Tumor Marker Trajectories and Survival Analysis in Patients With Normal Carcinoembryonic Antigen Ranges After Colorectal Cancer Resection.

BACKGROUND: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA. OBJECTIVE: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection. DESIGN: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018. SETTINGS: Retrospective cohort study. PATIENTS: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded. INTERVENTIONS: Standard curative radical resection was performed. MAIN OUTCOME MEASURES: Ten-year overall survival and disease-free survival were analyzed. RESULTS: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups. LIMITATIONS: Retrospective design. CONCLUSIONS: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract. TRAYECTORIAS DE MARCADORES TUMORALES Y ANLISIS DE SUPERVIVENCIA EN PACIENTES CON RANGOS NORMALES DE ANTGENO CARCINOEMBRIONARIO POSTERIOR A RESECCIN DE CNCER COLORRECTAL: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto ).

Optimizing stoma closure: A laparoscopic technique yielding the least contamination.

In this study, we introduce a novel method for stoma closure, aiming to reduce wound infection rates. This method involves creating the common channel of both limbs of a loop stoma extracorporeally, which is particularly beneficial during laparoscopic stoma closure surgery by potentially avoiding contamination of the wound. We applied this technique in 23 patients undergoing laparoscopic stoma reversal surgery, comprising both loop colostomy and ileostomy cases. Notably, postoperative outcomes were promising: only two patients experienced postoperative ileus, and importantly, there were no instances of wound infection. These findings suggest that our laparoscopic stoma reversal surgery approach is not only safe and feasible but also offers a significant advantage in reducing wound infection rates.

Diabetic severity and oncological outcomes of colorectal cancer following curative resection: A population-based cohort study in Taiwan.

BACKGROUND: Although diabetes is a poor prognostic factor for colorectal cancer (CRC), whether diabetes severity provides an additional predictive value for CRC prognosis remains unclear. The study aimed to investigate the prognostic differences after curative CRC resection among patients with different diabetic severities. METHODS: This population-based retrospective cohort study analyzed data registered between 2007 and 2015 in the Cancer Registry Database, which is linked to the National Health Insurance Research Database and National Death Registry. Patients with CRC who underwent curative radical resection for stage I-III disease were evaluated, with their diabetic status subdivided into no diabetes, diabetes without complication, and diabetes with complications. Cox regressions were applied to determine the association between diabetes severity and CRC survival, including overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS). RESULTS: A total of 59,202 patients with CRC were included. Compared with the no diabetes group, the diabetes without complication group has insignificantly worse OS (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09), DFS (HR, 1.08; 95% CI, 1.04-1.12), and CSS (HR, 0.98; 95% CI, 0.93-1.03), whereas those with complicated diabetes had a significantly higher risk of poor survival (OS: HR, 1.85; 95% CI, 1.78-1.92; DFS: HR, 1.75; 95% CI, 1.69-1.82; CSS: HR, 1.41; 95% CI, 1.33-1.49). Patients with CRC and diabetes also had a higher risk of recurrence than did those without diabetes. Sex and TNM staging were important effect modifiers. CONCLUSIONS: Among patients with CRC who undergo curative resection, the severity of the diabetes is inversely correlated with long-term outcomes, especially in women and patients in the earlier stages of CRC. PLAIN LANGUAGE SUMMARY: The prognostic impact of diabetes severity in colorectal cancer (CRC) is yet to be clarified. In this cohort study of 59,202 patients with CRC, compared with patients with CRC and without diabetes, those with uncomplicated diabetes had an insignificantly worse CRC survival, whereas those with complicated diabetes had a significantly higher risk of poor survival. Multidisciplinary medical care to prevent progression into diabetes with complications is needed to improve survival among patients with CRC and diabetes.

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. METHODS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. RESULTS: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02). CONCLUSIONS: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.

Effect of short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy on organ preservation in locally advanced rectal cancer.

