The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

Survival Evidence of Local Control for Colorectal Cancer Liver Metastases by Hepatectomy and/or Radiofrequency Ablation.

Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.

Development and Validation of a Novel Serum Prognostic Marker for Patients with Metastatic Colorectal Cancer on Regorafenib Treatment.

(1) Background: To investigate the prognostic value of cancer-inflammation prognostic index (CIPI) in patients with metastatic colorectal cancer (mCRC) on regorafenib treatment; (2) Methods: Patients with mCRC who were given regorafenib as later-line treatment at Kaohsiung and Linkou Chang-Gung Memorial Hospital between November 2014 and January 2021 were consecutively enrolled. All relevant clinicopathologic, laboratory data and survival status were recorded. Independent prognostic factors were determined by the multivariate Cox regression method; (3) Results: In total, 106 patients in the training cohort and 250 in the validation cohort were enrolled. The median OS for patients with CIPI ≥ 300 and < 300 in the training cohort was 3.8 and 9.0 months, respectively (hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.82-4.23; p < 0.0001). Time to regorafenib, liver metastasis and CIPI were independent factors by multivariate Cox regression analyses. A new scoring model demonstrated a good discriminatory ability to risk stratification of a patient's survival; (4) Conclusions: We identified CIPI as a novel serum marker highly associated with overall survival in patients with mCRC receiving regorafenib treatment. Further confirmatory studies are warranted.

Prognostic value of sarcopenia in patients with colorectal liver metastases undergoing hepatic resection.

The prognostic significance of sarcopenia has been widely studied in different cancer patients. This study aimed to analyze the influence of sarcopenia on long-term survival in patients with colorectal liver metastasis (CRLM) undergoing hepatic resection. A retrospective analysis of 182 patients undergoing hepatic resection for CRLM was performed. Sarcopenia was determinedusing the Hounsfield unit average calculation (HUAC), a measure of muscle quality-muscledensity at preoperative abdominal computed tomography scans. Sarcopenia was defined as an HUAC score of less than 22 HU calculated using receiver operating characteristic analysis. The prognostic relevance of clinical variables and overall survival (OS) and recurrence-free survival (RFS) was evaluated. Patients with sarcopenia were older (p < 0.001) and had higher prevalence of diabetics (p = 0.004), higher body mass index (BMI) (p < 0.001) and neutrophil-to-lymphocyte ratio (p = 0.026) compared to those without. Sarcopenia was not significantly associated with OS and RFS. Multivariate Cox's regression analysis showed that multinodularity (>3) (hazard ratio (HR) 2.736; 95% confidence interval (CI), 1.631-4.589; p < 0.001), high CEA level (≥20 ng/ml) (HR 1.793; 95% CI, 1.092-2.945; p = 0.021) and blood loss (≥300 cc) (HR1.793; 95% CI, 1.084-2.964; p = 0.023) were independent factors associated with OS. In subgroup analyses, sarcopenia was a significant factor of poor OS in the patients with multinodularity by univariate (p = 0.002) and multivariate analyses(HR 3.571; 95% CI, 1.508-8.403; p = 0.004). Multinodularity (>3) (HR 1.750; 95% CI, 1.066-2.872; p = 0.027), high aspartate aminotransferase level (HR 1.024; 95% CI, 1.003-1.046; p = 0.025) and male gender (HR 1.688; 95% CI, 1.036-2.748; p = 0.035) were independent factors of RFS. In conclusion, despite no significance in whole cohort, sarcopenia was predictive of worse OS in patients with multiple CRLM after partial hepatectomy.

Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir.

BACKGROUND: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line long-term monotherapy for treatment of chronic hepatitis B (CHB) infection. High virological relapse rates are found after cessation of either ETV or TDF in CHB patients. AIM: To compare hepatitis B virus (HBV) relapse rates in CHB patients without cirrhosis who discontinued ETV or TDF. METHODS: A retrospective-prospective study was conducted in 342 CHB patients (108 hepatitis B e antigen (HBeAg)-positive and 234 HBeAg-negative) who received ETV and 165 (46 HBeAg-positive, 119 HBeAg-negative) who received TDF were recruited. All patients had post-treatment follow-up for at least 6 months. All fulfilled the stopping criteria of the Asia-Pacific Association for the Study of the Liver of 2012. RESULTS: Patients who discontinued TDF had significantly higher rates and earlier times of virological and clinical relapse than those who discontinued ETV. This was also seen in propensity score (PS)-matched HBeAg-positive and HBeAg-negative patients. Multivariate analysis showed that being in the TDF group was an independent factor for virological and clinical relapse in all patients and PS-matched HBeAg-positive and HBeAg-negative patients. The rate of off-therapy HBsAg loss was comparable between the ETV and TDF groups after 2-3 years follow-up. Clinical relapse tended to be more severe in the TDF group compared with the ETV group. CONCLUSION: HBV relapse occurs sooner and is more severe after cessation of TDF than after cessation of ETV.

