In patients with locally advanced rectal cancer, preoperative chemoradiotherapy has proven to significantly improve local control and cause lower treatment-related toxicity compared with postoperative adjuvant treatment. Preoperative chemoradiotherapy followed by total mesorectal excision or tumor specific mesorectal excision has evolved as the standard treatment for locally advanced rectal cancer. The paradigm shift from postoperative to preoperative therapy has raised a series of concerns however that have practical clinical implications. These include the method used to predict patients who will show good response, sphincter preservation, the application of conservative management such as local excision or “wait-and-watch” in patients obtaining a good response following preoperative chemoradiotherapy, and the role of adjuvant chemotherapy. This review addresses these current issues in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy.
Colorectal cancer; Rectal cancer; Preoperative chemoradiotherapy; Conservative; Response
There are no previous large scale studies which have evaluated the phenotypes and clinical characteristics of Korean Crohn's disease patients who underwent intestinal resection. The purpose of this multicenter retrospective cohort study was to evaluate the clinical characteristics of Korean Crohn's disease patients who underwent intestinal resection during the study period. A total of 686 patients were enrolled in this study. The study period was over a 20-yr period (1990-2009). The patients were divided into the first-10-yr group and the second-10-yr group. The phenotypes and clinical characteristics were compared between the groups. The most common site of the disease was the ileal area (37.8%) and stricturing behavior was observed in 38.3% patients. The most common type of surgery was segmental resection of the small bowel (30.6%). These phenotypes showed a similar pattern in both the first and second study period groups and did not show any significant differences between the groups. The number of registered patients increased continuously. The phenotypes of Korean Crohn's disease patients who underwent intestinal resection are different compared with previously reported clinical characteristics of general Crohn's disease patients.
Crohn's Disease; Phenotypes; Intestinal Surgery
A diverting stoma is known to reduce the consequences of distal anastomotic failure following colorectal surgery. The aim of this study was to evaluate the efficacy of a diverting stoma after an ultra-low anterior resection (uLAR) for rectal cancer.
Between 2000 and 2007, 836 patients who underwent an uLAR were divided into two groups, depending on the fecal diversion: 246 received fecal diversion, and 590 had no diversion. Patient- and disease-related variables were compared between the two groups.
Thirty-two of the 836 patients (3.8%) had immediate anastomosis-related complications and required reoperation. Anastomosis leakage comprised 72% of the complications (23/32). The overall immediate complication rate was significantly lower in patients with a diverting stoma (0.8%, 2/246) compared to those without a diverting stoma (5.1%, 30/590; P = 0.005). The fecal diversion group had lower tumor location, lower anastomosis level, and more preoperative chemo-radiation therapy (P < 0.001). In total, 12% of patients in the diverting stoma group had complications either in making or reversing the stoma (30/246).
The diverting stoma decreased the rate of immediate anastomosis-related complications. However, the rate of complications associated with the diverting stoma was non-negligible, so strict criteria should be applied when deciding whether to use a diverting stoma.
Rectal neoplasms; Ileostomy; Colorectal surgery
To assess the incidence and factors predictive of early postoperative complications in Korean patients who undergo surgery for Crohn's disease (CD).
We retrospectively assessed 350 patients (246 males, 104 females; mean age, 30 ± 9 years) who underwent surgery for primary or recurrent CD at Asan Medical Center between January 1991 and May 2010. The incidence and predictive factors of early postoperative complications were analyzed by both univariate and multivariate analyses.
Of the 350 patients, 81 patients (23.1%) developed postoperative complications, the most common being septic complications (54 patients), including 19 cases of wound infection. Thirty patients (8.6%) required re-operations, and only one patient died. Multivariate analysis showed that four factors were independently associated with a high risk of early postoperative complications; preoperative moderate to severe anemia (hematocrit concentration <30%; odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6 to 5.9), hypoalbuminemia (serum albumin level <3.0 g/dL; OR, 2.6; 95% CI, 1.4 to 4.7), emergency surgery (OR, 4.0; 95% CI, 1.5 to 10.6), and covering stoma (OR, 2.6; 95% CI, 1.3 to 5.4). Correction of preoperative moderate to severe anemia and hypoalbuminemia decreased the incidence of postoperative complications. Mean hospital stay was significantly longer in patients with than without postoperative complications (31.3 ± 27.2 days vs. 10.3 ± 3.8 days, P < 0.001).
