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Although handheld ultrasound devices (HUDs) are commonplace, their ability to diagnose fecal retention (FR) remains unclear. This prospective observational study examined HUDs' usefulness in diagnosing FR in patients with constipation in a palliative care setting. Between 10 December 2020 and 30 June 2022, we compared rectal ultrasonographic findings obtained using HUDs with clinical manifestations in 64 males and 70 females (48%, 52%, 68 ± 11 years old) with constipation who had undergone computed tomography (CT). FR was diagnosed using a HUD and compared with CT and digital rectal examination (DRE) results. In total, 42 (31%), 42 (31%), and 41 (31%) patients were diagnosed using HUDs, CT, and DRE, respectively. Thirty-nine (93%) patients in the CT group were also diagnosed with FR using HUDs. A total of 89 of 92 patients with a negative CT diagnosis also had a negative HUD diagnosis. Among the 41 patients in the DRE group, 37 were also diagnosed with FR using HUDs. Among 93 patients with a negative DRE diagnosis, 86 had a negative HUD diagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of HUDs for CT were 93%, 97%, 93%, and 97%, respectively. Those of HUDs for DRE were 88%, 94%, 86%, and 95%, respectively. The concordance rates for FR diagnosis were 128/134 for CT and HUDs and 123/134 for DRE and HUDs. HUD was useful for diagnosing FR in this setting. HUDs could provide valuable support for appropriate treatment selection. Developing a constipation treatment algorithm based on rectal ultrasonographic findings is warranted in the future. [ABSTRACT FROM AUTHOR]

Background/Aims Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients. Methods From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course. Results Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m², 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care. Conclusion CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired. [ABSTRACT FROM AUTHOR]

Background and Aim: Non‐alcoholic fatty liver disease (NAFLD) can progress in non‐obese patients as in obese patients. Reports on long‐term prognosis in non‐obese NAFLD patients are controversial. Therefore, we aimed to examine the long‐term prognosis of non‐obese patients with NAFLD. Methods: This single‐center, retrospective cohort study enrolled biopsy‐proven non‐obese and obese NAFLD patients between January 2002 and December 2011 and followed them up until 31 March 2021, for death and clinical events (cardiovascular and liver‐related events and extrahepatic cancers). Results: Of the 223 NAFLD patients, 58 (26.0%) were non‐obese. Compared with obese patients, they had a lower fibrosis stage (0.8 ± 0.80 vs 1.2 ± 0.91; P = 0.004), milder lobular inflammation (0.9 ± 0.7 vs 1.1 ± 0.7; P = 0.02), and significantly lower serum creatinine, total bilirubin, ferritin, and type IV collagen 7S and higher high‐density lipoprotein levels. After a median follow‐up of 8.9 years, no significant difference was noted in mortality between the two groups (2 [3.4%] non‐obese vs 5 [3.0%] obese; log‐rank test, P = 0.63). Twelve patients (20.7%) in the non‐obese group and 32 (19.4%) in the obese group had clinical events. Although the obese group had a higher incidence of clinical events during the first 10 years of follow‐up, the non‐obese group had a higher incidence after that (log‐rank test, P = 0.67). The non‐obese group had a high incidence of malignancy (9 [15.5%] non‐obese vs 14 [8.3%] obese; P = 0.13). Conclusion: Non‐obese NAFLD does not necessarily have a good prognosis, and some cases have a poor prognosis such as extrahepatic cancers. Further validation is required in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Opioids are used in cancer pain management, however, their continuous use may not be tolerable owing to adverse effects such as constipation, sleepiness, nausea, and respiratory depression. Opioid-induced constipation reduces the quality of life of patients, and osmotic laxatives are conventionally recommended for preventing opioid-induced constipation. Recently, naldemedine, a peripherally acting μ-opioid receptor antagonist, can be used to safely and effectively treat opioid-induced constipation based on its etiological mechanism, without affecting central analgesia. In this study, we compared the effectiveness of magnesium oxide with that of naldemedine in preventing opioid-induced constipation. Naldemedine significantly prevented deterioration in the quality of defecation (the Japanese Patient Assessment of Constipation Quality of Life and complete spontaneous bowel movement) and reduced gastrointestinal adverse effects, mainly nausea, compared with magnesium oxide during 12-week administration. Opioid-induced constipation (OIC) may occur in patients receiving opioid treatment, decreasing their quality of life (QOL). We compared the effectiveness of magnesium oxide (MgO) with that of naldemedine (NAL) in preventing OIC. This proof-of-concept, randomized controlled trial (registration number UMIN000031891) involved 120 patients with cancer scheduled to receive opioid therapy. The patients were randomly assigned and stratified by age and sex to receive MgO (500 mg, thrice daily) or NAL (0.2 mg, once daily) for 12 weeks. The change in the average Japanese version of Patient Assessment of Constipation QOL (JPAC-QOL) from baseline to 2 weeks was assessed as the primary endpoint. The other endpoints were spontaneous bowel movements (SBMs) and complete SBMs (CSBMs). Deterioration in the mean JPAC-QOL was significantly lower in the NAL group than in the MgO group after 2 weeks. There were fewer adverse events in the NAL group than in the MgO group. Neither significant differences in the change in SBMs between the groups nor serious adverse events/deaths were observed. The CSBM rate was higher in the NAL group than in the MgO group at 2 and 12 weeks. In conclusion, NAL significantly prevented deterioration in constipation-specific QOL and CSBM rate compared with MgO. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10–20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Background: Constipation is a common, distressing complication in patients with cancer receiving palliative care. Elobixibat is a novel inhibitor of the ileal bile acid transporter that is used to treat chronic constipation by stimulating bowel function. However, its efficacy in patients with cancer has not been examined. This study investigated the drug's effectiveness in patients with cancer with chronic constipation. Patients and Methods: This prospective‐sampling, single‐center, observational study included hospitalized patients with cancer diagnosed, using the Rome IV criteria, with chronic constipation. Within 2 weeks of hospitalization, each participant was administered elobixibat (5–15 mg) daily until discharge. Spontaneous bowel movements (SBMs), complete spontaneous bowel movements (CSBMs), Bristol stool form scale (BSFS) scores, and the Patient Assessment of Constipation Quality of Life questionnaire (PAC‐QOL) scores were assessed before and after elobixibat administration. We also evaluated the relationship between the amount of food consumed and the SBM frequency. Results: Among the 83 participants, the mean pre‐ and post‐treatment frequencies of daily SBMs were 0.3 and 1.2 (p <.0001) and those of CSBMs were 0.1 and 0.6 (p <.0001), respectively. The mean pretreatment BSFS score was 1.6, whereas the post‐treatment value was 3.5 (p <.0001); the mean PAC‐QOL score (overall) improved from 1.01 to 0.74 (p =.01). There was no significant change in the daily SBM frequency between fasting and feeding states (1.2 vs. 1.3; p =.8), and there was no correlation between the amount of food intake and the SBM frequency after elobixibat administration (r =.03). Serious adverse events were not observed. Conclusion: This study showed that elobixibat is safe and effective for patients with cancer with chronic constipation, regardless of the food intake amount. Implications for Practice: Elobixibat was effective at relieving chronic constipation in patients with various cancers. Serious adverse events were not observed, and the relief of constipation was independent of variation in food intake. Constipation is a common, distressing complication in cancer patients receiving palliative care. This study investigated the effectiveness of elobixibat in cancer patients with chronic constipation. [ABSTRACT FROM AUTHOR]

