2022 Seoul Consensus on Clinical Practice Guidelines for Functional Constipation.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

Vaseline gauze packing for the treatment of acute hemorrhagic rectal ulcer: Two case reports.

RATIONALE: Acute hemorrhagic rectal ulcer (AHRU) is a relatively rare condition characterized by sudden onset, painlessness, and massive hematochezia in patients with severe underlying conditions. When AHRU is encountered, they can often be successfully controlled endoscopically, though recurrent bleeding is common and an alternative treatment must be sought if initial endoscopic treatment fails. We report 2 cases of AHRU which were successfully treated with Vaseline gauze packing after the failure of endoscopic hemostasis. PATIENT CONCERNS: The first patient was an 88-year-old female that visited our emergency department with hematochezia. She was immobilized because of a left pelvic bone fracture resulting from a slip-down. The initial endoscopy showed fresh blood in her rectum with diffuse ulceration near the dentate line but no active bleeding. However, Massive hematochezia has recurred during conservation. A second patient, an 86-year-old female, debilitated because of schizophrenia, dementia, and past subdural hemorrhage, visited our emergency department, also with massive hematochezia. Her initial endoscopy showed deep ulceration near the dentate line. After admission, she experienced massive hematochezia from an AHRU with an exposed vessel but endoscopic hemostasis failed to control bleeding. DIAGNOSES: Both patients were diagnosed as AHRU based on the endoscopic findings. INTERVENTIONS: In both cases, Vaseline gauze packing was performed for bleeding control. OUTCOMES: After Vaseline gauze packing, no further bleeding occurred and follow-up endoscopy showed definitive improvement of ulcers. LESSONS: Based on these cases, we suggest that Vaseline gauze packing may be the alternative treatment for the AHRU which is located near the dentate line when endoscopic hemostasis is difficult or failed. Although further research is needed, Vaseline gauze packing has several potential advantages for the treatment of AHRU, especially in cases involving critically ill elderly patients.

Recognition and attitudes of Korean physicians toward fecal microbiota transplantation: a survey study.

BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) represents a treatment option for recurrent Clostridioides difficile infection (CDI). Recently, FMT has been investigated in various clinical settings other than CDI. This study examined Korean physicians' recognition of FMT and their attitudes toward this procedure. METHODS: An online questionnaire included questions on indications for FMT, the FMT process, physicians' attitudes toward FMT for the treatment of CDI and non-CDI diseases, and possible concerns. RESULTS: Finally, 107 physicians responded to this survey: 66 (61.7%) had experience of performing FMT, and 86 (80.4%) replied that they were willing to perform FMT for CDI. Two-thirds of physicians (63.6%, n = 68) would perform FMT for recurrent CDI on patients who had at least three recurrences. The most common obstacle to performing FMT for the treatment of CDI was the lack of regulations or guidelines (55.1%, n = 59). Seventy-seven (72.0%) physicians would consider FMT for non- CDI diseases when conventional treatment had failed. The most common obstacle for FMT for the treatment of non-CDI diseases was low treatment efficacy (57.0%, n = 61). CONCLUSION: Two-thirds of Korean physicians had experience of performing FMT, and many performed FMT for recurrent CDI. The results of this study will prove useful to researchers and practitioners in FMT in Korea.

Colo-colonic intussusception with post-polypectomy electrocoagulation syndrome: A case report.

BACKGROUND: Post-polypectomy electrocoagulation syndrome (PPES) can occur after colonoscopic polypectomy and is usually treated conservatively with a positive prognosis. Nevertheless, there can be cases with complications developing. CASE SUMMARY: A 58-year-old woman, who had no previous medical history, visited the Emergency Department of another hospital with symptoms of abdominal pain and fever, 1 d after multiple colonoscopic polypectomies. An abdominopelvic computed tomography (CT) scan demonstrated colo-colonic intussusception, and she was transferred to our hospital to consider an operation. CT showed colo-colonic intussusception with PPES and no evidence of obstruction. The physical examination showed localized mild tenderness on the right sided abdomen. The patient fasted and was admitted for treatment with intravenous antibiotics (piperacillin/tazobactam 4.5 g each 8 h, ornidazole 500 mg each 12 h). After admission, the symptoms got better and a follow-up CT scan demonstrated resolution of the PPES and intussusception. The patient was discharged on hospital day 9. CONCLUSION: Colo-colic intussusception can occur with PPES, and it can be properly treated conservatively.

