Histopathologic vertical margin positivity in cold snare polypectomy and mucosal resection for sessile serrated lesions.

BACKGROUND AND AIMS: Data regarding the status of the vertical margin of sessile serrated lesions (SSLs) resected using cold snare polypectomy (CSP) are lacking, and whether a histopathologically positive vertical margin is related to recurrence remains unclear. Therefore, this preliminary study aimed to clarify the rates of positive or unassessable vertical and horizontal margins and the rate of muscularis mucosae resection in SSLs treated using CSP compared with those treated with EMR. METHODS: Histologic outcomes of patients treated with CSP or EMR for SSLs were evaluated in this single-center observational study. The primary outcome was the incidence of histopathologically positive vertical margins in CSP and EMR. Furthermore, the comparisons were adjusted for confounding factors using propensity score matching. RESULTS: Overall, 82 patients with SSLs were included in the CSP and EMR groups after matching. The incidence of positive histologic vertical margins in the CSP and EMR groups were 67.1% and 2.4%, respectively (P < .001). Regarding the evaluation of the presence of muscularis mucosae, 29.3% and 98.8% of patients in the CSP and EMR groups, respectively, had a complete muscularis mucosae resection (P < .001). CONCLUSIONS: A rigorous histopathologic evaluation revealed that for SSLs, CSP more frequently leads to positive vertical margins than EMR. (Clinical trial registration number: UMIN 000051569.).

The molecular profile of gastric intraepithelial foveolar type neoplasia based on somatic copy number alterations and multiple mutation analysis.

BACKGROUND: Gastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN. METHODS: The aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis. RESULTS: Two patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13-4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel. CONCLUSIONS: The current molecular profiles of IFN may help elucidate the mechanisms of IFN development.

Risk factors and pattern of metastatic recurrence after endoscopic resection with additional treatment for esophageal cancer.

Although esophageal cancers invading the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic resection (ER) are associated with a risk of lymph node metastasis, details of metastatic recurrence after additional treatment remain unknown. We aimed to identify the risk factors for metastatic recurrence and recurrence patterns in patients receiving additional treatment after ER for esophageal cancer. Between 2006 and 2017, patients with pT1a-MM/pT1b-SM esophageal cancer who underwent ER with additional treatment (esophagectomy, chemoradiotherapy [CRT], and radiation therapy) at 21 institutions in Japan were enrolled. We evaluated the risk factors for metastatic recurrence after ER with additional treatment. Subsequently, the rate and pattern (locoregional or distant) of metastatic recurrence were investigated for each additional treatment. Of the 220 patients who received additional treatment, 57, 125, and 38 underwent esophagectomy, CRT, and radiation therapy, respectively. In the multivariate analysis, lymphatic invasion was the sole risk factor for metastatic recurrence after additional treatment (hazard ratio, 3.50; P = 0.029). Although the risk of metastatic recurrence with additional esophagectomy was similar to that with CRT (hazard ratio, 1.01; P = 0.986), the rate of locoregional recurrence tended to be higher with additional esophagectomy (80.0% (4/5) vs. 36.4% (4/11)), leading to a better prognosis in patients with metastatic recurrence after additional esophagectomy than CRT (survival rate, 80.0% (4/5) vs. 9.1% (1/11)). Patients with lymphatic invasion have a high risk of metastatic recurrence after ER with additional treatment for pT1a-MM/pT1b-SM esophageal cancer. Additional esophagectomy may result in a better prognosis after metastatic recurrence.

Clinical characteristics of aneurysmal subarachnoid haemorrhage complicated by Takotsubo cardiomyopathy resulting in good neurological outcome.