Background and Aim: Gut microbiota composition is associated with the pathogenesis of non‐alcoholic fatty liver disease. However, the association between gut microbiota composition and non‐alcoholic fatty liver disease in non‐obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non‐obese and obese patients with non‐alcoholic fatty liver disease. Methods: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short‐chain fatty acid levels in fecal samples from 51 non‐obese patients with non‐alcoholic fatty liver disease (body mass index <25 kg/m2) and 51 obese patients with non‐alcoholic fatty liver disease (body mass index ≥30 kg/m2) who underwent pathological examination and 87 controls at five hospitals in Japan. Results: Although no significant differences between the non‐obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non‐obese patients with non‐alcoholic fatty liver disease compared with those in obese patients with non‐alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non‐obese patients with non‐alcoholic fatty liver disease. Conclusions: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non‐alcoholic fatty liver disease in non‐obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917). [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine tumors (NETs) are rare, but their worldwide incidence is gradually increasing. NETs are generally heterogeneous; however, in rare cases, they have been shown to change their phenotype (i.e., nonfunctional to functional or one functional phenotype to the addition of another functional phenotype). Here, we present two cases of liver metastatic NETs with phenotype transformation at the advanced stage that led to life-threatening events. Case presentation: A 73-year-old woman had a small intestinal nonfunctional NET with liver metastasis. After uncontrollable liver metastasis at the advanced stage, she developed duodenal perforation with hypergastremia. The patient was treated with octreotide and proton pump inhibitors and underwent endoscopic closure for duodenal perforation, but her general condition gradually deteriorated, and she died 2 weeks after duodenal perforation. Another patient, a 50-year-old man, had a functional NET (gastrinoma) with liver metastasis and duodenal ulcer. After uncontrollable liver metastasis at the advanced stage, he developed hypoglycemia. Although octoreotide and diazoxide were administrated for hyperalimentation, his hypoglycemia was uncontrollable, and he died after 4 months owing to general deterioration. Conclusion: The present cases show that advanced NETs with treatment-uncontrollable liver metastasis can transform their phenotype, specifically from a nonfunctional NET into a functional NET, and from one functional NET into the addition of another functional NET. These experiences suggest that the presence of treatment-resistant liver metastasis might be a hallmark of the potential to gain novel functions. [ABSTRACT FROM AUTHOR]

The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression. [ABSTRACT FROM AUTHOR]