Prognosticators of Long-Term Outcomes of TNM Stage II Colorectal Cancer: Molecular Patterns or Clinicopathological Features.

BACKGROUND: Patients with stage II colorectal cancer (CRC) have a higher risk of recurrence when they have certain risk factors, including clinical and pathological patterns. However, as the prognostic role of molecular patterns for stage II disease is still unclear, this study aimed to investigate it. METHODS: A total of 509 patients with stage II CRC were enrolled, and all clinical, pathological, and molecular data were collected. Molecular patterns included microsatellite instability (MSI); elevated microsatellite alterations at selected tetranucleotides (EMAST) status; and expression of RAS/RAF genes, genes of the APC pathway, and other gene mutations. The endpoints were oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local recurrence (LR), and distant recurrence (DR). Cox regression analysis was used. RESULTS: Numerous molecular patterns influenced the oncological outcomes on univariate analysis, but no variable reached significance in LR. On multivariate analysis, a mucinous component (MC) > 50% (P < 0.01) was significant for OS and CSS. Lymphovascular invasion (LVI; P< 0.01), MC > 50% (P < 0.01), and EMAST-H (P = 0.02) significantly influenced DFS, whereas LVI (P < 0.01), MC > 50% (P < 0.01), and TP53 mutation (P = 0.02) were significant for DR. CONCLUSIONS: In this study, MSI, EMAST, and RAS/RAF alterations did not influence the oncological outcomes. Overall, LVI and MC were two significant prognostic factors for DFS and DR. Thus, the histopathology, rather than the genes, plays a major role in the prognosis of patients with stage II CRC.

Transanal Total Mesorectal Excision Versus Laparoscopic Surgery for Rectal Cancer Receiving Neoadjuvant Chemoradiation: A Matched Case-Control Study.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has been indicated for locally advanced rectal cancer. While utilization of laparoscopy in rectal cancer surgery has been popular in recent years, tumors receiving nCRT is still a surgical challenge. Transanal total mesorectal excision (TaTME) has emerged as a focused area of laparoscopic surgery that is becoming an increasingly acceptable approach in the field of rectal surgery. METHODS: Between December 2013 and April 2015, a total of 50 patients (38 males) with post-nCRT middle or lower rectal cancer who then underwent TaTME at two separate institutions were prospectively documented. Overall, 100 matched control cohorts who received conventional laparoscopic rectal surgery (LapTME) were simultaneously retrieved from a prospectively registered database. Four parameters of sex, age, clinical stage, and American Society of Anesthesiologists (ASA) score were matched for surgical outcomes, and short-term oncological results, including complications and pathological outcomes, were analyzed. RESULTS: Both the TaTME and LapTME groups received 5-fluorouracil-based chemotherapy and 5 weeks of long-course radiation therapy. Mean operative time for the TaTME group was 182.1 ± 55.4 min (156.6 ± 37.8 min in two-team-approach cases) and 178.7 ± 34.8 min for the LapTME group. The TaTME group yielded longer distal margin lengths. No significant differences were observed in blood loss, intraoperative complication rate, conversion rate, anastomosis type, and free circumferential margin rate. CONCLUSION: This matched case-control study demonstrated that TaTME is safe and feasible. Compared with LapTME, TaTME not only achieves identical circumferential margin status without compromising other operative and quality parameters but also benefits patients by achieving a longer distal margin. Thus, TaTME has the potential to become an option in managing irradiated rectal cancer.

The evolving practice of hybrid natural orifice transluminal endoscopic surgery (NOTES) for rectal cancer.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has emerged as the area of focus in laparoscopic surgery. Hybrid NOTES (hNOTES) has some potential advantages for treating rectal cancer. METHODS: Between May 2013 and November 2013, a total of 20 patients (11 males) who received hNOTES at two institutes participating in the study were documented and reviewed. Surgical outcomes, including complications and pathological outcomes, were analyzed. RESULTS: The mean age of patients was 57.8 ± 10.1 years (range 34-78). Eleven patients received preoperative neoadjuvant chemoradiotherapy, with the mean distance between tumor and anal verge being 5.9 ± 1.7 cm (mean 2-8). The mean estimated intraoperative blood loss was 68 ± 106 ml (range 30-500), with one case converted to open procedure due to uncontrolled bleeding. Eight cases underwent simultaneous two-team approach. The mean operative time was 200.8 ± 47.7 min (range 110-285). Circular stapling was performed for 14 cases (70 %) as the anastomosis, and protective stoma performed for 17 cases (85 %). The overall postoperative complication rate was 25 %. Two cases (10 %) develop pelvic abscess due to leakage, which were controlled by medical treatments. The distal and circumferential margins were all free of tumor cells, and the mean distal margin length was 2.4 ± 0.98 cm (range 0.5-4). CONCLUSIONS: Hybrid NOTES for rectal cancer is safe and feasible. Rapid experience-building accelerates its evolution, as reflected here by the high stapling rate and the idea of a two-team approach. It has the potential to become an option of treating rectal cancers.