Clinical Practice Guidelines for Fecal Microbiota Transplantation in Korea.

Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.

IgA vasculitis mimicking drug-induced skin reaction and infectious colitis in an elderly patient: A case report.

RATIONALE: Immunoglobulin A vasculitis (IgAV) in adults is rare and shows worse symptoms and prognosis. In real-life clinics, IgAV in elderly patients may be difficult to diagnose because of its rarity and other common diseases to consider. This study reports a case of IgAV mimicking drug-induced skin reaction in an elderly patient. PATIENT CONCERNS: A 74-year-old female without any underlying disease presented to our emergency department as she was suffering from lower abdominal pain and diarrhea for 3 weeks. The patient was diagnosed with infectious colitis, and antibiotic treatment was administered at a local clinic. At presentation, the patient had rashes on both lower legs that developed after the antibiotic treatment, which was assumed as a drug eruption. Although antibiotic treatment was continued, the patient had persistent abdominal pain, diarrhea, hematochezia, and rashes. Proteinuria was developed on urinalysis. DIAGNOSES: Infectious colitis, IgAV. INTERVENTIONS: Sigmoidoscopy revealed easily bleeding erythematous mucosal lesions from the descending colon to the rectum. IgAV was suspected, and thus skin biopsy was performed. Histological findings of the skin biopsy showed leukocytoclastic vasculitis, which is compatible with IgAV. A nonsteroidal anti-inflammatory drug was administered for abdominal pain. The patient showed persistent proteinuria and a systemic steroid (prednisolone 50 mg [1 mg/kg]) was started. OUTCOMES: After administration of the nonsteroidal anti-inflammatory drug, the patient's abdominal pain was resolved rapidly. Under systemic steroid treatment, the patient showed significant symptomatic improvements, and after 2 weeks, the skin and colonic mucosal lesions were completely resolved. LESSONS: We present a case of adult-onset IgAV, which was initially diagnosed with infectious colitis and drug eruption. The history of skin reaction development after antibiotic treatment and the rarity of IgAV in elderly patients masked the diagnosis of IgAV. Despite its rarity, IgAV should be highly suspected in elderly patients with rashes, proteinuria, and signs of colitis.

The HDAC1 Inhibitor CBUD-1001 Enhances TRAIL-induced Apoptosis in Colorectal Cancer Cells.

BACKGROUND/AIM: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-tumor agent. However, resistance to TRAIL has been reported in a number of clinical trials. In this study, we investigated the molecular mechanisms by which a novel histone deacetylase (HDAC) inhibitor, CBUD-1001, sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. MATERIALS AND METHODS: Apoptotic cell death induced by CBUD-1001 and/or TRAIL was assessed on human CRC cells using the MTT assay, FACS analysis and nuclei staining. The involved molecular mechanisms were explored through western blotting analysis. RESULTS: We demonstrated that combined with CBUD-1001, TRAIL significantly enhanced TRAIL-induced apoptosis in CRC cells via mitochondria-mediated pathways. We also found that hyper-acetylation of histone by CBUD-1001 treatment leads to up-regulation of death receptor (DR) 5 in a dose- and time-dependent manner. Furthermore, we identified that enhanced sensitivity to TRAIL by combination with CBUD-1001 depends on the MAPK/CHOP axis, being a key mediator of DR5. CONCLUSION: A novel HDAC inhibitor CBUD-1001 sensitizes TRAIL-induced apoptosis via up-regulation of DR5, and that CBUD-1001 and TRAIL combination treatment offers an effective strategy to overcome TRAIL resistance in CRC cells.

Efficient Stool Collection Methods for Evaluating the Diarrhea Score in Mouse Diarrhea Models.

