Staging Paradox and recurrence pattern among stage IIB, IIC, and IIIA Colon cancers: a retrospective cohort study.

PURPOSE: The survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database. METHODS: Patients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined. RESULTS: A total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis. CONCLUSIONS: Based on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer.

Standardize the surgical technique and clarify the oncologic significance of robotic D3-D4 lymphadenectomy for upper rectum and sigmoid colon cancer with clinically more than N2 lymph node metastasis.

BACKGROUND: The territory of D3-D4 lymphadenectomy for upper rectal and sigmoid colon cancer varies, and its oncological efficacy is unclear. This prospective study aimed to standardize the surgical technique of robotic D3-D4 lymphadenectomy and clarify its oncologic significance. METHODS: Patients with upper rectal or sigmoid colon cancer with clinically suspected more than N2 lymph node metastasis were prospectively recruited to undergo standardized robotic D3-D4 lymphadenectomy. Immediately postsurgery, the retrieved lymph nodes were mapped to five N3-N4 nodal stations: the inferior mesenteric artery, para-aorta, inferior vena cava, infra-renal vein, and common iliac vessels. Patients were stratified according to their nodal metastasis status to compare their clinicopathological data and overall survival. Univariate and multivariate analyses were performed to determine the relative prognostic significance of the five specific nodal stations. Surgical outcomes and functional recovery of the patients were assessed using the appropriate variables. RESULTS: A total of 104 patients who successfully completed the treatment protocol were assessed. The standardized D3-D4 lymph node dissection harvested sufficient lymph nodes (34.4±7.2) for a precise pathologic staging. Based on histopathological analysis, 28 patients were included in the N3-N4 nodal metastasis-negative group and 33, 34, and nine patients in the single-station, double-station, and triple-station nodal metastasis-positive groups, respectively. Survival analysis indicated no significant difference between the single-station nodal metastasis-positive and N3-N4 nodal metastasis-negative groups in the estimated 5-year survival rate [53.6% (95% CI: 0.3353-0.7000) vs. 71.18% (95% CI: 0.4863-0.8518), P=0.563], whereas patients with double-station or triple-station nodal metastatic disease had poor 5-year survival rates (24.76 and 22.22%), which were comparable to those of AJCC/UICC stage IV disease than those with single-station metastasis-positive disease. Univariate analysis showed that the metastatic status of the five nodal stations was comparable in predicting the overall survival; in contrast, multivariate analysis indicated that common iliac vessels and infra-renal vein were the only two statistically significant predictors (P<0.05) for overall survival. CONCLUSIONS: Using a robotic approach, D3-D4 lymph node dissection could be safely performed in a standardized manner to remove the relevant N3-N4 lymphatic basin en bloc, thereby providing significant survival benefits and precise pathological staging for patients. This study encourages further international prospective clinical trials to provide more solid evidence that would facilitate the optimization of surgery and revision of the current treatment guidelines for such a clinical conundrum.

Wearable mobile health device for monitoring postoperative ambulation among patients with colorectal cancer undergoing minimally invasive surgery: A prospective comparison study.

BACKGROUND: This study aimed to evaluate the feasibility of using mHealth devices for monitoring postoperative ambulation among patients with colorectal cancer undergoing minimally invasive surgery (MIS). METHODS: Patients with colorectal cancer undergoing MIS were prospectively recruited to wear mHealth devices for recording postoperative ambulation between October 2018 and January 2021. The primary outcome was the compliance by evaluating the weekly submission rate of step counts. The secondary outcome was the association of weekly step counts and postoperative length of stay. RESULTS: Of 107 eligible patients, 53 patients wore mHealth devices, whereas 54 patients did not. The average weekly submission rate was 72.6% for the first month after surgery. The total step counts <4000 or >10 000 in the postoperative week one were negatively associated with postoperative length of stay (ß = -2.874, p = 0.038). CONCLUSIONS: mHealth devices provide an objective assessment of postoperative ambulation among patients with colorectal cancer undergoing MIS. CLINICAL TRIAL REGISTRATION: NCT03277235.

Changing patterns and surgical outcomes of small bowel obstruction in the era of minimally invasive surgery for colorectal cancer.

