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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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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

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

Backgrounds and Aims: To elucidate the survival benefits of adjuvant chemotherapy by decreasing incidence or by delaying time of tumor recurrence, we reported the long-term results of a nonrandomized prospective study comparing the adjuvant chemotherapy to no chemotherapy in stage III colorectal cancer., Patients: From 1991 to 1995, 463 patients with stage III colorectal cancer were divided to three groups which were no chemotherapy, weekly chemotherapy, and monthly chemotherapy (5-FU plus levamisole)., Results: The recurrent incidence was significantly decreased in patients with chemotherapy (47.8% vs. 63.9% of no chemotherapy, P = 0.001), resulting into better survival. The 10-year cancer-specific and overall survival rates of patients with chemotherapy vs. no chemotherapy were 52.1% vs. 37.8% and 46.9% vs. 29.9%, respectively (P < 0.001). Weekly chemotherapy had better survival than monthly chemotherapy (P < 0.05). There was no significant difference in recurrent time or types between the patients with and without chemotherapy. The percentages of patients with recurrence happened within 3 years were 85.2% and 84.6% of those with and without chemotherapy, respectively. Patients with advanced stage of T4b invasion depth, N2, and central node invasion had no significant survival benefits by adjuvant chemotherapy., Conclusions: Long-term survival benefits achieved by adjuvant chemotherapy is through decreasing recurrent incidence, not through postponing tumor recurrent time. That means adjuvant chemotherapy indeed cures some patients by eradicating occult tumor. In adjuvant setting, more powerful regimen for eradicating occult tumor is the keystone to improve long-term survival of stage III colorectal cancer.

Background and Aims: Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy is critical for improving survival outcome. With the aim of identifying more high risk factors for stage II colon cancer, this study aimed to determine whether the neutrophil-lymphocyte ratio (NLR) is a predictor of surgical outcomes in patients with stage II colon cancer who do not receive adjuvant chemotherapy., Materials and Methods: We enrolled 1,040 stage II colon cancer patients who had undergone colectomy at a single institution between January 1995 and December 2005 and did not receive adjuvant chemotherapy., Results: Of these 1,040 patients, 785 (75.5%) patients had a normal NLR and 255 (24.5%) had an elevated NLR. Those with an elevated NLR included patients ≥65 years, T4b cancer, carcinoembryonic antigen ≥5 ng/mL, and tumor obstruction or perforation. Patients with an elevated NLR had a significantly worse overall survival (OS) and worse disease-free survival (DFS) than did patients with a normal NLR. Cox regression analysis revealed that elevated NLR was an independent predictor of OS (P=0.012) but not DFS (P=0.255)., Conclusion: An elevated NLR is an independent predictor of OS but not DFS in stage II colon cancer patients who did not receive adjuvant chemotherapy. Preoperative NLR measurement in stage II colon cancer patients may be a simple method for identifying patients with a poor prognosis who can be enrolled in further trials of adjuvant chemotherapy.

Background and Aims: In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors., Materials and Methods: We retrospectively reviewed the database of the Colorectal Cancer Registry of Chang Gung Memorial Hospital between February 1995 and December 2005. Patients with colon cancer sited between the hepatic and splenic flexure that involved an adjacent organ without distant metastasis were defined as having locally advanced transverse colon cancer., Results: A total of 827 patients who underwent surgery for transverse primary colon cancer were enrolled in the study. Stage II and stage III colon cancer were diagnosed in 548 patients. Thirty-two (5.8%) patients were diagnosed with locally advanced tumors. Multivariate analysis revealed that stage III, preoperative carcinoembryonic antigen ≥5 ng/mL, a tumor with perforation or obstruction, and the presence of a locally advanced tumor were significant prognostic factors for both overall and cancer-specific survival. Postoperative morbidity rates differed significantly between the locally advanced and non-locally advanced tumor groups (22.7% vs. 12.3%, P < 0.01). No significant overall survival difference was observed among the stage II transverse colon tumors (P = 0.21)., Conclusion: Surgical resection of locally advanced transverse colon tumors resulted in a higher morbidity and mortality than that of non-locally advanced tumors, but the benefit of extensive surgery in the case of locally advanced tumors cannot be underestimated. Furthermore, this benefit is more pronounced in the case of stage II tumors.

