Use of Tumguide® in the Insertion of a Nasogastric Tube Into the Stomach of a Patient With Creutzfeldt-Jakob Disease in a Nursing Home: A Case Report.

A 77-year-old woman exhibited a rapid progression of dementia and declining physical function and, over a period of about four months, reached a state of akinetic mutism. A final diagnosis of Creutzfeldt-Jakob disease (CJD) was made. A nasogastric tube was inserted into the stomach, and then it was confirmed on X-ray that the end of the tube was in the correct position. She was discharged to a nursing home, where she received home medical care after discharge. One month after the nasogastric tube insertion, Tumguide® was used to assist in replacing the tube at this home. In home care settings where an X-ray machine may not be available, Tumguide® may assist with nasogastric tube insertion.

Clinical Features of Hypoxemia Due to Infection Under Home-Based Medication During the COVID-19 Pandemic Period.

BACKGROUND: Despite the growing demand for home-based medication during the COVID-19 pandemic period, there remains scarce evidence of hypoxemic infection in home-care settings. In this study, we investigated the clinical features of hypoxemic respiratory failure due to infection during the period under home-based medication (defined as 'home-care-acquired infection'). METHODS: This retrospective observational study enrolled patients with home-care-acquired infection, other than COVID-19, in two home-care clinics in Sapporo, Japan, between April 2020 and May 2021 (the early phase of the COVID-19 pandemic). The participants were divided into two groups according to whether they required additional home oxygen therapy, and were compared to assess the predictors of hypoxemic respiratory failure. Furthermore, the clinical features were compared with those in patients aged >60 years with COVID-19 who were admitted to Toyama University Hospital during the same period. RESULTS: A total of 107 patients with home-care-acquired infections were included in the study (median age, 82 years). Twenty-two patients required home oxygen therapy, and 85 did not. Thirty-day mortality rates were 32% and 8%. Among the patients in the hypoxemia group, none had desired a care-setting transition, following the advanced care planning. Multivariable logistic regression analysis showed that initial antibiotic treatment failure and malignant disease were independently associated with hypoxemic respiratory failure (odds ratio, 7.28 and 7.10; p=0.023 and p<0.005, respectively). In comparison with hypoxemia in the COVID-19 cohort, the lower incidence of febrile co-habitants and earlier onset of hypoxemia were significant in those due to home-care-acquired infection. CONCLUSION: This study demonstrated that hypoxemia due to home-care-acquired infection was characterized by distinct features, possibly different from those due to COVID-19 in the early pandemic period.

HOPS-R01 phase II trial evaluating neoadjuvant S-1 therapy for resectable pancreatic adenocarcinoma.

Although neoadjuvant therapy (Nac) is recommended for high-risk resectable pancreatic cancer (R-PDAC), evidence regarding specific regimes is scarce. This report aimed to investigate the efficacy of S-1 Nac for R-PDAC. In a multicenter phase II trial, we investigated the efficacy of Nac S-1 (an oral fluoropyrimidine agent containing tegafur, gimeracil, and oteracil potassium) in R-PDAC patients. The protocol involved two cycles of preoperative S-1 chemotherapy, followed by surgery, and four cycles of postoperative S-1 chemotherapy. Two-year progression-free survival (PFS) rates were the primary endpoint. Overall survival (OS) rates and median survival time (MST) were secondary endpoints. Forty-nine patients were eligible, and 31 patients underwent resection following Nac, as per protocol (31/49; 63.3%). Per-protocol analysis included data from 31 patients, yielding the 2-year PFS rate of 58.1%, and 2-, 3-, and 5-year OS rates of 96.8%, 54.8%, and 44.0%, respectively. MST was 49.2 months. Intention-to-treat analysis involved 49 patients, yielding the 2-year PFS rate of 40.8%, and the 2-, 3-, and 5-year OS rates of 87.8%, 46.9%, and 33.9%, respectively. MST was 35.5 months. S-1 single regimen might be an option for Nac in R-PDAC; however, the high drop-out rate (36.7%) was a limitation of this study.