INTRODUCTION: This study aimed to investigate whether the incidence, patterns, and surgical outcomes of small bowel obstruction (SBO) have changed in the era of minimally invasive surgery (MIS) for primary colorectal cancer (CRC). METHODS: Consecutive patients who underwent laparotomy for SBO were divided into MIS and traditional open surgery (TOS) groups based on the previous colorectal cancer operation technique used. The MIS group was selected from 1544 consecutive patients who underwent MIS as a treatment for primary CRCs between 2014 and 2022, while the TOS group was selected from 1604 consecutive patients who underwent TOS as a treatment for primary CRCs between 2004 and 2013. The demographics, clinicopathological features, and surgical outcomes were compared between the two groups. RESULTS: The SBO incidence in patients who underwent MIS for primary CRC was significantly lower than that in patients who underwent TOS (4.4%, n =68/1544 vs. 9.7%, n =156/1604, P <0.0001). Compared with the TOS group, the MIS group had significantly different ( P <0.0001) SBO patterns: adhesion (48.5 vs. 91.7%), internal herniation (23.5 vs. 2.6%), external herniation (11.8 vs. 1.9%), twisted bowel limbs (4.4 vs. 0.6%), ileal volvulus with pelvic floor adhesion (5.9 vs. 1.9%), and nonspecific external compression (5.9 vs. 1.3%). A subset analysis of patients with adhesive SBO (ASBO) showed that the MIS group tended to ( P <0.0001) have bands or simple adhesions (75.8%), whereas the TOS group predominantly had matted-type adhesions (59.4%). Furthermore, SBO in the MIS group had an acute (<3 months) or early (3-12 months) onset (64.7%), while that in the TOS group ( P <0.0001) had an intermediate or a late onset. When the surgical outcomes of SBO were evaluated, the TOS group had significantly more ( P <0.0001) blood loss and longer operation time; however, no significant difference was observed in the surgical morbidity/mortality (Clavien-Dindo classification ≧3, 11.8 vs. 14.1%, P =0.6367), hospitalization, and readmission rates between the two groups. Postoperative follow-up showed that the estimated 3-year (11.37 vs. 18.8%) and 6-year (25.54 vs. 67.4%) recurrence rates of SBO were significantly lower ( P =0.016) in the MIS group than in the TOS group. CONCLUSIONS: The wide adoption of MIS to treat primary CRC has led to a lower incidence, altered patterns, and reduced recurrence rates of SBO. Awareness of this new trend will help develop surgical techniques to prevent incomplete restoration of anatomical defects and bowel malalignments specifically associated with MIS for CRC, as well as facilitate timely and appropriate management of SBO complications whenever they occur.

Impact of positron-emission tomography on the surgical treatment of locoregionally recurrent colorectal cancer.

BACKGROUND: The effect of positron emission tomography (PET) on the surgical treatment of locoregionally recurrent colorectal cancer (LRRCRC) remains unclear and warrants further investigation. MATERIAL AND METHODS: A total of 193 patients with LRRCRC were identified from a prospectively maintained institutional database, of whom 134 LRRCRCs were deemed resectable and underwent resection with curative intent, whereas the remaining 59 LRRCRCs were unresectable. Patients with resectable LRRCRC were further classified according to whether recurrence was detected solely by PET (n = 35, PET-only group) or by a combination of computed tomography (CT)/magnetic resonance imaging (MRI) and PET (n = 99, CT/MRI/PET group). Clinicopathologic features, operative morbidity/mortality, and overall survival were compared between the patient groups based on long-term follow-up for at least 5 years. RESULTS: Patients in the PET-only group tended to have less extensive organ resection (p = 0.0074), less blood loss (p < 0.0001), and shorter operation time and hospitalization (p < 0.0001), but surgical complication and readmission rates were not significantly different (p > 0.05) compared with the CT/MRI/PET group. Although the PET-only group had significantly higher R0 resection rate (80 % vs. 54.55 %, p = 0.0079), they also had a higher risk (17.14 % vs. 2.02 %, p = 0.0011) of sham operation. The estimated 5-year and 10-year survival rates significantly decreased in order (p < 0.0001) from PET-only (85.71 % and 57.98 %) and CT/MRI/PET (41.41 % and 15.93 %) to unresectable group of patients (16.95 % and 1.88 %). Subset analysis of the CT/MRI/PET group indicated that PET improved surgical decision-making because 24 (24.2 %) LRRCRCs that manifested on CT/MRI as equivocal lesions were later confirmed by PET as resectable recurrences, while 18 (19.4 %) LRRCRCs that manifested on CT/MRI as resectable lesions were later diagnosed by PET as more disseminated unresectable recurrences and precluded futile surgery. CONCLUSION: PET alone can identify a subset (20.9 %) of LRRCRCs with less tumor burden for timely surgery; PET in combination with CT/MRI can better define the resectability of LRRCRCs. The positive impacts of PET can translate into better surgical outcomes, with enhanced safety and patient survival.

