Purpose The aim of this study was to examine the prognosis and associated risk factors, including adjuvant chemotherapy (CTx), in elderly patients with colon cancer.
Methods This retrospective study included patients who underwent radical resection for colon cancer between January 2010 and December 2014 at Asan Medical Center. The effects of stage, risk factors, and chemotherapy on overall survival (OS) and recurrence-free survival (RFS) were compared in patients aged ≥70 and <70 years.
Results Of 3,313 patients, 933 (28.1%) was aged ≥70 years. Of the 1,921 patients indicated for adjuvant CTx, 1,294 of 1,395 patients (92.8%) aged <70 years and 369 of 526 patients (70.2%) aged ≥70 years received adjuvant CTx. Old age (≥70 years) was independently associated with RFS in overall cohort. Among patients aged ≥70 years indicated for adjuvant CTx, the 5-year OS (81.6% vs. 50.4%, P<0.001) and RFS (82.9% vs. 67.4%, P=0.025) rates were significantly higher in those who did than did not receive adjuvant CTx. Additionally, adjuvant CTx was confirmed as independent risk factor of both OS and RFS in patients aged ≥70 years indicated for adjuvant CTx.
Conclusion Old age was associated with poor RFS and adjuvant CTx had benefits in OS as well as RFS in elderly patients eligible for adjuvant CTx.
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Purpose This study aimed to investigate preoperative predictors of lymphovascular invasion (LVI), which is a poor prognostic factor usually detected postoperatively in patients with colorectal cancer.
Methods Results for all patients operated on for colorectal cancer between January 1, 2006, and December 31, 2021, were retrospectively analyzed. Potential preoperative factors and postoperative pathology results were recorded. The patients were categorized as those with LVI and those without LVI. Potential factors that may be associated with LVI were compared between the 2 groups.
Results The study included 335 patients. The incidence of LVI was 3.11 times higher in patients with ascending colon tumors (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.34–7.23; P=0.008) and 4.28 times higher in those with metastatic tumors (OR, 4.28; 95% CI, 2.18–8.39; P<0.001). Diabetes mellitus was inversely related to LVI in colorectal cancer patients; specifically, LVI was 56% less common in colorectal cancer patients with diabetes mellitus, irrespective of its duration (OR, 0.44; 95% CI, 0.25–0.76; P<0.001).
Conclusion
The presence of preoperative LVI in colorectal cancer patients is difficult to predict. In particular, the effect of the effect of factors such as chronic disease accompanied by microvascular pathologies on LVI is still unclear. Advances in the neoadjuvant treatment of colorectal cancer patients, who are becoming more widespread every day, will encourage the investigation of different methods of preoperatively predicting LVI as a poor prognostic factor in these patients.
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Purpose The current study was conducted to examine the role of consolidation chemotherapy after neoadjuvant radiation therapy (NART) in decreasing the involvement of the mesorectal fascia (MRF) in high-risk locally advanced rectal cancers (LARCs).
Methods In total, 46 patients who received consolidation chemotherapy after NART due to persistent MRF involvement were identified from a database. A team of 2 radiologists, blinded to the clinical data, studied sequential magnetic resonance imaging (MRI) scans to assess the tumor response and then predict a surgical plan. This prediction was then correlated with the actual procedure conducted as well as histopathological details to assess the impact of consolidation chemotherapy.
Results The comparison of MRI-based parameters of sequential images showed significant downstaging of T2 signal intensity, tumor height, MRF involvement, diffusion restriction, and N category between sequential MRIs (P < 0.05). However, clinically relevant downstaging (standardized mean difference, > 0.3) was observed for only T2 signal intensity and diffusion restriction on diffusion-weighted imaging. No clinically relevant changes occurred in the remaining parameters; thus, no change was noted in the extent of surgery predicted by MRI. Weak agreement (Cohen κ coefficient, 0.375) and correlation (Spearman rank coefficient, 0.231) were found between MRI-predicted surgery and the actual procedure performed. The comparison of MRI-based and pathological tumor response grading also showed a poor correlation.
Conclusion Evidence is lacking regarding the use of consolidation chemotherapy in reducing MRF involvement in LARCs. The benefit of additional chemotherapy after NART in decreasing the extent of planned surgery by reducing margin involvement requires prospective research.
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Malignant disease,Prognosis and adjuvant therapy,Colorectal cancer,Surgical technique
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Original Articles
Malignant disease,Rectal cancer, Prognosis and adjuvant therapy,Colorectal cancer
Purpose Adjuvant chemotherapy (AC) is recommended for patients with stage II colorectal cancer with adverse features. However, the effect of adjuvant treatment in elderly patients with high-risk stage II colorectal cancer remains controversial. This study aimed to investigate the oncologic outcomes in elderly high-risk stage II colorectal cancer patients who underwent curative resection with or without AC.
Methods Patients aged over 70 years having stage II colorectal adenocarcinoma with at least 1 adverse feature who underwent radical surgery between 2008 and 2017 at a single center were included. We compared recurrence-free survival (RFS) and overall survival (OS) between patients who received more than 80% of the planned AC cycle (the AC+ group) and those who did not receive it (the AC− group).
Results The AC+ and AC– group contained 46 patients and 50 patients, respectively. The log-rank test revealed no significant intergroup differences in RFS (P = 0.083) and OS (P = 0.122). In the subgroup of 27 patients with more than 2 adverse features, the AC+ group (n = 16) showed better RFS (P = 0.006) and OS (P = 0.025) than the AC− group. In this subgroup, AC was the only significant factor affecting RFS in the multivariate analysis (P = 0.023). AC was significantly associated with OS (P = 0.033) in the univariate analysis, but not in the multivariate analysis (P = 0.332).
Conclusion Among elderly patients with stage II high-risk colorectal cancer, the AC+ group did not show better RFS or OS than the AC− group. However, selected patients with more than 2 adverse features might benefit from AC.
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Malignant disease,Prognosis and adjuvant therapy,Colorectal cancer
Purpose It is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer.
Methods Patients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS.
Results Eighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS.
Conclusion Tumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.
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Malignant disease,Prognosis and adjuvant therapy,Colorectal cancer,Biomarker & risk factor
Purpose There is no clear evidence of the benefit of adjuvant chemotherapy (AC) in stage IIA colon cancer. Therefore, we aimed to evaluate the prognostic factors and survival benefit of AC in this disease.
Methods A retrospective data collection for patients who underwent radical surgery for colon cancer between January 2008 and December 2015 was undertaken. The cohort was divided into the no-AC and AC groups.
Results We included 227 patients with stage IIA colon cancer in our study cohort, including 67 and 160 patients in the no-AC and AC groups, respectively. The number of retrieved lymph nodes and the presence of tumor complications as obstruction or perforation were independent risk factors for survival. In the no-AC group, there was a significant difference in survival according to the number of retrieved lymph nodes. In the AC group, there were significant differences in survival according to sidedness and preoperative carcinoembryonic antigen (CEA). There was no significant difference in survival between the no-AC and the AC groups.
Conclusion The number of retrieved lymph nodes and the presence of tumor complications were prognostic factors for stage IIA colon cancer but lymphovascular and perineural invasion were not. Sidedness and preoperative CEA could be used as factors to predict the benefit of adjuvant chemotherapy. Currently, it is believed that there is no benefit of AC for stage IIA colon cancer. Further studies are needed to determine the survival benefit of adjuvant chemotherapy in stage IIA colon cancer.