Radiomic features derived from pretherapeutic MRI predict chemoradiation response in locally advanced rectal cancer.

BACKGROUND: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant concurrent chemoradiotherapy (CRT) followed by surgical excision. Current evidence suggests a favorable prognosis for those with pathological complete response (pCR), and surgery may be spared for them. We trained and validated regression models for CRT response prediction with selected radiomic features extracted from pretreatment magnetic resonance (MR) images to recruit potential candidates for this watch-and-wait strategy. METHODS: We retrospectively enrolled patients with LARC who underwent pre-CRT MR imaging between 2010 and 2019. Pathological complete response in surgical specimens after CRT was defined as the ground truth. Quantitative features derived from both unfiltered and filtered images were extracted from manually segmented region of interests on T2-weighted images and selected using variance threshold, univariate statistical tests, and cross-validation least absolute shrinkage and selection operator (Lasso) regression. Finally, a regression model using selected features with high coefficients was optimized and evaluated. Model performance was measured by classification accuracies and area under the receiver operating characteristic (AUROC). RESULTS: We extracted 1223 radiomic features from each MRI study of 133 enrolled patients. After tumor excision, 34 (26 %) of 133 patients had pCR in resected specimens. When 25 image-derived features were selected from univariate analysis, classification AUROC was 0.86 and 0.79 with the addition of six clinical features on the hold-out internal validation dataset. When 11 image-derived features were used, the optimized linear regression model had an AUROC value of 0.79 and 0.65 with the addition of six clinical features on the hold-out dataset. Among the radiomic features, texture features including gray level variance, strength, and cluster prominence had the highest coefficient by Lasso regression. CONCLUSION: Radiomic features derived from pretreatment MR images demonstrated promising efficacy in predicting pCR after CRT. However, radiomic features combined with clinical features did not result in remarkable improvement in model performance.

Effects of S/B remedy containing Scutellaria baicalensis and Bupleurum scorzonerifolfium on hepatic interleukin-6 related signal transducer and activator of transcription 3 activation in mice through cell-cell interaction.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in regulating interleukin 6 (IL-6) related growth control of the liver. Our previous study demonstrated that a mixture containing Scutellaria baicalensis and Bupleurum scorzonerifolfium (S/B remedy) modulated the growth of hepatocytes during liver regeneration after 2/3 partial hepatectomy. The aim of this study was to investigate whether S/B remedy induced mouse hepatic STAT3 activation directly in hepatocytes or indirectly via non-parenchymal cell-hepatocyte interaction. Direct S/B remedy effects were studied using primarily isolated hepatocytes; while C57BL/6J mice were used to study indirect effects of S/B remedy using gadolinium chloride to deplete Kupffer cells' function. The results showed that S/B remedy and its active constituents did not directly activate growth-related signaling in primarily isolated hepatocytes. However, S/B remedy induced STAT3 and subsequently suppressor of cytokine signaling (SOCS3) activation in mouse liver and increased serum IL-6 level in a dose-dependent manner, which could be partially blocked by pretreatment with gadolinium chloride. Oligonucloetide microarray analysis from S/B remedy-treated peripheral blood leukocytes demonstrated an up-regulation of IL-6 gene expression. We conclude that S/B remedy did not directly induce STAT3 activation in vitro, but induced hepatic IL-6 related STAT3 activation through non-parenchymal cell-hepatocyte interaction in vivo. The results provide important information on the molecular mechanisms of S/B remedy for treatment of human liver diseases.

Taiwan Society of Colon and Rectal Surgeons Consensus on mCRC Treatment.

Therapeutic options for metastatic CRC (mCRC) have changed significantly in recent years, greatly increasing the complexity of therapeutic decision-making. Although oncology guidelines have helped improve the care process, guidelines may also limit the flexibility to individualize in-clinic decision-making. This consensus paper addresses specific gaps in the current international guidelines to assist Taiwanese colon and rectal experts make specific therapeutic choices. Over 3 years and three meetings with selected experts on "real-world" Taiwanese practice patterns for mCRC, consensus was achieved. The experts also discussed specific questions during in-depth one-on-one consultation. Outcomes of the discussion were then correlated with published evidence by an independent medical writer. The final consensus includes clinically implementable recommendations to provide guidance in treating Taiwanese mCRC patients. The consensus includes criteria for defining fit and unfit intensive treatment patients, treatment goals, treatment considerations of molecular profiles, treatment consideration, and optimal treatment choices between different patient archetypes, including optimal treatment options based on RAS, BRAF, and microsatellite instability (MSI) status. This consensus paper is the second in the Taiwan Society of Colon and Rectal Surgeons (TSCRS) Consensus series to address unmet gaps in guideline recommendations in lieu of Taiwanese mCRC management. Meticulous discussions with experts, the multidisciplinary nature of the working group, and the final drafting of the consensus by independent medical professionals have contributed to the strong scientific value of this consensus.

Influence of GSTP1 I105V polymorphism on cumulative neuropathy and outcome of FOLFOX-4 treatment in Asian patients with colorectal carcinoma.

Glutathione S-transferase P1 (GSTP1) participates in detoxification of potentially genotoxic compounds that may alter the efficacy and toxicity of platinum-based chemotherapy. We analyzed the influence of I105V polymorphism of GSTP1 on clinico-pathological features and outcomes in 166 Chinese patients with metastatic colorectal carcinoma who had been treated with first-line FOLFOX-4. Combined analysis of GSTP1 I105V, ERCC1-118, and XPD-751 polymorphisms was also conducted. The results showed that, in comparison with Caucasian populations, a remarkably lower prevalence of Val105 allele variants was noted (24.7%). Patients with Val105 allele variants had a higher response to FOLFOX-4 (56.1%vs 37.6%, P = 0.04), and a longer progression-free (P < 0.01) as well as overall (P < 0.01) survival. By adjusted analysis, this polymorphism was identified as an independent prognostic factor (P = 0.01). In combined analysis, patients without any risk genotype, including GSTP1-105 Ile/Ile, ERCC1-118 C/T or T/T, and XPD-751 Lys/Gln, had significantly longer progression-free and overall survivals (P < 0.01). In addition, patients with Val105 allele variants had a higher incidence of grade 3/4 cumulative neuropathy after different cycles of treatment. These data suggest that Asian populations have a lower prevalence of I105V polymorphism in GSTP1. I105V polymorphism in GSTP1, by reducing its enzymatic activity and consequential detoxification to oxaliplatin, could be a key determinant for a better outcome, but more neurotoxicity, to FOLFOX-4 treatment.

Harnessing stemness and PD-L1 expression by AT-rich interaction domain-containing protein 3B in colorectal cancer.

Background and Aims: Cancer stem cells (CSCs) have been shown to be responsible for the tumor initiation, metastasis, and therapeutic resistance of colorectal cancer (CRC). Recent studies have also indicated the importance of CSCs in escaping immune surveillance. However, the coordinated epigenetic control of the stem cell signature and the key molecule(s) involved in immunosurveillance of colorectal CSCs (CRCSCs) are unclear. Here, we investigated the role of a histone modifier, AT-rich interaction domain-containing protein 3B (ARID3B), in CRC. Methods: CRC patient-derived xenografts (PDXs) with knockout of ARID3B induced by CRISPR/Cas9 in vivo were used. Molecular/cellular biology assays were performed. Clinical data obtained from The Cancer Genome Atlas, as well as from our cohort (Taipei Veterans General Hospital), were analyzed. Results: ARID3B was crucial for the growth of CRC, and ARID3B promoted the stem-like features of CRC. Mechanistically, ARID3B activated Notch target genes, intestinal stem cell (ISC) genes, and programmed death-ligand 1 (PD-L1) through the recruitment of lysine-specific demethylase 4C (KDM4C) to modulate the chromatin configuration for transcriptional activation. Clinical sample analyses showed that the coexpression of ARID3B and the Notch target HES1 correlated with a worse outcome and that ARID3B and PD-L1 were highly expressed in the consensus molecular subtype 4 of CRC. Pharmacological inhibition of KDM4 activity reversed the ARID3B-induced signature. Conclusion: We reveal a noncanonical Notch pathway for activating Notch target genes, ISC genes, and PD-L1 in CRC. This finding explains the immune escape of CRCSCs and indicates a potential group that may benefit from immune checkpoint inhibitors. Epigenetic drugs for reversing stem-like features of CRC should also be investigated.

