Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial.

BACKGROUND: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. METHODS: This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2-4 weeks in the TNT group and 6-10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. DISCUSSION: The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. TRIAL REGISTRATION: Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.

Association of illness understanding with advance care planning and end-of-life care preferences for advanced cancer patients and their family members.

PURPOSE: Little has been determined regarding the association between patients' and families' illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers. METHODS: Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results. RESULTS: Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients' illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC. CONCLUSION: Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.

Erratum: Correction of the Text in the Article "Table": Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

This corrects the article on e327 in vol. 33, PMID: 30505258.

Erratum: Correction of Ethics Statement: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

[This corrects the article e327 in vol. 33, PMID: 30505258.].

Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

BACKGROUND: It is difficult to decide whether to inform the child of the incurable illness. We investigated attitudes of the general population and physicians toward prognosis disclosure to children and associated factors in Korea. METHODS: Physicians working in one of 13 university hospitals or the National Cancer Center and members of the general public responded to the questionnaire. The questionnaire consisted of the age appropriate for informing children about the prognosis and the reason why children should not be informed. This survey was conducted as part of research to identify perceptions of physicians and general public on the end-of-life care in Korea. RESULTS: A total of 928 physicians and 1,241 members of the general public in Korea completed the questionnaire. Whereas 92.7% of physicians said that children should be informed of their incurable illness, only 50.7% of the general population agreed. Physicians were also more likely to think that younger children should know about their poor prognosis compared with the general population. Physicians who opposed incurable illness disclosure suggested that children might not understand the situation, whereas the general public was primarily concerned that disclosure would exacerbate the disease. Physicians who were women or religious were more likely to want to inform children of their poor prognosis. In the general population, gender, education, comorbidity, and caregiver experience were related to attitude toward poor prognosis disclosure to children. CONCLUSION: Our findings indicate that physicians and the general public in Korea differ in their perceptions about informing children of poor prognosis.

Germ Cell Tumor Targeting Chemotherapy in Gastric Adenocarcinoma with an Endodermal Sinus Tumor Component: A Case Report.

The most common sites for extragonadal germ cell tumors are the midline mediastinum, retroperitoneum and, much less frequently, the stomach. The stomach-originated primary germ cell tumor carries a poor prognosis, especially when metastasis occurs to the liver, with a mean survival time of 1 month. We describe the case of a 77-year-old male who presented with usual symptoms of gastric malignancy. Gastrectomy was performed. Histopathology of surgically resected tissue revealed a mixture of adenocarcinoma and endodermal sinus tumor components with α-fetoprotein production. After liver metastasis was identified, oxaliplatin and capecitabine were administered as palliative chemotherapy. The response was poor. For the second-line therapy, bleomycin, etoposide, and cisplatin (BEP) therapy was initiated. The overall response to these drugs was a partial response and the residual liver lesion was considered to be resectable. The patient died of pneumonia 11 months following the BEP session, representing an overall survival time of 22 months. Gastric adenocarcinoma with a germ cell tumor component is uncommon and an effective combination of chemotherapeutic agents is not yet clear. In this case, the patient received germ cell tumor-targeting chemotherapy and showed a durable response. Hence, germ cell-targeting cytotoxic agents have potential as the 'front-line regimen'.

Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy.

PURPOSE: To investigate the significance of carbohydrate antigen 19-9 (CA19-9) levels for survival in locally advanced pancreatic cancer (LAPC) treated with concurrent chemoradiotherapy (CCRT). METHODS/PATIENTS: We retrospectively reviewed data from 97 LAPC patients treated with CCRT between 2000 and 2013. CA19-9 levels (initial and post-CCRT) and their changes [{(post-CCRT CA19-9 level - initial CA19-9 level)/(initial CA19-9 level)} × 100] were analyzed for overall survival. A cut-off point of 37 U/mL was used to analyze initial and post-CCRT CA19-9 levels. In order to define an optimal cut-off point for change in CA19-9 level, the maxstat package of R was applied. RESULTS: Median overall survival was 14.7 months (95% CI 13.4-16.0), and the 2-year survival rate was 16.5%. The estimated optimal cut-off point of CA19-9 level change was 94.4%. On univariate analyses, CA19-9 level change between initial and post-CCRT was significantly correlated with overall survival (median survival time 9.7 vs 16.3 months, p < 0.001). Multivariate analyses confirmed that CA19-9 level change from initial to post-CCRT was the only prognostic factor (p < 0.001). CONCLUSIONS: Change in CA19-9 level between initial and post-CCRT was a significant prognostic marker for overall survival in LAPC treated with CCRT. A CA19-9 level increase >94.4% might serve as a surrogate marker for poor survival in patients with LAPC undergoing CCRT, and the prognostic power surpassed other CA19-9 variables including initial and post-CCRT values.