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Purpose This study aimed to assess the evaluation of clinical outcomes and consequences of complications after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the peritoneal carcinomatosis (PC) from colorectal cancer.
Methods A total 26 patients underwent CRS and HIPEC for PC from colorectal cancer between March 2009 and April 2018. All the patients underwent CRS with the purpose of complete or near-complete cytoreduction. Intraoperative HIPEC was performed simultaneously after the CRS. Mitomycin C was used as chemotherapeutic agent for HIPEC.
Results Median disease-free survival was 27.8 months (range, 13.4–42.2 months). Median overall survival was 56.0 months (range, 28.6–83.5 months). The mean peritoneal cancer index (PCI) was 8.73 ± 5.54. The distributions thereof were as follows: PCI <10, 69.23%; PCI 10–19, 23.08%; and PCI ≥20, 7.69%. The completeness of cytoreduction was 96.2% of patients showed CC-0, with 3.8% achieved CC-1. The mean operation time was 8.5 hours, and the mean postoperative hospital stay was 21.6 days. The overall rate of early postoperative complications was 88.5%; the rate of late complications was 34.6%. In the early period, most complications were grades I–II complications (65.4%), compared to grades III–V (23.1%). All late complications, occurring in 7.7% of patients, were grades III–V. There was no treatment-related mortality.
Conclusion Although the complication rate was approximately 88%, but the rate of severe complication rate was low. In selective patients with peritoneal recurrence, more aggressive strategies for management, such as CRS with HIPEC, were able to be considered under the acceptable general condition and life-expectancy.
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Malignant disease, Rectal cancer,Prognosis and adjuvant therapy
Purpose We aimed to evaluate the postoperative complications of laparoscopic colorectal cancer (CRC) surgery and the adverse events of postoperative chemotherapy in elderly patients compared to younger patients and to identify the factors influencing the termination of postoperative chemotherapy.
Methods Between June 2015 and May 2018, 188 patients with CRC underwent laparoscopic surgery with curative intent. Patients aged ≥ 70 were defined as elderly. Postoperative complications and adverse events of chemotherapy were assessed by using the Clavien-Dindo classification and the Common Terminology Criteria for Adverse Events, respectively. The clinicopathological factors were analyzed retrospectively.
Results Seventy-eight patients were considered elderly with a mean age of 77.5 ± 5.5 years. Overall postoperative complications occurred in 68 patients (36.2%). Age and primary tumor location were independent predictors of overall postoperative complications. Smoking history was the only independent predictor of major postoperative complications. Of 113 patients who were recommended postoperative chemotherapy, 90 patients (79.6%) received postoperative chemotherapy. Overall adverse events occurred in 40 patients (44.4%). The American Society of Anesthesiologists physical status classification and chemotherapy regimen were significantly associated with overall adverse events. The chemotherapy regimen was the only factor significantly associated with severe adverse events. Of 90 patients, postoperative chemotherapy could not be completed in 11 (12.2%). Age was the only factor significantly associated with stopping postoperative chemotherapy (P = 0.003).
Conclusion This study shows that laparoscopic CRC surgery and postoperative chemotherapy were feasible in elderly patients. Further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding postoperative chemotherapy.
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Purpose The efficacy of adjuvant chemotherapy (AC) in stage IIa colon cancer is controversial. This study aimed to investigate the factors influencing survival in patients with stage IIa colon cancer, the role of AC, and the indications for AC utilization by surgical oncologists.
Methods Between January 2004 and December 2010, 736 patients with stage IIa colon cancer underwent curative resection in 1 of 6 participating hospitals. Factors related to survival were identified and analyzed according to whether AC was administered or not. After high- and low-risk groups were identified, their respective results were analyzed.
Results The 5-year overall survival (OS) of stage IIa colon cancer was 90.3%. With the exception of poorly differentiated histology, indications for AC did not include typical high-risk factors. The indications for AC were significantly younger patients, higher body mass index (BMI), lower American Society of Anesthesiologists (ASA) physical status classification, and higher histologic grade. BMI, preoperative carcinoembryonic antigen, and harvested lymph node (LN) count were significant factors for disease-free survival, while BMI and ASA physical status classification were significant factors for OS in the chemotherapy group. In the high-risk group, AC was associated with increased OS in univariate analysis. BMI and harvested LN count were statistically significant in multivariate analysis.
Conclusion Surgical oncologists consider the patient’s condition and postoperative course rather than high-risk factors to determine use of AC. Regardless of AC use, both the extent of surgery and the patient’s subsequent status affected the survival rate in the high-risk group. None of the factors identified influenced survival rate in the low-risk group.
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Ann Coloproctol. 2019;35(5):242-248. Published online October 31, 2019
Purpose Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer.
Methods This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary endpoints, respectively.
Results The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent.
Conclusion The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.
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Purpose No guidelines exist detailing when to implement a temporary ileostomy closure in the setting of adjuvant chemotherapy following sphincter-saving surgery for rectal cancer. The aim of this study was to evaluate the clinical and oncological outcomes of ileostomy closure during adjuvant chemotherapy in patients with curative resection of rectal cancer.
Methods This retrospective study investigated 220 patients with rectal cancer undergoing sphincter-saving surgery with protective loop ileostomy from January 2007 to August 2016. Patients were divided into 2 groups: group 1 (n = 161) who underwent stoma closure during adjuvant chemotherapy and group 2 (n = 59) who underwent stoma closure after adjuvant chemotherapy.
Results No significant differences were observed in operative time, blood loss, postoperative hospital stay, or postoperative complications in ileostomy closure between the 2 groups. No difference in overall survival (P = 0.959) or disease-free survival (P = 0.114) was observed between the 2 groups.
Conclusion Ileostomy closure during adjuvant chemotherapy was clinically safe, and interruption of chemotherapy due to ileostomy closure did not change oncologic outcomes.
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Purpose Anemia is associated with poor treatment results for a variety of cancers. The effect of low hemoglobin levels on long-term outcomes after the treatment of patients with an anal squamous cell carcinoma (SCC) remains unclear. For that reason, this study aimed to investigate the effect of anemia on treatment outcomes following chemoradiation for an anal SCC.
Methods This was a retrospective study of all patients who underwent curative treatment for an anal SCC between 2009 and 2015 at 2 trusts in the United Kingdom. Data were collated from prospectively collected cancer databases and were cross-checked with operating-room records and records in the hospitals’ patient management systems.
Results We identified 103 patients with a median age of 63 years (range, 36–84 years). The median overall survival was 39 months (range, 9–90 months), and the disease-free survival was 36 months (range, 2–90 months). During the follow-up period, 16.5% patients died and 13.6% patients developed recurrence. Twenty-two people were anemic prior to treatment, with a female preponderance (20 of 22). No differences in disease-free survival (P = 0.74) and overall survival (P = 0.12) were noted between patients with anemia and those with normal hemoglobin levels. On regression the analysis, the combination of anemia, the presence of a defunctioning colostomy, lymph-node involvement and higher tumor stage correlated with poor overall survival.
Conclusion In this study, anemia did not influence disease-free survival or overall survival. We suggest that the interaction between anemia and survival is more complex than previously demonstrated and potentially reliant on other coexisting factors.
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Byung Mo Kang, Jeong-Heum Baek, Sun Jin Park, Seong Kyu Baek, Ki-Jae Park, Hong-Jo Choi, Byung-Noe Bae, Sun Keun Choi, Kap Tae Kim, Jin-Su Kim, Suk-Hwan Lee
Ann Coloproctol. 2018;34(3):144-151. Published online June 30, 2018
Purpose This study compared the oncologic impact of postoperative chemotherapy and chemoradiotherapy on patients with rectal cancer without preoperative chemoradiation.
