Predictors for temporary stomas non-closure among non-metastatic rectal cancer patients undergoing curative resection: a retrospective analysis.

BACKGROUND: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. METHODS: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. RESULTS: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). CONCLUSION: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.

Preoperative risk stratification of permanent stoma in patients with non-metastatic mid and low rectal cancer undergoing curative resection and a temporary stoma.

BACKGROUND: Although a temporary stoma can mitigate the severity of anastomotic leakage, some rectal cancer patients retain a permanent stoma after sphincter-preserving surgery. Therefore, this study aimed to identify independent preoperative risk factors for permanent stoma and establish a prediction model for mid-and low-rectal cancer patients who underwent sphincter-preserving surgery and temporary stoma. METHODS: We retrospectively reviewed consecutive patients with non-metastatic rectal cancer between 2000 and 2015. The risk factors for permanent stomas were collected and analyzed. RESULTS: A total of 1020 rectal cancer patients with temporary stoma were included. The overall rate of permanent stoma was 17.5% (n = 179). Cancer progression and anastomotic complications are major causes of permanent stomas. Multivariate analysis showed that preoperative risk factors such as advanced age, male sex, preoperative CEA ≥ 10 ng/ml, T4 stage, N stage, low rectal tumor, and ASA ≥ III were independent preoperative risk factors after adjustment. The ROC curve of the risk factors and permanent stoma showed an AUC of 0.689, a cut-off value of 2.5, a sensitivity of 0.689, and a specificity of 0.622. The permanent stoma rates were significantly higher between risk scores ≤ 2 and > 2 (29.9% vs. 11.3%, p < 0.001). CONCLUSION: Preoperative CEA ≥ 10 ng/ml, T4 stage, N stage, low rectal tumor, advanced age, ASA ≥ III, and male sex were independent preoperative prognostic factors for a permanent stoma. The risk was higher with a score greater than two. Therefore, the risk of subsequent permanent stoma should be evaluated and informed to the patient prior to the primary surgery.

Smoking cessation for less than 10 years remains a risk factor of anastomotic leakage in mid-to-low rectal cancer patients undergoing sphincter-preserving surgery.

PURPOSE: Although cigarette smoking is a well-known risk factor for anastomotic leakage during rectal surgery, the proper duration of smoking cessation that can decrease anastomotic leakage in patients undergoing sphincter-preserving surgery is unclear. This study aimed to investigate the optimal duration of smoking cessation that can reduce this complication. METHODS: Between January 1, 2000, and December 31, 2012, we enrolled 1246 consecutive patients who underwent curative-intent sphincter-preserving surgery without preventive stoma at the Division of Colorectal Surgery of a tertiary referral center in Taiwan. Questionnaires were used to record their pre-surgical smoking status. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off duration of smoking cessation. Multivariate analysis was used to verify the effect of cigarette cessation on anastomotic leakage. RESULTS: The ROC curve showed a cut-off value of 10.5 years of cessation duration. Therefore, the former-smoker group was further divided using a cessation duration of 10 years. The overall anastomotic leakage rate was 5.29%. However, the anastomotic leakage rate in current smokers (9.3%) and in those who quit for < 10 years (12.9%) was significantly higher than that in non-smokers (3.3%) and those who quit for ≥ 10 years (4.5%). On multivariate analysis, current smokers (p = 0.022), former smokers with < 10 years of smoking cessation (OR 2.725; p = 0.029), male sex (p = 0.015), and low rectal cancer (p < 0.001) were all independently related to the development of anastomotic leakage. CONCLUSION: Smoking cessation for < 10 years remains a risk factor for anastomotic leakage in patients with mid-to-low rectal cancer undergoing sphincter-preserving surgery.

Preoperative Carcinoembryonic Antigen as a Poor Prognostic Factor in Stage I-III Colorectal Cancer After Curative-Intent Resection: A Propensity Score Matching Analysis.

