Evaluation of the applicability of weak shoulder and arm sparing signs in amyotrophic lateral sclerosis by multiple neurologists and neurology residents: A single-center study.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) exhibits selective muscle weakness. The weak shoulder and arm sparing signs, assessed by a single experienced neurologist, have been reported to be superior to previous signs in sensitivity and specificity. However, it is unknown whether the same results are observed when assessed by multiple neurologists. METHODS: Subjects were retrospectively identified from our department's inpatient database from 2014 to 2023. Medical Research Council (MRC) scores of the deltoid (Del), biceps brachii (BB), triceps brachii (TB), and first dorsal interosseous (FDI) muscles were evaluated. The weak shoulder sign was defined as positive when Del was weaker than BB and TB. The arm sparing sign was defined as positive when both Del and FDI were weaker than BB and TB. Sensitivity was analyzed in all ALS patients and in subgroups based on the region of symptom onset, presence or absence of upper motor neuron (UMN) signs, and the Japanese ALS Severity Classification. RESULTS: Seventy-one patients with ALS were identified. Eight neurologists and three neurology residents evaluated each patient's MRC scores. The weak shoulder and arm sparing signs were observed in 72% and 48% of patients, respectively, with no significant difference in sensitivity across patient subgroups. DISCUSSION: The weak shoulder and arm sparing signs showed high and moderate sensitivity, respectively, consistent with a previous report, even when evaluated by multiple examiners. This expands the clinical utility and increases the reliability of these signs, potentially contributing to accurate ALS diagnosis when combined with other clinical features and objective assessments.

Grade 3 Pancreatic Neuroendocrine Tumor Refractory to Chemotherapy Successfully Treated with Peptide Receptor Radionuclide Therapy Leading to Conversion Surgery.

A 59-year-old woman was diagnosed with a pancreatic neuroendocrine tumor (P-NET; Grade 3, Ki67: 25%) with multiple liver and lymph node metastases and started chemotherapy with streptozosin (500 mg/m2/day) in combination with lanreotide acetate (120 mg). After six courses of (daily) streptozosin, the patient had progressive disease, as assessed by computed tomography (CT), and peptide receptor radionuclide therapy (PRRT) was started as second-line treatment. As PRRT was remarkably successful and the tumor shrank, surgery was performed to resect the primary pancreatic tumor, liver metastases, and lymph node metastases. CT evaluation performed six months after the surgery showed a complete response.

Etiologic factors for Barrett's esophagus: toward countermeasures in Asia.

INTRODUCTION: Over the past several decades, Europe and the United States have experienced a rapid increase in esophageal adenocarcinoma. Research and countermeasures against Barrett's esophagus, its precancerous lesion, are progressing. Because esophageal adenocarcinoma has an extremely poor prognosis when diagnosed in an advanced stage, recommendations for early cancer detection have been made based on the various proven etiological factors of Barrett's esophagus and the actual cancer risk of Barrett's esophagus. In recent years, there have been indications of an increase in esophageal adenocarcinoma in Japan, and a similar trend of cancer will occur shortly in other Asian countries. Consequently, Asian countries must implement similar countermeasures against Barrett's esophagus and esophageal adenocarcinoma, referencing the knowledge gained thus far in Europe and the United States. AREAS COVERED: This review summarizes the latest findings on the etiologic factors of Barrett's esophagus and discusses the differences between Westerners and Asians. The current status of Barrett's esophagus in Japan and other Asian countries is also summarized. EXPERT OPINION: The etiological factors and cancer incidence of Barrett's esophagus in Asia diverge somewhat from those observed in Europe and America. Therefore, it is imperative to implement measures that are tailored to the actual circumstances of Asian people.

Successful Treatment of Bilocular Walled-off Necrosis with Transmural Naso-cyst Continuous Irrigation: A Case Report.

Recently, transmural naso-cyst continuous irrigation (TNCCI) has been reported as an effective and safe treatment for walled-off necrosis (WON). We herein report a case of bilocular WON that was successfully treated with TNCCI. The patient was a 60-year-old man. The patient underwent endoscopic ultrasound-guided cyst drainage of the main cavity and subcavity using a single transluminal gateway transcystic multiple drainage technique, which was ineffective. Subsequently, a lumen-apposing metal stent (LAMS) was placed in the main cavity and TNCCI was successfully performed in the subcavity. TNCCI with LAMS was effective in treating bilocular WON.

Risk factors and pattern of metastatic recurrence after endoscopic resection with additional treatment for esophageal cancer.