Preoperative anemia, low albumin level, emergency surgery, and covering stoma significantly increased the risk of early postoperative complications in patients with CD. Correcting preoperatively deficient nutritional factors may reduce postoperative morbidities.
Crohn disease; Surgery; Korea; Risk factors; Postoperative complications
The purpose of this study was to assess the risk factors for repeated abdominal surgery in Crohn's disease (CD) patients after the first abdominal surgery. Prior studies have tried to identify the risk factors for postoperative recurrence in CD patients, but the results of the studies have been inconsistent. Furthermore, few data on the risk factors for repeated abdominal surgery are available.
Clinical data on CD patients who underwent abdominal surgery from January 2000 to December 2009 were collected from seventeen university hospitals and one colorectal clinic. Data from a total of 708 patients were analyzed to find the risk factors for repeated abdominal surgery in CD patients. The mean follow-up period was 72 months.
The risk of repeated abdominal surgery was 3 times higher in young patients (below 16 years old) than in older patients (odds ratio [OR], 3.056; 95% confidence interval [CI], 1.021 to 9.150); P = 0.046). Stricturing behavior at diagnosis was also a risk factor for repeated abdominal surgery (OR, 2.438; 95% CI, 1.144 to 5.196; P = 0.021). Among operative indications, only intra-abdominal abscess was associated with repeated abdominal surgery (OR, 2.393; 95% CI, 1.098 to 5.216; P = 0.028). Concerning type of operation, an ileostomy might be a risk factor for repeated abdominal surgery (OR, 11.437; 95% CI, 1.451 to 90.124; P = 0.021). Emergency surgery (OR, 4.994; 95% CI, 2.123 to 11.745; P < 0.001) and delayed diagnosis after surgery (OR, 2.339; 95% CI, 1.147 to 4.771; P = 0.019) also increased the risk of repeated abdominal surgery.
Young age (below 16 years), stricturing behavior, intra-abdominal abscess, emergency surgery, and delayed diagnosis after surgery were identified as possible risk factors for repeated abdominal surgery in CD patients.
Crohn's disease; Recurrence; Surgery
The aim of this study was to evaluate outcomes of a total colectomy with ileorectal anastomosis in patients with slow transit constipation.
A retrospective review of 37 consecutive patients with slow transit constipation who underwent a total colectomy between 1994 and 2008 was undertaken. Preoperative and postoperative Wexner's constipation scores were collected and used to evaluate the outcomes after surgical treatment. Also patients' postoperative satisfaction scores were collected using a 4-point scale.
The 37 patients consisted of 31 women and 6 men, with a median age of 41 years (range, 17 to 71 years). Pre- and post-operative Wexner's scores were collected from 33 patients (89.1%), and the mean preoperative Wexner's score was 19.3 (range, 11 to 24), which decreased to an average post-operative score of 2.3 (range, 0 to 8). Neither intraoperative complications nor postoperative mortalities were noted. Five patients (13.5%) had early postoperative complications, and the most common complication was postoperative ileus (10.8%). Seven patients (18.9%) had late postoperative complications, and postoperative ileus (10.8%) was also the most common. Twenty seven of 33 patients were satisfied with their surgical outcome (81.8%).
A total colectomy with ileorectal anastomosis might be an effective surgical procedure with acceptable morbidity to treat medically intractable slow transit constipation.
Colonic inertia; Colectomy; Treatment outcome; Postoperative complication
Isolated diaphragmatic metastasis arising from colorectal cancer has been reported only one case in the literature presently. Here, we presented a new case and discussed the possible pathogenesis and the treatment options. A 42-year-old male patient had received anterior resection for sigmoid colon cancer. Although the increased serum CEA level was detected 20 months after the surgery, metastatic lesion could not be detected by repeated colonoscopy, CT scan, bone scan or PET scan for 35 months. We could detect a suspicious metastatic lesion on the liver by CT scan at 56 month after the surgery. During a second-look operation, we found a solitary metastasis on the diaphragm and removed it along with the 1 cm tumor-free resection margin. Although the prognosis associated with skeletal metastasis is poor, the complete resection of isolated diaphragmatic metastasis and subsequent appropriate adjuvant chemotherapy may achieve a cure the disease provided that other metastatic lesions are absent.