PURPOSE: We analyzed the effectiveness, safety, and mid-term oncological outcomes of short-course radiotherapy (SCRT) and oxaliplatin-based consolidation chemotherapy in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively evaluated 64 patients with LARC who underwent SCRT and tegafox (tegafur-uracil/leucovorin plus oxaliplatin) or mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) consolidation chemotherapy before surgery between January 2015 and December 2020. Tumor response, patient compliance, toxicity, surgical outcomes, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: Sixty-four patients with a mean age of 58.67 years (44 males) were included; 48 (75%) had tumors within 5 cm of the anal verge. Additionally, 93.8% of the patients underwent at least 2 months of chemotherapy, and three required dose reduction. Grade III toxicity occurred in 2 patients, and 10 had a clinical complete response and opted for non-operative management. One patient experienced tumor progression and underwent further treatment without surgery. Among the 53 patients who underwent surgery, 51 (96.2%) had sphincter preservation, 3 had Clavien-Dindo grade III complications, and no mortality occurred. The complete response rate for the entire cohort was 23.4%. Moreover, 47 patients (74.6%) had a neoadjuvant rectal score of < 16 after treatment. After a median follow-up time of 32.01 months, 6 (9.3%) had local recurrence, and 17 (26.6%) had distant metastasis. The 3-year OS, DFS and stoma-free rates were 89.5%, 65.5%, and 78.1% respectively. CONCLUSION: SCRT followed by oxaliplatin-based consolidation chemotherapy is safe and effective for tumor downstaging in LARC, further improving the sphincter preservation rate.

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging. METHODS: PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies. RESULTS: This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I2 = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I2 = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I2 = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I2 = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study. CONCLUSIONS: For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.

Potential short-term outcome advantage of low vs. high ligation of inferior mesenteric artery for sigmoid and rectal cancer: propensity score matching analysis.

BACKGROUND: Whether to ligate the inferior mesenteric artery at its root during anterior resection for sigmoid colon or rectal cancer is still under debate. This study compared the surgical outcomes, postoperative recovery, and anastomotic leakage between high and low ligation of the inferior mesenteric artery through a subgroup analysis. METHODS: This was a retrospective analysis of prospectively collected data. All patients who underwent colorectal resection for rectosigmoid cancer between December 2016 and December 2019 were enrolled. According to the surgical ligation level of the inferior mesenteric artery, the patients were categorized into either the high or low ligation group. The investigated population was matched using the propensity score method. RESULTS: Overall, 894 patients with sigmoid or rectal cancer underwent elective anterior resection with high (577 patients) or low (317 patients) ligation of the inferior mesenteric artery. After the propensity score matching, 245 patients in each group were compared. High ligation of the inferior mesenteric artery was associated with higher incidence of anastomotic leakage (14.9% vs. 5.6%, P = 0.041) for mid- to low-rectum tumors and a higher incidence of complications (8.6% vs. 3.3%, P = 0.013) of grades 1-2 according to the Clavien-Dindo classification system. CONCLUSION: Compared with high ligation, low ligation of the inferior mesenteric artery resulted in lower likelihood of morbidity and mortality in rectal and sigmoid cancers. Moreover, low ligation was less likely to result in anastomosis leakage in mid- to low-rectal cancers.

Increased standardised incidence ratio of cardiovascular diseases among colorectal cancer patients.

PURPOSE: Evidence regarding the relationship between colorectal cancer and the risk of cardiovascular disease (CVD) is limited. Thus, in this study, we aimed to determine the standardised incidence ratio (SIR) of CVDs in colorectal cancer patients in Taiwan. METHODS: A population-based cohort study enrolling the incident colorectal cancer population based on the Cancer Registry Database from 2007 to 2016 was conducted (n = 94,233, mean age: 62.4 years, 43.0% women). New cases of CVD, including coronary heart disease and ischemic stroke, through 31 December 2018 were obtained from the National Health Insurance Research Database and National Death Registry. Compared with the general population (n = 1,977,659, mean age: 44.3 years, 49.6% women), age- and sex-specific SIRs for CVDs were calculated by the time since diagnosis. RESULTS: A total of 6852 cardiovascular events occurred in colorectal cancer patients during a median follow-up of 4.4 years. The SIR of CVD was highest in the first year after diagnosis (SIR: 1.45, 95% confidence interval: 1.39-1.50); however, this decreased to the same value as that of the general population in later years. Similar patterns were observed for the SIR of coronary heart disease. However, the SIR of ischemic stroke among colorectal cancer patients was low from the second year following cancer diagnosis. CONCLUSIONS: Colorectal cancer patients are at an increased risk of developing CVD, especially coronary heart disease, during the first 3 years following colorectal cancer diagnosis.

Transrectal natural orifice specimen extraction in left hemicolectomy for tumours around the splenic flexure: Old wine in new bottles.

