Evaluation of the Validity of Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis Based on the Tokyo Guidelines 2018.

GOALS: We evaluated the validity of endoscopic transpapillary gallbladder drainage (ETGBD) as a bridging therapy prior to elective Lap-C for the patients with acute cholecystitis (AC). BACKGROUND: The Tokyo Guidelines 2018 recommend early laparoscopic cholecystectomy (Lap-C) for patients with AC, however, some patients require the preoperative drainage because of inadequate for early Lap-C du to background and comorbidities. STUDY: We performed a retrospective cohort analysis using data from our hospital records from 2018-2021. In total, 71 cases of 61 patients with AC underwent ETGBD. RESULTS: The technical success rate was 85.9%. Patients in the failure group had more complicated branching of the cystic duct. The length of time until feeding was started and until WBC levels normalized, and the length of hospital stay were significantly shorter in the success group. The median waiting period for surgery was 39 days in the ETGBD success cases. The median operating time, amount of bleeding, and length of postoperative hospital stay were 134 min, 83.2g, and 4 days, respectively. In patients who underwent Lap-C, the waiting period for surgery and the operating time were similar between the ETGBD success and failure groups. However, the temporary discharge period after drainage and the length of postoperative hospital stay were significantly longer in the patients with ETGBD failure. CONCLUSIONS: Our study revealed that ETGBD has equivalent efficacy prior to elective Lap-C despite some challenges that lower its success rate. Preoperativ ETGBD can improve patient quality of life by eliminating the need for a drainage tube.

Clinical complete response maintained for more than 5 years after aggressive chemoradiotherapy for advanced rectal cancer with necrotizing fasciitis: a case report.

We report the case of a 65-year-old male diagnosed with advanced rectal cancer associated with necrotizing fasciitis (NF). Since radical surgery, total pelvic exenteration with sacrectomy, was rejected because of detrimental effects on quality of life, chemoradiotherapy (CRT) was chosen as anti-cancer treatment after urgent debridement. Although CRT was paused unintentionally just after delivering the total dose of radiation owing to the relapse of NF, the patient has maintained clinical complete response (cCR) without any distant metastasis for >5 years. Advanced rectal cancer is recognized as an NF risk factor. No definitive treatment strategies have been reported for NF-inducing rectal cancer; however, some reports have demonstrated curative extended surgery. Thus, CRT may be a less-invasive treatment option for NF-inducing rectal cancer, whereas severe adverse effects including re-infection after debridement should be closely monitored.

Tooth Loss as a Predictor of Postoperative Complications and Prognosis in Patients with Colorectal Cancer.

PURPOSE: We hypothesized that preoperative tooth loss could predict general health conditions, including inflammation, postoperative complications (POCs), and overall survival (OS), in patients with colorectal cancer (CRC) and other gastrointestinal cancers. METHODS: Data of patients who underwent curative surgical resection for CRC during 2017-2021 at our hospital were retrieved. The primary outcomes were POCs, whereas the secondary endpoint was OS. According to the Japanese database, patients within each age range with more than the age-adjusted average number of teeth were classified as the Oral N (normal) group, whereas those with less than the age-adjusted average number of teeth were classified as the Oral A (abnormal) group. The relationship between tooth loss and POCs was assessed using a logistic regression model. RESULTS: Overall, 146 patients were enrolled, with 68 (46.6%) and 78 (53.4%) patients in the Oral N and A groups, respectively. In the multivariate analysis, the Oral A group was an independent risk factor for POCs [hazard ratio (HR), 5.89; 95% confidence interval (CI), 1.81-19.1; p < 0.01]. Similarly, univariate analysis revealed that the Oral A group tended to be associated with OS (HR, 4.57; 95% CI, 0.99-21.2; p = 0.052), but the association was not statistically significant. CONCLUSION: In CRC patients who underwent curative resection, tooth loss was a predictor of POCs. Although further investigations are needed, our results support the use of tooth loss as a simple and essential preoperative evaluation system.

Mesenteric location of lymph node metastasis for colorectal cancer.

BACKGROUND: The number of lymph node metastasis (LNM) is a strong prognostic factor in the treatment of colorectal cancer (CRC). However, the impact of the mesentery location on LNM remains unclear. We assessed the impact LNM location on the recurrence of stage III CRC. METHODS: Subjects with CRC and pathologically positive LNM were enrolled retrospectively. We defined three groups: LNM adjacent to the tumour (group A), metastases with horizontal or vertical spread (group B), and metastases with both horizontal and vertical spread (group C). Recurrence-free survival (RFS) was the primary outcome measure used for the study. RESULTS: A total of 241 (Group A: 121, B: 90, and C: 30) patients were recruited for the study. Multivariate analysis by Cox regression model indicated LNM location to be an independent predisposing risk factor for recurrence [group B: Hazard ratio (HR) 2.01, 95% Confidential interval (CI) 1.12-3.60, P = 0.019; group C: HR 3.00, 95% CI 1.34-6.72, P = 0.008]. Addition of mesentery spread to the N classification was significant risk factor for recurrence (mN2a: HR 2.01, 95% CI 1.07-3.78, P = 0.029; mN2b: HR 3.96, 95% CI 2.12-7.40, P < 0.01). Comparison of Harrell's C-index values was conducted, and the modified N staging risk was 0.6377, whereas the TNM N stage classification was 0.5869. CONCLUSION: Mesentery location of LNM was a risk factor and consideration of it might be beneficial for accurate prediction of CRC prognosis.

Inhibition of STAT3 Promotes Effector T Cell Infiltration But also Immunosuppression in the HCC Tumor Microenvironment.

