miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20-30% pathologic complete response. Because miRNAs are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Understanding the role and mechanism of dysregulated miRNAs in TNBC may help to develop novel diagnostic and prognostic strategy for TNBC patients. METHODS: The miRNA array profiles of 1299 breast cancer patients were collected from the Metabric database and subjected to analysis of the altered miRNAs between TNBC and non-TNBC. In Student's t-test and Kaplan-Meier analysis, four upregulated miRNAs correlated with poor survival in TNBC but not in non-TNBC. Four miRNAs were manipulated in multiple cell lines to investigate their functional role in carcinogenesis. From these results, we studied miR-105 and miR-93-3p in greater detail. The level of miR-105 and miR-93-3p were evaluated in 25 breast cancer tumor tissues. In addition, the diagnostic utility of circulating miR-105 and miR-93-3p were examined in 12 normal and 118 breast cancer plasma samples by ROC curve construction. RESULTS: miR-105 and miR-93-3p were upregulated and correlated with poor survival in TNBC patients. Both miR-105 and miR-93-3p were found to activate Wnt/ß-catenin signaling by downregulation of SFPR1. By this action, stemness, chemoresistance, and metastasis were promoted. Importantly, the combination of circulating miR-105/93-3p may serve as a powerful biomarker for TNBC, even in early-stage disease. CONCLUSIONS: miR-105/93-3p activates Wnt/ß-catenin signaling by downregulating SFRP1 and thereby promotes stemness, chemoresistance, and metastasis in TNBC cells. Most importantly, combined circulating miR-105/93-3p levels represent a prime candidate for development into a diagnostic biomarker for both early- and late-stage TNBC.

The prognostic impact of lipid biosynthesis-associated markers, HSD17B2 and HMGCS2, in rectal cancer treated with neoadjuvant concurrent chemoradiotherapy.

Neoadjuvant concurrent chemoradiotherapy has been widely used for rectal cancer to improve local tumor control. The varied response of individual tumors encouraged us to search for useful biomarkers to predict the therapeutic response. The study was aimed to evaluate the prognostic impact of lipid biosynthesis-associated biomarkers in rectal cancer patients treated with preoperative chemoradiotherapy. Through analysis of the previously published gene expression profiling database focusing on genes associated with lipid biosynthesis, we found that HSD17B2 and HMGCS2 were the top two significantly upregulated genes in the non-responders. We further evaluated their expression by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancer and statistically analyzed the associations between their expression and various clinicopathological factors, as well as survival. High expression of HMGCS2 or HSD17B2 was significantly associated with advanced pre- and post-treatment tumor or nodal status (P < 0.001) and lower tumor regression grade (P < 0.001). More importantly, high expression of either HMGCS2 or HSD17B2 was of prognostic significance, with HMGCS2 overexpression indicating poor prognosis for disease-free survival (P = 0.0003), local recurrence-free survival (P = 0.0115), and metastasis-free survival (P = 0.0119), while HSD17B2 overexpression was associated with poor prognosis for disease-free survival (P <0.0001), local recurrence-free survival (P = 0.0009), and metastasis-free survival (P < 0.0001). In multivariate analysis, only HSD17B2 overexpression remained as an independent prognosticator for shorter disease-free survival (P < 0.001) and metastasis-free survival (P = 0.008). In conclusion, high expression of either HSD17B2 or HMGCS2 predicted poor susceptibility of rectal cancer to preoperative chemoradiotherapy. Both acted as promising prognostic factors, particularly HSD17B2.

Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: a phase II TCOG study.

BACKGROUND: To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. PATIENTS AND METHODS: Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor. RESULTS: From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression. CONCLUSIONS: Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery.

[A comparison of convenience sampling and purposive sampling].

Convenience sampling and purposive sampling are two different sampling methods. This article first explains sampling terms such as target population, accessible population, simple random sampling, intended sample, actual sample, and statistical power analysis. These terms are then used to explain the difference between "convenience sampling" and purposive sampling." Convenience sampling is a non-probabilistic sampling technique applicable to qualitative or quantitative studies, although it is most frequently used in quantitative studies. In convenience samples, subjects more readily accessible to the researcher are more likely to be included. Thus, in quantitative studies, opportunity to participate is not equal for all qualified individuals in the target population and study results are not necessarily generalizable to this population. As in all quantitative studies, increasing the sample size increases the statistical power of the convenience sample. In contrast, purposive sampling is typically used in qualitative studies. Researchers who use this technique carefully select subjects based on study purpose with the expectation that each participant will provide unique and rich information of value to the study. As a result, members of the accessible population are not interchangeable and sample size is determined by data saturation not by statistical power analysis.

Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression.

Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC.

SKP2 overexpression is associated with a poor prognosis of rectal cancer treated with chemoradiotherapy and represents a therapeutic target with high potential.

The S-phase kinase-associated protein 2 (SKP2) oncoprotein is an E3 ubiquitin ligase. Overexpression of SKP2 was found in various human cancers, including colorectal cancers, but its potential role as a prognostic marker after neoadjuvant chemoradiotherapy (CRT) and for therapeutic intervention in rectal cancers is unknown. This study examined the correlation of SKP2 expression in the prognosis of rectal cancer patients and the viability of colorectal cancer cells treated with CRT. SKP2 immunoexpression was retrospectively assessed in pretreatment biopsies of 172 rectal cancer patients treated with neoadjuvant CRT followed by surgery. Results were correlated with clinicopathological features, therapeutic responses, and patient survival. Pharmacologic assays were used to evaluate the therapeutic relevance of Bortezomib in two colorectal cancer cell lines (HT-29 and SW480). High expression of SKP2 was correlated with the advanced Post-Tx nodal status (p = 0.002), Post-Tx International Union for Cancer Control stage (p = 0.002), and a lower-degree tumor regression grade (p < 0.001). Moreover, high expression of SKP2 (p = 0.027, hazard ratio 3.21) was an independent prognostic factor for local recurrence-free survival. In vitro, Bortezomib downregulated SKP2 expression, induced caspase activation, and decreased the viability of colorectal cancer cells with or without a combination with fluorouracil. Bortezomib also promoted caspase activation and gamma-H2AX formation in colorectal cancer cells concurrently treated with CRT. High expression of SKP2 was associated with a poor therapeutic response and adverse outcomes in rectal cancer patients treated with neoadjuvant CRT. In the presence of chemotherapy with or without radiotherapy, the promoted sensitivity of colorectal cancer cells to Bortezomib with an SKP2-repressing effect indicated that it is a potential therapeutic target.

The volume-outcome relationship in laparoscopic cholecystectomy: a population-based study using propensity score matching.

BACKGROUND: The volume-outcome relationship has been validated previously for surgical procedures and cancer treatments. However, no studies have longitudinally compared the relationships between volume and outcome, and none have systematically compared laparoscopic cholecystectomy (LC) surgery outcomes in Taiwan. This study purposed to explore the relationship between volume and hospital treatment cost after LC. METHODS: This cohort study retrospectively analyzed 247,751 LCs performed from 1998 to 2009. Hospitals were classified as low-, medium-, and high-volume hospitals if their annual number of LCs were 1-29, 30-84, ≥85, respectively. Surgeons were classified as low-, medium-, and high-volume surgeons if their annual number of LCs were 1-10, 11-24, ≥25, respectively. Hierarchical linear regression model and propensity score were used to assess the relationship between volume and hospital treatment cost. RESULTS: The mean hospital treatment cost was US $2,504.53, and the average hospital costs for high-volume hospitals/surgeons were 33/47% lower than those for low-volume hospitals and surgeons. When analyzed by propensity score, the hospital treatment cost differed significantly between high-volume hospitals/surgeons and low/medium-volume hospitals/surgeons (2,073.70 vs. 2,350.91/2,056.73 vs. 2,553.76, P < 0.001). CONCLUSIONS: Analysis using a hierarchical linear regression model and propensity score found an association between high-volume hospitals and surgeons and hospital treatment cost in LC patients. Moreover, the significant factors associated with hospital resource utilization for this procedure include age, gender, comorbidity, hospital type, hospital volume, and surgeon volume. Additionally, analysis of the treatment strategies adopted at high-volume hospitals or by high-volume surgeons may improve overall hospital treatment cost.

Quality of life and cost-effectiveness of different breast cancer surgery procedures: a Markov decision tree-based approach in the framework of Predictive, Preventive, and Personalized Medicine.

