Comprehensive genomic profiling and therapeutic implications for Taiwanese patients with treatment-naïve breast cancer.

BACKGROUND: Breast cancer is a heterogeneous disease categorized based on molecular characteristics, including hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression levels. The emergence of profiling technology has revealed multiple driver genomic alterations within each breast cancer subtype, serving as biomarkers to predict treatment outcomes. This study aimed to explore the genomic landscape of breast cancer in the Taiwanese population through comprehensive genomic profiling (CGP) and identify diagnostic and predictive biomarkers. METHODS: Targeted next-generation sequencing-based CGP was performed on 116 archived Taiwanese breast cancer specimens, assessing genomic alterations (GAs), including single nucleotide variants, copy number variants, fusion genes, tumor mutation burden (TMB), and microsatellite instability (MSI) status. Predictive variants for FDA-approved therapies were evaluated within each subtype. RESULTS: In the cohort, frequent mutations included PIK3CA (39.7%), TP53 (36.2%), KMT2C (9.5%), GATA3 (8.6%), and SF3B1 (6.9%). All subtypes had low TMB, with no MSI-H tumors. Among HR + HER2- patients, 42% (27/65) harbored activating PIK3CA mutations, implying potential sensitivity to PI3K inhibitors and resistance to endocrine therapies. HR + HER2- patients exhibited intrinsic hormonal resistance via FGFR1 gene gain/amplification (15%), exclusive of PI3K/AKT pathway alterations. Aberrations in the PI3K/AKT/mTOR and FGFR pathways were implicated in chemoresistance, with a 52.9% involvement in triple-negative breast cancer. In HER2+ tumors, 50% harbored GAs potentially conferring resistance to anti-HER2 therapies, including PIK3CA mutations (32%), MAP3K1 (2.9%), NF1 (2.9%), and copy number gain/amplification of FGFR1 (18%), FGFR3 (2.9%), EGFR (2.9%), and AKT2 (2.9%). CONCLUSION: This study presents CGP findings for treatment-naïve Taiwanese breast cancer, emphasizing its value in routine breast cancer management, disease classification, and treatment selection.

Transversus abdominis plane block for laparoscopic colorectal surgery: A meta-analysis of randomised controlled trials.

BACKGROUND: The effectiveness of transversus abdominis plane block (TAP) on pain management after laparoscopic colorectal surgery (CRS) remains unclear since the only relevant meta-analysis on this topic did not separate laparoscopic CRS from open CRS. The aim of the study was to compare the analgesic efficacy and safety of TAP with non-TAP in patients undergoing laparoscopic CRS. METHODS: Four databases were searched for randomized controlled trials (RCTs) on this topic using relevant keywords. Two authors independently completed evidence selection, data extraction, and critical appraisal. Available data were pooled in the random-effects model, and point estimates with 95% confidence interval (CI) were reported for postoperative pain at rest and on coughing, opioid consumption, length of hospital stay, and adverse events. RESULTS: A total of 14 RCTs (n = 1216) contributed to the present synthesis. Pooled result showed that patients in the TAP group had lower pain at rest than those in the non-TAP group at postoperative 2-h (mean difference [MD] = -1.42; P < 0.05), 4-h (MD = -0.97; P < 0.05), 12-h (MD = -0.75; P < 0.05), and 24-h (MD = -0.61; P < 0.05). Patients in the TAP group also had lower postoperative pain on coughing than those in the non-TAP group on the first day (MD = -1.02; P < 0.05). Moreover, TAP had lesser postoperative opioid consumption than non-TAP (standardized mean difference, -0.26; P < 0.05; I-square = 20%), and there were non-significant differences in hospital stay and adverse event between the two groups. CONCLUSION: Intraoperative TAP is a safe and feasible pain management for laparoscopic CRS, particularly it is recommended when patient-controlled analgesia is not delivered. Therefore, laparoscopic TAP block might be a favorable administered strategy.

Cytomegalovirus proctitis in non-human immunodeficiency virus infected patients: A case report and literature review.

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in both immunocompetent and immunocompromised patients. CMV is a ubiquitous Herpesviridae virus with a wide spectrum of pathologies in humans. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome, whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised. The clinical manifestations of CMV colitis or proctitis are demarcated by bloody diarrhea, ulcerations, ulcero-infiltrative changes, and pseudomembranous formation on colonoscopy. Gastrointestinal CMV infections complicated with deep rectal ulcer and fistula formation are rare in patients with systemic lupus erythematosus. Ganciclovir is also the gold standard therapy for CMV colitis or proctitis.

Genetic alterations and their therapeutic implications in epithelial ovarian cancer.