Methods This retrospective study analyzed 713 patients with a mean follow-up of 58 months who had undergone radical resection for stage II/III rectal cancer without preoperative treatment in nine hospitals from January 2004 to December 2009. The study population was categorized a chemotherapy group (CG, n = 460) and a chemoradiotherapy group (CRG, n = 253). Five-year overall survival (OS) and disease-free survival (DFS) were analyzed, and independent factors predicting survival were identified.
Results The patients in the CRG were significantly younger (P < 0.001) and had greater incidences of low rectal cancer (P < 0.001) and stage III disease (P < 0.001). Five-year OS (P = 0.024) and DFS (P = 0.012) were significantly higher in the CG for stage II disease; however, they were not significantly different for stage III disease. In the multivariate analysis, independent predictive factors were male sex, low rectal cancer and stage III disease for OS and male sex, abdominoperineal resection, stage III disease and tumor-positive circumferential margin for DFS. However, adjuvant therapy type did not independently affect OS (hazard ratio [HR], 1.243; 95% confidence interval [CI], 0.794–1.945; P = 0.341) and DFS (HR, 1.091; 95% CI, 0.810–1.470; P = 0.566).
Conclusion Adjuvant therapy type did not affect survival of stage II/III rectal cancer patients without neoadjuvant chemoradiotherapy. These results suggest that adjuvant therapy can be chosen based on the patient’s condition and the policies of the surgeons and hospital facilities.
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The aim of this study was to evaluate whether the perioperative carcinoembryonic antigen (CEA) ratio could be used as a determinant for adjuvant therapy after curative surgery in stage II colorectal cancer.
Methods
Data for 119 patients with stage II colorectal cancer who underwent radical surgery between 2010 and 2013 were collected. The perioperative CEA ratio was defined as the postoperative/preoperative serum CEA level, and the patients were grouped according to their perioperative CEA ratios: high ratio (≥0.5) and low ratio (<0.5). Overall survival rates were calculated, and their prognostic significances were analyzed.
Results
The overall survival rates of the high and the low perioperative CEA groups were 68.2% and 86.8%, respectively (P = 0.033). In patients with normal preoperative CEA levels (<5 ng/mL), the high perioperative CEA ratio group showed a worse survival rate than the low perioperative CEA ratio group (71.7% vs. 100.0%, P = 0.007). In patients with high preoperative CEA levels (≥5 ng/mL), the high perioperative CEA ratio group showed a worse survival rate than the low perioperative CEA ratio group (33.3% vs. 75.0%, P = 0.036). In the multivariate analysis, perioperative CEA ratio (P = 0.046), age (P = 0.034), and venous invasion (P = 0.015) were independent prognostic factors for survival.
Conclusion
The perioperative CEA ratio is a prognostic indicator for stage II colorectal cancer. Patients with normal preoperative serum CEA levels might also be considered for adjuvant therapy if their perioperative CEA ratios are higher than 0.5.
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The case of a 23-year-old female treated with aggressive high-dose therapy for Burkitt's lymphoma is reported. A positron emission tomography and computed tomography scan after completion of chemotherapy revealed a residual hypermetabolic lesion in the right pelvic cavity. A pelvic magnetic resonance imaging scan showed circumferential wall thickening at the tip of the appendix. A laparoscopic exploration and appendectomy were performed, and a pathologic examination of the resected appendix revealed xanthogranulomatous appendicitis. This is a rare case of a xanthogranulomatous appendicitis mimicking remnant Burkitt's lymphoma after completion of chemotherapy.
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The aim of this study is to evaluate the results for the insertion of totally implantable central venous access devices (TICVADs) by surgeons.
Methods
Total 397 patients, in whom TICVADs had been inserted for intravenous chemotherapy between September 2008 and June 2014, were pooled. This procedure was performed under local anesthesia in an operation room. The insertion site for the TICVAD was mainly in the right-side subclavian vein. In the case of breast cancer patients, the subclavian vein opposite the surgical site was used for insertion.
Results
The 397 patients included 73 males and 324 females. Primary malignant tumors were mainly colorectal and breast cancer. The mean operation time was 54 minutes (18-276 minutes). Operation-related complications occurred in 33 cases (8.3%). Early complications developed in 15 cases with catheter malposition and puncture failure. Late complications, which developed after 24 hours, included inflammation in 6 cases, skin necrosis in 6 cases, hematoma in 3 cases, port malfunction in 1 case, port migration in 1 case, and intractable pain at the port site in 1 case.
Conclusion
Insertion of a TICVAD under local anesthesia by a surgeon is a relatively safe procedure. Meticulous undermining of the skin and carefully managing the TICVAD could minimize complications.
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Many studies have shown that the completion of adjuvant chemotherapy improves the survival rate. Recently, laparoscopic surgery has been used to treat patients with colon cancer. We analyzed the relationship between the completion of adjuvant chemotherapy and the operation method.
Methods
We retrospectively analyzed the medical records of 147 patients diagnosed with colon cancer from January 1, 2009, to May 31, 2012. The numbers of patients who underwent laparoscopic and open surgery were 91 and 56, respectively. We analyzed the relationship between the operation method and various factors such as the completion rate of chemotherapy, the patient's age, gender, and physical activity, the postoperative hospital stay, the start time of chemotherapy, and the patient's body mass index (BMI), TNM stage, and type of health insurance.
Results
In the laparoscopic surgery group, the postoperative hospital stay (13.5 ± 14.82 days vs. 19.6 ± 11.38 days, P = 0.001) and start time of chemotherapy (17.7 ± 17.48 days vs. 23.0 ± 15.00 days, P = 0.044) were shorter, but the percent complete of chemotherapy (71/91 [78.0%] vs. 38/56 [67.8%], P = 0.121), and survival rate (88/91 [96.7%], 47/56 [83.9%], P = 0.007) were higher than they were in the open surgery group. Patients who were elderly, had a low BMI, and a high American Society of Anesthesiologists score were less likely to complete adjuvant chemotherapy than other patients were.
Conclusion
Laparoscopic surgery shows a shorter postoperative hospital stay, a shorter start time of chemotherapy, and a higher survival rate. Laparoscopic surgery may be expected to increase compliance of chemotherapy and to improve survival rate.
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The aim of this study was to investigate the clinicopathologic features of and the prognosis for colorectal cancers (CRCs) with microsatellite instabilities (MSIs).
Methods
Between 2006 and 2009, genotyping was performed on 245 patients with stage II/III CRCs to establish the MSI status. The clinicopathologic differences and the prognostic value of MSI were analyzed. The median follow-up period was 38 months (range, 7-68 months).
Results
Of the total 245 patients, 20 (8.2%) had MSI-high (H) and 225 (91.8%) had MSI-low (L) or stable (S) CRCs. Adjuvant chemotherapies were performed on 101 stage II (87.8%) and 107 stage III patients (82.3%). Patients with MSI-H CRCs more frequently had a family history of colon cancer (10% vs. 2.7%, P = 0.003), more frequently had a cancer located at the proximal colon (90.0% vs. 19.1%, P < 0.0001), and more often showed a mucinous phenotype or poor differentiation (35.0% vs. 7.1%, P = 0.001). Despite less frequent lymph node metastasis (25% vs. 55.6%, P = 0.01), the number of retrieved lymph nodes was higher (26.3 ± 13.1 vs. 20.7 ± 1.2, P = 0.04) in the MSI-H group. The overall survival and the disease-free survival (DFS) did not differ with respect to MSI status. However, in the stage II subgroup, the DFS for patients with MSI-H CRCs was significantly worse (72.2% vs. 90.7%, P = 0.03). The multivariate analysis performed on this subgroup revealed that MSI-H was an independent poor prognostic factor (adjusted hazard ratio, 4.0; 95% confidence interval, 1.0-15.6, P = 0.046).
