Summary Background The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral ...diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. Methods This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. Findings Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 38·0%; 95% CI 26·7–49·3 of 71 patients, placebo group 35 56·5%; 95% CI 44·1–68·8 of 62; p=0·034, risk ratio RR 0·67 95% CI 0·47–0·97; adenomas: metformin group 22 30·6%; 95% CI 19·9–41·2 of 71 patients, placebo group 32 51·6%; 95% CI 39·2–64·1 of 62; p=0·016, RR 0·60 95% CI 0·39–0·92). The median number of polyps was zero (IQR 0–1) in the metformin group and one (0–1) in the placebo group (p=0·041). The median number of adenomas was zero (0–1) in the metformin group and zero (0–1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. Interpretation The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. Funding Ministry of Health, Labour and Welfare, Japan.
Serrated polyps have recently been reported in patients with ulcerative colitis (UC); however, their prevalence and detailed characteristics remain unclear.
The prevalence and clinicopathological and ...biological characteristics of serrated polyps in patients with UC were retrospectively examined in a single tertiary inflammatory bowel disease center in Japan from 2000 to 2020.
Among 2035 patients with UC who underwent total colonoscopy, 252 neoplasms, including 36 serrated polyps (26 in colitis-affected segments, 10 in colitis-unaffected segments), were identified in 187 patients with UC. The proportion of serrated polyps was 1.8% (36/2035). Serrated polyps in colitis-affected segments were common with extensive colitis (88%), history of persistent active colitis (58%), and long UC duration (12.1 years). Serrated polyps in colitis-affected segments were more common in men (88%). Of the 26 serrated polyps in colitis-affected segments, 15, 6, and 5 were categorized as sessile serrated lesion-like dysplasia, traditional serrated adenoma-like dysplasia, and serrated dysplasia not otherwise specified, respectively. Sessile serrated lesion-like dysplasia was common in the proximal colon (67%) and with BRAF mutation (62%), whereas traditional serrated adenoma-like dysplasia and serrated dysplasia not otherwise specified were common in the distal colon (100% and 80%, respectively) and with KRAS mutations (100% and 75%, respectively).
Serrated polyps comprised 14% of the neoplasias in patients with UC. Serrated polyps in colitis-affected segments were common in men with extensive and longstanding colitis, suggesting chronic inflammation in the development of serrated polyps in patients with UC.
Background
Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases ...unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases.
Methods
We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups.
Results
The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for
Helicobacter pylori
. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (
TP53
mutation) of the tumors was relatively frequent in the VLR-group.
Conclusions
Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.
Why inflammation is common in ileal pouches with ulcerative colitis (UC) is unclear. We therefore clarified the morphological changes in pouches and afferent limbs (AL) of patients with UC and ...explored the relationship between these findings. We evaluated the morphological findings (histological and endoscopic inflammation as the Pouchitis Disease Activity Index PDAI histology subscore hPDAI and endoscopy subscore ePDAI, inflammatory bowel disease IBD-specific findings using the IBD score S
, colonic metaplasia using the colonic metaplasia score CMS, and goblet cell GC ratio) in the pouch and AL of patients with UC. A total of 261 pouchoscopies were analyzed. The pouch body had a higher hPDAI (p < 0.001), S
(p < 0.001), CMS (p < 0.001), GC ratio (p < 0.001), and ePDAI (p < 0.001) than the AL. The hPDAI was correlated with the S
(Spearman's coefficient r = 0.538; p < 0.001), CMS (r = 0.687; p < 0.001), and the ePDAI (r = 0.552; p < 0.001), but not with GC ratio (r = 0.175; p < 0.001) or the pouch usage duration (r = -0.057; p = 0.107). The incidence of histological inflammation was higher in specimens showing basal plasmacytosis with severe mononuclear cell infiltration (BP) than in those without BP (odds ratio OR 6.790, p < 0.001), BP was commonly found with crypt hyperplasia (OR 3.414, p < 0.001) and the crypt length correlated with neutrophil infiltration (r = 0.469; p < 0.001). Histological inflammation, colonic metaplasia, the GC ratio, endoscopic inflammation, and IBD-specific findings were commonly present in the pouch than in the AL. Histological inflammation occurs with IBD-specific findings and colonic metaplasia, and these signify endoscopic inflammation.
Persistent
(
) infection causes chronic inflammation, atrophy of the gastric mucosa, and a high risk of developing gastric cancer. In recent years, awareness of eradication therapy has increased in ...Japan. As
infections decrease, the proportion of gastric cancers arising from
uninfected gastric mucosa will increase. The emergence of gastric cancer arising in
uninfected patients though rarely reported, is a concern to be addressed and needs elucidation of its clinicopathological features.
To evaluate the clinicopathological features of early gastric cancer in
-uninfected patients.
A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019. Of these, 30 lesions in 30 patients were diagnosed as
-uninfected gastric cancer (HpUIGC). We defined a patient as
-uninfected using the following three criteria: (1) The patient did not receive treatment for
, which was determined by investigating medical records and conducting patient interviews; (2) Lack of endoscopic atrophy; and (3) The patient was negative for
after being tested at least twice using various diagnostic methods, including serum anti-
-IgG antibody, urease breath test, rapid urease test, and microscopic examination.