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) has yet to be used as a prognostic or adjuvant chemotherapy factor for colorectal cancer (CRC). METHODS: This retrospective cohort study included all stage I-III CRC patients with different preoperative serum CEA levels (≤ 5, 5-10, and > 10 ng/ml) at a single center between 1995 and 2010. Propensity score matching was performed in a 1:1 ratio between the two elevated CEA groups (5-10 ng/ml and > 10 ng/ml) and in a 1:2 ratio between the elevated and non-elevated groups (≤ 5 ng/ml), with a caliper of 0.05. RESULTS: After exclusion and matching, 3857 patients had preoperative CEA levels ≤ 5 ng/ml, 1121 patients had CEA levels between 5 and 10 ng/ml, and 1121 patients had CEA levels > 10 ng/ml. Elevated preoperative CEA showed an increased risk of overall survival (5-10 ng/ml: hazard ratio [HR] 1.376; > 10 ng/ml: HR 1.523; both p < 0.001), cancer-specific survival (5-10 ng/ml: HR 1.404; > 10 ng/ml: HR 1.712; both p < 0.001), and recurrence free interval (5-10 ng/ml: HR 1.190; > 10 ng/ml: HR 1.468; both p < 0.05). Patients with negative lymph node staging (LNs) and CEA > 10 ng/ml, as well as those with positive LNs and CEA ≤ 5 ng/ml, showed similar overall survival (5-year survival: 72% vs. 69%; p = 0.542) and recurrence free intervals (19.9 vs. 21.72 months; p = 0.662). CONCLUSIONS: A preoperative CEA level can be an independent prognostic factor for stage I-III CRC after curative resection. Patients with negative LNs and preoperative CEA level > 10 ng/ml should be considered for intensive follow-up or adjuvant chemotherapy.

Survival analysis of local excision vs total mesorectal excision for middle and low rectal cancer in pT1/pT2 stage and intermediate pathological risk.

BACKGROUND: Local excision (LE) is a feasible treatment approach for rectal cancers in stage pT1 and presents low pathological risk, whereas total mesorectal excision (TME) is a reasonable treatment for more advanced cancers. On the basis of the pathology findings, surgeons may suggest TME for patients receiving LE. This study compared the survival outcomes between LE with/without chemoradiation and TME in mid and low rectal cancer patients in stage pT1/pT2, with highly selective intermediate pathological risk. METHODS: This retrospective study included 134 patients who received TME and 39 patients who underwent LE for the treatment of intermediate risk (pT1 with poor differentiation, lymphovascular invasion, perineural invasion, relatively large tumor, or small-sized pT2 tumor) rectal cancer between 1998 and 2016. RESULTS: Overall survival (OS), disease-free survival (DFS), and cumulative recurrence rate (CRR) were similar between the LE (3-year DFS 92%) and TME (3-year DFS 91%) groups. Following subgrouping into an LE with adjuvant therapy group and a TME without adjuvant therapy group, the compared survival outcomes (OS, DFS, and CRR) were found not to be statistically different. The temporary and permanent ostomy rates were higher in the TME group than in the LE group (p < 0.001). Rates of early and late morbidity following surgery were higher in the TME group (p = 0.005), and LE had similar survival compared with TME. CONCLUSION: For patients who had mid and low rectal cancer in stage pT1/pT2 and intermediate pathological risk, LE with chemoradiation presents an alternative treatment option for selected patients.

Primary tumor location in stage III colon cancer has prognostic impact on subsequent liver metastasis.

BACKGROUND AND OBJECTIVES: We aim to investigate whether a difference exists between right-sided and left-sided colon cancer at the same disease stage and subsequent liver metastasis and identify whether tumor location can independently influence survival. METHODS: Right-sided colon cancer was defined as malignancy arising from the cecum to the transverse colon; left-sided colon cancer was defined as malignancy arising from the splenic flexure to the sigmoid colon. Clinicopathological features and survival data were collected for analysis. RESULTS: Overall, 1442 patients were included for analysis. The median follow-up time was 58.2 months. Patients with left-sided colon cancer had better 5-year overall survival (75.2% vs 61.7%, P = 0.005), 5-year cancer-specific survival (81.6% vs 73.4%, P = 0.001), and 5-year recurrence-free survival (70.9% vs 66.5%, P = 0.033) compared with patients having right-sided colon cancer. After the presentation of subsequent liver metastasis, patients with primary left-sided colon cancer had better 3-year cancer-specific survival ( P < 0.001). In the multivariate analysis, cancer location was an independent prognostic factor for cancer-specific survival (right vs left, HR: 1.276, 95% CI: 1.002-1.625). CONCLUSIONS: The primary tumor location can serve as a prognostic factor for treatment outcomes either in primary stage III colon cancer or subsequent liver metastasis.

Various clinicopathological features of patients with metachronous colorectal cancer in relation to different diagnostic intervals.