Purpose: Breast cancer is a complex disease with heterogeneous outcomes that may benefit from the implementation of Predictive, Preventive, and Personalized Medicine (PPPM/3PM) strategies. In this study, we aimed to explore the potential of PPPM approaches by investigating the 10-year trends in quality of life (QOL) and the cost-effectiveness of different types of surgeries for patients with breast cancer. Methods: This prospective cohort study recruited 144 patients undergoing breast conserving surgery (BCS), 199 undergoing modified radical mastectomy (MRM), and 44 undergoing total mastectomy with transverse rectus abdominis myocutaneous flap (TRAMF) from three medical centers in Taiwan between June 2007 and June 2010. Results: All patients exhibited a significant decrease in most QOL dimension scores from before surgery to 6 months postoperatively (p < 0.05); however, from postoperative year 1 to 2, improvement in most QOL dimension scores was significantly better in the TRAMF group than in the BCS and MRM groups (p < 0.05). At 2, 5, and 10 years after surgery, the patients' QOL remained stable. In the Markov decision tree model, the TRAMF group had higher total direct medical costs than the MRM and BCS groups (US$ 32,426, US$ 29,487, and US$ 28,561, respectively) and higher average QALYs gained (7.771, 6.773, and 7.385, respectively), with an incremental cost-utility ratio (ICUR) of US$ 2,944.39 and US$ 10,013.86 per QALY gained. Conclusions: TRAMF appeared cost effective compared with BCS and MRM, and it has been proved with considerable QOL improvements in the framework of PPPM. Future studies should continue to explore the potential of PPPM approaches in breast cancer care. By incorporating predictive models, personalized treatment plans, and preventive strategies into routine clinical practice, we can further optimize patient outcomes and reduce healthcare costs associated with breast cancer treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00326-4.

The promoting effect of adiponectin in hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Adipokines may explain the newly established association of obesity with hepatocellular carcinoma (HCC). This study investigated if adiponectin levels in HCC patients differed from healthy controls and their potential effect in the development of HCC. METHODS: Radioimmunoassay was used to determine serum adiponectin levels of 65 HCC patients and 165 healthy controls. The expressions of adiponectin protein in the tumor and adjacent non-tumor parts were examined by the immunoblotting method. Cell proliferation assays were used to assess the bioeffects of adiponectin in two human liver cancer cell lines. RESULTS: Serum adiponectin levels were significantly higher in the HCC patients than the controls. Significant correlations of serum adiponectin levels with serum triglyceride levels and insulin resistance were found in the controls, but not in the HCC patients. In contrast, serum adiponectin levels significantly correlated with serum albumin and alkaline phosphatase levels in the HCC patients, but this trend was not observed in the controls. The expression pattern of adiponectin protein between the paired tumor and adjacent non-tumor tissues significantly correlated with tumor size. In vitro, adiponectin increased cell proliferation in a dose-dependent manner. CONCLUSIONS: Increased adiponectin expressions were found in HCC and this increase might contribute to tumor growth.

5-year recurrence prediction after hepatocellular carcinoma resection: deep learning vs. Cox regression models.

Deep learning algorithms have yet to be used for predicting clinical prognosis after cancer surgery. Therefore, this study compared performance indices and permutation importance of potential confounders in three models for predicting 5-year recurrence after hepatocellular carcinoma (HCC) resection: a deep-learning deep neural network (DNN) model, a recurrent neural network (RNN) model, and a Cox proportional hazard (CPH) regression model. Data for 725 patients who had received HCC resection at three medical centers in southern Taiwan between April, 2011, and December, 2015, were randomly divided into three datasets: a training dataset containing data for 507 subjects was used for model development, a testing dataset containing data for 109 subjects was used for internal validation, and a validating dataset containing data for 109 subjects was used for external validation. Feature importance analysis was also performed to identify potential predictors of recurrence after HCC resection. Univariate Cox proportional hazards regression analyses were performed to identify potential significant predictors of 5-year recurrence after HCC resection, which were included in the forecasting models (P < 0.05). All performance indices for the DNN model were significantly higher than those for the RNN model and the conventional CPH model (P < 0.001). The most important potential predictor of 5-year recurrence after HCC resection was surgeon volume followed by, in order of importance, hospital volume, preoperative Beck Depression Scale score, preoperative Beck Anxiety Scale score, co-residence with family, tumor stage, and tumor size. The feature importance analysis performed to investigate interpretability in this study elucidated the potential use of deep learning models for predicting recurrence after HCC resection and for identifying predictors of recurrence. Further experiments using the proposed DNN model would clarify its potential uses for developing, promoting, and improving health policies for treating HCC patients after surgery.

Inverse Probability of Treatment Weighting in 5-Year Quality-of-Life Comparison among Three Surgical Procedures for Hepatocellular Carcinoma.