Conclusion
MSI-H CRCs had distinct clinicopathologic features, and MSI-H was an independent poor prognostic factor in stage II CRCs. Considering the majority of stage II patients were administrated adjuvant chemotherapy, the efficacy of adjuvant chemotherapy for treating MSI CRCs might be different from that for treating MSI-L/S tumors.
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Downregulation of acetyl-CoA synthetase 2 is a metabolic hallmark of tumor progression and aggressiveness in colorectal carcinoma Jeong Mo Bae, Jung Ho Kim, Hyeon Jeong Oh, Hye Eun Park, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang Modern Pathology.2017; 30(2): 267. CrossRef
Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a population-based study Francesco Iachetta, Federica Domati, Luca Reggiani-Bonetti, Valeria Barresi, Giulia Magnani, Luigi Marcheselli, Claudia Cirilli, Monica Pedroni Internal and Emergency Medicine.2016; 11(1): 41. CrossRef
Clinical, histological, and molecular risk factors for cancer recurrence in patients with stage II colon cancer Yann Touchefeu, Marie Provost-Dewitte, Thierry Lecomte, Alain Morel, Isabelle Valo, Jean-François Mosnier, Céline Bossard, Juliette Eugène, Emilie Duchalais, Jérôme Chetritt, Serge Guyetant, Stéphane Bézieau, Hélène Senellart, Morgane Caulet, Estelle Cauc European Journal of Gastroenterology & Hepatology.2016; 28(12): 1394. CrossRef
Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer H.M. Mohan, E. Ryan, I. Balasubramanian, R. Kennelly, R. Geraghty, F. Sclafani, D. Fennelly, R. McDermott, E.J. Ryan, D. O'Donoghue, J.M.P. Hyland, S.T. Martin, P.R. O'Connell, D. Gibbons, Des Winter, K. Sheahan European Journal of Surgical Oncology (EJSO).2016; 42(11): 1680. CrossRef
Different treatment strategies and molecular features between right-sided and left-sided colon cancers Hong Shen World Journal of Gastroenterology.2015; 21(21): 6470. CrossRef
Is a Microsatellite Instability Still Useful for Tailored Treatment in Stage II and III Colon Cancer? Nam Kyu Kim Annals of Coloproctology.2014; 30(1): 5. CrossRef
Adjuvant chemotherapy is routinely recommended for locally advanced colorectal cancer (CRC). There are very few data for the optimal starting date of adjuvant chemotherapy after the surgery. This study aimed to evaluate the effectiveness of earlier adoption of adjuvant chemotherapy after curative surgery for stage III CRC.
Methods
In this study, 159 patients with stage III CRC, who had undergone a curative resection, were enrolled retrospectively. Patients were categorized into 3 groups representing different timings to initiate the chemotherapy; less than 2 weeks (group 1), 3 to 4 weeks (group 2), and more than 5 weeks (group 3). The overall survival rate (OS) and the relapse-free survival rate (RFS) were analyzed to evaluate the effectiveness of adjuvant chemotherapy.
Results
The 5-year OSs of the patients were 73.7% in group 1, 67.0% in group 2, and 55.2% in group 3. The 5-year RFSs of the patients were 48.8% in group 1, 64.7% in group 2, and 57.1% in group 3. There were no significant differences in either the OS or the RFS (P = 0.200, P = 0.405).
Conclusion
Starting chemotherapy earlier than 6 weeks after surgery does not show any significant difference. Thus, although adjuvant chemotherapy should preferably begin within 6 weeks, the starting date should not necessarily be hastened, and the patient's general condition should be taken into consideration.
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There are still debates regarding the appropriate primary treatment policy for asymptomatic primary colorectal lesions in cases of unresectable metastatic colorectal cancer. Even though there are patients with asymptomatic primary tumors when starting chemotherapy, those patients may still undergo surgery due to complications related to primary tumors in the middle of chemotherapy; therefore, controversy exists regarding surgical resection of primary colorectal lesions in cases where symptoms are absent when making a diagnosis. Thus, based on the published literature, we discuss opinions that prefer first-line surgery for primary tumors as well as opinions favoring first-line chemotherapy for treating unresectable synchronous metastatic colorectal cancer. Although the upfront chemotherapy including targeted agents is suggested as an effective treatment in recent years, the first line surgery has been a preferred treatment for decades. The first line surgery is beneficial to prolong the survival duration given the retrospective analysis of randomized trial data. So far, no prospective comparison study has only focused on the first-line treatment modality; thus, future clinical studies focusing on the survival duration and the quality of life should be performed as soon as possible. Furthermore, at this point, multidisciplinary team approaches would be helpful in finding the appropriate therapy. Regardless of symptoms, the performance status and the tumor burden should be taken into consideration as well. In case of surgical resection, minimally invasive surgery, such as laparoscopic surgery, is recommended.
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The aims of this study were to investigate the survival results and the prognostic factors of adjuvant chemotherapy in stage II colon cancer in the sparsity of Korean data.
Methods
From 1993 to 2006, 363 curatively resected pathologic stage II colon cancer patients were enrolled. Six cycles of adjuvant chemotherapy was performed: intravenous bolus 5-fluorouracil (5-FU) 500 mg/m2 with leucovorin 20 mg/m2 for 2 hours daily for 5 days, followed by a 3-week resting period (n = 308). Fifty-five patients received only curative surgery. A high risk of recurrence was defined as the presence of one or more of the following factors: T4 tumor, lympho-vascular invasion, perineural invasion, perforation, obstruction, retrieved lymph node < 12, and poorly differention. The median follow-up period was 68 months (1 to 205 months).
Results
The five-year overall survival (OS) rate was 90.1%, and the five-year disease-free survival (DFS) rate was 84.7%. Among high-risk patients, the OS and the DFS rates of the treatment group were significantly higher than those of the non-treatment group (OS: 90.6% vs. 69.1%, P < 0.0001; DFS: 85.9% vs. 54.1%, P < 0.0001). Among low-risk patients, the survival results of the treatment group were also significantly superior (OS: 97.7% vs. 88.2%, P < 0.0001; DFS: 93.0% vs. 80.0%, P = 0.001). In the multivariate analysis, adjuvant chemotherapy was a significantly favorable prognostic factor for overall survival (hazard ratio, 0.41; 95% confidence interval, 0.22 to 0.75; P = 0.004).
Conclusion
In our population, adjuvant chemotherapy showed superior survival to curative surgery alone and significantly reduced the risk of death. A nationwide multicenter randomized trial is needed.