BACKGROUNDS: Clinicopathologic factors relating to developing metachronous colorectal cancer (CRC) have been reported. However, the effects of different diagnostic intervals on these risk factors required further analysis. PATIENTS AND METHODS: This retrospective study comprised 14,481 patients diagnosed from January 1995 to December 2012. Metachronous CRC was defined as the occurrence of a second colorectal cancer at least 1 year post-operatively. RESULTS: A total of 153 (1.06%) patients developed metachronous CRCs during the follow-up. Significantly higher rates of developing metachronous cancer occurred in male patients (1.2 vs 0.9%), patients with synchronous CRC (2.0 vs 1.0%), and patients with a positive family history of CRC (1.4 vs 0.9%). Pertaining to diagnostic intervals related to clinicopathological features, more severe staging was significant in the diagnostic interval between 2 and 3 years (35 vs 7.7%, 20.6%, 17.5%, P = .01) compared with other intervals. Male patients were more frequently detected to have CRC within 3 years compared with females (53.1 vs 29.1%, P = .005). For a diagnostic interval ≧ 5 years, a significantly higher rate of metachronous CRC located at the right colon was observed than that located at the left colon (36.6 vs 19.7%, p = 0.03). CONCLUSIONS: We evinced that a diagnostic interval between 2 and 3 years was a key time for metachronous CRC diagnosis with worse staging distribution. Based on current findings, we recommend the stratification of metachronous CRCs into diagnostic intervals of 1-2, 2-3, and ≧ 3 years, as they exhibit significantly different characteristics.

The dark side of laparoscopic surgery for colorectal cancer patients aged 75 years or older.

PURPOSE: The rate of postoperative morbidity and mortality is reportedly high in patients aged ≥ 75 years with colorectal cancer (CRC). In such patients, a comparison of the short-term outcome between open method and laparoscopy has not been clearly defined in Taiwan. We aimed to compare postoperative morbidity and mortality parameters after open method and laparoscopy in CRC patients aged ≥ 75 years. METHODS: We retrospectively analyzed patients who underwent surgery for CRC from February 2009 to September 2015 at the Linkou Chang Gung Memorial Hospital in Taiwan and analyzed their clinicopathological factors. Postoperative morbidity and mortality were analyzed for evaluating if laparoscopic surgery offers more favorable outcomes than open surgery in the elderly. RESULTS: A total of 1133 patients were enrolled and analyzed in this study; they were divided into two groups (open method vs. laparoscopy = 797 vs. 336). The anastomotic leakage rate was significantly higher in the laparoscopy group than in the open method group (3.3 vs. 0.9%, p = 0.003). Overall postoperative morbidity and mortality rates showed no significant difference between these two groups. Postoperative hospital stay was significantly shorter in the laparoscopy group than in the open method group (10.4 ± 8.7 vs. 13.8 ± 13.5 days, p < 0.001). CONCLUSIONS: Our results suggest that laparoscopy in patients aged ≥ 75 years with CRC had higher anastomosis leakage rate compared with open surgery but is acceptable and offers the benefit of a shorter hospital stay over open surgery.

Preoperative alkaline phosphatase elevation was associated with poor survival in colorectal cancer patients.

PURPOSE: Purpose To assess preoperative serum alkaline phosphatase (ALP) levels in colon adenocarcinomapatients with various clinical features and determine its prognostic value. METHODS: Between 2000 and 2013, 10,800 stage I-IV colon cancer patients who underwent surgery wereretrospectively enrolled. The relationship between ALP level and variables, including age, gender,carcinoembryonic Antigen (CEA) levels, aspartate aminotransferase (AST) level, bilirubin level, tumor size,liver cirrhosis, hepatitis, albumin level, histological type, and TNM-stage, were evaluated. The impact of ALP level elevation on survival was evaluated. RESULTS: Significant elevations in ALP level were found in patients with CEA ≥5 ng/ml (p<0.001); AST |≥43 U/L (p<0.001); total bilirubin ≥1.5 U/L (p<0.001); liver cirrhosis (p<0.001); albumin; <3.5g/dL (p <0.001); and stage IV disease (p=0.03).Patients with elevated ALP levels had significantly worse 5-year overall survival (OS) for colon (5-year OSrate: 71.5% vs. 78.3%, p<0.001; Fig. 1a) and rectal (5-year OS rate: 64.5% vs. 72.3%, p<0.001; Fig. 1b)cancer than patients with normal ALP levels. CONCLUSIONS: Elevated preoperative ALP levels was not only associated with liver disease, but it was alsorelated with advanced tumor status, and indicated a poor survival in colon and rectal cancer patients.