Colorectal neoplasm; Metastasis; Diaphragm; Carcinoembryonic antigen
Selecting the best surgical approach for treating complete rectal prolapse involves comparing the operative and functional outcomes of the procedures. The aims of this study were to evaluate and compare the operative and functional outcomes of abdominal and perineal surgical procedures for patients with complete rectal prolapse.
A retrospective study of patients with complete rectal prolapse who had operations at a tertiary referral hospital and a university hospital between March 1990 and May 2011 was conducted. Patients were classified according to the type of operation: abdominal procedure (AP) (n = 64) or perineal procedure (PP) (n = 40). The operative outcomes and functional results were assessed.
The AP group had the younger and more men than the PP group. The AP group had longer operation times than the PP group (165 minutes vs. 70 minutes; P = 0.001) and longer hospital stays (10 days vs. 7 days; P = 0.001), but a lower overall recurrence rate (6.3% vs. 15.0%; P = 0.14). The overall rate of the major complication was similar in the both groups (10.9% vs. 6.8%; P = 0.47). The patients in the AP group complained more frequently of constipation than of incontinence, conversely, in the PP group of incontinence than of constipation.
The two approaches for treating complete rectal prolapse did not differ with regard to postoperative morbidity, but the overall recurrence tended to occur frequently among patients in the PP group. Functional results after each surgical approach need to be considered for the selection of procedure.
Rectal prolapse; Abdomen; Perineum; Procedure
In Korea, anal cancer is rare disease entity with specific clinical characteristics. Therefore, no survival analysis with a sufficient patient population has been performed. The aim of this study was to evaluate the characteristics of Korean anal cancer, focusing on the survival according to tumor histologies, sex, and a specific age group, using the nationwide cancer registry.
Using the Korea Central Cancer Registry, we analyzed a total of 2,552 cases from 1993 to 2010. We assessed the 5-year relative survival by using tumor histology. In addition, survival differences of Surveillance Epidemiology and End Results (SEER) stage were analyzed for both sexes and for young-age cancer (younger than 40 years) and advanced-age cancer (older than 70 years).
The 5-year relative survival among anal cancer patients increased from 38.9% for the period 1993-1995 to 65.6% for the period 2006-2010. The anal squamous cell carcinoma was the most common histology and showed better survival than other types of cancer. Females demonstrated better survival than males in all SEER stages. The 5-year survivals for patients in whom anal cancer developed before the age of 40 and at or after the age of 40 were 62.4% and 51.6%, respectively. The 5-year survival for patients in whom cancer developed at or after the age of 70 was much worse than that for patients in whom the cancer had developed prior to that age.
Korean anal cancer has certain distinctive characteristics of survival according to tumor histology, sex, and age. Despite limitations on available data, this study used the nationwide database to provide important information on the survival of Korean patients with anal cancer.
Anal neoplasms; Korean; Survival
The incidence rates of colorectal cancer (CRC) in Korea have been increasing during the past decade. Therefore, it is important to understand the characteristics, including survival, of Korean CRC patients. The aim of this study was to use the nationwide cancer registry to evaluate the characteristics of Korean CRC, focusing on the survival, according to tumor location, sex, and specific age groups.
Using the Korea Central Cancer Registry (KCCR), we analyzed a total of 226,352 CRC cases diagnosed from 1993 to 2010. The five-year relative survivals were compared for the proximal colon, the distal colon, and the rectum. Survival rates were compared between men and women and between patients of young age (less than 40 years old) and patients of advanced age (70 years old or older).
The 5-year survival rates were improved in all subsites between 1993 and 2010. Distal colon cancer showed favorable survival compared to proximal colon or rectal cancer. Females demonstrated worse survival for local or regional cancers, and this difference was significant in for patients in their seventies. Young patients (<40 years old) showed better survival rates for overall and proximal colon cancer comparable to those for older patients (≥40 years old), but advanced age patients (≥70 years old) had worse survivals for all tumor subsites compared to their younger counterparts (<70 years old). These trends were similar in distant CRC.