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In patients with symptomatic incurable metastatic colorectal cancer (mCRC), the goal of resection of the primary lesion is to palliate cancer-related morbidity, including obstruction, bleeding, or perforation. In patients with asymptomatic primary tumors and incurable metastatic disease, however, the necessity of primary tumor resection is less clear. Although several retrospective analyses suggest survival benefit in patients who undergo resection of the primary tumor, applying this older evidence to modern patients is out of date for several reasons. Modern chemotherapy regimens incorporating the novel cytotoxic agents oxaliplatin and irinotecan, as well as the target agents bevacizumab and cetuximab, have improved median survival from less than 1 year with the only available single-agent 5-fluorouracil until the mid-1990s to over 2 years. In addition to significant prolongation of overall survival, combinations of novel chemotherapeutic and target agents have allowed improved local and distant tumor control, decreasing the likelihood of local tumor-related complications requiring surgical resection. Resection of an asymptomatic primary tumor risks surgical complications and may postpone the administration of chemotherapy that may offer both systemic and local control. In conclusion, the morbidity and the mortality of unnecessary surgery or surgery that does not improve quality of life or survival in patients with mCRC of a limited life expectancy should be carefully evaluated. With the availability of effective combinations of chemotherapy and target agents, systemic therapy for the treatment of life-threatening metastases would be a preferable treatment strategy for unresectable asymptomatic patients with mCRC.
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Great progress has been made in the adjuvant treatment of colon cancer. The aim of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy using the FOLFOX regimen in patients with stage III and high-risk stage II colon cancer.
Methods
Eighty-two patients who underwent a potentially curative resection for stage III or high-risk stage II colon cancer were enrolled in this retrospective study. They received FOLFOX4 or modified FOLFOX6. The primary endpoint was disease-free survival.
Results
During the median follow-up of 37 months (range, 21 to 61 months), 14 patients experienced disease relapse. The disease-free survival rate at 3 years was 82.9%: 84.6% for stage II and 82.6% for stage III. At the time of the analysis, 8 patients were dead from recurrence. The probability of overall survival at 5 years was 74.5%: 90% for stage II and 74.6% for stage III. Grade 3 or 4 hematologic adverse events included neutropenia (40.2%), anemia (2.4%), and thrombocytopenia (1.2%). Gastrointestinal toxicities included grade 3 or 4 nausea (4.9%) and stomatitis (2.4%). Peripheral sensory neuropathy was observed in 81.7% of the patients during treatment. Of the 11 patients (13.4%) who had grade 3 peripheral sensory neuropathy during treatment, grade 3 symptoms were persistent in 3 patients with gait disturbance at the time of analysis. No treatment-related deaths were recorded.
Conclusion
Postoperative chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with stage III and high-risk stage II colon cancer.
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Risk Stratification in Patients with Stage II Colon Cancer Ramzi Amri, Jonathan England, Liliana G. Bordeianou, David L. Berger Annals of Surgical Oncology.2016; 23(12): 3907. CrossRef
Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects Rachel M. McQuade, Joel C. Bornstein, Kulmira Nurgali International Journal of Clinical Medicine.2014; 05(07): 393. CrossRef
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Although intraoperative radiotherapy (IORT) is known to be a method that can reduce local recurrence in locally advanced colorectal cancer, it is not widely used. The aim of this study was to report our experience with IORT for locally advanced rectal cancer.
Methods
From 1991 to 1994, nine patients with locally advanced rectal cancer received IORT. External beam radiotherapy was given postoperatively in five patients and preoperatively in three. Seven patients received chemotherapy. IORT was done with 6-MeV or 9-MeV electrons, and 12 Gy was irradiated at the tumor bed. The median follow-up period was 84 months (range, 15 to 208 months).
Results
The median age of patients was 51 years (range, 42 to 73 years). All patients had advanced clinical T-stage (cT3/4) cancer. The overall and the disease-free survival rates were 66.7% and 66.7% at 5 years, respectively. One patient developed a local recurrence near the anastomosis site, which was out of the IORT field. Four patients died before the last follow-up; three from distant metastasis and one from secondary primary cancer. Adverse effects related to IORT did not occur.
Conclusion
Although the number of patients was small in this study, IORT is thought to be safe and effective in reducing local recurrence in locally advanced rectal cancer. However, the role of IORT should be refined in the era of preoperative radio-chemotherapy followed by total mesorectal excision.
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Laparoscopic abdominoperineal resection with intraoperative radiotherapy for locally advanced low rectal cancer Matej Skrovina, Renata Soumarova, Miloslav Duda, Roman Bezdek, Jiri Bartos, Adam Wendrinski, Petr Andel, Javed Parvez, Martin Straka, Lukas Adamcik Biomedical Papers.2014; 158(3): 447. CrossRef
Laparoscopic Resection with Intraoperative Radiotherapy for Local Advanced Rectal Cancer: A Preliminary Case Report Yimei Jiang, Xiaopin Ji, Shengguang Zhao, Ren Zhao, Yening Jin Journal of Laparoendoscopic & Advanced Surgical Techniques.2013; 23(3): 267. CrossRef
A review of the logistic role of l‐carnitine in the management of radiation toxicity and radiotherapy side effects Haseeb Ahmad Khan, Abdullah Saleh Alhomida Journal of Applied Toxicology.2011; 31(8): 707. CrossRef
PURPOSE Colorectal cancer (CRC) is one of the leading causes of cancer death in South Korea. Angiogenesis has been associated with invasion and metastasis of tumors and with the secretion of various growth factors. Bevacizumab is a humanized monoclonal antibody that recognizes and blocks vascular endothelial growth factor (VEGF) and that targets integrin alphaVbeta3 and matrix metalloproteinases (MMPs) as angiogensis inhibitors. The aims of this study were identification of the mechanism of target molecules related to angiogenesis and demonstration of identifiable invasion by using chemotherapeutic regimens in vitro. METHODS The five colorectal cancer cell lines were treated with bevacizumab using standard or combined regimens. The expression of integrin alphaVbeta3 was detected and the investigation of apoptosis was done by using flow cytometry.
The activations of MMP-2 and MMP-9 were measured by using gelatin zymography. RESULTS The apoptotic cell death was significantly increased for the combined regimens, especially for FOLFOX (5-FU, leucovorin, and oxaliplatin) with bevacizumab.
Bevacizumab inhibited the expression of integrin alphaVbeta3 in the HT29 (59%), LoVo (67%), and SW480 (17%) cell lines, but did not in the AMC5 and the RKO cell lines. The activations of MMP-2 and MMP-9 were significantly reduced by treatment with bevacizumab in the HT29 and the LoVo cell lines. In the HT29 and the LoVo cell lines, thus, bevacizumab inhibited invasion and metastasis activity through down-regulation of integrin alphaVbeta3 and MMPs. CONCLUSION Our results provide biological evidence of potent angiogenic activity and indicate that angiogenesis is a complex process that involves multiple factors, including VEGF, integrin alphaVbeta3, and MMPs.
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RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions Hossein Javid, Mahsa Akbari Oryani, Nastaran Rezagholinejad, Ali Esparham, Mahboubeh Tajaldini, Mehdi Karimi‐Shahri Cancer Medicine.2024;[Epub] CrossRef
PURPOSE Since micrometastasis is generally inhibited by primary cancer, surgical ablation of the tumor may stimulate the growth of residual cancer cells, if they exist. This supports the importance of early administration of postoperative chemotherapy. METHODS: We reviewed the cases of patients who underwent a laparoscopic resection and then received chemotherapy (5 fluorouracil+leucovorin or FOLFOX4) between September 2006 and May 2008. The chemotherapy was scheduled on the 7th or the 8th postoperative day, but was postponed when a final pathologic report was delayed or patients were discharged early. The safety of chemotherapy was evaluated in two ways. Early safety, such as the presence of surgical complications and medical toxicity, was prospectively assessed just before the beginning of the second cycle of chemotherapy. Late safety, such as medical toxicity, was retrospectively estimated from the 2nd to the last cycle. These safeties were compared between the two groups: the early chemotherapy group (n=50) for which chemotherapy started on the 7th or 8th postoperative day as scheduled and the delayed chemotherapy group (n=31) for which chemotherapy started after the 14th postoperative day. RESULTS Patient demographics were not different between the two groups. With regards to early safety, no differences in surgical complications existed between the two groups. In medical toxicities, there were no differences, except for a higher rate of nausea in the early chemotherapy group (20 percent vs. 10 percent, P=0.01). With regards to late safety, the two groups were not different in the development of medical toxicities. CONCLUSION: Because nausea is an easily controllable toxicity, we conclude that chemotherapy is safely started on the 7th or the 8th day after a laparoscopic colorectal cancer resection.