Down-regulation of RalGTPase-Activating Protein Promotes Colitis-Associated Cancer via NLRP3 Inflammasome Activation.

BACKGROUND & AIMS: Ral guanosine triphosphatase-activating protein α2 (RalGAPα2) is the major catalytic subunit of the negative regulators of the small guanosine triphosphatase Ral, a member of the Ras subfamily. Ral regulates tumorigenesis and invasion/metastasis of some cancers; however, the role of Ral in colitis-associated cancer (CAC) has not been investigated. We aimed to elucidate the role of Ral in the mechanism of CAC. METHODS: We used wild-type (WT) mice and RalGAPα2 knockout (KO) mice that showed Ral activation, and bone marrow chimeric mice were generated as follows: WT to WT, WT to RalGAPα2 KO, RalGAPα2 KO to WT, and RalGAPα2 KO to RalGAPα2 KO mice. CAC was induced in these mice by intraperitoneal injection of azoxymethane followed by dextran sulfate sodium intake. Intestinal epithelial cells were isolated from colon tissues, and we performed complementary DNA microarray analysis. Cytokine expression in normal colon tissues and CAC was analyzed by quantitative polymerase chain reaction. RESULTS: Bone marrow chimeric mice showed that immune cell function between WT mice and RalGAPα2 KO mice was not significantly different in the CAC mechanism. RalGAPα2 KO mice had a significantly larger tumor number and size and a significantly higher proportion of tumors invading the submucosa than WT mice. Higher expression levels of matrix metalloproteinase-9 and matrix metalloproteinase-13 were observed in RalGAPα2 KO mice than in WT mice. The expression levels of interleukin 1ß, NLRP3, apoptosis associated speck-like protein containing a CARD, and caspase-1 were apparently increased in the tumors of RalGAPα2 KO mice compared with WT mice. NLRP3 inhibitor reduced the number of invasive tumors. CONCLUSIONS: Ral activation participates in the mechanism of CAC development via NLRP3 inflammasome activation.

Diversity of Gut Microbiota Affecting Serum Level of Undercarboxylated Osteocalcin in Patients with Crohn's Disease.

Several reports have indicated a possible link between decreasing plasma levels of vitamin K and bone mineral density. It has been suggested that intestinal bacteria contribute to maintenance of vitamin K. Several factors are involved in the reduction of vitamin K in patients with Crohn's disease (CD). We aimed to assess the relationship between gut microbiota and alternative indicators of vitamin K deficiency in patients with CD. We collected the feces of 26 patients with clinically inactive CD. We extracted 16S rRNA from the intestinal bacteria in the feces and amplified it by polymerase chain reaction. The generated polymerase chain reaction product was analyzed using a 16S metagenomic approach by Illumina Miseq platform. Serum undercarboxylated osteocalcin concentration was used as an alternative indicator of vitamin K deficiency. There was a significant negative correlation between serum undercarboxylated osteocalcin and mean Chao1 index in cases of low activity. The diversity of the gut microbiota was significantly lower, and Ruminococcaceae and Lachnospiraceae were significantly decreased in the vitamin K-deficient group in comparison to the vitamin K-normal group. Taken together, these data suggested the significance of investigating the gut microbiota even in patients with clinically inactive CD for improving patients' vitamin K status.

The Etiology of Pancreatic Manifestations in Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic chronic and recurrent condition that comprises Crohn's disease and ulcerative colitis. A pancreatic lesion is one of the extraintestinal lesions in patients with IBD. Acute pancreatitis is the representative manifestation, and various causes of pancreatitis have been reported, including those involving adverse effects of drug therapies such as 5-aminosalicylic acid and thiopurines, gall stones, gastrointestinal lesions on the duodenum, iatrogenic harm accompanying endoscopic procedures such as balloon endoscopy, and autoimmunity. Of these potential causes, autoimmune pancreatitis (AIP) is a relatively newly recognized disease and is being increasingly diagnosed in IBD. AIP cases can be divided into type 1 cases involving lymphocytes and IgG4-positive plasma cells, and type 2 cases primarily involving neutrophils; the majority of AIP cases complicating IBD are type 2. The association between IBD and chronic pancreatitis, exocrine pancreatic insufficiency, pancreatic cancer, etc. has also been suggested; however, studies with high-quality level evidence are limited, and much remains unknown. In this review, we provide an overview of the etiology of pancreatic manifestation in patients with IBD.