Prognostic factors of patients with gastroenteropancreatic neuroendocrine neoplasms.

There is an increasing trend in the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) worldwide. The aim of the present study was to identify the prognostic factors of patients with GEP-NENs. A cross-sectional, retrospective chart review study was conducted among patients with pathologically proven GEP-NENs between January 2003 and December 2016 at Kaohsiung Chung-Gung Memorial Hospital. A total of 97 patients who met the inclusion criteria were included (male/female = 56/41, age: 57.7 ± 15.4 years). The presentation, clinical characteristics, and disease outcomes were reviewed and analyzed. The most common primary site of the GEP-NENs was the rectum (49.5%), followed by the pancreas (17.5%), duodenum (11.3%), stomach (10.3%), colon (6.2%), and appendix (5.2%), and most GEP-NENs were hormonally nonfunctional (94.8%). There were 56 tumors classified as G1 neuroendocrine tumors (NETs), 9 as G2 NETs, and 14 as G3 neuroendocrine carcinoma (NEC). Metastasis was found in 15 patients (15%). Curative treatments, such as surgery or endoscopic resection, were performed in 83.5% of patients (n = 81). The mean overall survival duration was 107.2 ± 7.8 months. The estimated 3- and 5-year overall survival rates for all patients were 84% and 82%, respectively. Logistic regression analysis showed that large tumor size, non-rectal NENs, high histopathological grading, lymphatic metastases and distant metastases were associated with poor survival. This study suggested that the presence of lymphatic or distant metastases at diagnosis is an independent risk factor for poor prognosis in patients with GEP-NENs.

Long-Term Consequences of Nonclosure of Mesenteric Defects after Traditional Right Colectomy.

BACKGROUND: There are still discrepancies among general/colorectal surgeons regarding closure of mesenteric defect in scientific literature. This study aimed to assess the long-term consequences of nonclosure of the mesenteric defect after open right colectomy. METHODS: A 7-year retrospectively collected and continuous database revealed 212 consecutive patients who had undergone traditional right colectomy without closing the mesenteric defects at Kaohsiung Chung-Gung Memorial Hospital; all patients were operated by a single surgeon. Among these patients, 17 were excluded (those who died within 30 days after surgery or those who received an end ileostomy). The mean age of the 195 patients (58% men and 42% women) was 61.6 ± 12.6 years, and the follow-up period was 4.1 ± 2.8 years (interquartile range 0.09 ~ 10.4). RESULTS: Forty-four patients (22.5%) encountered intestinal obstruction. Nine (20.4%) required surgical intervention. The cause of intestinal obstruction was adhesion (n=1), ventral hernia (n=1), and cancer recurrence (n=7). Conservative treatment was successful in 35 patients. The intestinal obstruction group (n = 44) were similar to the no-intestinal obstruction group (n = 151) in terms of the following parameters: age, sex, previous abdominal surgery, indication for colectomy, and procedure related complications. Carcinomatosis was found to increase the incidence of intestinal obstruction. No patient developed intestinal obstruction because of the nonclosure of mesenteric defects after right colectomy. CONCLUSION: This study suggested that routine procedure of closing the mesenteric defect after open right colectomy might not be beneficial. Additional studies with extended long-term follow-up periods are needed to confirm the benefits of the nonclosure.

Association between Helicobacter pylori eradication and the risk of coronary heart diseases.

