Alternations of the gut microbiota and the Firmicutes/Bacteroidetes ratio after biologic treatment in inflammatory bowel disease.

BACKGROUND: The inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) is a complex disease with multifactorial etiology. The intestinal dysbiosis have been investigated to play an important role in IBD pathogenesis and disease activity. The aim of our study was to analyze the intestinal microbiota composition in IBD across different severity levels and the impact of biologic therapy on microbiota modulation. METHODS: In this study, 27 IBD patients were recruited, including 14 patients undergoing biologic therapy for moderate to severe disease activity and 13 controls with inactive disease. The gut microbial composition was determined by 16 S ribosomal RNA gene sequencing of stool samples. RESULTS: Biologic therapy led to significant clinical improvement in IBD disease activity after 48 weeks. About species richness, community alpha diversity was significant lower in active CD patients and enriched gradually after biologic therapy. The beta-diversity regard to the difference of bacterial community composition showed significant difference between patients in biologic and control group. A decrease in Firmicutes and increase in Bacteroidetes abundance were observed in patients with active disease, both in CD and UC. Biologic treatment induced shifts in gut microbiota, with increased Firmicutes and decreased Bacteroidetes, as well as improved F/B ratio gradually after treatment, correlating with disease activity. CONCLUSIONS: Our study suggested that gut microbiota differences changed after biologic therapies among IBD with different disease activity, and a rising Firmicutes/Bacteroidetes ratio could be a potential predictor for disease activity and treatment response monitoring.

Primary Tumor Sidedness Associated with Clinical Characteristics and Postoperative Outcomes in Colon Cancer Patients: A Propensity Score Matching Analysis.

Background: Recent investigations have suggested that-sidedness is associated with the prognosis of colon cancer patients. However, the role of sidedness in surgical outcome is unclear. In this study, we tried to demonstrate the real role of sidedness in postoperative results for colon cancer patients receiving surgical intervention. Methods: This is a propensity score matching study using the database of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) from 2009 to 2013. Sidedness groups including right-sided and left-sided colon cancer were created according to the associated diagnosis and procedure codes. Postoperative 30-day mortality, morbidity, overall complications, and total length of hospital stay were analyzed after performing propensity score matching. Results: Out of a total of 24,436 colon cancer patients who received associated operations, 15,945 patients had right-sided cancer and 8941 patients had left-sided cancer. Right-sided colon cancer patients were accompanied by more preoperative comorbidities including old age, female sex, hypertension, dyspnea, anemia, hypoalbuminemia, and a high American Society of Anesthesiologists grade (SMD > 0.1). Postoperative mortality, morbidities including re-intubation, bleeding, urinary tract infection and deep vein thrombosis, postoperative overall complications, and total length of hospital stay were significantly associated with right-sided cancer (p < 0.05). After 1:1 propensity score matching, postoperative mortality was not significantly different between right-sided cancer (2.3%) and left-sided cancer (2.4%) patients. The patients with left-sided colon cancer had significantly more postoperative morbidities, more overall complications, and longer total length of hospital stay. Conclusions: Poor clinical characteristics and postoperative outcomes were noted in right-sided cancer patients. After propensity score matching, left-sided cancer patients had worse postoperative outcomes than those with right-sided cancer.

Risk Factors Associated with Postoperative Outcomes in Diverticular Disease Undergoing Elective Colectomy-A Retrospective Cohort Study from the ACS-NSQIP Database.

Recommendations for elective colectomies after recovery from uncomplicated acute diverticulitis should be individualized. The kinds of associated risk factors that should be considered for this approach remain undetermined. The aim of this study was to identify the risk factors associated with postoperative outcomes in patients with diverticular disease after receiving an elective colectomy. This is a retrospective study using the multi-institutional, nationally validated database of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP). The patients who were diagnosed with diverticular disease and received an elective colectomy were included in our risk factor analyses. Postoperative mortality, morbidity, and overall complications were measured. Univariate and multivariate analyses were used to demonstrate the risk factors. We analyzed 30,468 patients with diverticular disease, 67% of whom received an elective colectomy. The rate of 30-day mortality was 0.2%, and superficial surgical site infection was the most common postoperative morbidity (7.2%) in the elective colectomies. The independent risk factors associated with overall complications were age ≥ 75, BMI ≥ 30, smoking status, dyspnea, hypertension, current kidney dialysis, chronic steroid use, ASA III, and open colectomy. In laparoscopic colectomy, 67.5% of the elective colectomies, the associated risk factors associated with overall complications still included age ≥ 75, smoking, hypertension, chronic steroid use, and ASA III. Identification of patient-specific risk factors may inform the decision-making process for elective colectomy and reduce the postoperative complications after mitigation of those risk factors.