Korean CRC has certain distinct characteristics of survival according to tumor location, sex, and age. Despite the limitations of available data, this study contributes to a better understanding of survival differences in Korean CRC.
Colorectal neoplasms; Korean, Survival
The objective of the current study was to identify the clinicopathological risk factors affecting recurrence after a curative resection for stage I colorectal cancer.
We retrospectively studied 434 patients who underwent a curative resection for stage I colorectal cancer between January 1999 and December 2004. Postoperative oral chemotherapy was performed in 189 patients (45.3%). The following prognostic factors were correlated with recurrence: age, gender, preoperative carcinoembryonic antigen level, location of tumor, T stage, size of tumor, histologic differentiation, growth pattern, and lymphovascular invasion. The median follow-up duration was 65 months.
The overall recurrence rate was 4.6% (20/434). The median time to recurrence was 33 months. Two-thirds of the recurrence occurred more than two years after surgery. Risk factors associated with recurrence were rectal cancer (P = 0.009), T2 stage (P = 0.010), and infiltrative growth pattern (P = 0.020). A Cox proportional hazards regression analysis demonstrated that the infiltrative growth pattern was an independent predictor for recurrence. Tumor cell budding was observed in all pathologic reviews with recurrence.
Long-term follow-up is necessary for stage I colorectal patients with high risk factors like rectal cancer, T2 stage, and infiltrative growth pattern.
Colorectal neoplasms; Recurrence; Risk factors
To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection for the treatment of colorectal liver metastasis (CRLM).
Between 1996 and 2008, 177 patients underwent RFA, 278 underwent hepatic resection and 27 underwent combination therapy for CRLM. Comparative analysis of clinical outcomes was performed including number of liver metastases, tumor size, and time of CRLM.
Based on multivariate analysis, overall survival (OS) correlated with the number of liver metastases and the use of combined chemotherapy (P < 0.001, respectively). Disease-free survival (DFS) also correlated with the number of liver metastases (P < 0.001). In the 226 patients with solitary CRLM < 3 cm, OS and DFS rates did not differ between the RFA group and the resection group (P = 0.962 and P = 0.980). In the 70 patients with solitary CRLM ≥ 3 cm, DFS was significantly lower in the RFA group as compared with the resection group (P = 0.015).
The results indicate that RFA may be a safe alternative treatment for solitary CRLM less than 3 cm, with outcomes equivalent to those achieved with hepatic resection. A randomized controlled study comparing RFA and resection for patients with single small metastasis would help to determine the most efficient treatment modalities for CRLM.
Radiofrequency ablation; Hepatectomy; Colorectal neoplasms; Liver metastasis
This current study examined the clinicopathologic characteristics of patients with splenic flexure (SF) colon cancer and the association with the surgical outcomes to find the optimal procedure to treat this malady.
Materials and Methods
A total of 167 operated patients with SF colon cancer were consecutively recruited between 1993 and 2003. The clinicopathological, operative and survival data was reviewed and analyzed.
For the SF colon cancer patients, the proportion of males was higher than that for the right-sided colon patients or the sigmoid-descending junction & sigmoid (SD & S) colon patients (p≤0.05, respectively) and the age at the time of diagnosis was younger (p≤0.05). Obstruction was more frequent in the patients with SF colon cancer than that for the patients with colon cancer at other sites (p≤0.001). The incidence of mucinous adenocarcinoma for the SF patients was similar to that for the patients with right-sided colon cancer, but it was higher than that for the patients with SD & S colon cancer (11.4% vs. 6.5%, p=0.248 or 2.5%, respectively, p=0.001). Disease-free and overall survival did not differ between the patients who underwent a left hemicolectomy and extended surgery such as combined splenectomy or subtotal colectomy. Multivariate analysis showed that old age (≥60 years) and a N1-2 and M1 status were the independent risk factors for overall survival.
The SF colon cancers exhibited exclusively different characteristics as compared to colon cancers at other site colon cancers. It appears that left hemicolectomy was generally sufficient for a satisfactory oncological outcome, obviating concurrent splenectomy.