The evidences on the association of Helicobacter pylori (H. pylori) to coronary heart diseases (CHD) are conflicting. In order to answer this important but yet unanswered clinical health issue, a large cohort study such as big data from the Taiwan National Health Insurance Research Database should be more convincing. Therefore, we aimed to make use of these big data source to analyze and clarify the relevance of H. pylori eradication and CHD risks. We looked through a total of 208196 patients with peptic ulcer diseases (PUD) from the years of 2000 to 2011. First, 3713 patients who received H. pylori eradication within 365 days of the index date were defined as the group A. We randomly selected the same number of patients as cohort A from 55249 non-eradication patients to be the comparison group B using propensity scores (including age, gender and comorbidity) so that we could control the confounding variables of CHD and mortality. Importantly, we perform sensitivity analysis for the time-dependent association between H. pylori eradication and risk of CHD, interactions between patient demographic characteristics and therapy by age (≥ or < 65 years old). The results showed that a trend of decreased association of CHD in patients with early eradication was observed compared to those without eradication (2.58% vs. 3.35%, p = 0.0905). The mortality rate was lower in early eradication subgroup compared to cohort B (2.86% vs. 4.43%, p = 0.0033). Interestingly, there was also significant difference observed in composite end-points for CHD and death in the early eradication subgroup (0.16% vs.0.57%, p = 0.0133). Further, the cumulative CHD rate was significantly lower in younger patients (< 65 years old) with H. pylori eradication therapy started < 1 year compared to those patients without eradication at all (p = 0.0384); the treatment did not appear to have an effect in older patients (≥ 65 years old) (p = 0.1963). Multivariate analysis showed that hypertension and renal diseases were risk factors for CHD in patients without eradication whilst younger age (< 65 years old) initiated with H. pylori therapy was a protective factor. In conclusion, the trend of decrease in CHD occurrence after early H. pylori eradication in addition to the significant decrease in composite end points for CHD and death, the significantly lower cumulative CHD rate in younger patients < 65 years old with H. pylori treated within 365 days suggested that there was positive association between H. pylori eradication and CHD.

Temporary closure of colostomy with suture before colostomy takedown improves the postoperative outcomes.

PURPOSE: Temporary loop colostomy is a common surgical procedure used to avoid complications in high-risk distal anastomosis as well as pelvic inflammation. Issues regarding postoperative outcomes of colostomy takedown have been widely discussed in the literature, wound infection especially. Temporary closure of colostomy with suture before takedown was adopted in our study, which provided excellent traction to aid mobilization of stomy and avoided stool spillage to downgrade the wound classification to "clean contamination." We aimed to determine the effects of the procedure on postoperative outcomes. METHODS: This was a prospective case-control study at a single tertiary medical center. Patients presenting for elective colostomy takedown were included. Allis clamp (n = 50) or silk suture (n = 60) was applied to mobilize the colostomy, and results were compared. Operative time and wound infection rate were measured as primary postoperative outcomes. Univariate and multivariate analyses were used to demonstrate the association between the two groups and outcomes. RESULTS: In univariate analyses, significantly shorter operative time (median = 57 min, p = 0.003) and lower postoperative wound infection rate (3%, p = 0.03) were noted in the group receiving silk suture. Multivariate analyses results showed that silk suture was significantly associated with both operative time (B = - 8.5, p = 0.01) and wound infection (odds ratio = 0.18, p = 0.04). CONCLUSION: With the advantage of enhancing traction and decreasing contamination, the temporary closure of colostomy with suture improved takedown outcomes, including a shorter operative time and lower wound infection rate.

Association between complicated liver cirrhosis and the risk of hepatocellular carcinoma in Taiwan.

Hepatic encephalopathy, ascites, and variceal bleeding are the three major complications of cirrhosis. It is well known that cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC). However, little is known about whether the severity of liver cirrhosis has an effect on the incidence of HCC. This population-based cohort study aimed to explore the association between complicated cirrhosis and HCC, and identify the risk factors of HCC in patients with complicated cirrhosis. Data of the years 1997-2011 were extracted from the National Health Insurance Research Database of Taiwan. A total of 2568 patients with complicated cirrhosis without HCC at baseline were enrolled. After propensity score matching, another 2568 patients with non-complicated cirrhosis were included. Hazards Cox regression analysis by using a competing risk regression model to control for possible confounding factors was utilized to estimate the association of the complications of liver cirrhosis with the risk of HCC. We observed by using competing risk analysis that the adjusted hazard ratio (HR) for developing HCC during the follow-up period after the initial hospitalization was higher among the patients with baseline complicated cirrhosis than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval, CI, 1.10-1.37, p<0.001). Additionally, older patients (HR, 1.01; 95% CI, 1.01-1.02, p<0.001), males (HR, 0.84; 95% CI, 0.74-0.96, p = 0.009), and patients with alcohol-related cirrhosis (HR, 1.93; 95% CI, 1.65-2.26, p<0.001) had a statistically significant difference in the incidence of HCC. In conclusion, complicated liver cirrhosis is associated with a higher risk of HCC in Taiwan compared with cirrhosis without complications.

First-Line Helicobacter pylori Eradication in Patients with Chronic Kidney Diseases in Taiwan.