International standardization and optimization group for intersphincteric resection (ISOG-ISR): modified Delphi consensus on anatomy, definition, indication, surgical technique, specimen description and functional outcome.

AIM: Intersphincteric resection (ISR) is an oncologically complex operation for very low-lying rectal cancers. Yet, definition, anatomical description, operative indications and operative approaches to ISR are not standardized. The aim of this study was to standardize the definition of ISR by reaching international consensus from the experts in the field. This standardization will allow meaningful comparison in the literature in the future. METHOD: A modified Delphi approach with three rounds of questionnaire was adopted. A total of 29 international experts from 11 countries were recruited for this study. Six domains with a total of 37 statements were examined, including anatomical definition; definition of intersphincteric dissection, intersphincteric resection (ISR) and ultra-low anterior resection (uLAR); indication for ISR; surgical technique of ISR; specimen description of ISR; and functional outcome assessment protocol. RESULTS: Three rounds of questionnaire were performed (response rate 100%, 89.6%, 89.6%). Agreement (≥80%) reached standardization on 36 statements. CONCLUSION: This study provides an international expert consensus-based definition and standardization of ISR. This is the first study standardizing terminology and definition of deep pelvis/anal canal anatomy from a surgical point of view. Intersphincteric dissection, ISR and uLAR were specifically defined for precise surgical description. Indication for ISR was determined by the rectal tumour's maximal radial infiltration (T stage) below the levator ani. A new surgical definition of T3isp was reached by consensus to define T3 low rectal tumours infiltrating the intersphincteric plane. A practical flowchart for surgical indication for uLAR/ISR/abdominoperineal resection was developed. A standardized ISR surgical technique and functional outcome assessment protocol was defined.

GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL.

GalNAc-type O-glycosylation and its initiating GalNAc transferases (GALNTs) play crucial roles in a wide range of cellular behaviors. Among 20 GALNT members, GALNT2 is consistently associated with poor survival of patients with colorectal cancer in public databases. However, its clinicopathological significance in colorectal cancer remains unclear. In this study, immunohistochemistry showed that GALNT2 was overexpressed in colorectal tumors compared with the adjacent nontumor tissues. GALNT2 overexpression was associated with poor survival of colorectal cancer patients. Forced expression of GALNT2 promoted migration and invasion as well as peritoneal metastasis of colorectal cancer cells. In contrast, GALNT2 knockdown with siRNAs or knockout with CRISPR/Cas9 system suppressed these malignant properties. Interestingly, we found that GALNT2 modified O-glycans on AXL and determined AXL levels via the proteasome-dependent pathway. In addition, the GALNT2-promoted invasiveness was significantly reversed by AXL siRNAs. These findings suggest that GALNT2 promotes colorectal cancer invasion at least partly through AXL.

Technical feasibility of robotic vs. laparoscopic surgery for locally advanced colorectal cancer invading the urinary bladder.

BACKGROUND: The aim of this study was to determine if robotic surgery can reproduce the technical advantages and oncologic outcomes of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the urinary bladder. METHODS: We retrospectively reviewed the prospectively maintained data of patients with locally advanced colorectal cancer invading the urinary bladder undergoing robotic or laparoscopic surgery between June 2006 and November 2020. Clinicopathologic features, surgical outcomes, and oncologic efficacy were compared between patient groups of robotic or laparoscopic surgery. All patients underwent surgery with the intent of R0 resection for the primary tumor. Major surgical complications were defined as Clavien-Dindo grade ≥ III. Multivariate regression analysis was performed to identify risk factors. RESULTS: A total of 41 patients (M:F = 32:9; median age: 63 [42-88] years) were analysed; 32 underwent laparoscopic surgery and 9 underwent robotic surgery. There was no statistically significant difference between the two groups in baseline demographic and clinicopathologic features. There were no significant differences in terms of mean operative time (353.24 vs. 387.33 min), mean blood loss (315.00 vs. 171.11 mL), mean number of lymph nodes harvested (27.16 vs. 23.50), R0 resection (89.7 vs. 66.7%), conversion (12.5 vs. 11.1%), major complication rate (9.4 vs. 22.2%), mean time to flatus passage (4.8 vs. 4.1 days), mean postoperative length of hospital stay (18.9 vs. 19.8 days), 5-year disease-free survival rate (64.6 vs. 62.5%) and overall survival rate (75.3 vs. 83.3%). Multivariate analysis showed that R1 resection was the only independent prognostic factor for reduced disease-free survival (hazard ratio 21.386; 95% confidence interval 1.991-229.723; p = 0.0115). CONCLUSIONS: Robotic surgery can reproduce the technical advantages and oncologic outcomes of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the urinary bladder. However, larger studies are mandatory to clarify the role of robotic surgery in such a scenario.