Polymorphisms of MTHFR C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy.

BACKGROUND: This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan. METHODS: We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival. RESULTS: Overall survival (OS) was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60-0.98). Although the MTHFR A1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35-2.83). In haplotype analysis, better OS was found for colon cancer patients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55-0.97), but worse survival was linked to rectal cancer patients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08-2.18). CONCLUSIONS: Our findings suggest that MTHFR genotypes provide prognostic information for CRC patients treated with 5-FU-based chemotherapy.

Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy.

BACKGROUND: Rectal cancer patients have a higher incidence of pulmonary metastases than those with colon cancer. This study aimed to examine the effects of rectal cancer level on recurrence patterns in rectal cancer patients. METHODS: Patients with T3/T4 rectal cancers who underwent surgery between 2002 and 2006 were recruited in this study. All the patients were followed up on until death. Recurrence patterns and survival rates were calculated in relation to clinical variables. RESULTS: There were 884 patients were enrolled in this study. Patients with low-rectal cancer had significantly worse five-year overall survival (OS) and disease-free survival (DFS) rates (47.25% and 44.07%, respectively) than patients with mid-rectal (63.46% and 60.22%, respectively) and upper-rectal cancers (73.91% and 71.87%, respectively). The level of the tumor (P <0.001), nodal status (P <0.001), tumor invasion depth (P <0.001), and tumor differentiation (P = 0.047, P = 0.015) significantly affected the surgical outcomes related to OS and DFS in the univariate and multivariate analyses. Furthermore, the level of the rectal cancer was a significant risk factor (hazard ratio 1.114; 95% CI, 1.074 to 1.161; P <0.001) for local recurrence, lung metastases, bone metastases, and systemic lymph node metastases. Significantly higher incidence rates of bone (53.8%) and brain metastases (22.6%) after initial lung metastases rather than initial liver metastases (14.8% and 2.9%, respectively) were also observed. CONCLUSIONS: For rectal cancer patients who underwent surgical resection, the rectal cancer level significantly affected surgical outcomes including rates and patterns of distant metastases.

Associations between genetic polymorphisms of epidermal growth factor receptor (EGFR) and survival of colorectal cancer (CRC) patients treated with 5-fluorouracil-based chemotherapy.

PURPOSE: This retrospective cohort study investigated the association between epidermal growth factor receptor (EGFR) polymorphisms and clinical outcomes in colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU)-based chemotherapy. METHODS: We genotyped 3 EGFR polymorphisms including R497K, G-216T, and the (CA)n repeat, among 499 histologically confirmed CRC patients who had received 5-FU-based chemotherapy after surgery between 1995 and 2001. Survival analyses of EGFR polymorphisms were performed by the log rank test and Kaplan-Meier curves. We used the Cox proportional hazard model to evaluate the association between EGFR genotypes and clinical outcomes. Stratification analysis by gender, tumor stage, and subsite were also carried out. RESULTS: CRC patients with the EGFR (CA)n L/L genotype compared to those with the S/S+S/L genotype had a significantly better overall survival (L, ≥ 20 repeats; S, <20 repeats) (hazard ratio (HR) 0.74; 95 % confidence interval (CI) 0.57-0.95), particularly for patients who were male (HR 0.63; 95 % CI 0.44-0.90), who had stage IV disease (HR 0.70; 95 % CI 0.49-0.99), and who had rectal cancer (HR 0.62; 95 % CI 0.42-0.92). Better survival was prominent among patients with the combined genotypes of EGFR (CA)n L/L, G-216T G/G, and R497K K/K (HR 0.51; 95 % CI 0.30-0.87), compared to those with the most common genotypes of the EGFR (CA)n S allele, G-216T G/G, and R497K R allele. CONCLUSIONS: EGFR polymorphisms can serve as prognostic predictors for CRC patients receiving 5-FU-based chemotherapy.

Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer.

