Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?

BACKGROUND: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms. AIM: To clarify the stage at CRC diagnosis based on diagnostic routes. METHODS: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location. RESULTS: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups (P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49). CONCLUSION: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities.

Low-dose gemcitabine plus nab-paclitaxel versus standard-dose gemcitabine plus nab-paclitaxel in elderly patients with metastatic pancreatic cancer: A randomized Phase II trial.

Background and Aim: A multicenter, open-label randomized Phase II trial was conducted to determine whether low-dose gemcitabine plus nab-paclitaxel (GnP) could improve tolerability and show equivalent efficacy to the standard-dose GnP for elderly patients with metastatic pancreatic cancer. Methods: Consecutive patients aged ≥65 years with metastatic pancreatic cancer who presented at one of four Japanese referral centers between November 2016 and January 2021 were enrolled. The 60 patients were randomly assigned to low- or standard-dose groups with a 1:1 ratio. Patients in the low-dose GnP group received gemcitabine at a dose of 250 mg/m2 and nab-paclitaxel at 125 mg/m2. Results: Low-dose GnP significantly decreased the rate of cases requiring dose reduction (16.7% vs 63.3%). The response rate (36.7% vs 33.3%) and progression-free survival (7.3 vs 8 months) were comparable between the low- and standard-dose groups as determined by independent review. The difference in the median overall survival between the two groups was not significant (7.9 vs 12 months). The proportion of patients with hematologic and non-hematologic treatment-related adverse events was comparable between the two groups. Conclusion: Low-dose GnP had an equivalent efficacy to conventional therapy; however, it did not reduce adverse events.

Efficacy of antimicrobial therapy in patients with uncomplicated acute colonic diverticulitis: an updated systematic review and meta-analysis.

The need for antimicrobial therapy for uncomplicated acute diverticulitis of the colon remains controversial. We conducted a systematic review of the efficacy of antimicrobial agents against this disease, including new randomized controlled trials (RCTs) reported in recent years, and evaluated their efficacy using a meta-analytic approach. RCTs were searched using PubMed, EMBASE, Google Scholar, Cochrane Library, Ichushi-Web, and eight registries. Keywords were 'colonic diverticulitis', 'diverticulitis', 'antimicrobial agents', ''antibiotics, 'complication', 'abscess', 'gastrointestinal perforation', 'gastrointestinal obstruction', 'diverticular hemorrhage', and 'fistula'. Studies with antimicrobial treatment in the intervention group and placebo or no treatment in the control group were selected by multiple reviewers using uniform inclusion criteria, and data were extracted. Prevention of any complication was assessed as the primary outcome, and efficacy was expressed as risk ratio (RR) and risk difference (RD). A meta-analysis was performed using 5 RCTs of the 21 studies that were eligible for scrutiny in the initial search and which qualified for final inclusion. Three of these studies were not included in the previous meta-analysis. Subjects included 1039 in the intervention group and 1040 in the control group. Pooled RR = 0.86 (95% confidence interval, 0.58-1.28) and pooled RD = -0.01 (-0.03 to 0.01) for the effect of antimicrobial agents in reducing any complications. Recurrences, readmissions, and surgical interventions did not significantly show the efficacies of using antimicrobial agents. A meta-analysis of recently reported RCTs did not provide evidence that antimicrobial therapy improves clinical outcomes in uncomplicated acute diverticulitis of the colon.

Primary Retroperitoneal Mucinous Cystadenocarcinoma during Long-term Administration of Infliximab for the Treatment of Crohn's Disease.

We herein report a rare case of primary retroperitoneal mucinous cystadenocarcinoma (PRMC) in a 60-year-old man. The patient, who had been treated with infliximab for Crohn's disease of the colon for 13 years, was referred to our hospital for lower back pain. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging revealed multiple cystic lesions in the right retroperitoneum, the calcification of the cyst, and bone lesions. Bone and CT-assisted biopsies of the retroperitoneal lesions revealed poorly differentiated adenocarcinoma. The patient was diagnosed with PRMC with bone metastases using immunohistochemical staining and positron emission tomography/CT.

Dexmedetomidine is safe and effective for reducing intraprocedural pain in colorectal endoscopic submucosal dissection.