Therapeutic Efficacy and Adverse Events of Tacrolimus in Patients with Crohn's Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Only a few randomized controlled trials (RCTs) and some uncontrolled trials have reported the efficacy and adverse events (AEs) of tacrolimus (Tac) in patients with refractory Crohn's disease (CD). The aim of this study was to undertake a systematic review and meta-analysis of the therapeutic efficacy and AEs of Tac in patients with CD. METHODS: We investigated studies reporting the therapeutic efficacy of Tac in patients with CD from 1950 until December 2017. Study subjects were categorized into three groups: systemic administration of Tac for patients with luminal CD (Group 1); systemic administration of Tac for patients with perianal CD (Group 2); and topical administration of Tac for patients with localized CD (Group 3). The primary endpoint of this study was the remission rate. Secondary endpoints were partial response rate, factors related to remission, and the incidence of AEs. RESULTS: The remission rate of Group 1, 2, and 3 was 37.1, 32.0, and 22.7%, respectively. The partial response rate of those was 42.3, 42.9, and 44.3%, respectively. In addition, the incidence of AEs of those was 50.9, 65.5, and 40.0%, respectively. No life-threatening AEs were observed in any study. CONCLUSION: This systematic review and meta-analysis demonstrated that Tac therapy was effective for subpopulation of CD patients and that the incidence of AEs was tolerable. Therefore, Tac therapy should be considered an option for patients with CD. However, there have been few well-designed RCTs on this subject and further studies are required.

Current clinical issue of skin lesions in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with a number of extraintestinal complications, including skin lesions. Most reports have shown that skin lesions are found in 10-15% of IBD cases, although this depends on the definition of skin lesions. The representative skin lesions in patients with IBD are erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, and so on. These lesions are often associated with IBD progression, and intestinal lesions in particular require appropriate treatment. Recently, another clinical issue regarding skin lesions in patients with IBD, a so-called paradoxical reaction, during the treatment with anti-tumor necrosis factor (TNF)-α agents has emerged. These reactions are termed paradoxical reactions because the skin lesions sometimes resemble psoriasis, although the anti-TNF-α agents have been historically used to treat psoriasis. Paradoxical reactions are reportedly found in approximately 5-10% of patients using anti-TNF-α agents and are no longer rare. Now that the use of biologics is at its culmination, reports regarding paradoxical reactions are predicted to increase in number; thus, we must recognize skin lesions with IBD patients including this type of adverse events and manage them appropriately while consulting with dermatologists.

Gastric Xanthomas and Fundic Gland Polyps as Endoscopic Risk Indicators of Gastric Cancer.

Background/Aims: Fundic gland polyps (FGPs), hyperplastic polyps (HPs), and xanthomas (XTs) are common benign gastric lesions that can be diagnosed by endoscopic appearance alone in most cases. The aim of this study was to evaluate associations between gastric cancer and these benign lesions. Methods: Two expert endoscopists reviewed a series of gastroscopy images. FGPs, HPs, and XTs were diagnosed by endoscopic appearance, whereas all gastric cancers were confirmed pathologically. Results: Of the 1,227 patients reviewed, 114 (9.3%) had a concurrent or past history of gastric cancer. The overall prevalences of FGPs, HPs and XTs were 9.4%, 6.3% and 14.2%, respectively. HPs and XTs coexisted in 1.6% of patients, whereas other combinations were rarer. XTs were observed in 39.3% and 11.5% of patients with and without gastric cancer, respectively (p<0.001). In contrast, no gastric cancer patients had FGPs, whereas 10.4% of patients without cancer had FGPs (p<0.001). The prevalence of HPs was similar between the two groups (8.8% and 6.0% of patients with and without cancer, respectively, p=0.29). Multivariate and Mantel-Haenszel analyses demonstrated that XTs were positively associated and FGPs were negatively associated with gastric cancer. Conclusions: XTs and FGPs might be useful as endoscopic risk indicators for monitoring gastric cancer.