BACKGROUND/AIM: STAT3 is involved in the progression of several cancers, and has been proposed as target for therapy. Indeed, the multitargeted tyrosine kinase inhibitor drug regorafenib, which indirectly inhibits STAT3, can significantly enhance the effects of anti-programmed death receptor (PD)-1 therapy in hepatocellular carcinoma (HCC) models. Here, we studied the impact of a direct STAT3 inhibitor on the tumor microenvironment and PD-1 blockade efficacy in HCC models. MATERIALS AND METHODS: Orthotopic mouse models of HCC (RIL-175 and HCA-1 grafts in syngeneic mice) were used to test the efficacy of the selective STAT3 inhibitor STX-0119 alone or combined with anti-PD-1 antibodies. We evaluated the effects of therapy on tumor vasculature and the immune microenvironment using immunofluorescence (IF), cell viability assay and quantitative real-time (qRT)-PCR in tumor tissues. RESULTS: Combining anti-PD-1 antibodies with a STX-0119 failed to show a growth delay or survival benefit compared to each agent alone or control in any of the HCC models. Interestingly, evaluation of intratumoral CD8+ T cell infiltration by IF showed a significant increase after one-week treatment with STX-0119 (p=0.034). However, STX-0119 treatment simultaneously promoted increased immunosuppression in the tumor microenvironment by increasing the proportion of Tregs, tissue hypoxia and α-SMA activated cancer-associated fibroblasts (CAFs) measured by IF. Consistent with these findings, we found increased immature tumor vessels by IF and VEGF, Tgf-ß and Vash2 expression by qPCR. CONCLUSION: Pharmacologic STAT3 inhibition could significantly enhance CD8+ T cell infiltration in HCC but also significantly alter the immunosuppression and vascular abnormalization in the tumor microenvironment.

Lymph node metastasis is strongly associated with lung metastasis as the first recurrence site in colorectal cancer.

BACKGROUND: The lymphatic system is known to be the primary pathway of metastasis for colorectal cancer. However, beyond regional lymph node metastases, little is known about the pathway of lymphatic metastases and the differences in the recurrence site risk. The aim of this study was to clarify the relationship between lymph node metastasis and the first recurrence site in colorectal cancer. METHODS: Patients with colorectal cancer who underwent curative resection in our institution between January 2003 and December 2016 were included in this analysis. The relationship between the first recurrence site and clinicopathological factors was analyzed by the Cox regression model and competing risk regression model. RESULTS: In total, 1,249 patients with colorectal cancer were included in this analysis. We found that the stages of lymph node metastases (N0 vs N1: P = .008, N0 vs N2a: P < .001, N0 vs N2b: P < .001) were significantly associated with lung metastasis in the multivariate analysis. Furthermore, in the competing risk analysis, the stages of lymph node metastases were significantly correlated with lung metastasis (N0 vs N1: P = .002, N0 vs N2a: P < .001, N0 vs N2b: P < .001) but were not correlated with other recurrence sites. CONCLUSION: The severity of lymph node involvement had a strong correlation with lung metastases in patients with colorectal cancer.

Horizontal spread of pericolic lymph node metastasis as a prognostic factor for recurrence in Stage III colorectal cancer.

AIM: Main lymph node (LN) metastasis dissected with a high vascular tie at the root of the feeding artery is a poor prognostic factor in colorectal cancer (CRC). However, the effects of horizontal spread on recurrence after curative resection remain unclear. The purpose of this study is to evaluate the relationship between the horizontal spread of LN metastasis and recurrence in CRC. METHOD: In this retrospective study, 189 CRC patients (98 men, 91 women) who underwent curative resection at our hospital from 2003 to 2018 and had only pericolic LN metastasis were divided into two groups: patients with LN metastasis beside the tumour only (T group, n = 121) and those with LN metastasis with horizontal spread (S group, n = 68) (mean follow-up period 50.9 ± 34.1 months). The primary outcome was recurrence-free survival (RFS). We investigated the correlation between clinicopathological background factors and recurrence using Cox regression analysis. RESULTS: Fewer than three LN metastases (N1) were found in 157 patients (107 T group, 50 S group), and four or more metastases (N2a) were found in 32 patients (14 T group, 18 S group). Univariate analyses revealed significantly shorter RFS in the S group [hazard ratio (HR) 1.95, 95% CI 1.07-3.55; p = 0.03). Multivariate analyses revealed that horizontal spread is an independent risk factor for recurrence (HR 1.95, 95% CI 1.05-3.68; p = 0.03). CONCLUSION: Although further investigation is needed, horizontal spread of LN metastasis is a prognostic factor for recurrence in Stage III CRC.

Polarization of hybridized calcium phosphoaluminosilicates with 45S5-type bioglasses.

Hybridization of biocompatible glasses was examined in order to produce fibrous bioactive glass. This work employed two kinds of calcium phosphoaluminosilicates (CPSA) and the 45S5-type bioactive glass. The choice of these parent glasses was based on both electric conductivity and fiber-forming ability. Electrical conductivity was an important property in relation to polarization, which has recently been proved an effective method for bioactivation of calcium phosphate ceramics. CPSA was developed by one of the authors (MK) for biocompatible fibers several decades ago. CPSA exhibited poor conductivity, while 45S5-type glass was conductive due to the high content of Na(+), which can be the charge carriers for conduction according to our previous work. The electrical improvement of CPSA glass was carried out through hybridization with 45S5. The glasses with Na(+)-rich composition failed to be transformed into fibers, whereas the glasses with appropriate sodium content were successfully made into fibers. The appropriate compositions were in the range of 1/99 to 10/90 as 45S5/CPSA in mass ratio.