This prospective longitudinal cohort study analyzed long-term changes in individual subscales of quality-of-life (QOL) measures and explored whether these changes were related to effective QOL predictors after hepatocellular carcinoma (HCC) surgery. All 520 HCC patients in this study had completed QOL surveys before surgery and at 6 months, 2 years, and 5 years after surgery. Generalized estimating equation models were used to compare the 5-year QOL among the three HCC surgical procedures. The QOL was significantly (p < 0.05) improved at 6 months after HCC surgery but plateaued at 2−5 years after surgery. In postoperative surveys, the effect size was largest in the nausea and vomiting subscales in patients who had received robotic surgery, and the effect size was smallest in the dyspnea subscale in patients who had received open surgery. It revealed the following explanatory variables for postoperative QOL: surgical procedure type, gender, age, hepatitis C, smoking, tumor stage, postoperative recurrence, and preoperative QOL. The comparisons revealed that, when evaluating QOL after HCC surgery, several factors other than the surgery itself should be considered. The analysis results also implied that postoperative quality of life might depend not only on the success of the surgical procedure, but also on preoperative quality of life.

Long-term outcomes of laparoscopic cholecystectomy: a prospective piecewise linear regression analysis.

BACKGROUND: The objectives of this study were to examine longitudinal time trends, to predict thresholds of improvement in each dimension of health-related quality of life (HRQoL), and to identify long-term predictors of HRQoL. METHODS: This study analyzed 353 laparoscopic cholecystectomy (LC) patients. Disease-specific Gastrointestinal Quality-of-Life Index (GIQLI) and generic Short-Form 36-Item Health Survey (SF-36) scores were obtained immediately before surgery, then 3, 6, 12, and 24 months after surgery. Generalized estimating equations and piecewise linear regression models were used. RESULTS: The examined population significantly (p<0.05) improved in both SF-36 and GIQLI subscale scores. The HRQoL dimensions were substantially improved the sixth month after surgery and continued improving until they reached a plateau at 54.93 to 73.18 months. The data also showed the following explanatory variables for HRQoL: time, age, gender, Charlson Comorbidity Index, and preoperative GIQLI and SF-36 subscale scores. CONCLUSIONS: As shown by the findings, the HRQoL scores improved substantially by the sixth month after surgery and continued improving until they reached a 4- to 7-year threshold, indicating that change trends in HRQoL dimensions may vary. Although HRQoL scores were substantially improved after cholecystectomy, the improvements were associated with preoperative functional status and demographic characteristics.

Response shift effect on gastrointestinal quality of life index after laparoscopic cholecystectomy.

PURPOSE: Traditional pre- and post-surgery quality of life assessments are inadequate for assessing change in health-related quality of life (HRQoL) after laparoscopic cholecystectomy (LC). This study examined whether a response shift, a change in the internal standards of a patient, occurs in patients who have received LC. METHODS: Self-administered gastrointestinal quality of life index (GIQLI) was used to evaluate preoperative, postoperative, and retrospective postoperative HRQoL. Response shifts, unadjusted treatment effects, adjusted treatment effects, and their effect sizes were calculated. RESULTS: In all GIQLI domains, a significant response shift was indicated by the significantly higher pre-test scores compared to then-test scores (P < 0.05). The effect size of the response shift ranged from 0.19 for the physical impairment domain of the GIQLI to 0.49 for the total GIQLI score. It was observed the treatment effect was greater after adjusting for the presence of response shift. CONCLUSION: Patients who have received LC undergo a response shift that affects their outcome measurement at 6 months postoperative. Response shift is a potentially confounding factor and should be considered when designing clinical studies that employ self-administered HRQoL measures. This evidence of confounding effects warrants further study of response shift at longer intervals after LC, after other health care interventions, and in patients with varying preoperative health status.

Breast Cancer Surgery 10-Year Survival Prediction by Machine Learning: A Large Prospective Cohort Study.

Machine learning algorithms have proven to be effective for predicting survival after surgery, but their use for predicting 10-year survival after breast cancer surgery has not yet been discussed. This study compares the accuracy of predicting 10-year survival after breast cancer surgery in the following five models: a deep neural network (DNN), K nearest neighbor (KNN), support vector machine (SVM), naive Bayes classifier (NBC) and Cox regression (COX), and to optimize the weighting of significant predictors. The subjects recruited for this study were breast cancer patients who had received breast cancer surgery (ICD-9 cm 174-174.9) at one of three southern Taiwan medical centers during the 3-year period from June 2007, to June 2010. The registry data for the patients were randomly allocated to three datasets, one for training (n = 824), one for testing (n = 177), and one for validation (n = 177). Prediction performance comparisons revealed that all performance indices for the DNN model were significantly (p < 0.001) higher than in the other forecasting models. Notably, the best predictor of 10-year survival after breast cancer surgery was the preoperative Physical Component Summary score on the SF-36. The next best predictors were the preoperative Mental Component Summary score on the SF-36, postoperative recurrence, and tumor stage. The deep-learning DNN model is the most clinically useful method to predict and to identify risk factors for 10-year survival after breast cancer surgery. Future research should explore designs for two-level or multi-level models that provide information on the contextual effects of the risk factors on breast cancer survival.

