Prognostic Significance of Synchronous Colorectal Adenocarcinoma: A Matched-Pair Analysis.

OBJECTIVE: To determine the prognostic significance of the synchronous colorectal cancer (S-CRC) on survival and recurrence rate. METHODS: Authors conducted an analysis of 90 colorectal adenocarcinoma patients who received a curative (R0) resection with a full course of standard adjuvant treatment. A total of 45 patients diagnosed with S-CRC at the time of initial presentation were individually matched to a group of 45 solitary CRC patients in pair at a ratio of 1:1. The case-matched criteria included age (± 5 years), gender, tumor location, and tumor stage. For S-CRC, the most advanced pathologic lesion was defined as the index lesion, and the matching cancer stage was categorized according to the index lesion. The N-stage was determined based on all lymph nodes. RESULT: There were a higher number of retrieved nodes in patients with S-CRC than those with solitary CRC. The median (min, max) of the total number of retrieved nodes for S-CRC was 18 (3, 53) nodes, compared to 14 (4, 45) nodes for solitary CRC (p < 0.01). All patients were without distant metastasis (stage I to III). The total accumulative number of patients experiencing tumor recurrence was 9 (20%) amongst the solitary CRC patients and 18 (40%) amongst the S-CRC patients at the 15-year surveillance period (p<0.05). The disease-free survival (DFS) (mean + SD) was 147.6 + 9.3 months in the solitary CRC group, compared to 110.5 + 11.7 months in the S-CRC group (p<0.05). Amongst S-CRC patients, those having primary and synchronous tumors located across anatomical segments had poorer DFS (70.5 months) and higher 15-year tumor recurrence rate (17.8%) than those with all tumors in the same or contiguous anatomical segments. In addition, the S-CRC patients with all tumors located in contiguous segment had a longer DFS (123.7 months) than the other types of anatomical correlation. CONCLUSION: Patients with S-CRC had worse prognosis than those with solitary CRC. For S-CRC, the anatomical correlation between the primary and the synchronous tumors may influence DFS and recurrence rate.

Tissue Microvessel Density as a Potential Predictive Marker for Vascular Invasion in Colorectal Cancer.

OBJECTIVE: This study aimed to determine whether microvessel density (MVD) in the tumor tissues could be a potential predictive marker for vascular invasion (VI). METHODS: Surgical specimens of 73 patients with colorectal adenocarcinoma in Phramongkutklao Hospital were analyzed. Tissues of patients receiving preoperative radiation or prior anti-angiogenic therapy were excluded. Tumor MVD was determined using the average number of counted CD34-stained endothelial cells from two selected fields at 200x magnification in each slide. The presence of VI was defined by tumor involvement of endothelial cell-lined spaces. The optimal cut-off value of MVD to predict VI was examined using receiver operating characteristic analysis to assess the area under the curve and accuracy. RESULT: VI was detected in 17 of 73 specimens (23.3%). Colorectal cancer (CRC) specimens were classified according to MVD as low (61 specimens, 83.6%) and high density (12 specimens, 16.4%). Average MVD was slightly higher in specimens with VI (81.3±9.3) than those without VI (76.3±7.6), but without statistical significance (p = 0.736). The MVD's cut-off value of 60 vessels/200x field provided 88% sensitivity, 40% specificity, and 57.5% accuracy, with the area under the ROC curve of 0.5788. Patients with CRC having MVD of > 60 vessels/200x field were at significantly higher risk of VI than those with CRC having MVD of <60 vessels/200x field (P=0.009, Fisher's exact test). Univariate analysis revealed that MVD, nodal involvement and AJCC tumor stage were associated with the presence of VI (p <0.05). Further multivariate analysis of these three potential variables demonstrated MVD (OR, 11.994; 95% CI, 2.197 to 65.483; p <0.01) and nodal involvement (OR, 10.767; 95% CI, 1.973 to 58.748; p <0.05) as independent prognostic factors associated with VI. CONCLUSION: Based on our study, MVD immunostaining was an angiogenic marker that potentially be a predictive marker for VI.