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study.

Aim: This phase II study investigated safety and efficacy of dilpacimab or bevacizumab plus FOLFIRI in patients with previously treated metastatic colorectal cancer (mCRC). Materials & methods: Overall, 66 patients were treated (n = 34 dilpacimab + FOLFIRI; n = 32 bevacizumab + FOLFIRI). Progression-free survival, overall survival, response rates and tolerability were assessed. Results: Median progression-free survival for dilpacimab + FOLFIRI compared with bevacizumab + FOLFIRI was 3.78 months (95% CI: 2.07-7.20) versus 7.36 months (95% CI: 5.68-10.55) (hazard ratio: 3.57; 95% CI: 1.57-8.11; stratified). Median overall survival: 7.95 months for dilpacimab + FOLFIRI; not reached for bevacizumab + FOLFIRI. Objective response rates: 5.6% for dilpacimab + FOLFIRI and 14.7% for bevacizumab + FOLFIRI. Patients treated with dilpacimab + FOLFIRI experienced serious treatment-related adverse events (n = 4; 11.8%), including one case of intestinal perforation leading to death; none were reported for bevacizumab + FOLFIRI. Conclusion: Treatment with dilpacimab + FOLFIRI was not well tolerated and did not provide clinical benefit to patients with mCRC compared with bevacizumab + FOLFIRI. Clinical Trial Registration: NCT03368859 (Clinicaltrials.gov).

The necessity of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy: a retrospective cohort study.

BACKGROUND: This study aimed to evaluate the necessity of abdominal drainage after laparoscopic appendectomy in patients with complicated appendicitis. METHODS: Patients with acute appendicitis undergoing laparoscopic appendectomy at two hospitals between January 2014 and December 2018 were retrospectively included. Complicated appendicitis was defined as the American Association for the Surgery of Trauma (AAST) grade ≥ II. The patients were classified according to the AAST grade and the indwelling of abdominal drainage. The postoperative surgical outcomes and recovery were compared among patient groups to evaluate the impact of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy. RESULTS: A total of 1241 patients was retrospectively included. Among them, there were 820 patients with simple appendicitis (AAST grade I) and 421 patients with complicated appendicitis (AAST grade ≥ II). For complicated appendicitis, the drainage group (N = 192) tended to harbor more overall complications, intra-abdominal abscess formation, time to resume a soft diet, and the postoperative length of hospitalization (P = 0.0000 for all). Multivariate logistic regression confirmed that abdominal drainage increased the risk of overall complications [Odds ratio (OR) 2.439; 95% confidence interval (CI) 1.597-3.726; P ≤ 0.0001] and failed to decrease the risk of intra-abdominal abscess formation (OR 1.655; 95% CI 0.487-5.616; P = 0.4193). Multivariate linear regression analysis also showed that the drainage group harbored longer postoperative length of hospitalization (Coefficients: 20.697; 95% CI 15.251-26.143; P < 0.0001) and time to resume a soft diet (Coefficients: 45.899; 95% CI 34.502-57.297; P < 0.0001). CONCLUSIONS: Abdominal drainage did not prevent overall complications in patients with complicated appendicitis; paradoxically, it delayed the convalescence. Our results discourage the routine use of abdominal drainage and suggest that abdominal drainage should be performed sparingly.

Ramucirumab plus triplet chemotherapy as an alternative salvage treatment for patients with metastatic colorectal cancer.