Surgical resection is a mainstay in the treatment for patients with locally advanced rectal cancer. Despite the introduction of total mesorectal excision, which greatly reduces local recurrence, radiation therapy and chemotherapy have prevailed as integral parts of the modern treatment concept. Phase III studies have shown that postoperative chemoradiotherapy (CRT) improves the local control and overall survival compared with surgery alone in treating patients with stage II, III rectal cancer. Recently, a prospective randomized study with a large sample size and long-term follow-up reported that preoperative CRT resulted in improved local control and sphincter preservation, reduced toxicities, and improved overall survival compared with postoperative CRT. The results of this study provide evidence for the use of preoperative CRT in the treatment of patients with clinical stage II and III rectal cancer.
However, accurate pretreatment staging is required to minimize overtreatment and adverse effects.
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An Update on Preoperative Radiotherapy for Locally Advanced Rectal Cancer Seung-Gu Yeo, Dae Yong Kim Journal of the Korean Society of Coloproctology.2012; 28(4): 179. CrossRef
PURPOSE The aim of this study was to evaluate the value of mucinous histology as a predictive marker of 5-Fluorouracil (FU)-based adjuvant chemotherapy in stage II, III colon cancer. METHODS: Between January 1995 and December 2004, 987 patients who underwent curative resections for stage II, III sporadic colon cancer were classified into two groups, a mucinous carcinoma (MC) group and a non-mucinous carcinoma (NMC) group, based on the histology of the primary tumor.
The differences in their clinicopathological characteristics and the prognostic impact of 5-FU-based adjuvant chemotherapy for various tumor histologies were analyzed. RESULTS Of the 987 patients, MCs accounted for 6.8% (68 patients). MCs were more frequently located in the Rt. Colon (P<0.001) and were more frequently seen in young patients (less than 40 yr old) (P=0.028). The 5-yr survival rates between MC and NMC did not show any statistically significant difference. Patients, including both MC and NMC patients, who received 5-FU-based chemotherapy, revealed a better overall survival rate than patients with no adjuvant chemotherapy. In the multivariate analysis for the prognosis in NMC patients, 5-FU-based adjuvant chemotherapy, initial negative nodal status, and preoperative CEA <5 ng/mL were statistically significant prognostic factors (P values: <0.001, <0.001, and <0.001, respectively). In contrast, there was no statistically independent significance of 5-FU-based adjuvant chemotherapy in MC patients. CONCLUSION: In stage II and stage III sporadic colon cancer patients, response to 5-FU-based adjuvant chemotherapy in MC patients might be poor than it is in NMC patients.
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Early recurrence in patients undergoing curative surgery for colorectal cancer: is it a predictor for poor overall survival? Jung Wook Huh, Chang Hyun Kim, Sang Woo Lim, Hyeong Rok Kim, Young Jin Kim International Journal of Colorectal Disease.2013; 28(8): 1143. CrossRef
PURPOSE Colorectal cancers have been known to be refractory to chemotherapy in the past decades. Recently, novel agents have been developed and various data have shown an improved response rate and a survival benefit. However, considerable heterogeneity exists between cancers of the same tissue type, including colorectal cancer. Thus, Individualized chemotherapy that is tailored specifically to the characteristics of the tumor is necessary for an improved clinical outcome. RESULTS We evaluate the chemosensitivity of colorectal cancer to standard drugs (5-FU, oxaliplatin, and irinotecan) and to drugs used for other cancers (mitomycin, paclitaxel, and gemcitabine) by using Adenosine-triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS The degree of in-vitro response to a single anticancer medication was highest for 5-FU. According to stages, 5-FU is the most sensitive chemotherapeutic agent in Duke's B, irinotecan in Duke's C, and 5-FU in Duke's D patients. With tumor location, irinotecan is most sensitive in colon cancers and 5-FU in rectal cancers. The effect of treatment is superior in the test-guided therapy group in Duke's D colorectal cancer patients. CONCLUSIONS Chemosensitivity tests may be useful in selecting optimum drugs for patient who require chemotherapy. However, the results of this study do not strongly support the usefulness of this assay; further studies with a sufficient number of cases and an extended observation period are ongoing.
PURPOSE Irinotecan is a recently developed active agent in colorectal cancer. The combination of irinotecan and 5-fluorouracil (5-FU)/lecovorin (LV), known as the FOLFIRI regimen, has been approved for patients with metastatic colorectal cancer. The purpose of this study was to assess the efficacy and toxicity of the FOLFIRI regimen in the treatment of metastatic colorectal cancer. METHODS We reviewed the records of 65 patients who had received the FOLFIRI regimen from Jan. 2002 to Dec. 2005.
The combination chemotherapy consisted of irinotecan (150~180 mg/m2 on day 1, 15) as a 2~6 hour infusion followed by bolus infusion of 5-FU (400 mg/m2) and continuous infusion of 5-FU (600 mg/m2 on days 1, 2, 15, 16), concurrently with LV (20 mg/m2 on day 1, 2, 15, 16) as a 2 hour infusion. Cycles were repeated in three-week intervals. RESULTS Of the 65 patients who had received the FOLFIRI regimen, 34 were male and 31 cases female. The median age was 54.4 years. The primary tumor sites were the colon in 29 cases (44.6%) and the rectum in 36 cases (56.4%). The metastatic sites were the liver in 33 cases (50.8%), the peritoneum in 21 (32.3%), the lung in 14 (21.5%), a lymph node in 4, and the pelvis in 2. Twenty-seven patients (41.5%) had received the combination chemotherapy as the first line. Of the patients who received more than 3 cycles, complete response was none. Partial responses were 3 (7.1%), stable disease status in 25 cases (59.5%) and progressive disease status in 14 cases (33.3%). The rate of progressive disease status for patients who had received FOLFIRI as the 2nd or the 3rd line were much higher than that of those who had received it as the 1st line chemotherapy. Early stops (<3 cycles) of chemotherapy were due to toxicity, such as nausea, as diarrhea, in 15 of 19 cases (78.9%). CONCLUSIONS The objective response rate of FOLFIRI was 7.1% in metastatic colorectal cancers. Nausea, vomiting, and diarrhea were the main causes of intolerance to the chemotherapy in most of the patients.
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Quality of Life in Colorectal Cancer Patients according to the Severity of Symptom Clusters Classification Gyeonghui Jeong, Kyunghee Kim, Yeunhee Kwak Asian Oncology Nursing.2014; 14(2): 74. CrossRef
Intraperitoneal carcinomatosis accounts for 25~35% of recurrences of colorectal cancer, and peritoneal carcinomatosis from colorectal cancer has been regarded as a lethal condition. However, a combination of aggressive cytoreductive surgery and intraperitoneal chemotherapy has been tried and appears to be beneficial in selected patients. The primary goal of cytoreductive surgery is to remove all visible tumor within the peritoneal cavity. The goal of intraperitoneal chemotherapy is to eradicate the microscopic residual tumor and to prevent its recurrence.