Although esophageal cancers invading the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic resection (ER) are associated with a risk of lymph node metastasis, details of metastatic recurrence after additional treatment remain unknown. We aimed to identify the risk factors for metastatic recurrence and recurrence patterns in patients receiving additional treatment after ER for esophageal cancer. Between 2006 and 2017, patients with pT1a-MM/pT1b-SM esophageal cancer who underwent ER with additional treatment (esophagectomy, chemoradiotherapy [CRT], and radiation therapy) at 21 institutions in Japan were enrolled. We evaluated the risk factors for metastatic recurrence after ER with additional treatment. Subsequently, the rate and pattern (locoregional or distant) of metastatic recurrence were investigated for each additional treatment. Of the 220 patients who received additional treatment, 57, 125, and 38 underwent esophagectomy, CRT, and radiation therapy, respectively. In the multivariate analysis, lymphatic invasion was the sole risk factor for metastatic recurrence after additional treatment (hazard ratio, 3.50; P = 0.029). Although the risk of metastatic recurrence with additional esophagectomy was similar to that with CRT (hazard ratio, 1.01; P = 0.986), the rate of locoregional recurrence tended to be higher with additional esophagectomy (80.0% (4/5) vs. 36.4% (4/11)), leading to a better prognosis in patients with metastatic recurrence after additional esophagectomy than CRT (survival rate, 80.0% (4/5) vs. 9.1% (1/11)). Patients with lymphatic invasion have a high risk of metastatic recurrence after ER with additional treatment for pT1a-MM/pT1b-SM esophageal cancer. Additional esophagectomy may result in a better prognosis after metastatic recurrence.

A Report of Ulcerative Colitis With Relapse on the Rectal Side of the Loop Sigmoid Colostomy and Not on the Oral Side.

A patient who received a loop sigmoid colostomy was diagnosed with ulcerative colitis (pancolitis type) and treated with infliximab. Thereafter, he relapsed with intestinal inflammation only on the rectal side of the loop sigmoid colostomy and not on the oral side. Autologous fecal microbiota transplantation from the proximal intestine to the distal intestine was performed to treat the inflammation but was ineffective. He was treated with oral prednisolone and induced into remission. After analyzing fecal samples from the patient, we observed an alteration of the composition of the intestinal microbiota with intestinal inflammation, including a reduction of phylum Firmicutes in the inflamed distal intestine, whereas Firmicutes was conserved in the proximal non-inflamed intestine and recovered in the distal intestine after induction of remission. Thus, our results indicated that the inflammation was associated with an alteration of the intestinal microbiota.

A Final Report on the Real Impact of the COVID-19 Pandemic on the Diagnosis of Gastrointestinal Cancer in Akita Prefecture, Japan in 2022.

The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on the disruption of gastrointestinal cancer diagnoses remains unclear. This study investigated the actual impact on esophagogastric cancer (EGC) and colorectal cancer (CRC) diagnoses up to the third year of the pandemic in Akita Prefecture, Japan, using population-based registry data. We collected data on the annual number of EGC and CRC diagnoses using a database from the collaborative Akita Prefecture hospital-based registration. The net number of cancers diagnosed in the first three years of the pandemic (2020-2022) were compared with those diagnosed in the three years before the pandemic (2017-2019). Changes in the proportion of cancer stage and initial treatment for diagnosed EGC and CRC after the pandemic were then compared. The total number of EGCs was 9.3% lower in the first three years of the pandemic than in the three years before, probably due to its long-term declining trend. The total number of CRCs in the first three years of the pandemic exceeded that in the three years before, suggesting successful recovery of the diagnostic procedure. The proportion of cancer stages and initial treatment for EGCs and CRCs remained largely unchanged after the onset of the pandemic. Based on the population-based registry data from the first three years of the pandemic, the disruption of gastrointestinal cancer diagnoses caused by the pandemic is settling down without any substantial disease progression, even in Akita Prefecture, the area with the highest incidence of cancer in all of Japan.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Is blue light imaging without magnification satisfactory as screening for esophageal squamous cell carcinoma? Post-hoc analysis of multicenter randomized controlled trial.

OBJECTIVES: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. METHODS: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. RESULTS: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003). CONCLUSION: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists.

Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

BACKGROUND: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. METHODS: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. RESULTS: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. CONCLUSIONS: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Remarkable response as a new indicator for endoscopic evaluation of local efficacy of non-surgical treatments for esophageal cancer.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

Extraction and Fractionation of Human Gastric Mucins from Gastric Juice.

Mucin, a major component of the mucus, is considered to be one of the principal factors in the physiological defense mechanism of the gastrointestinal mucosa. Measuring the mucin content of human gastric mucus is a useful tool for the assessment of Helicobacter pylori (H. pylori) eradication or the involvement of mucus secretion in various gastroduodenal diseases. Here, we describe a methodology for the isolation of the mucin fraction from human gastric juice and the quantification of mucin.

Iron overload in patients with Crohn's disease with short bowel syndrome who received long-term parenteral nutrition with trace elements.