BACKGROUND: Takotsubo cardiomyopathy (TC) is a well-known complication of subarachnoid haemorrhage (SAH), often accompanied by neurogenic myocardial dysfunction. Although TC has been reported to be associated with higher morbidity and mortality among patients with aneurysmal SAH (aSAH), some patients have been reported to recover, the profiles and follow-up outcomes of these survivors remain unclear. MATERIALS AND METHODS: To characterize the profiles of patients with aSAH complicated by TC who experienced favourable outcomes using long-term follow-up data, a consecutive series of patients with aSAH were enrolled and TC diagnosis was based on the revised version of the Mayo Clinic criteria. Clinical outcomes were assessed at 6 months according to modified Rankin Scale scores. RESULTS: Among 165 consecutive patients with aSAH, 15 cases were complicated by TC, corresponding to an occurrence rate of 9.0%. Five patients with aSAH complicated by TC (33.3%) experienced a favourable outcome, and the mean value of systolic blood pressure on arrival was significantly lower than in those who experienced an unfavourable outcome (p = 0.032). CONCLUSION: According to analysis, it is possible cardiac dysfunction with decreased cerebral perfusion pressure and catecholamine toxicity transiently worsens conscious disturbance in aSAH complicated by TC. Therefore, it is important to carefully screen patients with aSAH to identify those complicated by TC, and for close collaboration of the multidisciplinary team to design appropriate treatment strategies.

Naphthyridine-Based Electron Push-Pull-Type Amine-Reactive Fluorescent Probe for Sensing Amines and Proteins in Aqueous Media.

In bioengineering, fluorescent amine-reactive probes are invaluable for the detection of amine species. In particular, targeting probes for lysine, which has a free amino group in amino acids, are a valid method for protein detection. For this purpose, many fluorescent "turn-on type" probes with amine reactivity have been developed; however, they require improvements. In the typical florescence probes, BODIPY and NBD analogs have small Stokes shifts based on absorption and emission and lability in an aqueous environment, respectively. In this study, a new class of fluorescent probes, 1,8-Nap-F, based on the electron push-pull-type 1,8-naphthyridine framework, was designed and investigated as an amine-reactive probe. Generally, electron push-pull-type fluorophores exhibit a large Stokes shift at the expense of fluorescent enhancement in aqueous media; thus, there is a trade-off between possessing a large Stokes shift and intense emission. However, 1,8-Nap-F reacts with primary amines, yielding emissive amine products with a large Stokes shift (>70 nm) without fluorescence quenching and side products, even in an aqueous environment, thereby overcoming the disadvantages of electron push-pull-type fluorophores and lability in aqueous conditions. By applying the specific features of 1,8-Nap-F, we achieved selective lysine detection and fluorescence bioimaging, such as endoplasmic reticulum-selective protein labeling and organelle staining, in living cells by utilizing amine-substituted derivatives.

Clinical outcomes and factors involved in the local control of proton beam therapy for oligometastatic liver tumors in patients with colorectal cancer.

BACKGROUND AND PURPOSE: There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate. MATERIALS AND METHODS: Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated. RESULTS: This study included 23 men and 18 women, with a median age of 66 (range 24-87) years. A total of 63 lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22 fractions. The median follow-up period was 27.6 months. The 3­year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as a factor associated with LC (P = 0.02). No grade ≥ 3 AEs were observed. None of the patients experienced liver failure during the acute or late phase. CONCLUSION: Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Prognostic Benefit of Additional Treatment After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although additional treatment is considered for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD), the actual benefits of this method remain to be elucidated. AIMS: We aimed to evaluate the prognostic benefits of additional treatment in such patients. METHODS: Between 2006 and 2017, we enrolled patients with pT1a-MM/pT1b-SM ESCC after ESD at 21 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were compared between the additional treatment and follow-up groups after propensity score matching, to reduce the bias of baseline characteristics. A subgroup analysis was performed according to the pathological findings: category A, pT1a-MM but negative for lymphovascular invasion (LVI) and vertical margin (VM); category B, tumor invasion into the submucosa ≤ 200 µm but negative for LVI and VM; category C, others. RESULTS: Of 593 patients with pT1a-MM/pT1b-SM ESCC after ESD, 101 matched pairs were extracted after propensity score matching. The OSs were similar between the additional treatment and follow-up groups (80.6% vs. 78.6% in 5 years; P = 0.972). In a subgroup analysis, the OS in the additional treatment group was significantly lower than that in the follow-up group (65.7% vs. 95.2% in 5 years; P = 0.037) in category A, whereas OS did not significantly differ in category C (76.8% vs. 69.5% in 5 years; P = 0.360). CONCLUSIONS: Additional treatment after ESD in patients with pT1a-MM/pT1b-SM ESCC was not associated with an improved prognosis.