There are various ways to perform intraperitoneal chemotherapy. One is postoperative intraperitoneal chemotherapy, and another is intraoperative hyperthermic chemotherapy during surgery. Hyperthermia increases the penetration of chemotherapy into tissues and the level of chemotherapy cytotoxicity. The timing of surgery in cases of intraperitoneal chemotherapy and the optimal dosage of drugs must be evaluated in further studies. In colorectal cancer, the peritoneum should be regarded as an intra-abdominal organ, like the liver. Therefore, intraperitoneal carcinomatosis must be treated by using a combination of aggressive surgical treatment and intraperitoneal chemotherapy. Eventually, the long-term overall survival will be increased.
The last several years have major advances in chemotherapy treatment for adjuvant and metastatic colorectal cancer.
We've come from an overall survival of 6 months in patients treated with best supportive care in the mid 1980s and even in the early 1990s. The use of 5-FU/leucovorin alone generates an overall survival of about 6 months. The addition of irinotecan/oxaliplatin allows patients to live a median of about 15 to 17 months. If we make use of all 3 active drugs, FOLFOX and FOLFIRI in a sequential manner, we'll be able to generate an overall survival of about 20 months. Recently, the addition of molecular therapy, in particular bevacizumab and cetuximab to these cytotoxic drugs has allowed us to break the brick wall that was placed at about 2 years median overall survival in large phase 3 trials in patients with metastatic colorectal cancer. The recent presentations provided further evidence that the standard of care in the treatment of advanced CRC consists of a combination of highly active cytotoxic chemotherapy plus the addition of a biologic agents, For clinical research, investigation of the best therapy for CRC has clearly shifted away from investigating conventional chemotherapy toward the question of how to make best use of all available active agents, particularly the novel biologics. Randomized trials have also shown that preoperative chemoradiation yields higher rates of pathologic complete response and local control, compared with radiotherapy alone. In this article, I review recent trials on preoperative and adjuvant therapy of localized rectal cancer. The roles of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also discussed, and other key issues in the treatment of localized rectal cancer are reviewed. The planned phase 3 first-line trial will continue to elucidate the role of the currently available biologics in the treatment of CRC. In this article, the important advances in optimal chemotherapy of colorectal cancer will be summarized and approaches to multidisciplinary treatment decision-making in both adjuvant and metastatic settings will be reviewd.
Neutropenic enterocolitis is observed in approximately 10~46% of patients with acute leukemia, as well as in patients with other diseases, like acquired immunodeficiency syndrom (AIDS), that lead to profound neutropenia. Patients who become neutropenic after combined chemotherapy are at special risk of developing neutropenic enterocolitis. With the recently increasing numbers of patients with solid tumors treated with high-dose chemotherapy, the frequency of this disease is expected to increase. However, this disease has been rarely reported in patients with colon cancer treated with leucovorin and 5-fluorouracil for adjuvant chemotherapy. We report a case of neutropenic enterocolitis after a treatment of 5-fluorouracil and leucovorin for sigmoid colon cancer.
PURPOSE Although large clinical trials have been performed attempting to find an optimal 5-fluorouracil (5-FU)-based regimen on the basis of activity and toxicity, there have been few data reporting the toxicity. We experienced a less severe toxicity than previous reports, so we undertook an analysis of the toxicity profiles of 5-FU-based chemotherapy on colorectal cancer patients. METHODS Forty-two patients were consecutively enrolled in this study from Sep. 2002 to Sep. 2003. The primary endpoints were the incidences of anorexia, nausea, vomiting, diarrhea, constipation, headache, stomatitis, alopecia, and leukopenia, as recorded with the standard National Cancer Institute- Common Toxicity Criteria (NCI-CTC). The regimen used in this study was intravenous infusion of 5-FU, 500 mg/m2, plus leucovorin (LV), 20 mg, daily for 5 days every 4 weeks for 6 cycles. Information on toxic profiles was obtained by questionnaire and blood test data during each cycle of treatment. RESULTS Of the patients, 73.8% experienced at least one type of toxicity. There were no clinical grade 3/4 toxicities. Toxicites (grade 1/2) were as follows: anorexia (51.2%), nausea (50.4%), constipation (24.6%), headache (11.5%), vomiting (4.0%), diarrhea (2.4%), alopecia (2.0%), stomatitis (0.4%), and leukopenia (4.0%). The most common adverse event was gastrointestinal toxicity (16.6%). There were no deaths attributed to non-hematologic toxicity. There was no dose reduction during any cycle of treatment. In a comparison of the incidence of toxicity by age (<65 and > or =65), gender, and TNM stage, univariate analysis found no statistical differences. CONCLUSIONS Our data would seem to confirm that Korean patients experienced less incidence and severity of toxicity than Western patients. We believe that the accumulated data provide sufficient evidence that colorectal patients in Korea actually experience a less severe toxicity of 5-FU-based chemotherapy when they are treated on this schedule. Considering this study, a race-specific dose determination for a colorectal cancer adjuvant chemotherapeutic setting is warranted.
PURPOSE Oxaliplatin is a recently developed active agent in colorectal cancer. Clinical observations have demonstrated synergistic effects of oxaliplatin with 5-fluorouracil (5- FU) and leucovorin (LV), even in 5-FU-resistant colorectal cancer. The purpose of this study was to determine response rates according to clinical factors after oxaliplatin, 5-FU and LV combination chemotherapy (FOLFOX 3) in metastatic colorectal cancer. METHODS We reviewed 44 patients who had received FOLFOX 3 from Jan. 2000 to Dec. 2002. The combination chemotherapy consisted of oxaliplatin (85 mg/m2 on day 1) as a 2~6 hour infusion followed by continuous infusion of 5-FU (1500 mg/m2 on day 1, 2), concurrently with LV (45 mg on day 1, 2) as a 2 hour infusion. Cycles were repeated by 2-week intervals.
We compared the response rates according to clinical factors such as primary sites, cycle, tumor differentiation, metastatic sites, serum CEA, and previous chemotherapy. RESULTS Of the 44 patients who had received the combination chemotherapy with oxaliplatin, 5-FU, and LV, 19 cases were male, 25 cases were female. The median age was 50.7 years.
The primary tumor sites were colon in 21 cases (47.7%), and rectum in 23 cases (52.3%). The metastatic sites were liver in 27 cases (61.4%), lung in 9 (20.5%), pelvis in 3, lymph node in 5, and peritoneum in 1. Thirty- five patients had received the combination chemotherapy as first line.
Complete response was observed in 3 cases (6.8%). Partial response was in 7 cases (15.9%), stable disease status in 15 cases (34.1%), progressive disease status in 19 cases (43.2%), respectively. There were a no significant differences in response rates according to primary sites, tumor differentiation, serum CEA, and previous chemotherapy.
However, with the metastatic sites, there were significant differences in response rates. Response rates were higher in lung (5/9), lymph node (3/4) metastases than any other metastatic sites (P <0.01). CONCLUSIONS The objective response rate of FOLFOX 3 was 22.7% in metastatic colorectal cancers. The only significant clinical factor was metastatic sites. The lung and lymph node metastases showed better response than metastatses to liver, pelvis, and peritoneum. To evaluate the differences of response rates according to metastatic sites, we need further study.