Early Integrated Palliative Care in Patients With Advanced Cancer: A Randomized Clinical Trial.

Importance: Limited data suggest that early palliative care (EPC) improves quality of life (QOL) and survival in patients with advanced cancer. Objective: To evaluate whether comprehensive EPC improves QOL; relieves mental, social, and existential burdens; increases survival rates; and helps patients develop coping skills. Design, Setting, and Participants: This nonblinded randomized clinical trial (RCT) recruited patients from 12 hospitals in South Korea from September 2017 to October 2018. Patients aged 20 years or older with advanced cancer who were not terminally ill but for whom standard chemotherapy has not been effective were eligible. Participants were randomized 1:1 to the control (receiving usual supportive oncological care) or intervention (receiving EPC with usual oncological care) group. Intention-to-treat data analysis was conducted between September and December 2022. Interventions: The intervention group received EPC through a structured program of self-study education materials, telephone coaching, and regular assessments by an integrated palliative care team. Main Outcomes and Measures: The primary outcome was the change in overall QOL score (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care) from baseline to 24 weeks after enrollment, with evaluations also conducted at 12 and 18 weeks. Secondary outcomes were social and existential burdens (assessed with the McGill Quality of Life Questionnaire) as well as crisis-overcoming capacity and 2-year survival. Results: A total of 144 patients (83 males [57.6%]; mean [SD] age, 60.7 (7.2) years) were enrolled, of whom 73 were randomized to the intervention group and 71 to the control group. The intervention group demonstrated significantly greater changes in scores in overall health status or QOL from baseline, especially at 18 weeks (11.00 [95% CI, 0.78-21.22] points; P = .04; effect size = 0.42). However, at 12 and 24 weeks, there were no significant differences observed. Compared with the control group, the intervention group also showed significant improvement in self-management or coping skills over 24 weeks (20.51 [95% CI, 12.41-28.61] points; P < .001; effect size = 0.93). While the overall survival rate was higher in the intervention vs control group, the difference was not significant. In the intervention group, however, those who received 10 or more EPC interventions (eg, telephone coaching sessions and care team meetings) showed a significantly increased probability of 2-year survival (53.6%; P < .001). Conclusions and Relevance: This RCT demonstrated that EPC enhanced QOL at 18 weeks; however, no significant improvements were observed at 12 and 24 weeks. An increased number of interventions sessions was associated with increased 2-year survival rates in the intervention group. Trial Registration: ClinicalTrials.gov Identifier: NCT03181854.

Long-Term Breast Cancer Outcomes of Pregnancy-Associated Breast Cancer (PABC) in a Prospective Cohort.

Background: Given that peak age of breast cancer (BC) is younger in Asians than in Western populations, relatively higher prevalence of pregnancy-associated breast cancer (PABC) has been reported. This study aimed to analyze the characteristics and clinical outcomes of PABC in Korea. Methods: We defined PABC as BC diagnosed during pregnancy or in the first postpartum year. We compared the clinicopathological characteristics and BC outcomes between patients with PABC and non-PABC patients in the prospective YBC cohort from Samsung Medical Center. Results: In total, 1492 patients were initially enrolled, and 1364 patients were included, of which 93 had PABC (6.8%). The median age of patients with PABC was 34 years. Hormone receptor expression was lower (64.6% vs 74.6%) and frequency of HER2 overexpression was higher (26.9% vs 17.6%) in patients with PABC than in non-PABC patients. The 5-year overall survival (OS) rates were 83.2% and 93.4% in patients with PABC and non-PABC patients, respectively (p < 0.001). The 5-year disease-free survival (DFS) rates were 72.2% and 83.8% in PABC and non-PABC patients. Conclusion: Compared to non-PABC patients, patients with PABC had poorer OS and DFS in this prospective cohort. Exploratory biomarker analysis for PABC is warranted.

Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species.

NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2', 7'-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOXTM Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO2 (Cysteine sulfinic acid, Cys-SO2H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO2 form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.

Clinical Practice Guideline for Care in the Last Days of Life.

A clinical practice guideline for patients in the dying process in general wards and their families, developed through an evidence-based process, is presented herein. The purpose of this guideline is to enable a peaceful death based on an understanding of suitable management of patients' physical and mental symptoms, psychological support, appropriate decision-making, family care, and clearly-defined team roles. Although there are limits to the available evidence regarding medical issues in patients facing death, the final recommendations were determined from expert advice and feedback, considering values and preferences related to medical treatment, benefits and harms, and applicability in the real world. This guideline should be applied in a way that takes into account specific health care environments, including the resources of medical staff and differences in the available resources of each institution. This guideline can be used by all medical institutions in South Korea.

Vascular events in Korean patients with myeloproliferative neoplasms and their relationship to JAK2 mutation.

Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients' diagnoses were essential thrombocythemia (ET n = 146), polycythemia vera (PV n = 120), primary myelofibrosis (n = 12), and unclassifiable MPN (MPNu n = 5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p = 0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p = 0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

A case of Wernicke's encephalopathy following fluorouracil-based chemotherapy.

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.

Mapping of local recurrence after pancreaticoduodenectomy for distal extrahepatic cholangiocarcinoma: implications for adjuvant radiotherapy.

OBJECTIVE: To generate a map of local recurrences after pancreaticoduodenectomy (PD) for patients with distal extrahepatic cholangiocarcinoma (DEHC) and to evaluate the adequate target volume coverage encompassing the majority of local recurrences when the clinical target volume (CTV) for pancreatic cancer was applied. METHODS: We retrospectively reviewed the records of DEHC patients who underwent pancreaticoduodenectomy and had postoperative CT scans acquired between 1991 and 2015 available. The sites of local recurrence were delineated on individual CT scans, and then, mapping was manually performed onto template CT images. Coverage of each site of local recurrence was evaluated by applying the CTV defined according to Radiation Therapy Oncology Group (RTOG) consensus guidelines (CTVRTOG ) for target delineation in the postoperative treatment of pancreatic head cancer. RESULTS: Of the 99 patients, 36 patients had a total of 62 local relapses identifiable by postoperative CT scans; the relapses were the most frequent in the choledochojejunostomy (CJ) site, 11 sites (17.7%); para-aortic area, 10 sites (16.1%), superior mesenteric artery area, 10 sites (16.1%); and portal vein area, 9 sites (14.5%). 21 sites (33.9%) were not covered by the CTVRTOG, and the most common site of local recurrence outside the CTVRTOG was the CJ site. CONCLUSION: When mapping of local relapses was evaluated according to the CTVRTOG, the choledochojejunostomy site was identified as a high-risk area of local recurrence but was insufficiently covered within the CTVRTOG. These findings may help construct a target volume for postoperative radiotherapy in DEHC. ADVANCES IN KNOWLEDGE: Mapping local recurrences can aid in defining appropriate target volume for postoperative radiotherapy in DEHC.

Factors That Influence Attitudes Toward End-of-Life Care Among Medical Students: Nationwide Survey for Fourth-Year Korean Medical Students.

BACKGROUND: Positive attitudes for end-of-life (EOL) care along with adequate education are key factors for the provision of quality EOL care. This national study was conducted to identify the factors that influence attitudes toward EOL care on medical students. METHOD: An anonymous survey was designed and administered to fourth-year medical students at all 41 medical schools in Korea. Topics related to EOL care were assessed in classroom teaching, bedside teaching, and feedback experiences during clinical clerkships. Seven questions for self-rated attitudes and affecting factors were analyzed toward EOL care. RESULTS: With a response rate of 49.2%, the median number of topics recognized by the students as having been delivered was 5 of 11 topics in classroom lectures and 1 of 8 topics in clinical experience. Although few (21.2%) participants indicated that they felt ready for EOL care practice, nevertheless, most felt that they should have adequate knowledge of and preparation for clinical competency in EOL care. Several parameters including respondent's demographics and exposure to EOL care topics in classroom and in bedside teaching influenced the responses to all 7 attitude questions. However, having more than 1 bedside experience was the only factor positively affecting all attitudinal measures. CONCLUSIONS: Clinical experience related to EOL care seems to be the utmost priory in fostering positive attitudes and competency among medical students.