AIM: Laparoscopic anterior resection with natural orifice specimen extraction (NOSE) has favourable short-term outcomes. However, NOSE is rarely adopted for left hemicolectomy procedures. This study aimed to review the feasibility, safety and short-term outcomes of transrectal NOSE in patients undergoing laparoscopic left hemicolectomy. METHOD: All consecutive patients who underwent laparoscopic left hemicolectomy surgery with transrectal NOSE in a single institution between January 2018 and December 2020 were reviewed. Transrectal NOSE was performed with an enterotomy at the upper rectum. The specimen was brought out via a transanal endoscopic microsurgery scope inserted through the anus. A supplementary video demonstrates this technique. Surgical outcomes, including complications, postoperative short-term recovery and the level of pain intensity, are presented. RESULTS: Twenty patients were reviewed. There were no immediate postoperative complications and no wound infections in these patients. The average time to tolerate a soft diet was 3.6 days, and the average postoperative hospital stay was 4.5 days. The average score on the numerical rating scale of postoperative pain was 3.0 on postoperative day 1. The median follow-up time was 23.5 months. CONCLUSION: Laparoscopic left hemicolectomy with transrectal NOSE is a safe and feasible procedure that leads to early postoperative recovery and a short hospital stay.

Comparison of short-term and medium-term outcomes between intracorporeal anastomosis and extracorporeal anastomosis for laparoscopic left hemicolectomy.

BACKGROUND: Few studies have evaluated the feasibility and safety of intracorporeal anastomosis (IA) for left hemicolectomy. Here, we aimed to investigate the potential advantages and disadvantages of laparoscopic left hemicolectomy with IA and compare the short- and medium-term outcomes between IA and extracorporeal anastomosis (EA). METHODS: We retrospectively analyzed 133 consecutive patients who underwent laparoscopic left hemicolectomies from July 2016 to September 2019 and categorized them into the IA and EA groups. Patients with stage 4 disease and conversion to laparotomy or those lost to follow-up were excluded. Postoperative outcomes between IA and EA groups were compared. Short-term outcomes included postoperative pain score, bowel function recovery, complications, duration of hospital stay, and pathological outcome. Medium outcomes included overall survival and disease-free survival for at least 2 years. RESULTS: After excluding ineligible patients, the remaining 117 underwent IA (n = 40) and EA (n = 77). The IA group had a shorter hospital stay, a shorter time to tolerate liquid or soft diets, and higher serum C-reactive protein level on postoperative day 3. There was no difference between two groups in operative time, postoperative pain, specimen length, or nearest margin. A 2-year overall survival (IA vs. EA: 95.0% vs. 93.5%, p = 0.747) and disease-free survival (IA vs. EA: 97.5% vs. 90.9%, p = 0.182) rates were comparable between two groups. CONCLUSIONS: Laparoscopic left hemicolectomy with IA was technically feasible, with better short-term outcomes, including shorter hospital stays and shorter time to tolerate liquid or soft diets. The IA group had higher postoperative serum C-reactive protein level; however, no complications were observed. Regarding medium-term outcomes, the overall survival and disease-free survival rates were comparable between IA and EA procedures.

Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis.

BACKGROUNDS: The inflammatory biomarker "C-reactive protein to albumin ratio (CAR)" has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. METHODS: We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. RESULTS: A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808-2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321-2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. CONCLUSIONS: High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

Short- and medium-term outcomes of intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a propensity score-matched study.

BACKGROUNDS: Though better short-term outcomes were frequently reported, differences in specimen parameters and the rate of subsequent peritoneal recurrence between intracorporeal anastomosis (IA) and extracorporeal anastomoses (EA) for laparoscopic right hemicolectomy have not been analyzed. We aimed to compare the pathologic differences and oncological outcomes between these two approaches. METHODS: We retrospectively analyzed 217 consecutive patients who underwent laparoscopic right hemicolectomies from September 2016 to April 2018 and classified them into IA and EA groups, based on the approach used. Propensity score matching analysis was performed, after which 101 patients were included in each group with the patients matched for demographics, tumor stage, and localization. RESULTS: The IA group had a longer operative time, shorter length of stay, shorter time to first flatus and tolerating a soft diet, and better pain scale scores at postoperative day 3. No inter-group differences in conversion, postoperative complication, mortality, or readmission rates were found. The IA group had a longer resected colon length (23.67 vs. 19.75 cm, p = 0.010) and nearest resected margin (7.51 vs. 5.40 cm, p = 0.010) for cancer near the hepatic flexure. There are comparable 3-year overall survival (87.7% vs. 89.6%, p = 0.604) and disease-free survival (75.0% vs. 75.7%, p = 0.842) between the IA and EA groups. The rate of peritoneal recurrence was similar between the two groups (5.9% vs. 7.9%, p = 0.580). CONCLUSIONS: The overall survival, disease-free survival, and the rate of peritoneal recurrence were comparable between the IA and EA procedures. IA ensures better recovery and comparable complications to EA and achieved a more precise tumor excision; thus, IA can be considered a safe procedure for patients with right-sided colon lesions.