Colonic neoplasms; Left colic flexure; Colectomy; Splenectomy
To determine the role of methylation in colorectal cancer patients with a family history, we enrolled 25 colorectal cancer patients with a family history of colorectal cancer but without a mutation in the hMLH1 and hMSH2 genes. Thirty patients with sporadic colorectal cancer were included as control. The methylation status of COX2, MGMT, hMLH1, TIMP3, p16, and MINT2 in normal mucosa and tumor were assessed using methylation-specific PCR. In patients with a family history, the methylation frequency ranged from 4.0% for TIMP3 to 44.4% for MGMT, whereas, in patients with sporadic colorectal cancer, it ranged from 6.7% for TIMP3 to 50.0% for p16. Nine of the 25 patients with family history (36.0%) were classified as methylation-prone, and nine of the 30 patients with sporadic cancers (30.0%) were as methylation-prone, making their methylation indices 0.19 and 0.16, respectively (p=0.522). As for the individual genes, the methylation rate of MGMT was higher in colorectal cancer patients with family history (44.0% vs. 13.0%, p=0.016), whereas the methylation rate of p16 was higher in sporadic colorectal cancers (50.0% vs. 8.7%, p=0.046). While CpG island methylation of tumor suppressor genes may play a role in colorectal carcinogenesis, the genes involved may be different between tumors of patients with and without a family history of colorectal cancer.
Colorectal Neoplasms; Familial; Carcinogenesis; Methylation; Microsatellite Instability
To determine whether family history of cancer may be a risk factor for the mutator phenotype in colorectal cancer, we recruited 143 consecutive colorectal cancer patients with a family history of accompanying cancers not meeting the Amsterdam criteria. Microsatellite instability (MSI) at 5 markers, hMLH1-promoter methylation, and expression of mismatch repair (MMR) proteins (hMLH1, hMSH2, hMSH6, hMPS1, and hPMS2) were determined. Among the relatives of familial colorectal cancer patients, colorectal cancer was the most common tumor type. Of the proband colorectal cancers, 26 (18.2%) showed high-level MSI (MSI-H); 47 additional tumors with mutator phenotype (32.9%) were identified by hMLH1-promoter methylation and/or loss of MMR protein expression. Mutator phenotype was associated with right-sided colon cancer and the type of accompanying cancer. Family history, which was differentially quantified according to the degree of relatives and the type of accompanying cancers, effectively discriminated MSI-H from microsatellite stable (MSS) and low-level microsatellite instability (MSI-L) and mutator phenotypes. Our findings indicate that familial colorectal cancer may be associated with multiple occurrences of colorectal or accompanying cancers and that family history could be correlated with microsatellite instability.
Familial Colorectal Cancer; Family History; Mutator Phenotype; Ncrosatellite Instability
Granulocytic sarcoma is an extramedullary tumor composed of immature granulocytic cells. These tumors usually occur simultaneously with or follow after the onset of acute myeloid leukemia (AML) or other myeloproliferative disorders. Rarely, it is the first manifestation of AML which appears several months before the onset of leukemia. We report a case of a 48-year-old man presenting with symptoms of small bowel obstruction. Laparotomy and open biopsy were performed. Immunohistochemical studies showed that the neoplastic cells were of myeloid lineage positive for myeloperoxidase and leukocyte common antigen, but negative for CD3, 20, 56, 79a, and cytokeratin. Initially, there was no evidence of blood or bone marrow involvement suggesting acute leukemia or other myeloproliferative disorders. The findings were consistent with the diagnostic findings of solitary granulocytic sarcoma (preleukemic). However, one month later, bone marrow biopsy revealed 57% myeloblasts. Sequentially, the patient developed FAB M2 acute myeloid leukemia. Induction chemotherapy including cytarabine and idarubicine was done which led to complete remission. Allograft bone marrow transplantation was performed later, and there is no evidence of recurrence till present.
Granulocytic sarcoma; Acute myeloid leukemia; Small bowel obstruction
Colonic hamartomas are rare polypoid lesions. We report an unusual case of multiple colonic hamartomatous polyps, including a giant hamartoma, unrelated to hereditary or familial polyposis syndromes, in a 48-year-old man. The diameter of the largest polyp was 9.5 cm, and endoscopy revealed that the lesion caused colonic obstruction. The clinical, endoscopic and histological aspects of this case are discussed.