AIMS: Patients with chronic kidney disease (CKD) and Helicobacter pylori (H. pylori) infection have a higher incidence of gastroduodenal diseases and therefore are recommended to receive eradication therapies. This study aimed to assess the efficacy of a 7-day standard triple therapy in patients with CKD (eGFR < 60 ml/min/1.73 m2) and to investigate the clinical factors influencing the success of eradication. METHODS: A total of 758 patients with H. pylori infection receiving a 7-day standard first-line triple therapy between January 1, 2013, and December 31, 2014, were recruited. Patients were divided into two groups: CKD group (N = 130) and non-CKD group (N = 628). RESULTS: The eradication rates attained by the CKD and non-CKD groups were 85.4% and 85.7%, respectively, in the per-protocol analysis (p = 0.933). The eradication rate in CKD stage 3 was 84.5% (82/97), in stage 4 was 88.2% (15/17), and in those who received hemodialysis was 87.5% (14/16). There were no significant differences in the various stages of CKD (p = 0.982). The adverse events were similar between the two groups (3.1% versus 4.6%, p = 0.433). Compliance between the two groups was good (100.0% versus 99.8%, p = 0.649). There was no significant clinical factor influencing the H. pylori eradication rate in the non-CKD and CKD groups. CONCLUSIONS: This study suggests that the H. pylori eradication rate and adverse rate in patients with CKD are comparable to those of non-CKD patients.

Meta-analysis of randomized controlled trials comparing outcomes for stapled hemorrhoidopexy versus LigaSure hemorrhoidectomy for symptomatic hemorrhoids in adults.

This purpose of the meta-analysis was to compare treatment outcomes for adult patients with symptomatic hemorrhoids treated by stapled hemorrhoidopexy or LigaSure hemorrhoidectomy. A search of public medical databases was made to identify randomized controlled trials (RCTs) comparing stapled hemorrhoidopexy (SH) with LigaSure hemorrhoidectomy (LH) for the treatment of adult patients with symptomatic grade 3 and grade 4 hemorrhoids. Postoperative pain as measured using a visual analog scale was the primary outcome, and rate of recurrent prolapse and postoperative bleeding were secondary outcome measures. Four RCTs were identified that met the inclusion criteria. Data for the pooled outcomes were analyzed using odds ratio (OR) analysis. None of the studies in the analysis indicated a significant difference between SH and LH for the outcomes VAS pain score, recurrence rate, or postoperative bleeding. Pooled analysis revealed a significant OR in favor of the SH method for recurrent prolapse (OR = 5.529, P = 0.016) for up to 2 years after surgery. No significant differences between the two methods were identified for VAS pain scores (OR = -1.060, P = 0.149) or postoperative bleeding OR = 1.188, P = 0.871). Pooled analysis of RCT results comparing SH to LH for symptomatic hemorrhoids revealed a significantly greater incidence of recurrent prolapse for SH. The two techniques were associated with similar levels of postoperative pain and postoperative bleeding.

Outcome of urinary bladder recurrence after partial cystectomy for en bloc urinary bladder adherent colorectal cancer resection.

PURPOSE: Around 10 % of colorectal cancers are locally advanced at diagnosis. There are higher incidences for sigmoid and rectal cancer adhered to urinary bladder (UB) rather than other segments of colon cancer. Surgeons often performed partial cystectomy as possible for preservation of patient's life quality. This study investigates prognostic factors in patients who underwent bladder preservation en bloc resection for UB adherent colorectal cancer. METHODS: From 2000 to 2011, 123 patients with clinically UB involvement colorectal cancer underwent primary colorectal cancer with urinary bladder resection. Seventeen patients were excluded because of the concurrent distant metastasis at diagnosis and another 22 patients were excluded because of total cystectomy with uretero-ileal urinary diversion. Finally, 84 patients with clinical stage IIIC (T4bN0M0, according to AJCC 7th edition) that underwent en bloc colorectal cancer resection with partial cystectomy were enrolled into this study for further analysis. RESULTS: Preoperative colovesical fistula and positive CT result were significantly more in the urinary bladder invasion group (p = 0.043 and 0.010, respectively). Pathological UB invasion is an independent predictor of intravesical recurrence (p = 0.04; HR, 10.71; 95 % CI = 1.12∼102.94) and distant metastasis (p = 0.016; HR, 4.85; 95 % CI = 1.34 ∼ 17.53) in multivariate analysis. CONCLUSIONS: For bladder preservation en bloc resection of urinary bladder adherent colorectal cancer, the pathological urinary bladder invasion is significantly associated with more urinary bladder recurrence and distant metastasis. This result helps surgeons make decisions at surgical planning and establish follow-up protocol.