BACKGROUND/AIM: The mouse diarrhea score is usually determined by evaluating stool consistency and shape. Thus, defecated stools should be collected without damage or contamination. The study aimed to develop improved mouse stool collection methods and diarrhea-scoring criteria. MATERIALS AND METHODS: We developed improved stool collection methods (paper towel methods) and compared them with previously used ones (stool collection using regular cages containing bedding chips or filter paper and metabolic cages). RESULTS: Compared to previously used methods, paper towel methods collected stools without bedding chips-induced contamination, mouse body/foot-induced damage, or sampling errors. When using paper towel methods, wet stools create water marks (diarrhea marks) on paper towels with strong water absorption capacity, by which diarrheal severity can be analyzed semi-quantitatively. To improve the objectivity in determining diarrhea scores, practical diarrhea-scoring criteria were also proposed. CONCLUSION: These results would be helpful to researchers facing difficulties in evaluating the mouse diarrhea score.

The Superoxide Dismutase Mimetic M40403, Improves 5-Fluorouracil-induced Small Intestinal Mucositis in a Mouse Model.

BACKGROUND/AIM: Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. MATERIALS AND METHODS: BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. RESULTS: M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. CONCLUSION: M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.

Early risk stratification for diffuse large B-cell lymphoma integrating interim Deauville score and International Prognostic Index.

The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.

Feasibility of Adopting the "Step-up Approach" in Managing Necrotizing Pancreatitis-induced Pancreatic-colonic Fistula.

Managing acute pancreatitis is clinically challenging because of the generally poor patient condition, the variety of treatment options depending on the severity and complications, and the uncertainty of outcomes. Recently, the step-up approach, which involves less invasive initial treatment and more invasive subsequent treatment, where necessary, has been proposed as the mainstay of managing pancreatitis. This paper presents a case of a 57-year-old man with severe acute pancreatitis, who developed an unexpected fistula in the rectum, which was treated successfully using the step-up approach. In managing this case, the authors faced clinical challenges in determining the infection of necrotic tissue in the early phase of the disease, the optimal timing and method of drainage, and the fistula closure or repair technique. Successful management of this case using the step-up approach validated current recommendations and suggests that it is a reasonable treatment strategy for pancreatic-colonic fistulas. This case also highlights the importance of an awareness that pancreatitis-associated complications can develop in an unexpected manner.

[Management of Acute Cholecystitis].

Acute cholecystitis is a common serious complication of gallstones. The reported mortality of acute cholecystitis is approximately 3%, but the rate increases with age or comorbidity of the patient. If appropriate treatment is delayed, complications can develop as a consequence with a grave prognosis. The current standard of care in acute cholecystitis is an early laparoscopic cholecystectomy with the appropriate administration of fluid, electrolyte, and antibiotics. On the other hand, the severity of the disease and patient's operational risk must be considered. In those with high operational risks, gall bladder drainage can be performed as an alternative. Currently percutaneous and endoscopic drainage are available and show clinical success in most cases. After recovering from acute cholecystitis, the patients who have undergone drainage should be considered for cholecystectomy as a definitive treatment. However, in elderly patients or patients with significant comorbidity, operational risks may still be high, making cholecystectomy inappropriate. In these patients, gallstone removal using the percutaneous tract or endoscopy may be considered.

Lymphocyte-mediated macrophage apoptosis during IL-12 stimulation.

In contrast to the well known immunostimulatory roles of IL-12, little has been known about its immunosuppressive roles. In the present study, IL-12-activated lymphocyte-mediated macrophage apoptosis was investigated by employing murine lymphocyte/macrophage cocultures. IL-12-activated lymphocytes and their culture supernatants induced an inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis in macrophages. The NO synthesis was markedly inhibited by blocking antibodies to IFN-γ and TNF-α, suggesting the key role of these lymphocyte cytokines in mediating the NO synthesis. The endogenously produced NO inhibited macrophage proliferation, and induced apoptosis in concordance with the accumulation of p53, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and DR5, and the activation of caspase-3, processes that were inhibited by N(G)-monomethyl-l-arginine, aminoguanidine (NO synthase inhibitors) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (an NO scavenger). These results were further supported by the findings obtained from the experiments employing IFN-γ-knockout and iNOS-knockout mice. Our study demonstrated a novel, non-contact-dependent mechanism of macrophage suppression by IL-12-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages due to endogenous NO synthesis induced by cytokines secreted from IL-12-activated lymphocytes.