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

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

ATG4B and pS383/392-ATG4B serve as potential biomarkers and therapeutic targets of colorectal cancer.

BACKGROUND: Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression.  Phosphorylation of ATG4B is crucial for activation of its protease activity.  However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC). METHODS: The ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays. RESULTS: ATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox's regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells. CONCLUSIONS: Our results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC.

Association of sarcopenia and expression of interleukin-23 in colorectal cancer survival.

BACKGROUND & AIMS: The relationship between sarcopenia and interleukin-23 (IL-23) has not been reported. We designed this study to investigate this relationship and the association of sarcopenia and interleukin-23 with poor prognosis of colorectal cancer. METHODS: We used the %FINDCUT SAS macro to determine the cutpoints of the skeletal muscle index (SMI) to define sarcopenia in colorectal cancer patients. Immunohistochemical staining was performed to detect high and low IL-23 expression in cancer samples. Clinicopathological features were also recorded. The prognosis of the 5-year disease-free survival and overall survival were analyzed using univariate and multivariate methods. RESULTS: A total of 114 patients with colorectal cancer were enrolled. The mean age was 63.2 years. Forty-six (40%) patients were female. Sarcopenia was defined as less than 50 cm2/m2 for men and 32 cm2/m2 for women and 52(46%) patients were defined as having sarcopenia. Sarcopenia was significantly associated with poor 5-year disease-free survival and overall survival (p = 0.003 and p = 0.001, respectively). Multivariate adjustment demonstrated that sarcopenia was an independent predictor of the 5-year disease-free survival (hazard ratio = 1.827, p = 0.024) and overall survival (hazard ratio = 3.669, p < 0.001). A lower SMI was detected in patients with high IL-23 expression (p = 0.045). After grouping the patients with sarcopenia and IL-23 expression, the patients with sarcopenia and high IL-23 expression had the worst disease-free survival (p = 0.013) and overall survival (p = 0.007). CONCLUSIONS: This is the first study to explore the significant association between IL-23 expression and sarcopenia in colorectal cancer. Sarcopenia combined with IL-23, as an inflammatory marker, significantly predicted poor survival.

Clinicopathological Association of Autophagy Related 5 Protein with Prognosis of Colorectal Cancer.

Gene mutation and pathogenesis bacteria are highly associated with colorectal cancer (CRC) development and progression. Autophagy is a self-clearance pathway to degrade abnormal proteins and infected bacteria in cells. Autophagy plays a dual role in cancer development. Among the autophagy-related (ATG) proteins, ATG5 is the key component required for the core machinery of autophagy. However, the role of ATG5 in CRC malignancy remains unclear. Herein, we found that a high ATG5 protein level was correlated with poor overall survival (OS) and disease-free survival (DFS) of 118 patients with CRC. After stratification with demographic and clinicopathologic factors, a high ATG5 protein level was significantly correlated with unfavorable overall survival in female and elder (>60 year) CRC patients and tumor tissues with poor differentiation, late T stages (III + IV), whereas the ATG5 protein level was positively associated with the overall survival in CRC patients without lymph node invasion and radiation therapy. In contrast, a high ATG5 protein level was significantly associated with worse DFS in CRC patients with early stage of AJCC and no radiation therapy. In addition, colorectal cancer cells stably harboring small interfering RNA (siRNA) against ATG5 diminished the tumorsphere formation and sensitized cancer cells to chemotherapeutic agents. Taken together, our results suggest that ATG5 might be a prognostic biomarker for CRC and a potential therapeutic target for CRC patients.

Taiwan Society of Colon and Rectum Surgeons (TSCRS) Consensus for Anti-Inflammatory Nutritional Intervention in Colorectal Cancer.