BACKGROUND: The leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is an adult intestinal stem cell marker frequently detected in human colorectal cancers (CRCs). However, the value of Lgr5 level in CRC prognosis and treatment prediction has not been well characterized. METHODS: We examined Lgr5 expression in 384 formalin-fixed paraffin-embedded CRC specimens from 296 CRC patients, including 64 patients treated with 5-fluorouracil (5-FU)-based chemotherapy. The effects of Lgr5 on cell proliferation, survival, and drug resistance were examined in cultured CRC cells. RESULTS: Elevated expression of Lgr5 was observed in CRC tissues, and Lgr5 protein levels were significantly correlated with an advanced American Joint Committee on Cancer stage (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and distant metastasis (P < 0.001). High expression levels of Lgr5 were significantly associated with shorter disease-free survival (P < 0.001) and shorter cancer-specific survival (P = 0.007) in CRC patients. Among the chemotherapy-treated subgroups, patients with low Lgr5 level showed a better response rate (65 %) than patients with high Lgr5 level (37 %) towards 5-FU-based treatment (P = 0.025). In cultured CRC cell lines, knocking down Lgr5 suppressed cell proliferation and colony formation ability, while it enhanced apoptosis and rendered cells more sensitive to chemotherapeutic agents. In contrast, overexpression of Lgr5 increased cell proliferation and enhanced chemoresistance. CONCLUSION: These results suggest that elevated Lgr5 level is associated with CRC progression and treatment response and has the potential to serve as a therapeutic target in CRC patients.

Impact of chemotherapy-related prognostic factors on long-term survival in patients with stage III colorectal cancer after curative resection.

BACKGROUND: This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection. METHODS: From 1996 to 2001, 1,054 patients with primary single colorectal cancer underwent curative resection. Seven hundred sixteen patients received various 5-fluorouracil (FU)-based adjuvant chemotherapy regimens, including oral and intravenous treatments. The chemotherapy-related parameters examined included therapeutic duration, frequency, route of administration, composition of combination therapies, and postoperative time interval from the operation to the start of chemotherapy. RESULTS: The therapeutic duration and postoperative time interval of starting therapy were independent prognostic factors, in addition to clinicopathological factors. The 8-year cancer-specific/overall survival rates in patients who received chemotherapy for >4 months (63.0/58.6%) were significantly higher than the rates in patients who received no chemotherapy (56.7/37.7%, P < 0.01) and those who remained on chemotherapy for 1-4 months (49.4/41.9%, P < 0.05). The 8-year cancer-specific/overall survival rates in patients who waited 1-5 weeks after surgery to receive chemotherapy (62.9/58.5%) were significantly higher versus rates in those who did not receive chemotherapy (56.7/37.7%) and those who did not receive chemotherapy until >5 weeks after surgery (52.3/45.9%) (both P < 0.05). Survival rates did not differ between patients who did not undergo chemotherapy, those for whom chemotherapy lasted 1-4 months, and patients who did not receive chemotherapy until >5 weeks after surgery. CONCLUSIONS: The appropriate duration of therapy and early chemotherapy after surgery were 2 of the most important factors in eradicating occult cancer and effecting long-term survival benefits in patients with stage III colorectal cancer.

Concurrent chemoradiotherapy in the treatment of locally recurrent rectal cancer.

BACKGROUND/AIMS: Long course concurrent chemoradiotherapy provides potential tumor downstaging. When local recurrent rectal cancer without distant metastases is diagnosed, a potentially curative resection can be performed. The aim of this study was to assess the outcome of concurrent chemoradiotherapy in treating isolated local recurrent rectal cancer. METHODOLOGY: Patients (n=102) with isolated local recurrent rectal cancer within the pelvis were scheduled for concurrent chemoradiotherapy, consisting of pelvic irradiation with a total dose of 50.4 Gy in 28 fractions. Chemotherapy was administered concurrently and included 85 mg/m2 oxaliplatin by venous infusion over 2 h on day 1, followed by 1,200 mg*m-2*day-1 of continuous venous infusion for 2 days. This regimen was repeated every 2 weeks for 6 cycles. The overall survival rate, responses, disease-free interval and toxicities were assessed. RESULTS: A total of 96 patients completed planned concurrent chemoradiation. Complete clinical responses were found in 13 of the 96 patients (14%), partial responses in 59 (61%), stable disease in 21 (22%) and disease progression in 3 (3%). The overall survival and disease-free survival rates in all the 96 patients were 45% and 14%, respectively. CONCLUSIONS: The treatment of locally recurrent rectal cancer is complicated. Concurrent chemoradiation can increase disease-free survival and overall survival by increasing complete resection rate of locally recurrent tumors and even complete response of the tumors. Ongoing treatment strategies aim to enhance response rates and to accurately assess the extent of local recurrent tumor response to concurrent chemoradiation.