PURPOSE Functional loss of mismatch repair has been reported to be the reason for resistance to several chemotherapeutic drugs. The expressions of hMLH1 and hMSH2 were examined to assess whether they correlated with the biological behavior and the chemotherapeutic responsiveness in paflents with sporadic colon cancers. METHODS Ninety-one patients with stage III primary colon cancer were included from the tumor registry of the Asan Medical Center, Seoul, Korea. All patients underwent a curative operation and postoperative chemotherapy with 5- fluorouracil and leucovorin for 6 cycles between 1993 and 1997. Immunohistochemical staining for hMLH1 and hMSH2 was performed using archival paraffin blocks. A positive expression was determined when unequivocal nuclear staining was identified in more than 10% of the cancer cells. The survival and the clinicopathologic variables regarding hMLH1 and hMSH2 expressions were assessed using the log-rank test and the Cox proportional regression method. RESULTS Either hMLH1 or hMSH2 expression was lost in nine cases (9.9%). hMLH1 and hMSH2 expressions were significantly correlated with tumor invasion (P=0.012) and tumor differentiation (P=0.017). The disease-free survival did not differ with respect to hMLH1 and hMSH2 expressions. The number of metastatic lymph nodes and the preoperative serum CEA level were independent predictors of disease-free survival on a multivariate analysis. CONCLUSIONS The loss of hMLH1 or hMSH2 expresscon appears to be involved in the differentiation of and the invasion by colon cancer. However, nether hMLH1 nor hMSH2 expression was correlated withthe 5-fluorouracil responsiveness.
5-Fluorouracil (5-FU) has been the main chemotherapeutic agent for the treatment of colorectal cancer for four decades with modest efficacy. Modulation of 5-FU by leucovorin or continuous infusion improves the response rate, but overall survival duration remains approximately 12 months. Many oral fluoropyrimidines have been studied, including capecitabine, UFT, S-1, and Eniluracil.
Capecitabine has demonstrated equivalent efficacy with 5-FU and has been approved as first line treatment. CPT-11 demonstrated non-crossover resistance with 5-FU and was proven to be effective treatment for patients who received prior 5-FU. CPT-11 in combination with 5-FU has demonstrated improved response rate and overall survival duration over 5-FU or CPT-11. Oxaliplatin plus 5-FU has offered another effective treatment option for colorectal cancer. Both 5-FU plus leucovorin in combination with CPT-11 or oxaliplatin are widely used first-line chemotherapies for advanced colorectal cancer. The combinations of capecitabine with CPT-11 or oxaliplatin are being developed. Several molecular targeting agents such as EGFR inhibitors and antiangiogenic agents have developed. Cetuximab induces a broad range of cellular responses in tumors expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. A key angiogenic pathway in the stimulation of tumour growth is the vascular endothelial growth factor (VEGF) pathway, inhibited by the monoclonal antibody bevacizumab. Phase II first line and phase III second line studies of oxaliplatin in combination with bevacizumab are now in progress. Optimal combinations and sequences of treatment are being studied, since several effective regimens have become available.
PURPOSE In advanced colorectal cancer, 5-Fluorouracil (5-FU) and Leucovorin (LV) have been used as a standard chemotherapy regimen. 5-FU is a popular chemotherapeutic drug for colorectal cancers and LV is the most effective modulator of 5-FU. Recently, some studies using Interferon (INF) combination therapy with 5-FU to enhance the anti-tumor effect of 5-FU have been performed. The outcomes were reportet to be better than those of studies using single agent therapy. However, the clinical effect of a combination therapy with INF is still controversial. So that, we performed this study to understand the advantages of INF combination therapy in advanced colorectal cancers in the Korean population. METHODS We recruited patients who had been diagnosed with for colorectal cancers and received operations and postoperative adjuvant chemotherapy in Uijongbu St. Mary's hospital, from July, 1995, to June, 1999. The patients were divided into two groups; control group treated with the Mayo clinic chemotherapy regimen of 5-FU plus LV, and study group treated with additional INF-alpha to 5-FU-LV combination treatment. We evaluated the clinical outcomes such as the overall survival rate, the recurrence rate, and the chemotoxicity between two groups. RESULTS In comparison of 5 year survival rates of two groups for each stage of the colorectal cancer, those of stage B2 were 90.9% in the control group and 80.0% in the study group. For stage C patients, the values were 80.2% in control group and 52.5% in the study group. The overall 5-year survival rates of the control group and the study group regardless of stages were 77.1%, and 63.4%, respectively. The 5-year disease-free survival rates for stage B2 were 82.8% in the control group and 72.9% in the study group. For stage C patients, those were 42.6% in the control group and 34.4% in the study group. The recurrence and metastatic rates were 19.2% (local recurrence; 2, metastasis; 12) in the control group and 36.1% (local recurrence; 3 metastasis; 27) in the study group. The overall incidences of chemotoxicity were 24.7% in the control group and 31.3% in the study group. CONCLUSIONS There was no evidence that chemotherapy using 5-FU and LV combined with INF-alpha in advanced colorectal cancer patients was more effective than the Mayo regimen of 5-FU and LV. More large scale clinical studies are warranted to evaluate the efficacy of additional INF therapy in colorectal cancer patients.
PURPOSE Although 5-fluorouracil (5-FU) has been used as the basis of chemotherapy regimen for colorectal cancer for more than 40 years, 5-FU as single agent treatment has rarely achieved objective response rates higher than 15% in advanced colorectal cancers. The modulation of 5-FU with biologic modifiers has resulted in higher response rates, but survival advantages was not meaningful. Oxaliplatin is one of the newly developed drugs with proven activity against colorectal cancer. To evaluate the therapeutic efficacy and safety profile of oxaliplatin, we reviewed patients who received oxaliplatin chemotherapy. METHODS We reviewed 48 patients who received combination chemotherapy with oxaliplatin, 5-FU, and leucovorin (LV) from Jan. 2000 to Dec. 2001. The combination chemotherapy consisted of oxaliplatin (85 mg/m2 on day 1) as a 2~6 hour infusion followed by continuous infusion of 5-FU (1,500 mg/m2 on day 1, 2), concurrently with LV (45 mg on day 1, 2) as a 2 hour infusion. The combination chemotherapy interval was 2 weeks. RESULTS Of the 48 patients who received the combination chemotherapy with oxaliplatin, 5-FU, and LV, 25 cases were male, 23 cases were female. The median age was 51.4 years.
The primary tumor sites were colon in 22 cases, and rectum in 26. According to TNM stage at diagnosis, 1 case was stage I, 5 cases were stage II, 21 cases were stage III, and 21 cases were stage IV. The metastatic sites were liver in 29 cases, lung in 10, pelvis in 7, peritoneum in 5, bone in 1, lymph node in 1, and spleen in 2. Previous chemotherapy were Mayo regimen in 43 patients, irrinotecan in 1 patient. Four patients had not received previous chemotherapy. Previously of the 48 patients, we could assess the chemotherapy response for 25 cases. Complete response was not observed.
Partial response was 3 cases (12%), stable disease in 12 cases (48%), progressive disease in 10 cases (40%). From 227 cycles analyzed, the main toxicity was gastrointestinal one.
Peripheral neuropathy was identifed in 5 cases. CONCLUSIONS We reviewed 48 patients with advanced colorectal cancer who received combination chemotherapy with oxaliplatin, 5-FU and LV. Of the 25 evaluable patients, the objective response rate was 12%. In our study, the combination chemotherapy with oxaliplatin, 5-FU, LV has not resulted in improved response rate, but overall toxicity was acceptable.