Malnutrition and systemic inflammatory response (SIR) frequently occur in patients with colorectal cancer (CRC) and are associated with poor prognosis. Anti-inflammatory nutritional intervention is not only a way to restore the malnourished status but also modulate SIR. Nine experts, including colorectal surgeons, physicians and dieticians from 5 hospitals geographically distributed in Taiwan, attended the consensus meeting in Taiwan Society of Colon and Rectum Surgeons for a 3-round discussion and achieved the consensus based on a systematic literature review of clinical studies and published guidelines. The consensus recommends that assessment of nutritional risk and SIR should be performed before and after CRC treatment and appropriate nutritional and/or anti-inflammatory intervention should be adapted and provided accordingly.

The Impact of Comorbid Diabetes on Short-Term Postoperative Outcomes in Stage I/II Colon Cancer Patients Undergoing Open Colectomy.

PURPOSE: This study aimed at evaluating the impact of comorbid diabetes on short-term postoperative outcomes in patients with stage I/II colon cancer after open colectomy. METHODS: The data were extracted from the National Inpatient Sample database (2005-2010). Short-term surgical outcomes included in-hospital mortality, postoperative complications, and hospital length of stay. RESULTS: A total of 49,064 stage I/II colon cancer patients undergoing open surgery were included, with a mean age of 70.35 years. Of them, 21.94% had comorbid diabetes. Multivariable analyses revealed that comorbid diabetes was significantly associated with a lower risk of in-hospital mortality and postoperative complications. Compared to patients without diabetes, patients with uncomplicated diabetes had lower percentages of in-hospital mortality and postoperative complications, but patients with complicated diabetes had a higher percentage of postoperative complications. In addition, patients with diabetes only, but not patients with diabetes and hypertension only, had a lower percentage of in-hospital mortality than patients without any comorbidity. CONCLUSION: The present results suggested the protective effects of uncomplicated diabetes on short-term surgical outcomes in stage I/II colon cancer patients after open colectomy. Further studies are warranted to confirm these unexpected findings and investigate the possible underlying mechanisms.

Preoperative malnutrition with mild hypoalbuminemia associated with postoperative mortality and morbidity of colorectal cancer: a propensity score matching study.

BACKGROUND: Malnutrition with hypoalbuminemia (albumin < 35 g/L) is an important factor in predicting risks associated with colorectal cancer surgery. However, there is limited data about the effects of mild hypoalbuminemia with small decreases in albumin on postoperative complications. METHODS: This is a retrospective study using the multi-institutional, nationally validated database of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) to investigate mild hypoalbuminemia and its association with postoperative mortality and morbidity by using a propensity score matching method. RESULTS: In a group of 30,676 colorectal cancer patients who received surgery, 5230 had mild hypoalbuminemia (< 35 and > =30 g/L) and 21,310 had normal albumin levels (> = 35 g/L). Significant differences were noted in 21 clinical characteristics between the two groups. After 1:2 propensity score matching postoperative mortality was significantly associated with mild hypoalbuminemia (OR = 1.74; p < 0.001). There were significant associations between mild hypoalbuminemia and 11 postoperative morbidities including deep vein thrombosis, pulmonary embolism, superficial and deep surgical site infection, pneumonia, septic shock, ventilator> 48 h, blood transfusion, return to operating room, stroke and re-intubation. Mild hypoalbuminemia was also associated with overall complication (B = 0.064, p < 0.001) and length of total hospital stay (B = 2.236, p < 0.001). CONCLUSIONS: In colorectal cancer, this is the first propensity score matching study of malnutrition with mild hypoalbuminemia which demonstrates that a mild decrease in serum albumin contributes significantly to poor postoperative outcome.

Xanthium strumarium Fruit Extract Inhibits ATG4B and Diminishes the Proliferation and Metastatic Characteristics of Colorectal Cancer Cells.

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA2. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells.

Risk of delayed bleeding after hemorrhoidectomy.