Anorectal melanoma: review of 22 consecutive cases.

BACKGROUND/AIMS: To evaluate outcome and prognostic factors of patients with anorectal melanoma. METHODOLOGY: Twenty-two consecutive patients with anorectal melanoma received operation from 1993 through 2011 were reviewed. The definitions of stage I, II and III are local disease, locoregional lymphadenopathy and metastatic disease, respectively. RESULTS: The patients included 8 men and 14 women, aged from 36 to 83 years (mean, 58.4 years). At the end of the follow-up period, 19 patients died of disease and only 3 patients were alive with disease. Only two patients were alive longer than 5 years after operation. For stage I and II tumors that underwent clinical curative resection (n=17), stage II (p=0.04), tumor size >3 cm (p=0.008) and invasion depth to muscle (p=0.021) all showed poorer prognosis in overall survival. Though wide local excision (WLE) were performed in the patients with earlier tumors, there was no statistical difference in overall (p=0.063) and disease-free survival (p=0.333) between WLE and radical surgery. Furthermore, patients with WLE had more chance of local recurrence than radical surgery (6/7 vs. 3/10, p=0.050). Four salvage radical operations could be performed after local recurrence in WLE group. CONCLUSIONS: WLE increases the chance of local recurrence more than radical surgery. Care should be taken to avoid microseeding during performed WLE.

Risk factors for lymph node metastasis in pT1 and pT2 rectal cancer: a single-institute experience in 943 patients and literature review.

BACKGROUND: Local excision has become an alternative for radical resection in rectal cancer for selected patients. The purpose of this study was to assess the clinicopathologic factors determining lymph node metastasis (LNM) in patients with T1-2 rectal cancer. METHODS: Between January 1995 and December 2009, a total of 943 patients with pT1 or pT2 rectal adenocarcinoma received radical resection at a single institution. Clinicopathologic factors were evaluated by univariate and multivariate analyses to identify risk factors for LNM. RESULTS: A total of 943 patients (544 men and 399 women) treated for T1-2 rectal cancer were included in this study. LNM was found in 188 patients (19.9%). In multivariate analysis, lymphovascular invasion (LVI; P < 0.001, hazard ratio 11.472), poor differentiation (PD; P = 0.007, hazard ratio 3.218), and depth of invasion (presence of pT2; P = 0.032, hazard ratio 1.694) were significantly related to nodal involvement. The incidence for LNM lesions in the presence of LVI, PD, and pT2 was 68.8, 50.0, and 23.1%, respectively, while that for pT1 carcinomas with no LVI or PD was 7.5%. CONCLUSIONS: LVI, PD, and pT2 are independent risk factors predicting LNM in pT1-2 rectal carcinoma.

Can neutrophil-to-lymphocyte ratio predict the survival of colorectal cancer patients who have received curative surgery electively?

PURPOSE: We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) on disease-free survival in patients with stages I to III colorectal cancer (CRC). METHODS: There were 3857 patients identified from our database. We used receiver operating characteristic (ROC) analysis to identify the best cutoff value of NLR. A 5-year disease-free survival was used as end point. Survival analysis was used to assess the NLR effect, after stratification by several clinopathologic factors. RESULTS: In the ROC analysis, NLR = 3 had the highest sensitivity and specificity. Elevated NLR (>3) in colon cancer seemed to accompany larger tumor size (~5 cm) and more advanced T stage. By multivariate analysis, elevated NLR in colon cancer was associated with an increased risk of disease progression or cancer death [hazard ratio (HR) 1.377, 95 % confidence interval 1.104-1.717, P = 0.014]. However, elevated NLR in rectal cancer lost its significance in multivariate analysis (HR 1.121, 95 % confidence interval 0.941-1.336, P = 0.200). Patients with elevated NLR had worse outcome, especially for colon cancer. CONCLUSIONS: Preoperative NLR influenced the disease-free survival in patients with stages I to III CRC. Elevated NLR (>3) was associated with worse outcome (5-year disease-free survival 66.3 % vs. 78.9 % in colon cancer, P < 0.001; 60. 5 % vs. 66.2 % in rectal cancer, P = 0.008). The difference was larger in colon cancer than in rectal cancer. NLR should be considered as a prognostic factor for stages I to III CRC patients after curative surgery.