Changing approaches to cholecystectomy in elderly patients: a 10-year retrospective study in Taiwan.

BACKGROUND: The prevalence of symptomatic gallbladder diseases increases with age. The present study evaluated cholecystectomy risk factors and hospital resource utilization in an elderly (aged 60 years and older) population of patients who had undergone open cholecystectomy (OC) or laparoscopic cholecystectomy (LC). METHODS: The study analyzed 20,538 OC and 29,318 LC procedures performed in Taiwan from 1996 to 2007. Odds ratio (OR) and 95% confidence interval were calculated to assess the relative change rate. Regression models were employed to predict length of stay (LOS) and total surgical cost. RESULTS: Patient characteristics associated with increased likelihood of undergoing LC were age 60-69 years, female gender, and lack of current co-morbidities. Length of stay associated with both OC and LC decreased during the study period. Total surgical cost for elderly OC patients increased during the study period, whereas that for elderly LC patients declined. Compared to OC patients, LC patients had significantly larger changes in LOS (-2.27 days) and total surgical cost ($ -368.64 U.S. dollars) (p < 0.001). The following factors were associated with considerable increases in both LOS and total surgical cost: advanced age, female gender, presence of one or more co-morbidities, treatment in a regional or a district hospital, and long LOS. CONCLUSIONS: Decreases in hospital resource utilization were larger in elderly LC patients than in elderly OC patients. Health care providers and patients should observe that hospital resource utilization may depend on hospital attributes as well as patient attributes. These analytical results should be applicable to similar elderly populations in other countries.

Machine Learning Algorithms to Predict Recurrence within 10 Years after Breast Cancer Surgery: A Prospective Cohort Study.

No studies have discussed machine learning algorithms to predict recurrence within 10 years after breast cancer surgery. This study purposed to compare the accuracy of forecasting models to predict recurrence within 10 years after breast cancer surgery and to identify significant predictors of recurrence. Registry data for breast cancer surgery patients were allocated to a training dataset (n = 798) for model development, a testing dataset (n = 171) for internal validation, and a validating dataset (n = 171) for external validation. Global sensitivity analysis was then performed to evaluate the significance of the selected predictors. Demographic characteristics, clinical characteristics, quality of care, and preoperative quality of life were significantly associated with recurrence within 10 years after breast cancer surgery (p < 0.05). Artificial neural networks had the highest prediction performance indices. Additionally, the surgeon volume was the best predictor of recurrence within 10 years after breast cancer surgery, followed by hospital volume and tumor stage. Accurate recurrence within 10 years prediction by machine learning algorithms may improve precision in managing patients after breast cancer surgery and improve understanding of risk factors for recurrence within 10 years after breast cancer surgery.

Wnt-1 protein as a prognostic biomarker for hepatitis B-related and hepatitis C-related hepatocellular carcinoma after surgery.

BACKGROUND: Up-regulation of Wnt-1 protein has been reported in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) tissues and cell lines. It is known to play a fundamental role in signaling cancer progression, whereas its prognostic role in HCC remains unexplored. METHODS: As a prognostic biomarker, this study analyzed Wnt-1 protein expression in 63 histology-verified HCC patients receiving curative resection. In each paired tumor and nontumor specimen, Wnt-1 levels were semiquantitatively measured by Western blotting and expressed by tumor/nontumor ratio. The data were further correlated with quantitative real-time PCR as well as with beta-catenin and E-cadherin expression by immunohistochemistry. Cumulative tumor recurrence-free survival curves were constructed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: The results showed that 26 (group I) and 37 (group II) HCC patients had an expression ratio of Wnt-1 > or =1.5 and <1.5, respectively. The amount of Wnt-1 estimated by tumor/nontumor ratio correlated with the results by quantitative real-time PCR. High tumor Wnt-1 expression correlated with enhanced nuclear beta-catenin accumulation, diminished membranous E-cadherin expression, and increased tumor recurrence after curative tumor resection. CONCLUSIONS: These results suggest that Wnt-1 may be used as a predisposing risk factor for HCC recurrence. The use of tumor Wnt-1 as prognostic biomarker may identify patients with HBV- and/or HCV-related HCC patients with a high risk of tumor recurrence who may then benefit from further intensive therapy after surgery.

The minimal clinically important difference in the Gastrointestinal Quality-of-Life Index after cholecystectomy.

BACKGROUND: The minimal clinically important difference (MCID) for the Gastrointestinal Quality of Life Index (GIQLI) is unknown, which limits its application and interpretation. This study aimed to estimate MCIDs for the GIQLI scores of patients after they had undergone cholecystectomy. METHODS: This study had 267 participants. All the participants completed the GIQLI and four anchor items, namely, "How would you describe your overall symptoms, emotions, physical functions, and social functions since your last visit?" The response options were "much worse," "somewhat worse," "same," "somewhat better" and "much better." The MCID was defined according to those who responded with "somewhat better." RESULTS: The mean age of the participants was 57.81 ± 14.93 years, and 37.08% of the patients were women. The MCID group included 67, 78, 44, and 22 patients with MCIDs of 6.42, 6.86, 7.64 and 6.46 points respectively for scores on the symptoms, emotions, physical functions, and social functions subscales, respectively. The effect sizes of four anchors in the "somewhat better" group (0.38-0.49) exceeded those of the same group (0.25-0.38). CONCLUSIONS: This study showed that after patients had undergone cholecystectomy, the clinically significant mean changes in their scores on the GIQLI subscales for symptoms, emotions, physical functions, and social function were respectively 6.42, 6.86, 7.64, and 6.46 points. After patients have undergone cholecystectomy, the MCIDs for the GIQLI subscales can play an important role in interpretation of the scores, application of them in clinical practice, and verification of treatment effects.

Preoperative Health-Related Quality of Life Predicts Minimal Clinically Important Difference and Survival after Surgical Resection of Hepatocellular Carcinoma.

Despite the growing use of minimal clinically important difference (MCID) as a cancer outcome measure, no study has reported clinically significant outcomes in cancer patients. We defined MCID and evaluated the use of preoperative HRQoL for predicting MCID and survival after surgical resection of hepatocellular carcinoma (HCC). In total, 369 patients completed the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and the SF-36 at baseline and at two years post-operative at three tertiary academic hospitals. The corresponding MCID values were 3.6 (SF-36 physical component summary), 4.2 (SF-36 mental component summary), 5.4 (FACT-General total score), and 6.7 (FACT-Hep total score). The predictors of achieving postoperative MCID were significantly higher in patients who had low preoperative HRQoL score, advanced age, high education level, and high BMI (p < 0.05). However, patients with a high preoperative HRQoL score, high education level, high BMI, and low Charlson comorbidity index score were significantly associated with survival (p < 0.05). Preoperative HRQoL scores were predictive of MCID and overall survival after surgical resection of HCC. The findings of this study may be useful for managing the preoperative expectations of candidates for HCC resection and for developing shared decision-making procedures for patients undergoing surgical resection of HCC.

Impact of preoperative anxiety and depression on quality of life before and after resection of hepatocellular carcinoma.

OBJECTIVE: The impact of anxiety and depression symptoms (ADS) is often estimated in terms of clinical endpoints such as the risk of complications and probabilities of readmission and survival. The purpose of this study was to provide a benchmark for capturing the negative effects of ADS on quality of life after hepatocellular carcinoma (HCC) surgery and to provide an evidence base for future research and clinical interventions aimed at understanding and remediating these effects. METHODS: This prospective study analyzed 410 HCC patients at three tertiary academic hospitals. The Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Functional Assessment of Cancer Therapy- Hepatobiliary (FACT-H) were administered before HCC surgery and at 6 months, 1 year, and 2 years after HCC surgery. Generalized estimating equations were used to estimate differences-in-differences models for examining the effects of ADS. RESULTS: At baseline, 9.0% of the participants had anxiety symptom (BAI > 10), 17.1% had depression symptom (BDI > 13), and 7.1% had ADS. Throughout the study period, anxiety and depression (differences-in-differences value) had significant (P < 0.001) negative net effects on mean scores for all FACT-H dimensions, and the differences gradually increased over time. From baseline through all follow-up years, the two groups significantly (P < 0.001) differed in scores for all FACT-H dimensions, and the differences increased over time. CONCLUSIONS: For healthcare providers, this study highlights the need for continued monitoring for ADS in patients who have undergone hepatic resection and the need for timely and appropriate psychological care for these patients.