Chronic intestinal pseudo-obstruction due to al amyloidosis: a case report and literature review.

A 59-year-old woman presented to our hospital with a 6-month history of nausea, weight loss, and abdominal distension. Physical examination revealed abdominal distension without tenderness, and edema, numbness, and multiple peripheral neuropathy in the limbs. Blood test results showed anemia, hypoproteinemia, and hypoalbuminemia. Immunoelectrophoresis detected kappa-type Bence-Jones protein in both the serum and urine. Bone marrow examination did not reveal an increase of plasma cells. Computed tomography showed intestinal distension and retention of intestinal contents. No obstructive intestinal lesions were observed. Lower gastrointestinal endoscopy showed a decrease in the vascular visibility of the rectal mucosa. Histological findings showed amyloid deposition, which was positive for amyloid light-chain (AL) κ. Thus, she was diagnosed with chronic intestinal pseudo-obstruction (CIPO) due to gastrointestinal and neurological involvement of AL amyloidosis. Her abdominal symptoms were gradually improved by the insertion of an ileus tube and medication. Although we recommended chemotherapy for stopping her disease progression, she did not want to receive it. She died 1 year later because of her pneumonia. We should keep in mind that amyloidosis is an important cause of CIPO. Histopathological examination by endoscopic biopsy is required for exact diagnosis and appropriate treatment for CIPO due to amyloidosis.

Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease.

Autophagy, an intracellular degradation mechanism, has many immunological functions and is a constitutive process necessary for maintaining cellular homeostasis and organ structure. One of the functions of autophagy is to control the innate immune response. Many studies conducted in recent years have revealed the contribution of autophagy to the innate immune response, and relationships between this process and various diseases have been reported. Inflammatory bowel disease is an intractable disorder with unknown etiology; however, immunological abnormalities in the intestines are known to be involved in the pathology of inflammatory bowel disease, as is dysfunction of autophagy. In Crohn's disease, many associations with autophagy-related genes, such as ATG16L1, IRGM, NOD2, and others, have been reported. Abnormalities in the ATG16L1 gene, in particular, have been reported to cause autophagic dysfunction, resulting in enhanced production of inflammatory cytokines by macrophages as well as abnormal function of Paneth cells, which are important in intestinal innate immunity. In this review, we provide an overview of the autophagy mechanism in innate immune cells in inflammatory bowel disease.

Clinicopathological comparison between acute gastrointestinal-graft-versus-host disease and infectious colitis in patients after hematopoietic stem cell transplantation.

The aim of this study is to elucidate the differences of the clinicopathological characteristics between acute gastrointestinal (GI)-graft-versus-host disease (GVHD) and infectious colitis (IC) after hematopoietic stem cell transplantation (HSCT). Of the 282 patients who underwent HSCT at our institution between January 1991 and December 2015, we could investigate 182 patients in detail. Of the 182 patients, we selected those who underwent colonoscopy and were diagnosed with acute GI-GVHD or IC after HSCT. Patients' backgrounds, colonoscopic findings, and pathological findings were retrospectively analyzed. There were 30 patients who had colonoscopy performed and diagnosed with acute GI-GVHD or IC after HSCT. Of the 30 patients, 20 had acute GI-GVHD and 10 had IC. All the cases of acute GI-GVHD were diagnosed by endoscopic biopsy and 4 of the IC patients had Clostridium difficile associated colitis. In the IC group, the period from the transplantation up to diagnosis was significantly shorter than acute GI-GVHD group (10.0 days vs. 43.2 days, p = 0.03). In the acute GI-GVHD group, tortoiseshell-like mucosal patterns were significantly more common than the IC group (70% vs. 0%, p < 0.001). Furthermore, there were some cases presenting normal mucosal appearance despite the diagnosis with acute GI-GVHD by pathological findings. Clinically, we should consider IC when abdominal symptoms appeared in the early period after HSCT. Endoscopically, tortoiseshell-like mucosal pattern was a characteristic feature of acute GI-GVHD. In addition, it is essential to perform mucosal biopsy for diagnose of acute GI-GVHD even in patients showing the normal mucosal appearance.