Crohn's disease patients often need regular home parenteral nutrition (HPN) for intestinal failure due to multiple intestinal resections. Trace elements are necessary for long-term HPN but the requirement volume of iron is undetermined. We describe three patients with Crohn's disease with short bowel syndrome (SBS) who had iron overload as a result of long-term HPN including iron. Serum ferritin level was significantly decreased through depleting intravenous iron administration in all cases. One patient needed regular insulin injection and phlebotomy for diabetes mellitus due to hemochromatosis, and intravenous iron administration had a significant impact on the patient's health. Long-term routine intravenous iron administration should be cautious in SBS patients to avoid the overload.

Peroral cholangioscopy for the evaluation of bile duct stricture in hepatocellular carcinoma on a preoperative examination.

Objective: Bile duct tumor thrombosis in hepatocellular carcinoma (HCC) is a relatively rare event with a poor prognosis. Furthermore, bile duct tumor thrombus in HCC may be misdiagnosed when only imaging modalities are used. The efficiency of peroral cholangioscopy (POCS) in evaluating bile duct lesions has been reported. Patients: We present three cases of HCC with bile duct strictures in which POCS was performed as a preoperative evaluation. Results: In these three cases, diagnosing whether the lesion was a bile duct tumor thrombus on CT and endoscopic retrograde cholangiopancreatography was difficult. We performed POCS in three cases and were able to diagnose the presence of bile duct tumor thrombus of HCC, including differentiation from extrinsic compression of the bile duct. Conclusion: POCS for HCC with bile duct features is useful for the preoperative diagnosis of bile duct tumor thrombus, especially in cases where the surgical procedure depends on the presence of bile duct tumor thrombus.

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Disproportionate cancer worries in ultra-short-segment Barrett's esophagus in Japan.

Objectives: Although Barrett's esophagus (BE), especially ultra-short-segment BE (USSBE), is very frequently diagnosed in Japan, how subjects feel about receiving a diagnosis of BE is unclear. We therefore prospectively investigated cancer worry in subjects who received a BE diagnosis. Methods: Self-administered questionnaires were sent to subjects who were diagnosed with BE at three health checkup institutes in Akita Prefecture, Japan. The cancer worry scale (CWS) was used to quantitatively assess the fear of developing cancer. The BE subjects were classified into USSBE <1 cm and non-USSBE ≥1 cm groups. Factors associated with the CWS were investigated using logistic regression analyses. Results: A total of 325 (31%) subjects, comprising 229 USSBE and 96 non-USSBE patients were included in this study. Compared with the USSBE group, the non-USSBE group had a significantly higher frequency of a history of a BE diagnosis and perception of carcinogenesis. However, the CWS was similar between the USSBE and non-USSBE groups, with a median CWS of 12.5 (3.75) versus 12.7 (3.65). A multivariate logistic regression analysis revealed that while positive reflux symptoms were significantly associated with a positive CWS, the BE length was not significantly associated with it, with an odds ratio (95% confidence interval) of 1.3 (0.75-2.2). Conclusions: A BE diagnosis promotes a similar level of worry about cancer among subjects, irrespective of the length of BE. In Japan, since USSBE poses a much lower cancer risk than non-USSBE, the former may frequently be associated with a disproportionate cancer worry relative to the latter. (UMIN000044010).

Impact of Functional Status on Development of Clostridioides difficile Infection and Increase in Inhospital Mortality among Antibiotic Users.

INTRODUCTION: Functional status is one of the surrogates of advanced age, an established risk factor for Clostridioides difficile infection (CDI). We aimed to investigate the usefulness of functional status in the clinical management of CDI. METHODS: We enrolled all hospitalized adult patients receiving antibiotics from a retrospective hospital-based cohort in Japan between 2016 and 2020. Using the Barthel index (BI), which is an objective scale of functional status, we investigated the association of BI with developing CDI and its impact on inhospital mortality in patients with CDI. RESULTS: We enrolled 17,131 patients with 100 cases of CDI. Multivariable analysis revealed that lower BI (≤25) was an independent risk factor for developing CDI (adjusted odds ratio, 4.11; 95% confidence interval, 2.62-6.46). Furthermore, a combination of BI and Charlson comorbidity index (CCI) showed an adjusted odds ratio of 36.40 (95% confidence interval, 17.30-76.60) in the highest risk group. A high-risk group according to the combination of BI and CCI was estimated to have significantly higher inhospital mortality in patients with CDI using the Kaplan-Meier method (p = 0.017). A combination of lower BI and higher CCI was an independent predictor of inhospital mortality even in the multivariable Cox regression model (adjusted hazard ratio, 3.00; 95% confidence interval, 1.01-8.88). CONCLUSIONS: Assessment of functional status, especially combined with comorbidities, was significantly associated with developing CDI and may also be useful in predicting inhospital mortality.