BACKGROUND: Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients. METHODS: We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets. RESULTS: Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target. CONCLUSIONS: Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.

Single-incision robotic colectomy versus single-incision laparoscopic colectomy: A matched case control study.

BACKGROUND: Single incision laparoscopic colectomy (SILC) and single incision robotic colectomy (SIRC) are both advanced minimally invasive operative techniques. However, studies comparing these two surgical methods have not been published. The purpose of this study is to compare and evaluate the short-term outcomes of SIRC with those of SILC. METHODS: A total of 21 consecutive patients underwent SIRC and 136 consecutive patients underwent SILC in separate institutes between January 2013 and December 2019. We used retrospective cohort matching to analyze these patients. RESULTS: Prior to matching, patients who underwent SIRC had a lower percentage of American Society of Anesthesiologists (ASA) grades III-IV (5% vs. 19%, P = 0.11) compared with patients who underwent SILC. The SIRC group revealed a higher proportion of sigmoid colon lesions and anterior resections than the SILC group (61% vs. 45%, P = 0.16). After 1:4 cohort matching, 21 patients were enrolled in the SIRC group and 84 patients were enrolled in the SILC group. No statistically significant difference in terms of operative time (SIRC: 185 ± 46 min, SILC: 208 ± 53 min; P = 0.51), estimated blood loss (SIRC: 12 ± 22 ml, SILC: 85 ± 234 ml; P = 0.12), and complications (SIRC: 4.7%, SIRC: 7.1%; P = 0.31) was observed between these groups. Length of postoperative hospital stay (SIRC: 8.3 ± 1.7 days, SILC: 9.3 ± 6.5; P = 0.10) and number of harvested lymph nodes (SIRC: 21.3 ± 10.3, SILC: 21.3 ± 9.5; P = 0.77) were also similar between the two groups. In subgroup analysis, numbers of harvested lymph node is less in SIRC than SILC (SIRC: 18.1 ± 4.7 vs. SILC: 18.9 ± 8.1, P = 0.04) in anterior resection. CONCLUSION: SIRC and SILC are safe and feasible procedures with similar surgical and pathological outcomes for right- and left-side colectomy.

Neoadjuvant concurrent chemoradiotherapy followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery for low-lying rectal adenocarcinoma: a single center study.

PURPOSE: To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma. METHODS AND MATERIALS: A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student's t testing were used to make parametric comparisons, and Fisher's exact test or the Mann-Whitney U test were used to make nonparametric comparisons. RESULTS: Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. CONCLUSION: TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.

Liquid Biopsy Detects Relapse Five Months Earlier than Regular Clinical Follow-Up and Guides Targeted Treatment in Breast Cancer.

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have the potential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generation sequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, we report the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receiving surgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNA PIK3CA N345K mutation five months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date, clinical implications of the PIK3CA N345K variant remain insufficiently investigated; however, everolimus treatment resulted in the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a second ctDNA analysis suggested a relapse, and the patient clinically progressed after five months of everolimus therapy. This case report demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The study further indicates its usefulness for the choice of targeted treatments, suggesting that the variant PIK3CA N345K might be associated with everolimus sensitivity.

Targeted sequencing of cancer-related genes in nasopharyngeal carcinoma identifies mutations in the TGF-ß pathway.

Approximately, 25% of nasopharyngeal carcinoma (NPC) patients develop recurrent disease. NPC may involve relatively few genomic alterations compared to other cancers due to its association with Epstein-Barr virus (EBV). We envisioned that in-depth sequencing of tumor tissues might provide new insights into the genetic alterations of this cancer. Thirty-three NPC paired tumor/adjacent normal or peripheral blood mononuclear cell samples were deep-sequenced (>1000×) with respect to a panel of 409 cancer-related genes. Newly identified mutations and its correlation with clinical outcomes were evaluated. Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF-κB, and TGF-ß pathways. In addition, patients harbored CNV among 409 cancer-related genes and missense mutations in TGF-ß/SMAD signaling were associated with poor overall survival and poor recurrence-free survival, respectively. The CNV events were correlated with plasma EBV copies, while mutations in TGFBR2 and SMAD4 abrogate SMAD-dependent TGF-ß signaling. Functional analysis revealed that the new TGFBR2 kinase domain mutants were incapable of transducing the signal, leading to failure of phosphorylation of SMAD2/3 and activation of downstream TGF-ß-mediated cell growth arrest. This study provides evidence supporting CNV and dysregulated TGF-ß signaling contributes to exacerbating the NPC pathogenesis.

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.

FANCA D1359Y mutation in a patient with gastric polyposis and cancer susceptibility: A case report and review of literature.