PURPOSE: Delayed post-hemorrhoidectomy bleeding (DPHB) is a rare but serious complication. We investigated the incidence and risk factors of DPHB in patients undergoing hemorrhoidectomy using the LigaSure device or the Ferguson procedure. METHODS: This retrospective study included 382 consecutive patients with symptomatic grades II to IV hemorrhoids who received either LigaSure (184 patients) or Ferguson (198 patients) hemorrhoidectomy procedures. Thirty-two patients who experienced DPHB after discharge were followed up. RESULTS: Significantly fewer Ferguson group patients had DPHB compared to the LigaSure group (5.1% vs. 11.9%; P = 0.015). In the overall population, the risk of DPHB was higher in (1) males compared to that of females (OR = 3.39; 95% CI 1.50-7.69, P = 0.003); (2) in the LigaSure group compared to the Ferguson group (OR = 2.77; 95% CI 1.23-6.24, P = 0.01); and (3) in patients with constipation (OR = 6.59; 95% CI 2.73-15.89, P < 0.0001). Males in the LigaSure group had a significantly higher rate of delayed bleeding than those in the Ferguson group (20% vs. 5.8%, P = 0.004); no significant differences were found in females (4.9% vs. 4.5%, P = 0.878). Subgroup analysis showed that in males, risk of DPHB increased significantly with postoperative constipation (OR = 4.73, 95% CI 1.45-15.43, P = 0.010) and the LigaSure procedure (OR = 3.99, 95% CI 1.37-11.62, P = 0.011). In females, the risk of DPHB was significantly associated with postoperative constipation (OR = 8.80, 95% CI 2.24-34.54, P = 0.002). CONCLUSIONS: The LigaSure procedure and constipation are independent risk factors for DPHB in patients undergoing hemorrhoidectomy and can be used as predictors of outcome.

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

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

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

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

Increased expression of interleukin-23 associated with progression of colorectal cancer.

BACKGROUND AND OBJECTIVES: The prognostic significance of interleukin-23 in colorectal cancer remains unclear. We designed this study to investigate the association between colorectal cancer and interleukin-23 (IL-23) or interleukin-23 receptor (IL-23R) expression and the resulting clinical features and survival. METHODS: Immunohistochemical staining was performed for IL-23 and IL-23R in colorectal cancer samples. H-score was calculated to compare the expression of IL-23 and IL-23R. The median of H-score was used as the cut-off value to separate patients into high or low expression groups. The differences in clinicopathological features were evaluated. Cox regression hazard ratios were used for survival analysis. RESULTS: A total of 129 colorectal cancer patients were enrolled. H-score for the late TNM stage patients was higher than that for the early TNM stage patients (P = 0.002). Patients with high IL-23 expression were associated with advanced pathological T category (P < 0.001) and late TNM stage (P = 0.003). High IL-23 expression was associated with poor 5-year disease-free survival and overall survival in patients (P = 0.048 and P = 0.028, respectively). Multivariate adjustment demonstrated a significant association between high IL-23 expression and overall survival (hazard ratio = 1.865, P = 0.041). CONCLUSIONS: Elevated IL-23 expression was associated with poor outcome and can be used as a prognostic biomarker for colorectal cancer. J. Surg. Oncol. 2017;115:208-212. © 2016 Wiley Periodicals, Inc.

Meta-analysis of outcomes of patients with stage IV colorectal cancer managed with chemotherapy/radiochemotherapy with and without primary tumor resection.

BACKGROUND: Colorectal cancer is the third leading cause of death worldwide. Currently, novel chemotherapeutic agents are first-line therapy for unresectable stage IV colorectal cancer, while benefits of noncurative primary tumor resection in advanced disease remain debatable. OBJECTIVE: This meta-analysis evaluated outcomes of patients with unresectable stage IV colorectal cancer receiving systemic chemotherapy with or without primary tumor resection. MATERIALS AND METHODS: A database search of PubMed and Cochrane Library databases identified 167 studies that were screened for relevance. After 119 were excluded, 48 were assessed for eligibility and 26 were included for meta-analysis, including 24 retrospective studies, one prospective study, and one randomized, controlled trial. Extracted data included patient demographics (age, sex), clinical data (tumor stage, metastasis), targeted therapy agents, and surgical data (with/without tumor resection). Patients' overall and progression-free survival was compared between groups with/without primary tumor resection. RESULTS: The 26 studies included 43,903 patients with colorectal cancer, with 29,639 receiving chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed medically with chemotherapy/chemoradiotherapy alone without primary tumor resection. Patients receiving primary tumor resection plus chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51-0.68; P<0.001), with significant differences in overall survival between patients with and without primary tumor resection (HR 0.58, 95% CI 0.49-0.68; P<0.001). Longer overall survival was also found among patients receiving primary tumor resection who were treated with bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46-0.86; P=0.003). Patients from three studies who received primary tumor resection had longer progression-free survival (HR 0.73, 95% CI 0.58-0.91; P=0.005). Results are limited by retrospective data, inconsistent complications data, and publication bias. CONCLUSION: Study results support primary tumor resection in stage IV colorectal cancer, but significant biases in studies suggest that randomized trials are warranted to confirm findings.