BACKGROUND: Ramucirumab is indicated for salvage treatment after failure of first-line treatment for metastatic colorectal cancer (mCRC). However, the application of ramucirumab at later-line treatment in real-world practice has not received much discussion. METHODS: In this retrospective study, we enrolled 70 patients with mCRC who received ramucirumab plus chemotherapy at National Taiwan University Hospital between 2018 and 2019. RESULTS: Compared with those who received third- or later-line ramucirumab treatment, patients who received second-line ramucirumab treatment had significantly longer median time to treatment discontinuation (mTTD; 6.7 vs 3.6 months, P = .004) and median overall survival (mOS; not reached vs 7.6 months, P = .009). Multivariate analyses revealed that second-line ramucirumab and triplet chemotherapy backbone were the only independent predictive factors for long mTTD and mOS. Patients who received ramucirumab with triplet chemotherapy had a significantly longer mOS than did patients who received ramucirumab with doublet chemotherapy (not reached vs 5.6 months, P = .002). Among those receiving second-line ramucirumab treatment, combination with triplet chemotherapy led to a longer mTTD than did combination with doublet chemotherapy, but the difference was non-significant (not reached vs 4.4 months, P = .108). By contrast, in patients receiving fourth- or later-line ramucirumab, combination with triplet chemotherapy led to significantly longer mTTD than did combination with doublet chemotherapy (8.0 vs 2.9 months, P = .032). CONCLUSION: Ramucirumab plus triplet chemotherapy may be an alternative regimen in patients with mCRC, particularly as a later-line treatment modality.

Robotic versus laparoscopic surgery for rectal cancer after neoadjuvant chemoradiotherapy: A propensity-score matching analysis.

BACKGROUND: We aimed to investigate the advantages of robotic versus laparoscopic surgery for rectal cancer after neoadjuvant chemoradiotherapy as these remains unclear. METHODS: We retrospectively recruited eligible patients with rectal cancer undergoing robotic or laparoscopic surgery following neoadjuvant chemoradiotherapy. We compared the surgical outcomes between patients undergoing either robotic surgery or laparoscopic surgery was based on the propensity-score matching analysis. RESULTS: A total of 171 patients were recruited, including 76 who underwent robotic surgery and 95 who underwent laparoscopic surgery. There were no significant differences in clinical and pathological characteristics between the groups after propensity-score matching (56 matched pairs). Longer operation times (324.964 ± 83.435 vs. 246.232 ± 111.324 min, p < 0.001) and more blood loss (187.679 ± 176.615 vs. 98.214 ± 107.011, p < 0.001) were observed in the robotic group. The major complication rates were similar between the treatment groups after propensity matching (p = 0.086). There were no significant differences in disease-free survival rates (p = 0.205) and overall survival rates (p = 0.837) between the groups. CONCLUSION: Robotic surgery is associated with similar technical safety and oncologic efficacy compared to laparoscopic surgery for the treatment of rectal cancer after neoadjuvant chemoradiotherapy; it is an acceptable option for patients requiring minimally invasive surgery. Nevertheless, the longer operation times and greater blood loss seen in the present study are a stark reminder that the convenience and surgical precision, on which the marketing of robotic surgery is rooted, are yet to be proven and require further investigation.

Multielectrode Radiofrequency Ablation for Resectable Metachronous Liver Metastasis from Colorectal Cancer.

The outcome of radiofrequency ablation (RFA) for liver metastases from colorectal cancer (CRLM) has been thought to be inferior to metastasectomy. However, the recent development of multielectrode RFA (multi-RFA) systems has made the ablation zone larger and more complete. Thus, we assessed the survival benefits of this modality in cases of metachronous CRLM. This retrospective study assessed patients diagnosed with resectable metachronous CRLM between 2013 and 2016; 132 patients were categorized by treatment for liver metastases: multi-RFA (n = 68), hepatectomy (n = 34), or systemic treatment only (n = 30). Therapeutic effectiveness, outcomes, and intervention-related complications were compared between groups. Median overall survival (OS), recurrence-free survival (RFS), and intrahepatic recurrence-free survival (IHRFS) were 69.8, 85.2, and 59.7 months for the hepatectomy group; 53.4, 41.3, and 32.3 months for the multi-RFA group; and 19.1, 7.1, and 7.1 months for the systemic treatment group. No significant differences were observed between the multi-RFA and hepatectomy groups after a median follow-up of 59.8 months. This study demonstrated that multi-RFA and hepatectomy provide similar survival benefits for patients with resectable CRLM. Multi-RFA may represent a reliable treatment option for the management of resectable liver metastases.

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

BACKGROUND: CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied. METHODS: We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC. RESULTS: Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m2) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m2 was significantly associated with CIMP-high CRC in younger patients. CONCLUSIONS: We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m2 and CIMP-high CRC in patients younger than 50 years.

Metronomic chemotherapy with tegafur-uracil following radical resection in stage II colorectal cancer.