Gastric polyposis is a rare disease. Not all polyps progress to cancer. Monoallelic mutation in Fanconi anemia (FA) genes, unlike biallelic gene mutations that causes typical FA phenotype, can increase risks of cancers in a sporadic manner. Aberrations in the FA pathway were reported in all molecular subtypes of gastric cancer. We studied a patient with synchronous gastric cancer from gastric polyposis by conducting a 13-year long-term follow up. Via pathway-driven massive parallel genomic sequencing, a germline mutation at FANCA D1359Y was identified. We identified several recurrent mutations in DNA methylation (TET1, V873I), the ß-catenin pathway (CTNNB1, S45F) and RHO signaling pathway (PLEKHG5, R203C) by comparing the genetic events between benign and malignant gastric polyps. Furthermore, we revealed gastric polyposis susceptible genes and genetic events promoting malignant transformation using pathway-driven targeted gene sequencing.

PTPRT and PTPRD Deleterious Mutations and Deletion Predict Bevacizumab Resistance in Metastatic Colorectal Cancer Patients.

BACKGROUND: Bevacizumab-based regimens are used as standard treatments for colorectal cancer. Unfortunately, there are no established predictive markers for bevacizumab response. METHODS: Tumor samples from 36 metastatic colorectal cancer patients treated with bevacizumab plus chemotherapy were analyzed by next-generation sequencing of all coding exons of more than 400 genes. Single gene and signaling pathway analyses were performed to correlate genomic data with response. RESULTS: Among the genes most frequently mutated in our cohort, only mutations in PTPRT, a phosphatase involved in JAK/STAT signaling, were associated with response status, with deleterious mutations being enriched in non-responders. Pathway analysis revealed that deleterious mutations in genes of the JAK/STAT pathway, namely in PTPRT and the related gene PTPRD, correlated with resistance. Mutations in RTK/PI3K/RAS, Wnt and TGFß pathways did not associate with response. Lack of response was observed in all patients with deleterious mutations or copy number loss of PTPRT/PTPRD (n = 10), compared to only 30.8% (n = 8) of patients without such alterations (relative risk, 3.25; 95% CI, 1.83⁻5.79, p = 0.0003). Similarly, PTPRT/PTPRD deleterious alterations were associated with shorter progression-free survival, an association that was retained in multivariate analysis (HR, 3.33; 95% CI, 1.47⁻7.54; p = 0.0038). CONCLUSION: Deleterious alterations in PTPRT/PTPRD are potential biomarkers for bevacizumab resistance.

Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma.

BACKGROUND: Patient-derived xenograft (PDX) tumor model has become a new approach in identifying druggable tumor mutations, screening and evaluating personalized cancer drugs based on the mutated targets. METHODS: We established five nasopharyngeal carcinoma (NPC) PDXs in mouse model. Subsequently, whole-exome sequencing (WES) and genomic mutation analyses were performed to search for genetic alterations for new drug targets. Potential drugs were applied in two NPC PDX mice model to assess their anti-cancer activities. RNA sequencing and transcriptomic analysis were performed in one NPC PDX mice to correlate with the efficacy of the anti-cancer drugs. RESULTS: A relative high incident rate of copy number variations (CNVs) of cell cycle-associated genes. Among the five NPC-PDXs, three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase inhibitor CDKN2A deletion. Furthermore, CCND1 overexpression was observed in > 90% FFPE clinical metastatic NPC tumors (87/91) and was associated with poor outcomes. CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated with EBV DNA load in NPC patients' plasma and could serve as a screening test to select potential CDK4/6 inhibitor treatment candidates. Based on our NPC PDX model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor, proved to have anti-tumor effects by inducing G1 arrest. One NPC patient with liver metastatic was treated with Palbociclib, had stable disease response and a drop in Epstein Barr virus (EBV) EBV titer. CONCLUSIONS: Our integrated information of sequencing-based genomic studies and tumor transcriptomes with drug treatment in NPC-PDX models provided guidelines for personalized precision treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for NPC.

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.

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.

Massively parallel sequencing and genome-wide copy number analysis revealed a clonal relationship in benign metastasizing leiomyoma.

Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations.

Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with peritoneal metastasis.