The risk factors of local recurrence and distant metastasis on pT1/T2N0 mid-low rectal cancer after total mesorectal excision.

BACKGROUND: Radical resection is associated with good prognosis among patients with cT1/T2Nx rectal cancer. However, still some of the patients experienced cancer recurrence following radical resection. This study tried to identify the postoperative risk factors of local recurrence and distant metastasis separately. METHODS: This retrospective, single-center study comprised of 279 consecutive patients from Linkou branch of Chang Gung Memorial Hospital in 2005-2016 with rectal adenocarcinoma, pT1/T2N0M0 at distance from anal verge ≤ 8cm, who received curative radical resection. RESULTS: The study included 279 patients with pT1/pT2N0 mid-low rectal cancer with median follow-up of 73.5 months. Nineteen (6.8%) patients had disease recurrence in total. Nine (3.2%) of them had local recurrence, and fourteen (5.0%) of them had distant metastasis. Distal resection margin < 0.9 (cm) (hazard ratio = 4.9, p = 0.050) was the risk factor of local recurrence. Preoperative carcinoembryonic antigen (CEA) ≥ 5 ng/mL (hazard ratio = 9.3, p = 0.0003), lymph node yield (LNY) < 14 (hazard ratio = 5.0, p = 0.006), and distal resection margin < 1.4cm (hazard ratio = 4.0, p = 0.035) were the risk factors of distant metastasis. CONCLUSION: For patients with pT1/pT2N0 mid-low rectal cancer, current multidisciplinary treatment brings acceptable survival outcome. Insufficient distal resection margin attracted the awareness of risk factors for local recurrence and distant metastasis as a foundation for future research.

Prognostic value of regional lymph node involvement in patients with metastatic colorectal cancer: palliative versus curative resection.

BACKGROUND: Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes. METHODS: We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN-) group and another 980 in the LN-positive (LN+) group. RESULTS: LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN- group. LN- patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN- group (LN- vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN- vs. LN+ 19.5% vs. 24.3%; p = 0.890). CONCLUSIONS: Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN- patients. LN+ patients had poorer long-term outcomes compared with that in LN- patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN- patients.

Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?

BACKGROUND: Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients. PATIENTS AND METHODS: Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses. RESULTS: Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257-0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172-.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219-1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346-9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788-7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found. CONCLUSIONS: Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.

Association of a Preoperative Leisure-Time Physical Activity With Short- and Long-term Outcomes of Patients Undergoing Curative Resection for Stage I to III Colorectal Cancer: A Propensity Score Matching Analysis.