BACKGROUND: Stage II colorectal cancer has a relatively good prognosis. Adjuvant chemotherapy following surgery is the standard treatment for stage III colorectal cancer but is not routinely recommended for all stage II colorectal cancer patients. We aimed to evaluate the clinical outcomes, treatment results, and prognostic factors in stage II colorectal cancer patients who underwent curative surgery with/without oral tegafur-uracil (UFT). METHODS: We included stage II colorectal cancer patients who underwent curative surgery and were followed up for at least 5 years after surgery at the National Taiwan University Hospital between January 2008 and December 2012. Excluding patients receiving neoadjuvant therapy, adjuvant therapy other than UFT, and those lost follow-up, patients treated with UFT (UFT group) and those without adjuvant therapy (surgery alone group) were analyzed for their clinical outcomes and prognostic factors. RESULTS: A total of 233 patients were recruited. Of these, 104 (44.64%) underwent only surgery while 129 (55.36%) received adjuvant chemotherapy with oral UFT following surgery. Recurrence or death occurred within 5 years in 60 patients (25.75%), with a significant difference between the surgery alone (36/104, 34.62%) and UFT groups (24/129, 18.61%) (p = 0.007). The UFT group demonstrated significantly superior 5-year disease-free (p = 0.003) and overall survival rates (p = 0.001), respectively. Patient age of ≤35.3 or ˃72.7 years, UFT duration of <486.8 days, 7.1 cm < tumor size ≤13.2 cm, number of harvested lymph nodes ≤13.5, and mucinous adenocarcinoma were associated with poorer 5-year overall survival. CONCLUSION: The present data suggest that UFT following curative surgery may be associated with lower recurrence and improved survival in patients with stage II colorectal cancer.

A Pilot Study of Metabolomic Pathways Associated With Fatigue in Survivors of Colorectal Cancer.

BACKGROUND: Over 30% of cancer survivors experience chronic fatigue. An alteration in energy metabolism is one of the hypothesized mechanisms for cancer-related fatigue (CRF). No studies have evaluated for changes in metabolic profiles in cancer survivors with CRF. The purpose of this pilot study was to evaluate for differences in metabolic profiles between fatigued and non-fatigued survivors of colorectal cancer (CRC). METHODS: Survivors were recruited from the surgical outpatient department and the oncology clinic of a medical center in northern Taiwan. Fatigue was assessed using the Fatigue Symptom Inventory. Fasting blood samples were collected on the day the fatigue questionnaire was completed. Metabolomic profile analysis was performed using non-targeted, liquid chromatography/time-of-flight mass spectrometry. Fold change analyses, t-tests, and pathway analyses were performed to identify differences in metabolomic profiles between the fatigued and non-fatigued survivors. RESULTS: Of the 56 CRC survivors in this study, 28.6% (n = 16) were in the fatigue group. Statistically significant differences in carnitine, L-norleucine, pyroglutamic acid, pyrrolidonecarboxylic acid, spermine, hydroxyoctanoic acid, and paraxanthine were found between the two fatigue groups. In addition, two pathways were enriched for these metabolites (i.e., glutathione metabolism, D-glutamine and D-glutamate metabolism). CONCLUSIONS: Findings from this pilot study provide preliminary evidence that two pathways that are involved with the regulation of ATP production and cellular energy (i.e., glutathione metabolism, D-glutamine and D-glutamate metabolism) are associated with fatigue in CRC survivors. If these findings are confirmed, they may provide new therapeutic targets to decrease fatigue in cancer survivors.

Study protocol for an International Prospective Observational Cohort Study for Optimal Bowel Resection Extent and Central Radicality for Colon Cancer (T-REX study).

This is a prospective observational cohort study aiming to include 4000 patients with stages I to III colon cancer treated at 35 specialist institutions in Japan, South Korea, Germany, Russia, Lithuania and Taiwan. The anatomical distribution of lymph nodes and feeding arteries are investigated using surgical specimens according to pre-specified categorizing methods using intraoperative anatomical markings. Primary analyses are performed to identify the general principles of metastatic lymph node distribution in terms of its relation to the location of the primary tumor and feeding arteries. Secondary analyses will be used to estimate prognostic outcomes according to bowel resection length and central radicality and will be used to evaluate the quality of resected surgical specimens. Through in-depth lymph node mapping, standardized criteria for the definite area of 'regional' lymph node resection in routine surgical procedures can be identified, which is expected to contribute to international standardization in colon cancer surgery (ClinicalTrials.gov NCT02938481).