In Taiwan, colorectal cancer with peritoneal carcinomatosis is considered a terminal condition. We examined the clinical outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment for colorectal cancer with peritoneal carcinomatosis in Taiwan.We enrolled patients with colorectal cancer and peritoneal metastasis from Taipei Medical University, Wanfang Hospital between January 1999 and December 2014. Of the enrolled patients, 3 had mucinous-type tumors. In total, we enrolled 31 patients who underwent a total of 33 procedures. Of the 31 patients, 2 received the HIPEC procedure twice. Cytoreductive surgery was performed followed by HIPEC. The hazard ratios of death following cytoreductive surgery and HIPEC were calculated using the Cox proportional hazards model.The 2- and 5-year overall survival rates of these patients following cytoreductive surgery and HIPEC were 57% and 38%, respectively. The completeness of cytoreduction (CC) scores were CC-0, CC-1, CC-2, and CC-3 in 18 (54.5%), 3 (9%), 7 (21.2%), and 5 (15.2%) patients, respectively. The mean peritoneal cancer index (PCI) was 16.20, and the mean postoperative PCI (PPCI) was 4.6. The major risk factors for death in these patients were a total PCI score > 20, total PPCI score > 0, and CC score ≥ 2 (P = 0.022, 0.031, and 0.0001, respectively; log-rank test). Multivariate analysis revealed that the total PPCI score was the strongest predictor of death following cytoreductive surgery and HIPEC in these patients.In Taiwan, performing cytoreductive surgery and administering HIPEC for treating colorectal cancer with peritoneal metastasis are feasible and resulted in long-term survival. In addition, the total PPCI score was related to poor prognosis following cytoreductive surgery and HIPEC in patients with colorectal cancer and peritoneal metastasis.

The outcomes of therapeutic decision in lower 3rd rectal cancer patients.

To investigate the outcomes of the selective neoadjuvant concurrent chemoradiotherapy (CCRT) in lower 3rd rectal cancer patients in different groups (with or without neoadjuvant CCRT), especially in survival rate, local recurrence rate, and sphincter preservation rate.From January 1999 to December 2012, 69 consecutive patients who had histologically proven adenocarcinoma of lower 3rd rectum, defined preoperatively as lower tumor margin within 7 cm from the anal verge as measured by rigid sigmoidoscopy, received total mesorectum excision (TME). Our inclusion criteria of neoadjuvant CCRT are lower 3rd rectal cancer, stage II/III, and large (diameter >5 cm or >1/2 of circumference). Neoadjuvant concurrent CCRT had begun to apply lower 3rd rectal cancer patients or not. The radiation techniques of neoadjuvant CCRT for lower 3rd rectal cancer patients were all conventional fraction intensity modulated radiotherapy (IMRT) and concurrent fluoropyrimidine chemotherapy.Five-year overall survival rate, disease-free survival rate, and local recurrence rate for lower 3rd rectal cancer patients in group I were 51%, 45%, and 25%, respectively. On the contrary, 5-year overall survival rate, disease-free survival rate, and local recurrence rate for lower rectal cancer patients in group II were 70%, 70%, and 3%, respectively. The 5-year sphincter sparing rate was increased from 38.2% to 100% after the beginning of neoadjuvant CCRT. Analyzing local recurrence, overall survival rate, disease-specific survival rate, and sphincter sparing rate in group II were statistically significant superior to group I.Five-year overall survival rate, disease-free survival rate, and sphincter sparing rate for lower 3rd rectal cancer patients were improved after the addition of neoadjuvant CCRT. No unacceptable toxicity was noted after conventional fraction IMRT and concurrent fluoropyrimidine chemotherapy. Our study showed neoadjuvant CCRT could be valuable for lower 3rd rectal cancer patients.

Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma.

TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients.

Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients.

Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS, NRAS, or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS, and BRAF mutations predict response to cetuximab treatment in mCRC patients.

The impact of the lymph node ratio is greater than traditional lymph node status in stage III colorectal cancer patients.

BACKGROUND: The prognostic value of nodal status in colorectal cancer (CRC) patients may be influenced by the total number of lymph nodes (LNs) harvested. This study evaluates the impact of LN ratio (LNR) on CRC patients' outcome. METHODS: A total of 612 stage III CRC patients who underwent curative-intent surgery between 2004 and 2008 were enrolled. The measured end point was postoperative disease-free survival (DFS) and overall survival (OS). RESULTS: The metastatic LN numbers were significantly higher in patients with more than 12 LN harvested (4.6 ± 5.81 vs. 2.7 ± 1.97, P < 0.001). The mean LNR was 22.9 ± 20 % (range = 2-100 %, median = 16.7 %). As the cutoff value of LNR was set above 17 %, the impact of the LNR on 5-year DFS became statistically significant. In univariate analysis, the 5-year DFS and OS for patients with high-LNR tumors was 54.4 and 57.3 %, respectively, significantly lower than those for patients with low-LNR tumors (72.8 and 76.4 %; P < 0.001). In multivariate analysis, the independent factors affecting the 5-year DFS and OS were tumor depth, carcinoembryonic antigen level, and LNR. CONCLUSION: The LNR, set at the median value or 17 %, could be an independent prognostic factor for stage III CRC patients.