Pretreatment Microvessel Density for Predicting of Tumor Responsiveness to Neoadjuvant Chemoradiotherapy of Locally Advanced Rectal Cancer.

OBJECTIVE: This study aimed to assess whether pretreatment tumor tissue microvessel density (MVD) could be a potential predictive marker for Mandard response in LARC treated with nCRT. METHODS: A retrospective analysis was performed in pretreatment paraffin-embedded specimens of 31 pathologically confirmed rectal adenocarcinoma. All patients received nCRT and subsequent total mesorectal resection. Tumor MVD was determined by an average number of counted CD34-stained endothelial cells from two selected fields at 200x magnification in each slide and categorized into two groups: low MVD ( 60). The tumor response was determined using the Mandard tumor regression grading system. The subjects were grouped according to their TRG into responder (TRG 1-3) and non-responder (TRG 4-5). RESULT: Twenty out of thirty-one patients (64.5%) were defined as responders. Eleven patients (35.5%) were defined as non-responders. MVD was significantly associated with tumor responsiveness to nCRT (p < 0.05). High MVD was shown to be an independent risk factor associated with tumor resistance to nCRT (OR, 22.58; 95% CI, 1.943-262.34; p = 0.013). A strong correlation was found between MVD and TRG (correlation coefficient value of 0.642, p <0.01), between MVD and vascular invasion (correlation coefficient value of 0.618, p <0.01), and between nodal involvement and vascular invasion (correlation coefficient value of 0.521, p <0.01). A moderate correlation was found between nodal involvement and vascular invasion (correlation coefficient value of 0.406, p <0.05). CONCLUSION: High MVD in pretreatment tumor tissue was significantly associated with the tumor resistance to nCRT.

Synchronous Advanced Colorectal Neoplasia: Clinicopathologic Features and Prognostic Significance.

OBJECTIVE: This study aimed to compare the clinico-pathologic features, recurrence rate and disease-free survival between colorectal cancers (CRCs) with synchronous advanced colorectal neoplasia (SCN) and solitary CRCs to determine the prognostic significance of SCN. METHODS: A retrospective review of prospectively collected data of patients with CRCs was conducted in Phramongkutklao Hospital from January 2009 to December 2014. Patients were categorized in 3 groups: 1) solitary CRCs, 2) CRCs with advanced colorectal adenomas (ACAs) but having no another cancer and 3) synchronous colorectal cancers (S-CRCs) with or without ACAs. Patients undergoing curative resection and complete standard adjuvant treatment were recruited to evaluate the prognostic significance of SCN.  Clinicopathologic features, recurrence rate and disease-free survival were analyzed to compare among different groups.  Result: Among 328 recruited patients, 282 were classified as solitary CRCs (86%), 23 as CRCs with ACAs (7%) and 23 as S-CRCs (7%). Patients with CRCs with SCN (groups 2 and 3) were significantly older than patients with solitary CRCs (p <0.01), and SCN was found more commonly among males (15.2%) than females (12.3%) (p=0.045). In all, 288 patients achieved a curative resection and accomplished complete standard postoperative adjuvant treatment. Of these, the accumulative number of patients experiencing tumor recurrence was 11.8, 21.2, 24.6, 26.4 and 26.7% at the 1-, 3-, 5-, 7- and 10-year surveillance period, respectively. The disease-free survival of the groups with SCN was marginally higher than that of solitary CRCs groups (p=0.72) (solitary CRCs, 120.7±4.4 months; CRCs/ACAs, 127.4±13.9 months and S-CRCs: 126.2±13.6 months). CONCLUSION: CRCs with SCN were found at a more advanced age than those with solitary CRCs. SCN was found more often among males than females. After achieving curative resection and complete adjuvant treatment, the recurrence rate and disease-free survival of CRCs with SCN did not significantly differ from those of solitary CRCs.

Study of the vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) in primary colorectal cancer specimens.

OBJECTIVE: Determine the relationship between vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) in primary colorectal cancer specimens including the prognostic value by evaluating the correlation between various common reported prognostic histopathologic indictors and these two angiogenic parameters. The Inter-observer reliability on VEGF and MVD measurement was also determined. MATERIAL AND METHOD: Anti-VEGF and anti-factor CD34 monoclonal antibodies immunohistochemical staining was performed in 40 randomly selected formalin-fixed paraffin-embedded colorectal cancer specimens of non-stage-IV patients who underwent curative resection using. Immunoreactive in 25% or more carcinoma cells was categorized as positive. The intensity of VEGF expression was graded in a semiquantitative fashion, ranging from 0 to 2 Tumor MVD was determined by counting any endothelial cells stained with CD34 per two randomly selected fields at x200 magnification in each slide. The correlation between VEGF expression and MVD was evaluated. Inter-observer agreement was assessed by comparing the results of VEGF and MVD measurements made by two pathologists. RESULTS: A moderate correlation was found between the percentage of positive immunoreactive cells and the intensity of VEGF immunoreactive staining (correlation value of 0.436, p < 0.05). MVD was found having no correlation with both the percentage of positive immunoreactive cells and intensity of VEGF immunoreactive staining (the correlation value of -0.056, p = 0.732 and 0.108, p = 0.506, respectively). Neither MVD nor VEGF expression in primary colorectal cancer tissue was found having a significant correlation with any common reported prognostic histopathologic indictors. In counting CD34-stained endothelial cells, this study revealed a high intra-observer correlation coefficient of 0.886 (95% CI: 0.715-0.955) for the first pathologist and 0.913 (95% CI: 0.782-0.965) for the second. High inter-observer reliability was found in both MVD and VEGF measurement with a substantial agreement (agreement: 95%, kappa = 0.643) between the two pathologists. CONCLUSION: In primary colorectal cancer tissues, there was no significant relationship between MVD and VEGF expression. This study revealed a high intra and inter-observer reliability on VEGF and MVD measurement. Neither MVD nor VEGF expression provided predictive value of advanced or aggressiveness of disease. Further studies on larger sample size would help validate these results.

Identification of patients with high-risk for pulmonary metastases after curative resection of colorectal cancer.

BACKGROUND: The presence of distant metastases from colorectal cancer (CRC) does not preclude curative treatment. Early detection of pulmonary metastases at a potentially curable stage could improve survival. The aim of the present study was to assess the prognostic significance of commonly reported clinicopathologic features to identify high-risk patients who would likely benefit from more intensive chest surveillance for pulmonary metastases. MATERIAL AND METHOD: A total of 351 consecutive patients, with surgical stages I-III colorectal cancer, who underwent curative resection at Phramongkutklao hospital from 1999 to 2005, were followed regularly according to the established guidelines with routine physical examination, serum carcinoembryonic antigen (CEA) and colonoscopic surveillance. Imaging studies for detecting metastases were computed tomography (CT), plain film radiography, and ultrasonograpy. Clinical and pathologic features were analyzed for their association with pulmonary metastasis. RESULTS: There were 145 patients who had been operated for longer than five years after curative intent surgery. Of these, nineteen patients were lost to follow-up or died from other causes that were unrelated to colorectal cancer. Pulmonary metastases were detected in 26 patients by either CXR or CT scan. Median time to pulmonary metastasis was 19 months (95 percent CI, 12-35). According to an univariate analysis, with log-rank test, identified four factors associated with pulmonary metastasis: Tumor stage T4, Nodal stage N2, elevation of serum CEA > 3.4 ng/ml and presence of lymphovascular invasion(LVI). According to a multivariate analysis, with Cox regression, found an elevation of serum CEA > 3.4 ng/ml which was an independent factor that was significantly associated with pulmonary metastasis (Hazard ratio (HR), 8.9; 95 percent CI, 3.6-22; p < 0.01). The present study revealed that 50 percent of patients who had more than one of these risk factors would eventually develop pulmonary metastases. CONCLUSION: An elevation of serum CEA > or = 3.4 ng/ml was found as an independent factor that was significantly associated with pulmonary metastasis whereas tumor stage T4, nodal stage N2 and presence of lymphovascular invasion (LVI) were not independent clinicopathologic features associated with subsequent pulmonary metastases. Chest CT scan has greater sensitivity than chest radiography in detection of pulmonary metastasis and should be considered as an imaging study of choice for intensive chest surveillance for patients who had more than one of these risk factors.

Incisional surgical site infection in colorectal surgery patients.

BACKGROUND: Knowledge of specific risk factors for incisional Surgical Site Infection (SSI) is essential to create a specific SSI risk stratification index for colorectal surgery patients. OBJECTIVE: Identify factors increasing the risk of incisional SSI that lead to the development of a more efficient tool for predicting and comparing surgical site infection rates among surgeons and institutions performing the same type of procedure for colorectal surgery patients. MATERIAL AND METHOD: The authors conducted a prospective incisional SSI surveillance in 229 consecutive patients who underwent open colon and rectal resections performed in Phramongkutklao Hospital between October 1, 2008 and September 30, 2010. Independent risk factors for SSIs were identified by multivariate analysis. RESULTS: The present study identified six independent risk factors significantly associated with a higher risk of incisional SSI that included Body mass index (BMI) > 30 (Odd ratio (OD) = 4.4; 95% confidence interval (CI) = 1.235-15.502; p = 0.022), hypoalbuminemia (< 3.5 g/dl) (Odd ratio (OR) = 2.8; 95% confidence interval (CI) = 1.003-7.587; p = 0.049), Hartmann's procedure (Odd ratio (OR) = 2.6; 95% confidence interval (CI) = 1.037-6.729; p = 0.042), postoperative hypotension, (Odd ratio (OR) = 2.3; 95% confidence interval (CI) = 1.043-5.268; p = 0.039) and postoperative hypothermia (Odd ratio (OR) = 5.6; 95% confidence interval (CI) = 1.112-28.482; p = 0.037). CONCLUSION: Risk factors identified in the present study can be considered for creating a specific incisional SSI risk stratification index for colorectal surgery patients. This specific risk stratification index will be a more efficient tool for predicting and comparing SSI rates among surgeons and institutions.

Local perianal nerve block versus spinal block for closed hemorrhoidectomy: a ramdomized controlled trial.

OBJECTIVE: To compare analgesic effectiveness, postoperative pain, complications, and patients' satisfaction between two randomly allocated groups--one group that had local perianal nerve block and another group that had spinal block following closed hemorrhoidectomy. MATERIAL AND METHOD: Sixty-seven patients underwent elective hemorrhoidectomy. Of these, 33 were randomly allocated to receive spinal anesthesia (SA) while 34 received perianal local analgesia (LA) with bupivacaine. Pain measurement at 6 and 24 hours following hemorrhoidectomy, the quantity of postoperative analgesic medication administered, patient's satisfaction and complications were recorded. RESULTS: Among the patients who had SA, there were 5 patients (15.2%) who developed hypotension during surgery. There was no reported case of hypotension among those who had LA. There was no significant difference in degree of median postoperative pain at 6 hours (LA: 38 vs. SA: 50 with VAS; p = 0.09) and at 24 hours (LA: 31 vs. SA: 35 with VAS; p = 0.35) between the two groups. Patients had a high satisfaction on both anesthetic methods. Patients in the SA group required more parenteral analgesics (p = 0.03) and had a higher incidence of urinary retention than those in the LA group (SA: 30.3% vs. LA: 8.8%, p = 0.03). CONCLUSION: Local perianal nerve block for hemorrhoidectomy is feasible and safe and superior to spinal block due to a lower incidence of post-op urinary retention and less requirement of parenteral analgesics post-op.