Cellular changes in hepatocytes and intestinal endothelium after hepatoduodenal ligament occlusion and protective effects of caspase inhibition.

INTRODUCTION: Hepatic vascular control is used by many surgeons to prevent massive hemorrhage during hepatectomy. However, this may carry a risk of ischemic damage to the hepatocytes. Another major drawback of intraoperative occlusion of the hepatoduodenal ligament is portal stasis with resultant intestinal congestion which may cause adverse effects on the intestinal functions. CD44 is a transmembrane glycoprotein present in many types of epithelial cells. By mediating the attachment of dividing crypt cells to the basal lamina via hyaluronan, CD44 is considered to play a role in maintaining the intestinal villus integrity. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. ZVAD-fmk is a cell-permeable irreversible inhibitor of caspase and might block the processing of many caspases. This study is designed with the purpose to evaluate the impact of intraoperative occlusion of the hepatoduodenal ligament on hepatocyte and intestine functions and also to evaluate the potential influence of ZVAD-fmk on the hepatocyte and intestine functions. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized to 5 groups. Group 1(C) underwent sham operation. Group 2 (HDL30) underwent occluding the hepatoduodenal ligament by for 30 minutes. Group 3 (HDL 15) underwent occluding the hepatoduodenal ligament by for 15 minutes, releasing for 5 minutes, underwent occlusion for another 15 minutes. Group 4 (ZHDL30) first received ZVAD-fmk, then underwent occluding the hepatoduodenal ligament by for 30 minutes. Group 5 (ZHDL15) first received ZVAD-fmk, then underwent occluding the hepatoduodenal ligament for 15 minutes, releasing for 5 minutes, underwent occlusion for another 15 minutes. After removing the temporary occlusion, liver tissue and proximal jejunum were harvested. Hepatocyte and intestine apoptosis were quantitated using the TUNEL method. CD 44 status of jejunum were determined by immunohistochemical staining. RESULTS: Hepatocyte apoptosis was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk effectively attenuated this phenomenon in both groups. There was no significant difference between group (HDL30) and group (HDL15). Jejunal apoptosis was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk effectively attenuated this phenomenon in both groups. There was no significant difference between group (HDL30) and group (HDL15). CD44 expression on jejunum was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk failed to effectively diminish this phenomenon. CONCLUSION: Occlusion of the hepatoduodenal ligament significantly increased both hepatocyte and jejunal apoptosis and pretreatment with ZVAD-fmk could effectively diminish such phenomenon. CD44 expression on jejunum was also significantly increased by intraoperative occlusion of the hepatoduodenal ligament, yet pretreatment with ZVAD-fmk failed to show significant effect on such phenomenon.

Low preoperative serum albumin in colon cancer: a risk factor for poor outcome.

OBJECTIVE: The number of colon cancer patients is increasing worldwide. Malnutrition and comorbidities are frequently associated with these patients. The relationships between the preoperative malnutrition and the outcomes of colon cancer patients are unclear; this study aimed to clarify these issues. METHODS: A total of 3,849 consecutive colon cancer patients were enrolled in an analysis of short-term outcomes and 2,529 patients were included in an analysis of the long-term outcomes. These patients were divided into the hypoalbuminemic and normal groups according to the definition of hypoalbuminemia (serum albumin < 35 g/L). RESULTS: Advanced age, female gender, abnormal CEA levels, right colon or large tumors, mucinous adenocarcinoma, poor differentiation, stage II cancer, TNM advancing T stage, old cardiovascular accident, diabetes, and liver cirrhosis were more likely to be associated with hypoalbuminemia. Hypoalbuminemic patients had a higher rate of postoperative mortality and morbidity, including complications related to wounds, lungs, the urinary system, and anastomosis. The 5-year overall survival rates of patients with normal albumin and hypoalbuminemia were 78.0% and 60.0%, respectively (P < 0.0001), and the 5-year relapse-free survival rates were 78.9% and 73.5%, respectively (P = 0.0042). In a multivariate analysis, the albumin level was also significantly correlated with 5-year overall survival (<35 vs. ≥ 35, HR 1.75; 95% CI 1.49-2.08) and 5-year relapse-free survival (<35 vs. ≥ 35, HR 1.28; 95% CI 1.04-1.56). CONCLUSIONS: Hypoalbuminemia is a predictor of poor surgical outcomes of colon cancer and is a poor prognosis factor for long-term survival of colon cancer after curative operation.