BACKGROUND: Physical activity might be directly or indirectly linked to the risk of colorectal cancer and the prognosis of patients with colorectal cancer. OBJECTIVE: This study aimed to elucidate whether preoperative physical activity plays a role in reducing short-term postoperative complications and improving long-term survival of patients with colorectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a department of colorectal surgery in a tertiary teaching hospital between January 1995 and December 2016. PATIENTS: Patients who underwent curative resection for stage I to III primary colorectal cancer were enrolled. According to the preoperative leisure-time weekly metabolic equivalent of task values, patients were divided into 2 groups: the metabolic equivalent of task <12 group and the metabolic equivalent of task ≥12 group. A 1:1 propensity score matching was used to reduce imbalance and selection biases based on 6 covariates, namely, age, sex, BMI, tumor location, tumor stage, and adjuvant chemotherapy administration. MAIN OUTCOME MEASURES: χ tests were used to analyze short-term postoperative complications. Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival. RESULTS: In the matched cohort patients, significant differences in overall postoperative complications and mortality were observed in favor of the metabolic equivalent of task ≥12 group, although there was no difference in any single item of postoperative morbidity. The results of the Kaplan-Meier analysis and log-rank test demonstrated a significant survival benefit in the metabolic equivalent of task ≥12 group compared with the metabolic equivalent of task <12 group both for disease-free and overall survival. LIMITATIONS: This study is limited by its retrospective nature. CONCLUSIONS: This single-institute study provides evidence of the association of preoperative leisure-time physical activity with short-term postoperative morbidity and mortality, as well as long-term survival. See Video Abstract at http://links.lww.com/DCR/B189. ASOCIACIÓN DE ACTIVIDAD FÍSICA DE TIEMPO LIBRE PREOPERATORIA CON RESULTADOS A CORTO Y LARGO PLAZO DE PACIENTES SOMETIDOS A RESECCIÓN CURATIVA POR CÁNCER COLORRECTAL EN ESTADIO I-III: UN ANÁLISIS DE COINCIDENCIA DE PUNTAJE DE PROPENSIÓN ANTECEDENTES: LA ACTIVIDAD FíSICA PUEDE ESTAR DIRECTA O INDIRECTAMENTE RELACIONADA CON EL RIESGO DE CÁNCER COLORRECTAL Y EL PRONÓSTICO DE LOS PACIENTES CON CÁNCER COLORRECTAL.: Este estudio tuvo como objetivo dilucidar si la actividad física preoperatoria desempeña un papel en la reducción de las complicaciones postoperatorias a corto plazo y en mejorar la supervivencia a largo plazo de los pacientes con cáncer colorrectal.Este fue un análisis retrospectivo de datos recolectados prospectivamente.Este estudio se realizó en un departamento de cirugía colorrectal en un hospital universitario terciario entre Enero de 1995 y Diciembre de 2016.Se incluyeron pacientes sometidos a resección curativa por cáncer colorrectal primario en estadio I-III. De acuerdo con el equivalente metabólico semanal en el tiempo libre de los valores de la tarea preoperatorio, los pacientes se dividieron en dos grupos: el equivalente metabólico del grupo de tarea <12 y el equivalente metabólico del grupo de tarea ≥ 12. Se utilizó una coincidencia de puntaje de propensión 1: 1 para reducir los desequilibrios y los sesgos de selección basados en seis covariables, principalmente, edad, sexo, índice de masa corporal, ubicación del tumor, estadio del tumor y administración de quimioterapia adyuvante.Las pruebas de Chi-cuadrado se utilizaron para analizar las complicaciones postoperatorias a corto plazo. Los análisis de Kaplan-Meier se utilizaron para evaluar la supervivencia libre de enfermedad y la supervivencia general.en los pacientes de la cohorte emparejada, se observaron diferencias significativas en las complicaciones postoperatorias generales y la mortalidad a favor del equivalente metabólico del grupo de tareas ≥ 12, aunque no hubo diferencias en ningún elemento único de morbilidad postoperatoria. Los resultados del análisis de Kaplan-Meier y la prueba de log-rank demostraron un beneficio de supervivencia significativo en el equivalente metabólico del grupo tarea ≥ 12 en comparación con el equivalente metabólico del grupo tarea <12 tanto para la supervivencia libre de enfermedad como para la supervivencia general.Este estudio está limitado por su naturaleza retrospectiva.Este estudio de instituto único proporciona evidencia de la asociación de la actividad física preoperatoria en el tiempo libre con la morbilidad y mortalidad postoperatorias a corto plazo, así como la supervivencia a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B189. (Traducción-Dr. Yesenia Rojas-Kahlil).

Advantage of laparoscopy surgery for elderly colorectal cancer patients without compromising oncologic outcome.

BACKGROUND: Laparoscopic surgery has achieved significant results in elderly patients with colorectal cancer (CRC). In this study, we compared the short-term and long-term outcomes of open surgery and laparoscopic surgery in patients with CRC aged above 75 years at a single tertiary medical center. METHODS: We analyzed 967 patients who underwent curative resection for primary colorectal adenocarcinoma without distant metastasis between January 2009 and December 2015, in a single institution. Of the enrolled patients, 305 underwent laparoscopic surgery, and 662 received open laparotomy surgery. RESULTS: Compared to the patients who underwent open surgery, those who received laparoscopic surgery had significantly shorter postoperative stay (10.3 vs. 13.5 days p < 0.001) and similar postoperative morbidity (p = 0.354) and mortality (p = 0.082). In the laparoscopy cohort, six of 305 patients were converted to open surgery and one died. The long-term overall survival, cancer-specific survival, and recurrence rate were similar between both cohorts in each stage. CONCLUSIONS: Laparoscopic surgery is suitable for elderly patients owing to shorter postoperative stay, similar long-term outcomes with open surgery, and acceptable low conversion rates. For long-term overall and oncological outcomes, the results of laparoscopic surgery were similar to that of open surgery in each TNM stage.

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.

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.

Comparison of laparoscopic and open surgery for colorectal malignancy in obese patients: a propensity score-weighted cohort study.

BACKGROUND: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer. METHODS: Employing an institutional database from 2009 to 2019, we assessed individuals with a body mass index of ≥30 kg/m2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. We used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches. RESULTS: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 mo). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class > III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity-score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy. CONCLUSIONS: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery.