3'-terminal hydroxyl group. One of them, named Tx2.1, recognizes the anticodon and D-loop of tRNA via interaction with its stem I domain, similarly to the parental T-box, and selectively charges N-biotinyl-L-phenylalanine (Bio-lPhe) onto the 3' end of the cognate tRNA in trans. We also demonstrated the ribosomal synthesis of a Bio-lPhe-initiated peptide in a Tx2.1-coupled in vitro translation system, in which Tx2.1 catalyzed specific tRNA aminoacylation in situ. This suggests that such ribozymes could have coevolved with a primitive translation system in the RNA world.

Changing clinical and molecular characteristics of hepatitis E virus infection in Mie Prefecture, Japan: Disappearance of indigenous subtype 3e strains.

AIM: To evaluate the clinical and molecular characteristics of hepatitis E virus (HEV) infection in Mie Prefecture, Japan, from 2004 through 2018. METHODS: The clinical information of hepatitis E cases was collected from 21 medical institutions in Mie Prefecture. The nucleotide sequences of infecting HEV strains were determined for cases with available serum samples. The origins or transmission routes were inferred from phylogenetic analyses of the nucleotide sequences. RESULTS: Fifty-three patients were diagnosed with HEV infection. The number of cases increased each year through 2012 and then decreased. Analyses of the clinical characteristics of the cases indicated that even mild cases were detected in the latter 10 years of the study. Nucleotide sequence analyses were undertaken on 38 of the 53 cases. The HEV subtype 3e (HEV-3e) strains identified for 13 cases were closely related to a swine HEV-3e strain that was isolated from the liver of a pig bred in Mie Prefecture. The number of cases infected with the indigenous Mie HEV-3e strains increased until 2012 but have not been reported since 2014. In the latter half of the study, cases involving various HEV strains of different genotypes and subtypes emerged. CONCLUSIONS: The disappearance of indigenous Mie HEV-3e strains appeared to be the primary cause for the decrease in hepatitis E cases in Mie Prefecture. The disappearance might have been associated with improved hygienic conditions on pig farms or the closure of contaminated farms. The results suggest that indigenous HEV strains can be eradicated by appropriate management.

Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptom.

Immunoglobulin light-chain (AL) amyloidosis is characterized by the deposition of insoluble fibrils composed of immunoglobulin light chains secreted by monoclonal plasma cells. Given the recent advances in the therapy of AL amyloidosis, it is important to diagnose this disease as early as possible. Herein, we describe the case of a 62-year-old man with hepatitis C virus (HCV)-related cirrhosis presenting with hematochezia. Colonoscopy showed multiple submucosal hematomas within the region ranging from the transverse colon to the sigmoid colon. Kappa immunoglobulin light-chain amyloid deposition was also detected. Bone marrow examination revealed a monoclonal abnormal plasma cell population. Thus, the patient was diagnosed with systemic immunoglobulin light-chain amyloidosis. The hematochezia was conservatively managed. However, because of liver failure caused by liver cirrhosis, the patient developed massive pleural effusion and died of respiratory failure. Postmortem examination revealed amyloid deposition in the esophagus, stomach, duodenum, ileum, descending colon, pancreas, heart, and lung. In these organs, amyloid deposition was limited to the vascular wall. We concluded that AL amyloidosis can present hematochezia arising from submucosal hematoma in the large colon before other systemic symptoms appear.

Investigating the origin and global dispersal history of hepatitis E virus genotype 4 using phylogeographical analysis.