Acid responsiveness of emissive morpholinyl aminoquinolines and their use for cell fluorescence imaging.

Herein, we report emissive aminoquinoline derivatives (TFMAQ) containing alkylmorpholine and arylmorpholine groups and their photophysical properties, acid-responsiveness, and organelle targeting. The alkylmorpholine group is well-known to favour accumulation in lysosomes and be acid-responsive, but, counterintuitively, the TFMAQ derivatives containing ethylmorpholine groups showed limited accumulation in lysosomes and, instead, preferential accumulation in lipid droplets. The findings reported here will aid the development of organelle/tissue specific dyes for cell imaging and diagnosis.

Combined assessment of clinical and pathological prognostic factors for deciding treatment strategies for esophageal squamous cell carcinoma invading into the muscularis mucosa or submucosa after endoscopic submucosal dissection.

OBJECTIVES: We aimed to clarify the prognostic factors for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD). METHODS: This retrospective study enrolled such patients at 21 institutions in Japan between 2006 and 2017. We evaluated 15 factors, including pathological risk categories for ESCC-specific mortality, six non-cancer-related indices, and treatment strategies. RESULTS: In the analysis of 593 patients, the 5-year overall and disease-specific survival rates were 83.0% and 97.6%, respectively. In a multivariate Cox analysis, male sex (hazard ratio [HR] 3.56), Charlson comorbidity index (CCI) ≥3 (HR 2.53), ages of 75-79 (HR 1.61) and ≥80 years (HR 2.04), prognostic nutrition index (PNI) <45 (HR 1.69), and pathological intermediate-risk (HR 1.63) and high-risk (HR 1.89) were prognostic factors. Subsequently, we developed a clinical risk classification for non-ESCC-related mortality based on the number of prognostic factors (age ≥75 years, male sex, CCI ≥3, PNI <45): low-risk, 0; intermediate-risk, 1-2; and high-risk, 3-4. The 5-year non-ESCC-related mortality rates for patients without additional treatment were 0.0%, 10.2%, and 45.8% in the low-, intermediate-, and high-risk groups, respectively. Meanwhile, the 5-year ESCC-specific mortality rates for the pathological low-, intermediate-, and high-risk groups were 0.3%, 5.3%, and 18.2%, respectively. CONCLUSIONS: We clarified prognostic factors for patients with pT1a-MM/pT1b-SM ESCC after ESD. The combined assessment of non-ESCC- and ESCC-related mortalities by the two risk classifications might help clinicians in deciding treatment strategies for such patients.

Clinical benefit of the multibending endoscope for gastric endoscopic submucosal dissection: a randomized controlled trial.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a technically difficult and time-consuming procedure. We aimed to investigate the efficacy and safety of ESD using a multibending endoscope to treat superficial gastrointestinal neoplasms. METHODS: Patients with a single early gastric cancer who met the absolute or expanded indications for ESD according to the Japanese gastric cancer treatment guidelines were enrolled and randomly assigned to undergo ESD using a conventional endoscope (C-ESD) or a multibending endoscope (M-ESD). Randomization was stratified by ESD operator experience and tumor location. The primary outcome was ESD procedure time, calculated as the time from the start of submucosal injection to complete removal of the tumor. RESULTS: 60 patients were analyzed (30 C-ESD, 30 M-ESD). The mean (standard deviation [SD]) ESD procedure times for M-ESD and C-ESD were 34.6 (SD 17.2) and 47.2 (SD 26.7) minutes, respectively (P = 0.03). Muscle layer damage occurred significantly less frequently with M-ESD (0.2 [SD 0.7] vs. 0.7 [SD 1.0]; P = 0.04). There were no significant differences between the two techniques in procedure time or damage to muscle layers for tumors located in the lower third of the stomach. CONCLUSIONS: ESD procedure time was significantly shorter with the multibending endoscope and fewer muscles were damaged. We recommend multibending endoscopy for ESD in the upper and middle thirds of the stomach to reduce procedure time and incidence of complications.

The additional diagnostic impact of positron emission tomography-computed tomography for lymph node metastasis from colorectal cancer: A prospective lymph node level analysis.