Assessment of the Addition of Hypoalbuminemia to ACS-NSQIP Surgical Risk Calculator in Colorectal Cancer.

The aim of this study was to evaluate the benefit of adding hypoalbuminemia to the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Surgical Risk Calculator when predicting postoperative outcomes in colorectal cancer patients.The ACS-NSQIP Surgical Risk Calculator offers qualified risk evaluation in surgical decision-making and informed patient consent. To date, malnutrition defined as hypoalbuminemia, an important independent surgical risk factor in colorectal cancer, is not included.This is a retrospective, multi-institutional study of ACS-NSQIP patients (n = 18,532) who received colorectal surgery from 2009 to 2012. Models were constructed for predicting postoperative mortality and morbidity using the risk factors of the ACS-NSQIP Surgical Risk Calculator before and after adding hypoalbuminemia as a risk factor. The 2 models' performance was then compared using c-statistics and Brier scores. The ACS-NSQIP database in 2008 was used for validation of the created models.The prevalence of hypoalbuminemia (27.8%) is higher in colorectal cancer, when compared with other most common cancers. In univariate analyses, hypoalbuminemia was significantly associated with postoperative mortality and morbidity in colorectal cancer patients. In multivariate logistic regression analyses, 15 postoperative complications, including mortality and serious morbidities, were significantly predicted by hypoalbuminemia. Most of the models with hypoalbuminemia showed better performance and validation in predicting postoperative complications than those without hypoalbuminemia.In colorectal cancer, hypoalbuminemia, with levels below 3.5 g/dL, serves as an excellent assessment tool and preoperative predictor of postoperative outcomes. When combined with hypoalbuminemia as a risk factor, the ACS-NSQIP Surgical Risk Calculator offers more accurate information and estimation of surgical risks to patients and surgeons when choosing treatment options.

Loss of histone variant macroH2A2 expression associates with progression of anal neoplasm.

AIMS: The macroH2A histone variants are epigenetic marks for inactivated chromatin. In this study, we examined the expression of macroH2A2 in anal neoplasm from anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (SCC). METHODS: AIN and anal SCC samples were analysed for macroH2A2 expression, HIV and human papilloma virus (HPV). The association of macroH2A2 expression with clinical grade, disease recurrence, overall survival and viral involvement was determined. RESULTS: macroH2A2 was expressed in normal squamous tissue and lower grade AIN (I and II). Expression was lost in 38% of high-grade AIN (III) and 71% of anal SCC (p=0.002). Patients with AIN with macroH2A2-negative lesions showed earlier recurrence than those with macroH2A2-positive neoplasm (p=0.017). With anal SCC, macroH2A2 loss was more prevalent in the HPV-negative tumours. CONCLUSIONS: Loss of histone variant macroH2A2 expression is associated with the progression of anal neoplasm and can be used as a prognostic biomarker for high-grade AIN and SCC.

Tumor-infiltrating CD8(+) T lymphocytes associated with clinical outcome in anal squamous cell carcinoma.

BACKGROUND: The prognostic significance of tumor-infiltrating CD8(+) T lymphocytes in anal squamous cell carcinoma (SCC) remains unclear. We designed the study to investigate the association between CD8(+) T cells and clinical prognosis among anal SCC patients. METHODS: The density of CD8(+) T cells was assessed by immunohistochemistry. The numbers of CD8(+) T cells were counted and their relationship with clinicopathological factors and survival was explored. RESULTS: A strong positive correlation was noted between intratumoral and peritumoral CD8(+) T cells (r = 0.77, P < 0.001). High intratumoral and peritumoral CD8(+) T cells was associated with well tumor differentiation, early-stage diagnosis, and better prognosis (P < 0.05). Better disease-free survival rates were demonstrated in patients with high CD8(+) T cell density in intratumoral nest (P = 0.01); peritumoral stroma (P = 0.004); and both in combination (P = 0.01). High peritumoral CD8(+) T cell was associated with overall survival (P = 0.025). In HIV-infected patients, high CD8(+) T cell density also had association with disease-free survival (P < 0.05). CONCLUSIONS: High tumor-infiltrating CD8(+) T cell density showed the potential to indicate a favorable effect on prognosis and survival for anal SCC patients.