Natural history of gastric cancer from a retrospective review of endoscopic images of older patients with interval gastric cancer.

AIM: Interval gastric cancers (IGC) are defined as those diagnosed after negative results of endoscopy carried out within the past 10 years. We aimed to investigate the characteristics of IGC and the natural history of gastric cancer (GC) from a retrospective view of endoscopic images of older patients with IGC. METHODS: We retrospectively reviewed endoscopic images of 240 patients with GC who were aged >60 years. We compared past endoscopic images with newer ones, in which GC was diagnosed. IGC were classified into two categories: missed cancers and new cancers. RESULTS: Of the 240 patients with GC, 32 had past endoscopic images that qualified for a precise review. A total of 14 cases involved new cancers, whereas 18 involved missed cancers. Most of the IGC were stage I for at least 2 years; however, a small subset was unresectable at >2 years after a negative endoscopy. Furthermore, the rate of endoscopic treatment was significantly higher for IGC compared with that for non-IGC. CONCLUSIONS: In people aged >60 years, most IGC remain in an early stage for at least 2 years; however, at >2 years after a negative endoscopy, some are unresectable. These results suggest that most early-stage GC will not develop into advanced cancers within 2 years; thus, a 2-year interval might be within the permissible range for patients with negative endoscopy results for any lesions. Geriatr Gerontol Int 2018; 18: 997-1002.

Can Trainees Safely Perform Endoscopic Treatments for Common Bile Duct Stones? A Single-center Retrospective Study.

Objective There are no reports on whether or not trainees can safely carry out endoscopic procedures for the removal of common bile duct (CBD) stones. The aim of this study was to investigate the efficacy and safety of endoscopic treatments for CBD stones by trainees. Methods Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 1,016 consecutive patients at our institution during the 6-year study period. The endoscopically treated patients with CBD stones were included in this study. Physicians who had experienced ≥300 ERCP procedures were defined as experts, while those who had experienced <300 procedures were defined as trainees. The trainees were replaced by an expert when they could not achieve the established criteria. Patients were divided into the following three groups to retrospectively examine the patients' backgrounds, details of endoscopic treatments, and intra-/post-operative complications: Group A, completed by trainees under supervision of an expert; B, treated by an expert who switched in for a trainee in the middle of the procedure; and C, completed by an expert. Results A total of 325 patients with CBD stones underwent endoscopic treatments. The number included in Groups A, B, and C was 176, 102, and 47, respectively. The bile duct catheter insertion successes rates for Groups A, B, and C were 99.0%, 97.1%, and 100% (p=0.09), and the complete stone removal rates were 94.2%, 94.8%, and 100%, respectively (p=0.07), showing no significant difference among the three groups. Furthermore, the frequency of intra-/post-operative complications was not significantly different among the three groups (p=0.48, p=0.12, respectively). Conclusion This study showed that trainees could safely perform endoscopic procedures in accordance with our facility's criteria during ERCP.

A case of a rectal stricture related to ischemic proctitis following rupture of an aortic aneurysm.