BACKGROUND: We conducted a prospective study to determine the diagnostic performance of positron emission tomography-computed tomography (PET-CT) for lymph node metastasis in colorectal cancer patients. METHODS: We enrolled patients scheduled to receive curative surgery with lymph node dissection for colorectal adenocarcinoma who underwent contrast-enhanced abdominopelvic CT and PET-CT before surgery and who had primary lesions of cT2 or deeper. A radiologist determined the fluorodeoxyglucose uptake and the standardized uptake value (SUV) and metabolic volume (MV) to diagnose metastasis in cases with enlarged lymph nodes (≥7 mm long in minor diameter) on contrast-enhanced CT. Two gastrointestinal surgeons intraoperatively identified target lymph nodes to assess the association between images and pathological findings. The diagnostic performance (i.e., sensitivity, specificity, and positive and negative predictive values) for lymph node metastasis was determined using multilevel logistic modeling. RESULTS: A total of 205 colorectal cancer patients were enrolled from February 2018 to April 2020 and 194 patients were analyzed in this study. The sensitivity, specificity, and positive and negative predictive values of PET-CT were 15.3% (13.4%-17.5%), 100.0% (99.0%-100.0%), 100.0% (51.2%-100.0%), and 98.7% (98.5%-99.0%), respectively. CONCLUSION: PET-CT is a useful modality for determining the presence of metastasis in swollen lymph nodes on contrast-enhanced CT in colorectal cancer patients.

The effects of intensive oral care before surgery for gastric cancer patients.

OBJECTIVES: Oral function management has been recognized as important strategy for preventing postoperative complications. In this historical cohort study, we focused on the patients who planed gastrectomy, and investigated the appropriate duration and frequency of preoperative oral care to prevent complications after surgery. METHODS: Patients who planed surgery for gastric cancer between 2012 and 2018 were enrolled. We defined intensive oral care (IOC) as initial intervention at least three weeks before surgery and follow-up intervention within a week before surgery. As the primary outcome, the incidence of postoperative infectious complications was compared between the IOC and non-intensive oral care groups. RESULTS: A total of 576 patients were enrolled, including 66 with IOC. The incidence of infectious complications was 2/66 (3.0%) in the IOC group and 64/510 (12.5%) in the non-intensive oral care group. After adjusting for confounding factors, patients with IOC exposure had a lower chance of developing postoperative infectious complications (odds ratio; 0.217, 0.051-0.927). CONCLUSIONS: Intensive oral care can help prevent postoperative infectious complications after gastrectomy. These findings suggest that appropriate preoperative oral care includes at least two interventions: three weeks or more before and within one week before surgery.

[A case of rectum metastasis of breast cancer].

A 53-year-old woman visited the hospital of this study complaining of constipation. Colonoscopy revealed a circumferential tumor with severe stenosis, and a computed tomography scan showed neoplastic lesions in the rectum and right breast area. Histology was poorly differentiated adenocarcinoma, requiring differentiation between type 4 and metastatic rectal cancer. Additional immunohistochemical tests were performed and a rectal metastasis of breast cancer diagnosis was made. Hormonal therapy was effective and the tumor volume was significantly reduced. Rectal metastasis of breast cancer is said to be rare. However, in the case of patients diagnosed with breast cancer or with a history of breast cancer, considering the possibility of gastrointestinal metastasis using histopathological examination is important.

The effectiveness of proton beam therapy for liver metastatic recurrence in gastric cancer patients.

OBJECTIVE: The purpose of this cross-sectional study was to evaluate the efficacy and safety of proton beam therapy for liver metastatic recurrence in gastric cancer patients. METHODS: Consecutive patients who underwent proton beam therapy from 2010 to 2015 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. Seven patients were enrolled. The median diameter of target lesions was 31 mm (13-68 mm). The most frequent dosage was 72.6 Gy equivalent in 22 fractions. The effectiveness was assessed based on the local control, overall survival and progression-free survival rates. The local control, overall survival and progression-free survival rates were calculated using the Kaplan-Meier method. Adverse events were described according to the patients' medical records. RESULTS: The median follow-up period was 41.7 months (20.7-66.3 months). The 3-year local control, overall survival and progression-free survival rates were 85.7, 68.6 and 43%, respectively. All patients completed proton beam therapy without interruption. No grade ≥3 adverse events were observed. CONCLUSIONS: Proton beam therapy might be a treatment option for patients with liver metastasis of gastric cancer.