BACKGROUND & AIMS: Hepatitis E virus (HEV) genotype 4 has mainly been isolated from sporadic hepatitis cases and swine in Asian countries. We analysed the origin and global dispersal history of genotype 4 using a Bayesian phylogeographical approach. METHODS: The 412-nucleotide sequences of open reading frame 2 of genotype 4 (47 Japanese, 40 Chinese, 1 Indian, 8 Indonesian, 1 Korean, 1 Taiwanese, 2 Danish and 2 Italian), of which sampling date and location were known, were collected. Evolutionary rate, divergence time, demographic growth and phylogeography were co-estimated in the Bayesian statistical inference framework implemented in the BEAST package to model spatial dispersal on a time-scaled genealogy. RESULTS: The most probable origin of genotype 4 was Japan and the time of origin was 1909 (95% highest posterior density, 1871-1940). Seven lineages of genotype 4 migrated from Japan to China. The analysis also showed the migration of genotype 4 from Japan or China to India and Indonesia and from China to Indonesia, Taiwan, Korea and a few European countries. CONCLUSIONS: Swine trade between countries coincided with the migration time and direction of genotype 4 in some cases and was considered the primary cause of dispersal. However, there was no clear cause of dispersal for some cases, for which no records of pig trade were found. Future research should analyse additional nucleotide sequences paired with epidemiological data from various countries to improve our understanding of HEV dispersal.

Light energy allocation at PSII under field light conditions: how much energy is lost in NPQ-associated dissipation?

In the field, plants are exposed to fluctuating light, where photosynthesis occurs under conditions far from a steady state. Excess energy dissipation associated with energy quenching of chlorophyll fluorescence (qE) functions as an efficient photo-protection mechanism in photosystem II. PsbS is an important regulator of qE, especially for the induction phase of qE. Beside the regulatory energy dissipation, some part of energy is lost through relaxation of excited chlorophyll molecules. To date, several models to quantify energy loss through these dissipative pathways in PSII have been proposed. In this short review, we compare and evaluate these models for PSII energy allocation when they are applied to non-steady state photosynthesis. As a case study, an investigation on energy allocation to qE-associated dissipation at PSII under non-steady state photosynthesis using PsbS-deficient rice transformants is introduced. Diurnal and seasonal changes in PSII energy allocation in rice under natural light are also presented. Future perspective of studies on PSII energy allocation is discussed.

Diurnal and developmental changes in energy allocation of absorbed light at PSII in field-grown rice.

The allocation of absorbed light energy in PSII to electron transport and heat dissipation processes in rice grown under waterlogged conditions was estimated with the lake model of energy transfer. With regard to diurnal changes in energy allocation, the peak of the energy flux to electron transport, J(PSII), occurred in the morning and the peak of the energy flux to heat dissipation associated with non-photochemical quenching of Chl fluorescence, J(NPQ), occurred in the afternoon. With regard to seasonal changes in energy allocation, J(PSII) in the rapidly growing phase was greater than that in the ripening phase, even though the leaves of rice receive less light in the growing phase than in the ripening period in Japan. This seasonal decrease in J(PSII) was accompanied by an increase in J(NPQ). One of the reasons for the lower J(PSII) in the ripening phase might be a more sever afternoon suppression of J(PSII). To estimate energy dissipation due to photoinhibition of PSII, J(NPQ) was divided into J(fast), which is associated with fast-recovering NPQ mainly due to qE, and J(slow), which is mainly due to photoinhibition. The integrated daily energy loss by photoinhibiton was calculated to be about 3-8% of light energy absorption in PSII. Strategies for the utilization of light energy adopted by rice are discussed. For example, very efficient photosynthesis under non-saturating light in the rapidly growing phase is proposed.

Allocation of absorbed light energy in PSII to thermal dissipations in the presence or absence of PsbS subunits of rice.

The thermal dissipation (TD) of absorbed light energy in PSII is considered to be an important photoprotection process in photosynthesis. A major portion of TD has been visualized through the analysis of Chl fluorescence as energy quenching (qE) which depends on the presence of the PsbS subunit. Although the physiological importance of qE-associated TD (qE-TD) has been widely accepted, it is not yet clear how much of the absorbed light energy is dissipated through a qE-associated mechanism. In this study, the fates of absorbed light energy in PSII with regard to different TD processes, including qE-TD, were quantitatively estimated by the typical energy allocation models using transgenic rice in which psbS genes were silenced by RNA interference (RNAi). The silencing of psbS genes resulted in a decrease in the light-inducible portion of TD, whereas the allocation of energy to electron transport did not change over a wide range of light intensities. The allocation models indicate that the energy allocated to qE-TD under saturating light is 30-50%. We also showed that a large portion of absorbed light energy is thermally dissipated in manners that are independent of qE. The nature of such dissipations is discussed.