Objectives: Endoscopic submucosal dissection (ESD) is effective for the resection of colorectal intramucosal lesions. This study was performed to examine the safety and effectiveness of using dexmedetomidine (DEX) in the anesthesia regimen of patients with colorectal lesions undergoing ESD. Methods: We retrospectively examined 287 consecutive patients who underwent ESD for colorectal lesions in our institution from January 2015 to December 2021. Outcomes including the frequency of intraprocedural pain and adverse events were compared between the DEX and no DEX groups. Moreover, univariate and multivariate analyses were conducted for each clinical factor of intraprocedural pain. Intraprocedural pain was defined as patient-reported abdominal pain or body movement during the procedure. Results: The incidence of intraprocedural pain was significantly lower in the DEX than in the no DEX group (7% vs. 17%, p = 0.02). The incidence of hypotension was also significantly higher in the DEX group (7% vs. 0%, p = 0.01), but no cerebrovascular or cardiac ischemic events occurred. In the univariate analyses, the diameter of the resected specimen, procedure time, no use of DEX, and total midazolam dose was associated with intraprocedural pain. The midazolam dose and DEX administration were significantly negatively correlated and the diameter of resected specimen and procedure time were significantly positively correlated. Multivariate logistic regression showed that no use of DEX was independently associated with intraprocedural pain (p = 0.02). Conclusions: Adding DEX to the anesthesia regimen in patients undergoing colorectal ESD appears to be safe and effective for reducing intraprocedural pain.

Two cases of esophageal basaloid squamous cell carcinoma which achieved long-term survival by endoscopic submucosal dissection and additional chemoradiotherapy.

Herein, we report two rare basaloid squamous cell carcinoma (BSCC) cases. Esophagogastroduodenoscopy revealed a submucosal tumor-like lesion and a biopsied specimen showed a finding suspected of BSCC in both cases. Both lesions underwent endoscopic submucosal dissection with en bloc resection, and long-term survival was achieved using additional chemoradiotherapy. The standard treatment for BSCC has not been determined, and there are few reports of esophageal BSCC treated using endoscopic resection. Endoscopic submucosal dissection and additional chemoradiotherapy for superficial BSCC may be effective treatment options.

Longly-attached cap can contribute to en bloc underwater endoscopic mucosal resection of 20-30 mm colorectal intramucosal lesions.

Background and study aims Underwater endoscopic mucosal resection (UEMR) is effective for colorectal intramucosal lesions. The aim of this study was to evaluate whether a longly-attached cap in UEMR improves the en bloc resection rate for 20-30 mm lesions. Patients and methods We performed a retrospective study at a tertiary institute. Candidates for the study were systematically retrieved from an endoscopic and pathological database from October 2016 to December 2020. We assessed the procedural outcomes with UEMR for lesions ≥ 20 mm in size and the clinical factors contributing to en bloc resection. Results A total of 52 colorectal lesions that underwent UEMR were included. The median procedure time was 271 (66-1264) seconds. The en bloc resection rate and R0 resection rate were 75 % and 73 %, respectively. Intraprocedural perforation occurred in one (1.9 %) case, but no bleeding occurred. Delayed bleeding occurred in one (1.9%) case, but no delayed perforation occurred. Regarding tumor size, macroscopic type, tumor location, and the presence or absence of a history of abdominal operation, there was no significant difference between the en bloc resection and piecemeal resection groups. The visibility of the whole lesion, a longly-attached cap, and sessile serrated lesions were more frequently observed in the en bloc resection group than in the piecemeal resection group ( P  < 0.001, P  = 0.01, and P  = 0.04, respectively). Multivariate analysis showed that a longly-attached cap was the only independent factor associated with en bloc resection ( P  = 0.02). Conclusions A longly-attached cap might contribute to en bloc resection.

Association between antispasmodics and detection of lesions by screening esophagogastroduodenoscopy.

Background and Aim: Whether administration of antispasmodics as a component of premedication contributes to detection of lesions by screening esophagogastroduodenoscopy (EGDS) remains unclear. Our primary aim was to investigate this possibility. Methods: The cohort in this retrospective study comprised consecutive asymptomatic individuals who had undergone screening EGDS as part of a health check-up at the Japanese Red Cross Wakayama Medical Center from October 2015 to September 2020. The investigated lesions comprised esophageal squamous cell carcinoma or adenocarcinoma, gastric adenoma or adenocarcinoma, and duodenal adenoma or adenocarcinoma. Results: Targeted lesions were detected in 72 of 31 484 participants (0.23%), 18 260 and 13 224 of whom had received and not received pre-procedure antispasmodics, respectively. The rates of detection of lesions in these groups were 0.21% (38/18260) and 0.26% (34/13224), respectively (P = 0.40). Multivariate logistic regression analysis showed no association between administration of antispasmodics and rates of detection of targeted lesions [P = 0.24, Odds ratio (95% CI): 1.46 (0.78-2.75)]. Conclusions: Antispasmodics, which were administered to more than half of the study cohort, did not improve the rate of detection of targeted lesions.

Primary Hepatic Neuroendocrine Carcinoma with Thrombocytopenia Due to Diffuse Bone Marrow and Splenic Infiltration: An Autopsy Case.