[A Case of Endoscopic Submucosal Dissection for Recurrent Gastric Cancer after Chemotherapy with Arterial Infusion].

The patient was a 90-year-old male. For early gastric cancer on the posterior wall of the upper gastric body, which is not indicated for endoscope treatment, chemotherapy with arterial infusion was carried out at other facilities at the request of the patient and his family. Thereafter, he suffered a relapse during follow-up, for which our hospital carried out endoscopic submucosal dissection(ESD). The outcome was a resection without cure. Taking into consideration his age and the fact that the scoring system for early gastric cancer with excised lesions without cure by ESD indicated a medium risk, we carried out no additional treatment but did conduct a follow-up. There has been no recurrence for 15 months following surgery. ESD does not provide evidence with regard to recurrence after other treatments. This patient had a scar following arterial infusion chemotherapy and a local injection solution was not infused into the submucosa right under the lesion. Although the treatment of exfoliation was difficult due to fibrosis of the submucosa, en-bloc resection was possible without any complications.

The Phosphatidylinositol 3-Kinase p110α/PTEN Signaling Pathway Is Crucial for HIV-1 Entry.

Human immunodeficiency virus type 1 (HIV-1) drives multiple signaling pathways to facilitate its cellular entry and replication. The interaction between HIV-1 envelope (env) protein and target cell surface CD4 first activates the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, and the subsequent interaction between HIV-1 env glycoprotein and CCR5/CXCR4 coreceptors establishes viral fusion and entry. Four isoforms of the class-I PI3K catalytic subunits (p110α, p110ß, p110γ, and p110δ) have been identified so far, but the isoform(s) involved in the HIV-1 entry is still unknown. This study aimed to identify the PI3K isoform(s) using recently developed isoform-specific inhibitors and the roles of their negative regulators, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1), in HIV-1 infection. We found that the PI3K p110α isoform-specific inhibitor PIK-75 suppressed HIV-1 entry in HIV-1 permissive T cells, PM1 cells, and TZM-bl cells (HeLa cell-derived indicator cells that coexpress CD4, CCR5, and CXCR4) and decreased the HIV-1-induced phosphorylation of Akt. Moreover, wild-type PTEN (but neither phosphatase-deficient PTEN nor wild-type SHIP1) was a key regulator of HIV-1 entry. Cell-to-cell fusion by HIV-1 env-CD4 interaction was suppressed in the presence of PI3K p110α-specific inhibitor. These data suggest that the PI3K p110α/PTEN signaling pathway is indispensable for HIV-1 entry, including HIV-1 env-mediated cell-to-cell fusion.

Clinical impact of periodontal disease on postoperative complications in gastrointestinal cancer patients.

BACKGROUND: The effectiveness of perioperative oral management in gastrointestinal surgery remains unclear. To elucidate the clinical significance of oral care, we investigated the relationship between the oral environment and postoperative infectious complications (POICs) in patients undergoing gastrointestinal surgery. METHODS: This was a single-institute and historical cohort study of 341 patients. The participants were isolated from consecutive patients undergoing planned radical resection for gastrointestinal carcinoma from January 2016 to June 2017. Dentists assessed the oral environment for periodontal disease, hygiene status, dry mouth, fur on tongue, and tooth stumps. All patients received scaling and tooth brushing instructions. A stepwise logistic regression analysis was conducted to identify risk factors for POICs among the different oral statuses. RESULTS: The surgical procedures performed were gastrectomy in 123 (36.1%), colorectal resection in 185 (54.2%), and pancreatoduodenectomy or others in 38 (11.1%). POICs occurred in 48 patients (14.1%), including deep organ space infection in 20, surgical site infection in 11, anastomotic leakage in 5, urinary tract infection in 4, pneumonia in 2, and others in 6. After adjusting for confounding factors, periodontal disease was isolated as an independent risk factor for POICs (odds ratio 2.091, p = 0.037, 95% confidence interval 1.045-4.183). Other variables of oral environment such as hygiene status, dry mouth, fur on tongue, and tooth stumps did not have a significant impact on POICs. CONCLUSIONS: Periodontal disease is a risk factor for infectious complications after gastrointestinal surgery.