Glutamine protects mice from acute graft-versus-host disease (aGVHD).

Despite current immunosuppressive therapies, acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, therapeutic effects of intraperitoneal glutamine (Gln) administration (1g/kg/day) in a mouse aGVHD model were evaluated. Gln administration significantly inhibited the GVHD-induced inflammation and tissue injury in the intestine, liver, skin and spleen. Gln therapy improved the score of clinical evidence of aGVHD and prolonged the median survival of aGVHD mice. Gln administration in aGVHD mice increased the fraction of Foxp3+/CD4+/CD25+ cells in the blood measured on day 7, and decreased the serum levels of tumor necrosis factor-α measured on days 7, 14 and 21 after aGVHD induction. These results demonstrated that Gln administration may be useful in protecting the host from aGVHD.

Rosiglitazone prevents graft-versus-host disease (GVHD).

The effect of rosiglitazone, an agonist of peroxisome proliferator-activated receptor-γ (PPARγ), was investigated in a mouse parent-to-F1 GVHD model. Rosiglitazone inhibited mixed lymphocyte reactions, inducing enhanced apoptosis in CD4+, CD8+, and B220+ cells, but not in NK1.1+, Mac-1+, CD4+/CD25+ and CD3+/NK1.1+ cells. Rosiglitazone administration prevented GVHD in the liver, skin, spleen and intestine. Rosiglitazone inhibited GVHD-induced increases in serum levels of tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6, and IL-12, and the GVHD-induced decreases in transforming growth factor-beta and IL-10. Immunophenotyping of splenic leukocytes demonstrated that while rosiglitazone treatment increased the population percentages of both donor and host CD4+/CD25+ and CD3+/NK1.1+ cells, the treatment resulted in lower fractions of both donor and host CD8+ cells. Rosiglitazone inhibited the GVHD-induced decreases in the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), as well as the GVHD-induced increase in the splenic p-Akt and nuclear factor-kappa B expression. These results indicate that rosiglitazone and PPARγ activation may be useful in protecting the host from GVHD.

Comparison of the Influence on the Liver Function Between Thyroid Hormone Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well-Differentiated Thyroid Cancer.

PURPOSE: An elevated thyroid stimulating hormone level (TSH) is essential to stimulate the uptake of radioiodine into thyroid remnants and metastases of thyroid cancer when a patient undergoes high-dose radioiodine therapy. Nowadays, recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used instead of the classic method of thyroid hormone withdrawal (THW). However, beyond the therapeutic effects, clinical differences between the two methods have not yet been clearly demonstrated. The aim of this work was to investigate the effects of the two methods, especially on liver function. METHODS: We identified 143 evaluable patients who were further divided into two groups: THW and rh-TSH. We first reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. We called these liver enzyme levels "base AST" and "base ALT." We also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for high-dose radioiodine therapy. We called these liver enzyme levels "follow-up AST" and "follow-up ALT." We compared the changes in base and follow-up liver enzyme levels and the other chemistry profiles between the two groups. RESULTS: The base AST and base ALT levels of the two groups were within normal range, and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up liver enzyme levels between the two groups showed significant differences. Patients in the THW group had higher follow-up AST and ALT levels than did the rh-TSH group. Patients in the THW group also had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However there were no statistically significant differences in ALP, total bilirubin, and triglyceride levels between the two groups. CONCLUSIONS: In this retrospective analysis of liver function, the use of rh-TSH for high-dose radioiodine therapy had less of an effect on liver function and cholesterol levels than dose thyroid hormone withdrawal. This suggests that rh-TSH can be used effectively and safely especially for patients with metabolic syndrome.