The frequency of HpUIGC was 1.2% (30/2462) for the patients in our study. The study included 19 males and 11 females with a mean age of 59 years. The location of the stomach lesions was divided into three sections; upper third (U), middle third (M), lower third (L). Of the 30 lesions, 15 were U, 1 was M, and 14 were L. Morphologically, 17 lesions were protruded and flat elevated type (0-I, 0-IIa, 0-IIa + IIc), and 13 lesions were flat and depressed type (0-IIb, 0-IIc). The median tumor diameter was 8 mm (range 2-98 mm). Histological analysis revealed that 22 lesions (73.3%) were differentiated type.The HpUIGC lesions were classified into fundic gland type adenocarcinoma (7 cases), foveolar type well-differentiated adenocarcinoma (8 cases), intestinal phenotype adenocarcinoma (7 cases), and pure signet-ring cell carcinoma (8 cases). Among 30 HpUIGCs, 24 lesions (80%) were limited to the mucosa; wherein, the remaining 6 lesions showed submucosal invasion. One of the submucosal invasive lesions showed more than 500 μm invasion. The mucin phenotype analysis identified 7 HpUIGC with intestinal phenotype and 23 with gastric phenotype.
We elucidated the clinicopathological characteristics of HpUIGC, revealing recognition not only undifferentiated-type but also differentiated-type. In addition, intestinal phenotype tumors were also observed and could be an important tip.
Recently, a new entity “myoepithelioma‐like tumor of the vulvar region (MELTVR)” was proposed as a rare mesenchymal neoplasm arising in vulvar regions of adult women. While MELTVRs morphologically ...resemble soft tissue myoepitheliomas and extraskeletal myxoid chondrosarcomas, they have a unique immunohistochemical profile (positive for epithelial membrane antigen and estrogen receptor, negative for S100 protein and glial fibrillary acidic protein, and loss of INI1/SMARCB1 expression), and lack EWSR1 and NR4A3 gene rearrangement, as seen by fluorescence in situ hybridization. MELTVRs are usually well‐demarcated tumors, with no reports of extensive infiltrative growth. In the current report, we present an unusual case of MELTVR showing infiltrative growth and harboring only a few estrogen receptor‐positive cells, which might indicate a variation in this rare tumor.
Purpose
To estimate the role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI) in predicting hypervascularization outcome of non-hypervascular hypointense hepatic ...lesions in high-risk patients for hepatocellular carcinoma (HCC).
Methods
Under the premise of non-hyperenhance in arterial phase (AP) and hypointensity in hepatobiliary phase (HBP) of EOB-MRI, 29 fresh lesions from 22 patients with chronic viral hepatitis (median (range) age: 69(57–82) years) were prospectively enrolled. During continuously followed-up by EOB-MRI, lesional vascularity in AP, the signal intensity (SI) ratios of lesions-to-parenchyma in HBP images (post-contrast ratio) and adjusted enhancement with reference of unenhanced images (EOB enhancement ratio) were examined.
Results
After 644 (220–2912) days of follow-up, 20 lesions changed into hyperenhancement in AP of EOB-MRI (hypervascularized group), while nine remained non-hyperenhanced (maintained non-hypervascular group). There is no statistical difference of post-contrast ratio at the initial detection. The post-contrast ratios in hypervascularized group were different between each follow-up time point when followed-up ≥ three (
P
< 0.01) and four (
P
< 0.05) times, and exposed a linear downward trend with time. Between the hypervascularized and maintained non-hypervascular groups, there were significant differences in the post-contrast ratio at endpoint for three-times’ follow-up (
P
< 0.001); and at the second (
P
= 0.037), third follow-up time points (
P
= 0.005), endpoint (
P
= 0.005) for four-times’ follow-up. EOB enhancement ratio showed inter-group difference only at endpoint for three-times’ follow-up (
P
= 0.008).
Conclusion
For non-hypervascular, HBP hypointense hepatic lesions, decreasing trend of SI in HBP may early predict unfavorable hypervascularized outcome.
Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed ...pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.
A 56-year-old, severely malnourished man presented with loss of consciousness due to hypoglycemia. Echocardiography revealed left ventricular apical ballooning, indicating takotsubo cardiomyopathy. ...Although his caloric intake was gradually increased to avoid refeeding syndrome, hypoglycemia was refractory, and repetitive glucose administration was required. On day 4 of admission, he developed severe refractory hypoglycemia with a progressive decrease in blood pressure. Consequently, pulseless ventricular tachycardia followed by pulseless electrical activity developed. Although venoarterial extracorporeal membrane oxygenation was introduced, the patient did not respond to the treatment and died. Autopsy revealed myocardial degeneration and contraction-band necrosis, indicative of takotsubo cardiomyopathy. No coronary stenosis was observed. The liver showed moderate hepatocyte atrophy and autophagosomes, consistent with starvation and not with refeeding syndrome. We speculated that refractory hypoglycemia induced extreme catecholamine secretion, which led to severe complications of takotsubo cardiomyopathy, such as fatal arrhythmia and extremely low cardiac output. Early recognition of these critically ill patients and timely therapeutic interventions, including strict glycemic control and adequate caloric intake, may improve patient outcomes.
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