Background and study aims Ischemic proctitis is a rare disease and comprises 2 % to 5 % of cases of ischemic colitis, because the rectum has abundant blood supply and rich collaterals. Herein, we report a case of a 73-year-old male patient with a pronounced rectal stricture caused by ischemic proctitis resulting from an abdominal aortic rupture and treated by endoscopic balloon dilation therapy. To date, only 3 cases of rectal stricture related to ischemic proctitis including our case have been reported, and this is the first case of rectal stricture related to ischemic proctitis, which was successfully treated by endoscopic balloon dilation.

A case of nodal malignant lymphoma presenting with arterial bleeding related to its duodenal penetration.

A 62-year-old man with a chief complaint of dysphagia visited our hospital. Enhanced computed tomography showed the tumor near the duodenal wall and lymphadenopathy in the left supraclavicular fossa and para-aortic lymph node. Upper gastrointestinal endoscopy showed an ulcer accompanied with a fistula in the anterior wall of duodenal bulb, suggesting that the tumor penetrated into duodenal wall. Biopsy from the lymph node in the left supraclavicular fossa indicated diffuse large B-cell lymphoma. Although chemotherapy was planned, massive arterial bleeding occurred from the part of duodenal penetration. Endoscopic hemostasis was unsuccessfully performed. Therefore, we performed transcathether arterial embolization for hemostasis. After the procedure, the patient received six cycles of chemotherapy, and he achieved complete response. He has been alive 5 years without recurrence. There were many cases of gastrointestinal bleeding from primary gastrointestinal lymphomas, while there were few cases with nodal involvement by malignant lymphoma resulting in bleeding from gastrointestinal tract. We herein report a case of duodenal bleeding by nodal involvement of diffuse large B-cell lymphoma with review of literature.

Efficacy and safety of endoscopic procedures for common bile duct stones in patients aged 85 years or older: A retrospective study.

The Endoscopic procedures for common bile duct (CBD) stones are reportedly safe in the elderly patients. However, the definition of the elderly is different in each report. If the elderly are defined as people aged 85 years or older, data on the effectiveness and safety of endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones are limited. This study investigated the efficacy and safety of endoscopic procedures for CBD stones in patients aged 85 years or older. 1,016 consecutive ERCP procedures were performed at our institution from January 2009 to December 2014. Of these, 235 cases with CBD stones were finally analyzed. Group A patients were younger than 85 years and Group B patients were 85 years or older. Patient background, details of endoscopic therapy, complications, and related factors were retrospectively reviewed for 185 cases in Group A, and 50 cases in Group B. Patients in Group B showed high rates of dementia and cerebrovascular disorders and larger CBD stones and diameters, in comparison with patients in Group A. The complete removal rate of bile duct stones was slightly higher in Group A. However, there was no difference between the two groups in recurrence rate of CBD stones, complication and mortality rates, and length and cost of hospitalization. Despite some differences between the two groups, endoscopic procedures for CBD stones in patients aged 85 years or older can be performed effectively and safely without increasing medical costs.

Systemic amyloidosis with gastrointestinal involvement: Diagnosis from endoscopic and histological views.

Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. Although a mucosal biopsy is necessary for a definitive diagnosis and several studies have reported positive results for each possible biopsy site, there remain many unclear features in various aspects. This review focuses on the current literature to determine a better understanding of the diagnosis from endoscopic and histological views in patients with systemic amyloidosis with gastrointestinal involvement. A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed. Endoscopic findings vary based on the organ and the depositing amyloids. A fine granular appearance or polypoid protrusions are likely to occur in the duodenum. AL, Aß2M, and ATTR amyloids are likely to deposit submucosally, while AA amyloid is easily deposited in the superficial layer of the mucous membrane. Furthermore, it is necessary to consider the collection of biopsy specimens from the duodenum, which has high positive biopsy rates. However, the difference in the positive biopsy rates depends on whether endoscopic findings are available or whether the appropriate number has not been fully elucidated. A duodenal biopsy is strongly recommended to confirm the deposition of amyloid in patients with systemic amyloidosis having gastrointestinal involvement. Because amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are required; gastroenterologists and endoscopists play important roles.