An 82-year-old man with fever and back pain was referred to our hospital and was thus found to be thrombocytopenic. A bone marrow biopsy revealed the diffuse infiltration of poorly differentiated neuroendocrine carcinoma (NEC). Computed tomography revealed a large hepatic mass. Considering the risk of bleeding due to thrombocytopenia, a needle biopsy was not performed. The patient rapidly deteriorated and died 10 days after presentation. An autopsy confirmed the diagnosis of primary hepatic NEC, with diffuse metastasis to the spleen, bone marrow, and systemic lymph nodes. This is an extremely rare case of NEC presenting with thrombocytopenia due to extensive bone marrow and splenic infiltration.

Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

OBJECTIVE: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results. DESIGN: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours. RESULTS: Overall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, p<0.01). Subgrouping was also relevant with respect to tumour ingrowth (lower with covered stents for intrinsic tumours; 1.6% vs 27.7%, p<0.01) and stent migration (higher with covered stents for extrinsic tumours: 15.3% vs 2.5%, p<0.01). CONCLUSIONS: Due to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Outcome measures reported in abstracts of randomized controlled trials in leading clinical journals: A bibliometric study.

BACKGROUNDS: The CONSORT for Abstracts checklist published in 2008 recommends that authors report effect size for their studies. Meanwhile, the FDA strongly recommends reporting both ratio and difference measures. However, the measures of effect used in recent clinical trial reports remain unknown. This study is aimed to reveal trends regarding the measures of effect of interventions described in abstracts of recent randomized controlled trials (RCTs) in leading journals. METHODS: A bibliometric analysis of data was obtained by electronic searches. Human RCTs published in 2016 in the following five journals were searched using PubMed: Annals of Internal Medicine, British Medical Journal, Journal of American Medical Association, The Lancet, and New England Journal of Medicine. Main outcome is numbers of studies reporting each measure in their abstracts. RESULTS: Among abstracts of 334 articles, measures most frequently used were relative risk alone (n = 169), followed by absolute risk alone (n = 92), and raw data alone (n = 58). Reporting of the following measures was relatively limited: both ratio and difference measures (n = 8), raw data with ratio measures (n = 5), and raw data with difference measures (n = 2). None of the studies reported raw data with both ratio and difference measures. Only 15 articles described multiple measures of effect in their abstracts. CONCLUSIONS: More than half of the RCT abstracts published in the five leading journals in 2016 reported risk ratio alone to indicate effect size. Even abstracts in the five leading journals did not adhere fully to the CONSORT for Abstracts or FDA recommendations.

Bone metastasis as a recurrence of early papillary adenocarcinoma of the stomach.

Papillary adenocarcinomas of the stomach are rare and associated with a high rate of lymphovascular invasion and distant metastasis. However, the association between papillary adenocarcinoma and bone metastasis in gastric cancer remains largely unexplored. We report a rare case of bone metastasis as a recurrence of early papillary adenocarcinoma of the stomach after curative surgery. A 75-year-old man with a pedunculated polyp at the pylorus of the stomach was diagnosed with papillary adenocarcinoma after biopsy of the lesion, and the polyp was surgically resected. Pathohistological examination revealed intramucosal cancer without lymphovascular invasion or lymph node metastasis. Eight months after surgery, imaging studies showed osteolysis in the right sacrum, and the lesion was diagnosed as a bone metastasis after biopsy. The patient received palliative chemotherapy and radiotherapy for the bone metastasis, which resulted in relief of his leg pain. Subsequently, he was provided supportive care when his condition deteriorated, and he died 8 months after the diagnosis of bone metastasis. Our case shows that bone metastasis should not be overlooked, even though it is rare in gastric cancer patients. Papillary adenocarcinoma of the stomach should be carefully followed up through imaging examinations, even after curative resection.

Status of use of protease inhibitors for the prevention and treatment of pancreatitis after endoscopic retrograde cholangiopancreatography: An epidemiologic analysis of the evidence-practice gap using a health insurance claims database.

Existing evidence suggests that protease inhibitors (PIs) used to prevent or treat pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) are ineffective, and their use is not recommended by clinical practice guidelines. However, in Japan, PIs are administered with the aim to prevent or treat post-ERCP pancreatitis. This study aimed to clarify the gap between guideline recommendations and contents of practice. We used the health insurance claims database of Japan Medical Data Center. Among patients who had undergone ERCP, those with acute pancreatitis or post-ERCP pancreatitis recorded in claims as disease names were defined as post-ERCP pancreatitis patients. The study period was divided into three terms according to the date of publication of clinical practice guidelines for acute pancreatitis. Among 2,945 patients who had undergone ERCP, 2,847 were eligible for analysis. Of these, 1,375 (48.3%) patients had claims with pancreatitis recorded as the disease name; PIs were prescribed to 1,238 (90.0%). Rates of prescription of PIs were 72.3% in 2005-07, 70.9% in 2008-09, and 83.6% in 2010-15, showing a significant increase (p < 0.001). In conclusion, PIs are administered in clinical practice in Japan for the purpose of preventing or treating pancreatitis, with an increasing trend in prescription in recent years.