Background and Aims: The role of carcinoembryonic antigen (CEA) in the early detection of recurrence during the postoperative follow-up of colorectal cancer remains unclear. We hypothesize that the tumor with longer lead time of CEA elevation to the definite recurrence may have a better prognosis because of its slower growth rate and closer observation., Materials and Methods: From 1995 to 2003, 4,841 consecutive patients who received curative resection of localized colorectal adenocarcinoma were enrolled from a prospective database. The patients with persisting CEA elevation after operation had been already excluded. Postoperative follow-up, including physical examination, imaging, and CEA test, were performed according to a surveillance program. A CEA >/=5 ng/mL was defined as elevated. The definition of the CEA lead time was the period between CEA elevation and detection of recurrence. All statistical analyses were performed by SPSS package for Windows (Microsoft, Redmond, WA, USA)., Results: The postoperative median follow-up time for the 4,841 patients was 68 months. A total of 999 patients (20.6%) had CEA elevation and recurrence. Among these patients, recurrence was confirmed in 727 patients (72.8%)before, at the same time, or within 3 months of CEA elevation and thus had a short lead time of CEA elevation (SLT group). In 272 patients (27.2%), recurrence was confirmed after more than 3 months of CEA elevation and thus had a longer lead time of CEA elevation (LLT group). The recurrence pattern showed similarities in these two groups. A total of 193 patients (193/999, 19.3%) received a second radical operation, and 806 patients (80.7%) were inoperable. The re-resection rate between the SLT group (146 patients, 20.1%) and the LLT group (47 patients, 17.3%) was not significantly different. The overall survival rate after recurrence showed no difference between these two groups (P = 0.123)., Conclusion: Most cases of recurrence were detected at nearly the same time when the CEA level was elevated. Therefore, a more sensitive test is needed for early detection. The relationship between the lead time of CEA and the clinical outcome was not statistically significant. A more aggressive approach to the patient who has CEA elevation and is highly suspect of recurrence may be needed.

Background and Aims: Signet ring cell carcinoma of the rectum (SCCR) is a rare type of rectal carcinoma. This study examined the clinical significance of SCCR., Patients and Methods: From our medical records we retrospectively identified 61 SCCR patients and compared their clinical data and outcomes to those of 144 consecutive patients with non-SCCR mucinous rectal adenocarcinomas (NSMR) and 2,414 consecutive patients with nonmucinous rectal adenocarcinomas (NMR)., Results: . The incidence of SCCR was 1.39% of rectal cancers. Mean patient age at onset of SCCR (48.1years, range 15-80) was significantly lower than that for NSMR (57.4 years, 9-88) and NMR (62.6 years, 12-94). The proportion of late stage (TNM III+IV) tumors was significantly higher in SCCR (90%) than in NSMR (69%) and NMR (48%). There were more tumors located in the lower rectum in SCCR (46%) than in NSMR (34%) and NMR (29%). SCCR tumors were significantly larger (5.68+/-3.84 cm) than NSMR (4.27+/-1.78 cm) and NMR tumors (3.76+/-1.71 cm). A higher percentage of patients with SCCR (42.6%) received abdominoperineal resection for treatment. In tumors with TNM stage IV the rate of tumor spread via the hematogenous route was significantly lower in SCCR (18.5%) than in NSMR (43.5%) and in NMR (69%). The rate of tumor spread via seeding to the peritoneum was lower in SCCR (22.2%) than in NSMR (43.5%) but higher than in NMR (2.7%). The rate of tumor spread via the lymphatic route was higher in SCCR (44.4%) than in NSMR (26.1%) and significantly higher than in NMR (12.3%). The 1-, 2-, and 5-year overall SCCR survival rates were 73.9%, 36.3%, and 23.3% respectively, which were significantly poorer than those of NSMR and NMR. For the 28 stage III and R0 SCCR tumors the 1-, 2-, and 5-year disease-free survival rates of SCCR were 84.0%, 44.2%, and 30.3%, respectively, which are comparable with general data of stage III rectal cancer in the world., Conclusion: Diffuse infiltration of signet ring cells enhances the tendency of mucinous carcinomas of the rectum in more local extension and easier lymphatic spreading but not at peritoneal seeding. Although SCCR had the poorest prognosis, this outcome may be due to the advanced tumor stage rather than histology itself.