Benefit of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Bidirectional Chemotherapy for Patients with Gastric Cancer with Peritoneal Carcinomatosis Considering Cytoreductive Surgery.

Comprehensive treatment comprising neoadjuvant laparoscopic HIPEC (L-HIPEC) and bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) followed by cytoreductive surgery (CRS) for gastric cancer with peritoneal carcinomatosis (PC) has been developed. However, its benefits and patient selection criteria have not been thoroughly investigated. We retrospectively reviewed 113 patients, with 25 having received comprehensive treatment (L-HIPEC, BISIC, and then CRS-HIPEC; the BISIC group) and 88 having received direct CRS-HIPEC (the CRS group). The BISIC group showed greater tumor clearance in terms of post-CRS peritoneal cancer index ((PCI) 6 vs. 14, p = 0.002) compared to CRS group. The median survival was 20.0 months in the BISIC group and 8.6 months in the CRS group (p = 0.031). Multivariable analysis revealed that the factors associated with increased survival were the BISIC protocol, age, and post-CRS tumor clearance. BISIC significantly improved survival in cases of moderate severity (PCI 11-20) and severe cases (PCI 21-39) without increasing the morbidity rate. We recommend the use of this neoadjuvant strategy for patients with gastric cancer-associated PC and an initial PCI of >10 to provide superior survival outcomes.

Genetic alterations in peritoneal metastatic tumors predicted the outcomes for hyperthermic intraperitoneal chemotherapy.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered for patients with peritoneal metastasis (PM). However, patients selection that relies on conventional prognostic factors is not yet optimal. In this study, we performed whole exome sequencing (WES) to establish tumor molecular characteristics and expect to identify prognosis profiles for PM management. Methods: In this study, blood and tumor samples were collected from patients with PM before HIPEC. Tumor molecular signatures were determined using WES. Patient cohort was divided into responders and non-responders according to 12-month progression-free survival (PFS). Genomic characteristics between the two cohorts were compared to study potential targets. Results: In total, 15 patients with PM were enrolled in this study. Driver genes and enriched pathways were identified from WES results. AGAP5 mutation was found in all responders. This mutation was significantly associated with better OS (p = 0.00652). Conclusions: We identified prognostic markers that might be useful to facilitate decision-making before CRS/HIPEC.

Feasibility of Breast Cancer Metastasis Assessment of Ex Vivo Sentinel Lymph Nodes through a p-H&E Optical Coherence Microscopic Imaging System.

Frozen-sectioned hematoxylin-eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images.

Exendin-4 Attenuates Hepatic Steatosis by Promoting the Autophagy-Lysosomal Pathway.

Dysregulated hepatic steatosis may lead to chronic liver inflammation and nonalcoholic steatohepatitis (NASH). Recent studies have suggested that exendin-4, a glucagon-like peptide-1 agonist, may be a promising therapeutic for hepatic steatosis and NASH. However, the molecular mechanisms underlying the antihepatic steatosis actions of exendin-4 are not fully clear. Here, we demonstrate that autophagy is activated by either palmitic acid (PA) or oleic acid (OA) in HepG2 cells, and exendin-4 further enhances the autophagy-lysosomal pathway. We show that inhibition of autophagy by shLC3 attenuates exendin-4-mediated antisteatotic activity. Furthermore, expression of a key lysosomal marker, lysosome associated membrane protein 1 (LAMP1), is upregulated in OA + exendin-4-treated cells. The colocalization of LAMP1 and LC3 puncta further suggests that autophagic flux was enhanced by the cotreatment. Based on these findings, we conclude that autophagic flux might play an important role in the antisteatotic action of exendin-4.

The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI.

BACKGROUND: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). METHODS: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. RESULTS: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2-7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0-2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2-2.6) years. CONCLUSIONS: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.

Metformin reduces radiation-induced cardiac toxicity risk in patients having breast cancer.

To analyze the effects of metformin in reducing radiation-induced cardiac toxicity (RICT) risk during adjuvant radiotherapy (RT) after surgery for early-stage breast cancer women. We compare the consecutive occurrence of major heart events (heart failure and coronary artery disease) in women with early-stage breast cancer receiving adjuvant breast RT with metformin and in those receiving RT without metformin. A retrospective national cohort study was conducted using the Taiwan Cancer Registry of 2004-2014. This study included 6,993 women with early-stage breast cancer who received adjuvant breast RT. Metformin users were defined as patients prescribed metformin for >28 days during adjuvant breast RT. An inverse probability of treatment weighting (IPTW) Cox hazards model was used to estimate metformin effects on the occurrence of major heart events. Among women with breast cancer status post-surgery under adjuvant breast RT, 2,062 were prescribed metformin and 4,931 were not prescribed metformin. Cox proportional hazard regression analysis, with adjustment using IPTW, indicated that metformin use during adjuvant breast RT significantly reduces the risk of major heart events (adjusted hazard ratio [aHR], 0.789; 95% confidence interval [CI], 0.645-0.965; P = 0.021). In another negative control exposure, thiazolidinedione use during adjuvant breast RT did not statistically reduce consecutive RICT risk (aHR, 1.106; 95% CI, 0.768-1.594; P = 0.589). Our results suggest that metformin use during adjuvant breast RT was associated with reduced RICT risk in women with early-stage breast cancer.

Effects of duodenal-jejunal bypass surgery in ameliorating nonalcoholic steatohepatitis in diet-induced obese rats.

BACKGROUND: Duodenal-jejunal bypass (DJB) is an important component of many types of current bariatric surgery including Roux-en-Y gastric bypass, mini-gastric bypass, biliopancreatic diversion, duodenal switch, and DJB plus sleeve gastrectomy. Surgery is often observed to ameliorate nonalcoholic steatohepatitis (NASH), but without a clearly delineated mechanism. In this study, we investigated the effects of DJB in diet-induced obese rats with NASH. MATERIALS AND METHODS: Male Wistar rats were divided into four groups and fed the following diets over 6 months: A) normal chow (NC group, n=6); B) methionine-choline-deficient (MCD)-high-fat (HF) diet (HF group, n=6); C) MCD-HF diet for 3 months followed by DJB and MCD-HF diet for subsequent 3 months (DJB group, n=6); and D) MCD-HF diet for 3 months followed by treatment with pioglitazone (PGZ) with MCD-HF diet for subsequent 3 months (PGZ group, n=6). Body weight, glucose tolerance, the homeostatic model assessment-insulin resistance index, and lipid profiles were compared. Liver and visceral adipose tissue histology, inflammatory marker and hepatic stellate cell (HSC) activity, and hepatocyte autophagy were assessed. RESULTS: Compared with the HF group, the DJB group showed improved body weight, insulin sensitivity, lipid metabolism, and steatosis severity. The DJB group exhibited a significantly lower nonalcoholic fatty liver disease activity score than the HF and PGZ group (P<0.001 and P=0.003, respectively). Furthermore, DJB significantly reduced fat mass and adipocyte size. These effects were also observed in the PGZ group. Therefore, we speculated that the improvements induced by DJB are closely related to an alteration in insulin sensitivity. Moreover, DJB reduced HSC activity and TNF-α expression and enhanced hepatocyte autophagy. CONCLUSION: DJB improves NASH through several mechanisms, particularly by altering insulin sensitivity, inflammatory responses, HSC activity, and hepatocyte autophagy.

Experience of applying cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for ovarian teratoma with malignant transformation and peritoneal dissemination.

OBJECTIVES: The prognosis of ovarian teratoma with malignant transformation and peritoneal dissemination (PD) is poor. This condition is rare but associated with a high recurrence rate even after aggressive debulking surgery and adjuvant chemotherapy. In the present paper, we describe our experience of using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for this condition. METHODS: The data of ten female patients having ovarian teratoma with malignant transformation and PD between June 2007 and June 2017 were collected and reviewed retrospectively. CRS-HIPEC was performed according to the standard protocol. Patient characteristics, pathological reports, tumor markers, perioperative operative parameters, postoperative events, and disease status during the follow-up period were recorded. RESULTS: The primary ovarian neoplasms were pure mature cystic teratoma with malignant transformation (n=6, including 5 of mucinous adenocarcinoma), mixed germ cell tumor with mature cystic teratoma and yolk sac tumor (YST) (n=1), pure immature teratoma (n=1), immature teratoma with growing teratoma syndrome (GTS) (n=1), and immature teratoma mixed YST with GTS (n=1). The mean levels of tumor markers, including carcinoembryonic antigen, cancer antigen 19-9 (CA19-9), and CA125, were markedly elevated. The recurrence rate was 10%. The median and mean disease-free survival (DFS) after CRS-HIPEC were 22.3 and 36.2 months, respectively, and the 5-year DFS rate is 88%. CONCLUSION: CRS-HIPEC is a safe therapeutic option for reducing the recurrence rate in selected patients with PD originating from ovarian teratoma with malignant transformation.

Multidisciplinary team intervention associated with improved survival for patients with colorectal adenocarcinoma with liver or lung metastasis.

BACKGROUND AND OBJECTIVES: To investigate whether multidisciplinary team (MDT) intervention is associated with improved survival for patients with colorectal adenocarcinoma with liver or lung metastasis (CRA-LLM). METHODS: We enrolled 161 consecutive patients with histologically confirmed CRA-LLM at Taipei Medical University-Wan Fang Hospital between January 2007 and December 2017. In total, 75 patients with CRA-LLM received MDT intervention, and 86 patients did not receive MDT intervention. To evaluate prognostic factors for overall death, we performed univariate and multivariate Cox regression analyses of the overall death rate in all patients. Overall survival rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test (P < .001). RESULTS: A multivariate Cox regression analysis of the overall death rate in patients with CRA-LLM showed that age ≤ 65 years, systemic chemotherapy, curative-intent treatments, and MDT intervention are strong prognostic factors. The adjusted hazard ratio of death risk for age ≤ 65 years, systemic chemotherapy, curative-intent treatments, and MDT intervention were 0.60 (95% confidence interval [CI], 0.40-0.92; P = .019), 0.19 (95% CI, 0.12-0.32; P = .001), 0.25 (95% CI, 0.13-0.50; P = .001), and 0.40 (95% CI, 0.25-0.65; P = .001), respectively. The 3-year overall survival rates in patients with CRA-LLM receiving MDT intervention and not receiving MDT intervention were 48.75% and 24.21%, respectively. CONCLUSION: MDT intervention is associated with improved survival for patients with CRA-LLM.

Intensity-modulated radiotherapy with systemic chemotherapy improves survival in patients with nonmetastatic unresectable pancreatic adenocarcinoma: A propensity score-matched, nationwide, population-based cohort study.

PURPOSE: In the era of intensity-modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of IMRT exclusively, such as concurrent chemoradiotherapy (CCRT), sequential induction chemotherapy followed by radiotherapy (CT-RT), and systemic chemotherapy (CT) alone, for treating unresectable pancreatic adenocarcinomas (PAs) without metastasis. Through propensity score matching, we designed a nationwide, population-based, head-to-head cohort study to determine the effects of various treatments on unresectable PAs. PATIENTS AND METHODS: We minimized the confounding effects of various treatment outcomes in patients with unresectable PAs from the Taiwan Cancer Registry database by dividing them as follows: group 1, CCRT; group 2, sequential CT-RT; group 3, nontreatment; and group 4, CT alone. RESULTS: The matching process yielded a final cohort of 2960 patients (740 patients each in groups 1, 2, 3, and 4). In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (95% confidence interval) derived for the definitive CCRT and sequential CT-RT groups compared with the CT alone group were 0.443 (0.397-0.495) and 0.633 (0.568-0.705), respectively. CONCLUSIONS: A combination of IMRT and systemic CT for the treatment of unresectable PAs might increase survival compared with CT alone.

Is there an oncological interest in the combination of CRS/HIPEC for peritoneal carcinomatosis of HCC? Results of a multicenter international study.

INTRODUCTION: Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. METHODS: An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. RESULTS: The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). CONCLUSION: CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

Outcomes of adjuvant treatments for resectable intrahepatic cholangiocarcinoma: Chemotherapy alone, sequential chemoradiotherapy, or concurrent chemoradiotherapy.

BACKGROUND: Prospective randomized trials have not been used to evaluate the efficacy of adjuvant therapies after intrahepatic cholangiocarcinoma (ICC) resection. METHODS: We analyzed data from the Taiwan Cancer Registry database of ICC patients receiving resection. To compare outcomes, patients with ICC were enrolled and categorized into the following adjuvant treatment modality groups: group 1, concurrent chemoradiotherapy (CCRT); group 2, sequential chemotherapy (CT) and radiotherapy (RT); and group 3, CT alone. RESULTS: We enrolled 599 patients with resectable ICC who received surgery without distant metastasis. Of these patients, 174 received adjuvant CCRT (group 1), 146 received adjuvant sequential CT and RT (group 2), and 279 received adjuvant CT alone (group 3). Multivariate Cox regression analysis indicated that pathologic stage and positive margin were significantly poor independent predictors. After adjustment for confounders, adjusted hazard ratios (95% confidence intervals) for overall mortality at advanced pathologic stages III and IV were 0.55 (0.41-0.74) and 0.92 (0.70-1.33) in groups 1 and 2, respectively, compared with group 3. CONCLUSIONS: Adjuvant CCRT improved survival in resected ICC with advanced pathologic stages or a positive margin in early pathologic stages compared with adjuvant CT alone or adjuvant sequential CT and RT.

Adjuvant radiotherapy and chemotherapy improve survival in patients with pancreatic adenocarcinoma receiving surgery: adjuvant chemotherapy alone is insufficient in the era of intensity modulation radiation therapy.

In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT-RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population-based, head-to-head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT-RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT-RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314-0.504) and 0.307 (0.235-0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone.

Tumor location is an independent predictive factor for distant metastasis and metastatic sites of rectal adenocarcinoma in patients receiving total mesorectal excision.

Background and Objectives: To evaluate the predictive factor for and patterns of distant metastasis in patients with rectal adenocarcinoma receiving total mesorectal excision (TME). Methods: We enrolled 217 consecutive patients who had histologically confirmed rectal adenocarcinoma and underwent surgery at Taipei Medical University- Wanfang Hospital between January 2000 and December 2014. TME was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. We performed univariate and multivariate Cox regression analyses of the distant metastasis rate in all patients to evaluate predictive factors. Overall survival (OS) rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test. Results: A multivariate Cox regression analysis of the distant metastasis rate in patients with rectal adenocarcinoma identified tumor locations and American Joint Committee on Cancer (AJCC) stages as prognostic risk factors. The adjusted hazard ratios (aHRs) of distant metastasis for the upper-third, middle-third, and AJCC stage I-II cancers were 0.08 (95% CI, 0.01-0.69; p = 0.021), 0.41 (95% CI, 0.15-0.99; p = 0.047), and 0.20 (95% CI, 0.10-0.66; p = 0.008), respectively. The 5-year lung metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 0%, 3.37%, and 13.33%, respectively (log-rank, p = 0.001), and the 5-year liver metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 2.12%, 9.10%, and 11.76%, respectively (log-rank, p = 0.096). The 5-year OS rates also differed with different rectal adenocarcinoma locations. The 5-year OS rates for upper, middle, and lower rectal cancers were 96%, 86%, and 64%, respectively (log-rank, p < 0.001). Conclusion: A poor OS rate and high lung or liver metastasis rate were observed in distal rectal adenocarcinoma. Longer intensive surveillance of the chest, abdomen, and pelvis after TME in distal rectal adenocarcinoma could be necessary.

Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways.

Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1ß, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal goblet cell carcinomas with peritoneal carcinomatosis: results from a single specialized center.

BACKGROUND: Goblet cell carcinomas (GCCs) of the appendix are rare and aggressive malignancies with early peritoneal dissemination. The aim of the present article is to describe our experience in the management of GCCs with peritoneal carcinomatosis (PC) through cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) and to determine the impact of multiple clinical characteristics on the prognosis. METHODS: From a prospectively maintained database of patients receiving CRS and HIPEC for peritoneal surface malignancy, the data of 15 patients with GCC and PC were collected. Neo-adjuvant laparoscopic HIPEC was performed if indicated. CRS and HIPEC with mitomycin-C or 5-fluorouracil plus oxaliplatin were performed. Adjuvant chemotherapy was also arranged if suitable for the patient's condition. RESULTS: Nine males and six females with a mean age of 52.4 years were enrolled. The estimated median survival after the diagnosis of GCC with PC and after definitive CRS-HIPEC was 28 and 17 months, respectively. The 1-, 2-, 3-, 4-year survival rates were 86%, 69%, 57%, and 24%, respectively. Log-rank test revealed that the significant independent risk factors for more favorable outcomes were age >50 years, peritoneal cancer index (PCI) <27, postoperative PCI <20, administration of HIPEC, and adjuvant chemotherapy. Multivariate analyses confirmed that administration of HIPEC played a crucial role in providing prognostic benefit. CONCLUSION: The management of GCC with PC remains challenging. We recommend CRS and HIPEC, followed by adjuvant systemic chemotherapy, as a promising strategy to improve survival, especially in selected patients with low PCI and possibility to achieve complete cytoreduction.

A critical reappraisal for the value of tumor size as a prognostic variable in rectal adenocarcinoma.

Background and Objectives: To investigate critical prognostic factors for local recurrence in patients with rectal adenocarcinoma. Methods: We enrolled 221 consecutive patients who had histologically confirmed adenocarcinoma of the rectum and underwent surgery in our hospital between January 2000 and December 2014. Total mesorectal excision was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. To evaluate prognostic factors for local recurrence, we performed univariate and multivariate Cox regression analyses of the local recurrence rate in all patients. Overall survival rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test. Results: After the inclusion of only model variables of local recurrence with the highest or lowest univariate risk, a tumor size of <5 cm, a negative circumferential margin, well-to-moderately differentiated adenocarcinoma, low anterior resection, not receiving adjuvant RT, pathological T1-T3 stages, and upper- and middle-third rectal cancers were identified as strong prognostic factors with hazard ratios of 0.18, 0.20, 0.03, 0.01, 0.25, 0.18 and 0.18, respectively (95% confidence intervals [CIs], 0.06-0.58, 0.05-0.82, 0.03-0.38, 0.04-0.23, 0.05-0.64,0.09-0.70 and 0.06-0.54, respectively). After the multivariate Cox regression analysis of the local recurrence rate, a pathological tumor size of ≥5 cm was identified as the only prognostic risk factor (95% CI, 0.03-0.66; P = 0.013). The 5-year local recurrence rates among the patients having tumors measuring <5 cm and ≥5 cm in size were 1.40% and 23.00%, respectively (log-rank, P = 0.0001). The 5-year overall survival rates in the patients having tumors measuring <5 cm and ≥5 cm in size were 82.60% and 71.20%, respectively (log-rank, P = 0.001). Conclusion: A pathological tumor size of ≥5 cm is an independent prognostic factor for local recurrence in rectal adenocarcinoma.

Experiences with cytoreduction surgery plus hyperthermic intraperitoneal chemotherapy in Taiwan.

Our hospital was the first institution to offer cytoreduction surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Taiwan. Therefore, we report our experience and outcomes among patients who underwent HIPEC.Since 2002, 164 eligible patients underwent HIPEC, and we excluded cases of laparoscopic or prophylactic HIPEC. The cases were categorized according to whether they were treated before 2012 (Period 1: 80 cases) or after 2012 (Period 2: 84 cases).The rates of surgical morbidity were 46.3% during Period 1 and 20.2% during Period 2 (P < .01), and the rates of severe complications were 25% during Period 1 and 9.5% during Period 2 (P < .01). The 5-year overall survival rate was 35.8%, with rates of 13.4% for gastric cancer, 27.3% for colon cancer, 70.0% for appendiceal cancer, and 52.4% for ovarian cancer (median follow-up: 34 months). The survival rate was 42.1% when we achieved a cytoreduction score of 0/1, compared with 21.1% in the group with a cytoreduction score of 2/3 (P < .01). Severe complications were associated with a 5-year survival rate of 23.4%, compared with 37.9% among cases without severe complications (P = .01). Complete cytoreduction was achieved in 78.6% of the patients if they underwent their first surgery at our hospital.We have become an experienced hospital for CRS plus HIPEC. Although our complication rate for CRS plus HIPEC was high, it was within the acceptable range. Long-term survival was achieved in a few cases.

Cyproheptadine use in hepatocellular carcinoma.

This study was conducted to compare the effectiveness of Cyproheptadine (CY) use in patients with different stages of HCC who received different therapeutic modalities; such a comparison has not been conducted by previous large, prospective, randomized studies. We conducted a cohort study using the Taiwan Cancer Registry Database for analysis. We included patients diagnosed as having HCC from January 1, 2002, to December 31, 2011. The patient cohort comprised those who received different treatments, and we compared patients who received CY with those who did not. In total, 70,885 patients were included, and the mean follow-up duration was 1.95 years. The adjusted hazard ratio (aHR) of all-cause deaths significantly decreased in all stages in the patients who received palliative treatments with CY use compared with those who received palliative treatments without CY use (all P < 0.0001 and aHR = 0.76, 0.80, 0.66, and 0.66 for stages I, II, III, and IV, respectively). Among the patients who received no treatment, CY use alone reduced the risk of all-cause deaths in stages I-IV (all P < 0.0001 and aHR = 0.61, 0.57, 0.54, and 0.52 for stages I, II, III, and IV, respectively). Among the patients with clinical stage I-II HCC (as determined by the American Joint Committee on Cancer) who received curative treatments, CY use did not reduce all-cause deaths. CY use might improve survival in patients with HCC receiving palliative treatments or no treatment regardless of clinical stages.

A polygenic risk score for breast cancer risk in a Taiwanese population.

BACKGROUND: Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population. METHODS: In total, 446 breast cancer patients and 514 healthy controls were recruited for this case-control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC). RESULTS: Logistic regression results showed that nine individual SNPs were significantly associated with breast cancer risk after multiple testing. Among all SNPs, six variants, namely FGFR2 (rs2981582), HCN1 (rs981782), MAP3K1 (rs889312), TOX3 (rs3803662), ZNF365 (rs10822013), and RAD51B (rs3784099), were selected to create PRS model. A dose-response association was observed between breast cancer risk and the PRS. Women in the highest quartile of PRS had a significantly increased risk compared to women in the lowest quartile (odds ratio 2.26; 95% confidence interval 1.51-3.38). The AUC for a model which contained the PRS in addition to clinical risk factors was 66.52%, whereas that for a model which with established risk factors only was 63.38%. CONCLUSIONS: Our data identified a genetic risk predictor of breast cancer in Taiwanese population and suggest that risk models including PRS and clinical risk factors are useful in discriminating women at high risk of breast cancer from those at low risk.