Robotic transanal total mesorectal excision assisted by laparoscopic transabdominal approach: A preliminary twenty-case series report.

BACKGROUND: Laparoscopy-assisted robotic transanal total mesorectal excision is a novel surgical technique for rectal cancer resection. Compared to prior DaVinci Si system case series, this case series is the first to report robotic taTME assisted by laparoscopy (r-taTME) in which the "transanal team" operates via the DaVinci Xi system. As a result, we aim to delineate and discuss preliminary findings from our robotic taTME experiences. METHODS: A total of twenty patients (twelve males) who underwent robotic taTME assisted by laparoscopy (r-taTME) between January 2016 and November 2016 at a single institution were documented. Surgical outcomes, including complications, pathological outcomes, and short-term results, were then retrospectively analyzed. RESULTS: All patients underwent r-taTME via a two-team approach. The "abdominal team" operated via a single port method (ileostomy site), while the "transanal team" operated via the DaVinci Xi system. The mean patient age was 56.7 ± 14.3 years (range 31-79), and the mean distance from tumor to anal verge was 6.0 ± 2.7 cm (range 2-10). The mean estimated intraoperative blood loss was 88 ± 107 ml (range 30-500), and circular stapling was utilized to restore continuity in 80% of study patients. The overall postoperative complication rate was 35%, and the mean distal margin length was 3.1 ± 1.3 cm. There were three patients who had a circumferential margin (CRM) involved by cancer cells (≤1 mm). CONCLUSION: Our preliminary series report demonstrates that utilization of r-taTME assisted by laparoscopy is safe and feasible. Development of a novel transanal approach that allows single-port access alongside a multi-arm robotic system may increase the convenience and efficiency of future operation.

ERCC1 codon 118 C→T polymorphism associated with ERCC1 expression and outcome of FOLFOX-4 treatment in Asian patients with metastatic colorectal carcinoma.

We analyzed the influence of codon 118 C→T polymorphism of ERCC1 on its protein expression levels, clinicopathological features, and outcome of 168 Chinese patients with metastatic colorectal carcinoma that had been treated with first-line FOLFOX-4 chemotherapy. A high prevalence of C/C genotype was noted (47.6%, n = 80; 168 patients in total). A marked increase of ERCC1 protein expression levels was also noted in patients with C/T or T/T genotypes (70%vs 20%; P < 0.01), which was associated with significantly lower response to FOLFOX-4 (36.4%vs 57.5%; p = 0.01), and shorter progression-free (7 months vs 13 months; P < 0.01) and overall (16 months vs 25 months; P < 0.01) survival times. By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.02). These data suggest that Asian populations have a significantly higher prevalence of the C/C genotype in ERCC1 codon 118, which could be a key determinant for good responses to oxaliplatin-based treatment and favorable outcomes.

Very low prevalence of XPD K751Q polymorphism and its association with XPD expression and outcomes of FOLFOX-4 treatment in Asian patients with colorectal carcinoma.