Efficacy of a Decision Aid Consisting of a Video and Booklet on Advance Care Planning for Advanced Cancer Patients: Randomized Controlled Trial.

CONTEXT: Few randomized controlled trials of advance care planning (ACP) with a decision aid (DA) show an effect on patient preferences for end-of-life (EOL) care over time, especially in racial/ethnic settings outside the U.S. OBJECTIVES: The objective of this study was to examine the effect of a decision aid consisting of a video and an ACP booklet for EOL care preferences among patients with advanced cancer. METHODS: Using a computer-generated sequence, we randomly assigned (1:1) patients with advanced cancer to a group that received a video and workbook that both discussed either ACP (intervention group) or cancer pain control (control group). At baseline, immediately after intervention, and at 7 weeks, we evaluated the subjects' preferences. The primary outcome was preference for EOL care (active treatment, life-prolonging treatment, or hospice care) on the assumption of a fatal disease diagnosis and the expectation of death 1) within 1 year, 2) within several months, and 3) within a few weeks. We used Bonferroni correction methods for multiple comparisons with an adjusted P level of 0.005. RESULTS: From August 2017 to February 2018, we screened 287 eligible patients, of whom 204 were enrolled to the intervention (104 patients) or the control (100 patients). At postintervention, the intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within 1 year (P < 0.005). Assuming a life expectancy of several months, the change in preferences was significant for active treatment and hospice care (P < 0.005) but not for life-prolonging treatment. The intervention group showed a significant increase in preference for active treatment, life-prolonging treatment, and hospice care on the assumption of a fatal disease diagnosis and the expectation of death within a few weeks (P < 0.005). From baseline to 7 weeks, the decrease in preference in the intervention group was not significant for active treatment, life-prolonging treatment, and hospice care in the intervention group in the subset expecting to die within 1 year, compared with the control group. Assuming a life expectancy of several months and a few weeks, the change in preferences was not significant for active treatment and for life-prolonging treatment but was significantly greater for hospice care in the intervention group (P < 0.005). CONCLUSION: ACP interventions that included a video and an accompanying book improved preferences for EOL care.

Attitudes of the General Public, Cancer Patients, Family Caregivers, and Physicians Toward Advance Care Planning: A Nationwide Survey Before the Enforcement of the Life-Sustaining Treatment Decision-Making Act.

CONTEXT: To respect a patient's wish for end-of-life care, "the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life" was enacted in South Korea in 2016. Current understanding of people who would be involved in advance care planning (ACP) is crucial to disseminate it systematically. OBJECTIVES: The objective of this study was to investigate awareness and attitudes toward ACP in South Korea. METHODS: A multicenter, nationwide cross-sectional study was conducted, a survey regarding ACP among four groups that would have different positions and experiences: 1001 cancer patients, 1006 family caregivers, 928 physicians, and 1241 members of the general public. RESULTS: A total of 15% of the general population, 33% of the patients and caregivers, and 61% of the physicians had knowledge of advance directives. More than 64% of the general population, above 72% of the patients and caregivers, and 97% of the physicians were willing to do so when the disease status was aggravated or terminal. The possibility for changing the plan, uncertainty as to whether directives would actually be followed, and psychological discomfort were common reasons for not wanting to engage in ACP. Routine recommendations for a specific medical condition, heightened accessibility, and health insurance support were common factors that could help facilitate ACP. CONCLUSION: Our findings suggest that strategies for promoting ACP should reflect different perspectives among the general public, patients, family caregivers, and physicians. Public advocacy, resources for approaching and integrating ACP into routine health care, as well as systematic support provisions are needed.

The impact of primary tumor location in patients with metastatic colorectal cancer: a Korean Cancer Study Group CO12-04 study.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSION: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.

Prognostic significance of CD44s expression in biliary tract cancers.

BACKGROUND: CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers. METHODS: Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed. RESULTS: Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37-86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211-.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630-3.393; P = .377) had no prognostic significance for survival. CONCLUSIONS: CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

Prognostic Significance of Survivin Expression and Combined Analysis with Cancer Stem Cell and Epithelial-Mesenchymal Transition-related Markers in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy.

AIM: To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial-mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated. RESULTS: The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003). CONCLUSION: Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.