Xeroderma pigmentosum group D (XPD) participates in DNA unwinding during nucleotide excision repair, which may alter the efficacy of platinum-based chemotherapy. We analyzed the influence of codon 751 Lys-->Gln polymorphism of XPD on its protein expression levels, clinico-pathological features, and outcome of 188 Chinese patients with metastatic colorectal carcinoma (CRC) that had been treated with first-line Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX-4) chemotherapy. The results showed that in comparison with Caucasian populations, a remarkably lower prevalence of Lys/Gln genotype was noted (16%, n = 30). No between-group difference in XPD protein expression of patients with or without this polymorphism was noted (56.5%vs 59.7%; P = 0.783). Patients with Gln751 allele have a significantly lower response to FOLFOX-4 treatment (36.7%vs 58.2%, P = 0.03), and shorter progression-free (7 vs 11 months; P < 0.01) and overall (14 vs 22 months; P < 0.01) survivals. The incidence of grade 3/4 oxaliplatin-neuropathies was very similar in both groups (13.3%vs 16.5%; P = 0.67). By adjusted analysis, this polymorphism was further identified as an independent prognostic factor (P = 0.03). These data suggest that Asian populations have a significantly lower prevalence of codon 751 Lys/Gln polymorphism in XPD, which could be a key determinant for good response to oxaliplatin-based treatment and favorable outcomes.

Author Correction: MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells.

In the version of Supplementary Fig. 6c originally published with this Article, the immunoprecipitation (IP) and immunoblotting (IB) tags in the top panel were mislabelled. In addition, in Supplementary Fig. 6e, the blot of the IP: Numb; IB: ß-Trcp panel for HCT15 was mistakenly duplicated for HCT116. The correct versions of these figures are shown below. An independent repeat of the experiments presented in Supplementary Fig. 6c and e, showing results that are consistent with those reported in the unprocessed blots, have been deposited in figshare ( 10.6084/m9.figshare.7570685 ).

Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer.

Metastasis accounts for the high mortality rate associated with colorectal cancer (CRC), but metastasis regulators are not fully understood. To identify a novel gene involved in tumor metastasis, we used oligonucleotide microarrays, transcriptome distance analyses, and machine learning algorithms to determine links between primary and metastatic colorectal cancers. Aminopeptidase A (APA; also known as ENPEP) was selected as our focus because its relationship with colorectal cancer requires clarification. Higher APA mRNA levels were observed in patients in advanced stages of cancer, suggesting a correlation between ENPEP and degree of malignancy. Our data also indicate that APA overexpression in CRC cells induced cell migration, invasion, anchorage-independent capability, and mesenchyme-like characteristics (e.g., EMT markers). We also observed TWIST induction in APA-overexpressing SW480 cells and TWIST down-regulation in HT29 cells knocked down with APA. Both APA silencing and impaired APA activity were found to reduce migratory capacity, cancer anchorage, stemness properties, and drug resistance in vitro and in vivo. We therefore suggest that APA enzymatic activity affects tumor initiation and cancer malignancy in a TWIST-dependent manner. Results from RT-qPCR and the immunohistochemical staining of specimens taken from CRC patients indicate a significant correlation between APA and TWIST. According to data from SurvExpress analyses of TWIST1 and APA mRNA expression profiles, high APA and TWIST expression are positively correlated with poor CRC prognosis. APA may act as a prognostic factor and/or therapeutic target for CRC metastasis and recurrence.

Is decrease of tumor volume correlated with stage change after preoperative concurrent chemoradiotherapy?

BACKGROUND/AIMS: The significance of tumor volume and its change after concurrent chemoradiotherapy (CCRT) was evaluated. METHODOLOGY: Standard-dose external radiation and oral UFUR plus leucovorin were used to treat 30 middle and lower rectal adenocarcinoma patients. Volume of tumor calculated from images obtained by dynamic MRI of the rectum before and after CCRT was compared to pathological results after definite resection and other clinical data. RESULTS: The T-stage in 15 patients (50%), the N-stage in 13 (72.2%), and overall, the TNM stage in 18 (60%), were downstaged, including 7 (23.3%) with complete responses (CR). Volume of tumor before CCRT (Vpre) and after CCRT (VPost) was 10.3+/-6.1cm3 and 4.2+/-2.2cm3, respectively, and VPre correlated with initial T stage, N stage, age, and location. The net decrease ratio (NDR) of tumor volume was related to Vpre and initial T stage. As to the downstaging effect, VPre was related to incidence of CR; NDR was related to the downstaging of the N stage. CONCLUSIONS: All tumors showed volume reduction after CCRT, but the downstaging benefits were not in proportion to the size change. Initially larger tumors had higher ratios of volume reduction, and smaller tumors had higher chance of CR.

Long-term prognosis of patients with obstructing carcinoma of the right colon.

BACKGROUND: The long-term prognosis of patients with colon cancer is dependent on many factors. The aim of this retrospective study was to assess the long-term prognosis of patients with obstructing carcinoma of the right colon. METHODS: From 1981 to 1988, 256 patients at the Veterans General Hospital-Taipei who were status postcurative resection of right colon adenocarcinoma were classified as obstruction group (n = 35) or nonobstruction group (n = 221) as appropriate. RESULTS: Analysis revealed no differences in age, sex, tumor location, or stage (P >0.05) between the two groups. However, the overall and distant recurrence rates were significant higher in obstructed patients than in nonobstructed patients. Further, long-term crude and cancer-specific survival rates were significantly lower in obstructed patients when examining either overall patient outcome or stage-matched outcomes. Multivariate analysis demonstrated that obstruction and tumor stage were both independent prognostic factors. CONCLUSIONS: Obstruction status was an independent prognostic factor for patients with right colon carcinoma. The long-term prognosis of patients with obstructing carcinoma of the right colon was poor.

RER and LOH association with sporadic colorectal cancer in Taiwanese patients.

BACKGROUND/AIMS: This association study was undertaken to determine replication error and loss of heterozygosity in colorectal tumors using a set of 10 microsatellite markers linked to APC, hMSH2, hMLH1, DCC, P53, NM23, HPC1 and MET genes as well as tumor suppressor genes on 8p22. METHODOLOGY: Thirty-nine patients diagnosed and confirmed with sporadic colorectal cancer were biopsied. Their stored frozen tissues were subsequently retrieved for simultaneous analyses of replication error and loss of heterozygosity via an automated fluorescent microsatellite assay. RESULTS: Replication error was observed in 8/39 of the cases (20.5%) and had significantly higher frequency in the patients younger than 60 yr (P = 0.049). More than one third of informative tumors showed loss of heterozygosity at P53, DCC and APC genes (57.9%, 35.3% and 33.3%, respectively). Loss of heterozygosity at TP53-Dint marker was significantly associated with survival status (P = 0.038) in which a higher frequency was observed in the patients who died from colorectal cancer. Of 22 informative tumors, 6 (27.3%) showed loss of heterozygosity at the D8S254 marker that is suspected to be near one or more tumor suppressor genes and was significantly associated with gender (P = 0.046). All 6 cases of loss of heterozygosity at D8S254 were found in male patients. The frequencies of loss of heterozygosity at the NM23, hMSH2, hMLH1 and HPC1 genes were 18.5%, 12.1%, 9.1% and 7.4%, respectively. None of the cases examined displayed loss of heterozygosity at the MET oncogene. CONCLUSIONS: Additional microsatellite markers other than those associated with colorectal cancer were used to conduct the study of genomic instability and alterations in colorectal cancer tumors. The present results for the sporadic occurrence of colorectal cancer in Taiwanese patients further extend the correlation of clinical pathology and prognosis with the analysis of replication error and loss of heterozygosity.

Prospective study of the functional results of transanal endoscopic microsurgery.

BACKGROUND/AIMS: Most clinical research addresses the technological advances and oncological outcomes of transanal endoscopic microsurgery. Our aim was to examine the functional results. METHODOLOGY: From August 1999 to November 2000, 22 Taiwanese patients (14 men, 8 women; median age, 68 years) undergoing transanal endoscopic microsurgery were prospectively examined. Functional questionnaires and anorectal manometry were assessed before surgery and at 2 weeks, 6 weeks, 3 months, and 1 year. RESULTS: The median distance from the anal verge to the tumor was 10 cm. The median tumor diameter was 2.0 cm. The median duration of surgery was 120 minutes. No surgical mortality or morbidity and no local recurrence occurred during a median follow-up of 23 months. The mean stool frequency and consistency were significantly better at 3 months after surgery than before surgery. The maximal resting pressure significantly decreased after surgery. The maximal contraction pressure and maximal tolerated volume were significantly lower at 2 and 6 weeks than before surgery; these values recovered at 1 year. CONCLUSIONS: Transanal endoscopic microsurgery is safe for the cure of benign tumors and the palliative excision of malignant tumors in middle and upper rectum. Anorectal function was preserved and improved, though some anorectal manometric parameters changed over time.

Tumor marker CEA in monitoring of response to tegafur-uracil and folinic acid in patients with metastatic colorectal cancer.

BACKGROUND/AIMS: The assessment of response to chemotherapy of solid tumors is generally made by measurement of tumors visualized by imaging, commonly computed tomography scanning. However, response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging study, such as diffuse peritoneal dissemination. Furthermore, response assessment by imaging is expensive and time consuming. This study was carried out in an effort to evaluate the correlation between serial change on imaging and on CEA (carcinoembryonic antigen) levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. METHODOLOGY: Between May 1998 and August 1999, a total of 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. Oral tegafur-uracil 300 mg/m2/day and folinic acid 60 mg/day were administered concurrently for four weeks, repeated every five weeks, as the first-line treatment. Tumor marker CEA was examined before and during the whole course of treatment. Response based on CEA assessment was defined as a more-than 50% drop in serum CEA level for more than four weeks. The correlation between serial change on CEA and on imaging for assessing chemotherapeutic response was evaluated. RESULTS: Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% confidence interval, 18.0% to 47.0%), including five complete responses and eight partial responses, was achieved by imaging studies. The pretreatment CEA levels were elevated beyond the normal cut-off value in 34 (85%) patients. The response rate evaluated by CEA assessment was 42.5% (17/40). Nine responders (22.5%) based on CEA had no remission on imaging. Agreement in assessment by imaging study and by CEA was observed in 20 patients (50%), including eight responders, five stable diseases, and seven progressive diseases. The sensitivity of falling CEA levels in the prediction of true responders on imaging was 62%. The sensitivity of elevated CEA levels for the prediction of progressive disease was 70%. Concerning the diagnostic accuracy, change in CEA levels in the prediction of true responders and progressive disease on imaging were 65% and 85%, respectively. On a follow-up of 24 months, patients with remarkable falling CEA levels survived significantly longer than non-responders (P = 0.0184, log-rank test). CONCLUSIONS: The measurement of CEA levels might be useful in monitoring chemotherapeutic response and in predicting the prognosis of patients with metastatic colorectal cancer. Serum CEA level may be used as a means of monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice.

EIA versus RIA in detecting carcinoembryonic antigen level of patients with metastatic colorectal cancer.

BACKGROUND/AIMS: Little literature exists comparing the differences between enzyme immunoassay (EIA) and radioimmunoassay (RIA) in the detection of serum carcinoembryonic antigen (CEA) levels of patients with metastatic colorectal cancer. Because EIA has the advantage of avoiding the use of radioisotopes, the potential of using EIA instead of RIA in detecting CEA of patients with colorectal cancer is of interest to us. METHODOLOGY: Between March and August 2001, a total of 120 blood specimens, including 60 specimens from patients with metastatic colorectal cancer and another 60 from patients with non-malignant diseases, were examined in this study. Serum CEA levels were examined by EIA and RIA methods in parallel. The CEA-EIA tests were done using EIA kits manufactured by Abbott Laboratories at Illinois in the United States. Comparison was done with the conventional CEA-RIA tests using RIA kits manufactured by CIS laboratory at France. The blood samples were sent to Veterans General Hospital-Taipei for EIA and RIA determination. The cut-off value for CEA was set at 5.0 ng/mL. RESULTS: The correlation between the Abbott-EIA and the CIS-RIA methods in detecting serum CEA levels was high. The results give a correlation coefficient of 0.992 with a linear regression line y=0.975 x + 0.215 (p<0.0001). Agreement in the Abbott-EIA and CIS-RIA tests in diagnosis was observed in 113 patients (94%), including 53 positive (>5 ng/mL) and 60 negative (<5 ng/mL) in both tests. The sensitivity was similar in both assays (83% vs. 80%) at a cut-off level of 5 ng/mL. The ability to discriminate between colorectal cancer and non-malignant diseases was good in both assays (p<0.001). The specificity and positive predictive value were slightly higher with the Abbott-EIA method compared with CIS-RIA assay (92% vs. 83% and 91% vs. 83%, respectively). The Abbott-EIA method achieved a similar diagnostic accuracy to CIS-RIA method (88% vs. 82%). CONCLUSIONS: These data suggest that the Abbott-EIA has similar diagnostic power to CIS-RIA in the measurement of CEA levels of patients with metastatic colorectal cancer, with an additional advantage of avoiding the use of radioisotopes. We believe that ELA has the potential to replace RIA in the measurement of CEA in clinical practice.

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.