Hamartoma; giant hamartoma
Capecitabine is an oral fluoropyrimidine carbamate and it is known as an effective radiosensitizer. Capecitabine and its metabolite reach their peak concentration in the plasma at 1~2 hours after a single oral administration of capecitabine and the levels fall rapidly thereafter. To verify the radiosensitizing effect of capecitabine that is based on such pharmacokinetic characteristics, we performed a retrospective analysis on the optimal timing of capecitabine administration with performing preoperative chemoradiation for locally advanced rectal cancer.
Materials and Methods
Among 171 patients who were treated with preoperative radiotherapy and concurrent capecitabine administration for rectal cancer, 56 patients were administered capecitabine at 1~2 hours before radiotherapy (group A), and at other time in the other 115 patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the completion of chemoradiation. The radiosensitizing effect of capecitabine was evaluated on the basis of the pathological response.
Complete pathological regression of the primary tumor was observed in 12 patients (21.4%) for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the capecitabine ingestion time showed marginal significance.
When performing preoperative chemoradiation for locally advanced rectal cancer, the radiosensitizing effect of capecitabine was enhanced when it was administered 1 hour before radiotherapy.
Rectal neoplasms; Combined modality therapy; Capecitabine
Serum carcinoembryonic antigen (s-CEA) is used to detect recurrence and predict prognosis in colorectal cancer. However, the cutoff values of s-CEA for prognosis have not been determined. We therefore tried to determine the preoperative s-CEA levels predictive of survivals in colorectal cancer patients. We retrospectively analyzed the medical records of 989 patients who underwent curative resection for colorectal cancer between July 1990 and December 1997, with a mean follow-up of 46 months (range, 3-129 months). When patients were divided into four subgroups with the cutoff values of s-CEA at 3,6, and 17 ng/mL, their 5-yr disease-free survival rates were 85.3% (<3.0 ng/mL), 70.0% (3-6 ng/mL), 64.2% (6-17 ng/mL), and 55.2% (>17 ng/mL) (p<0.001). Multivariate analysis showed that factors predictive of survival included age (p=0.028), tumor stage (p<0.001), cell differentiation (p=0.016), and gross type (p=0.007), location (p=0.003) and preoperative s-CEA (p<0.001). Using the above-described cutoff levels, a significant difference in survival was observed only in patients with stage III tumors (p=0.007) when analyses were performed by stage. We can suggest the new cutoff values of s-CEA used in the present study.
Carcinoembryonic Antigen; Prognosis; Colonic Neoplasm
Lymph node involvement is the most important prognostic factor of rectal cancer. Cancer originating from sites other than the rectum rarely metastasizes to the mesorectal lymph node. We report a rectal cancer patient with a synchronous metastatic prostatic carcinoma to the mesorectal lymph node.
Mesorectal; Lymph node; Prostatic carcinoma
The aim of this study was to evaluate the responsiveness to CPT-11 with respect to hMLH1 and hMSH2 protein expressions in primary colorectal tumors.
Materials and Methods
91 patients with colorectal cancer treated having undergone surgery and postoperative CPT-11-based adjuvant chemotherapy, between 1997 and 2002, were prospectively recruited. Tumor samples were immunohistochemically analyzed for the expressions of hMLH1, hMSH2, p53 and CEA proteins.
Of the 91 tumors, 6 (6.6%) and 4 (4.4%) showed loss of hMLH1 and hMSH2 protein expressions, respectively. The response rate of patients with tumors not expressing either hMLH1 or hMSH2 was higher than that of those expressing either of these proteins (p=0.026). Patients with tumors not expressing hMLH1 showed a significantly better response to CPT-11 (p=0.04). The responsiveness was not associated with the expressions of hMSH2, p53 or CEA. There were no correlations between drug toxicity and the expressions of hMLH1, hMSH2 or p53. The overall survival was better in patients responsive to CPT-11-based chemotherapy compared to non-responders.
The immunohistochemical determination of loss of hMLH1 and hMSH2 expressions may be used in determining the responsiveness to CPT-11-based chemotherapy. Our results suggest that hMLH1 protein expression may be a predictor for CPT-11 responsiveness in patients with colorectal cancer.
Colorectal neoplasm; CPT-11; Response; hMLH1; hMSH2
Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer.
Materials and Methods
A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m2 capecitabine in two potions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation.
Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed.
Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.
Rectal cancer; Preoperative; Chemoradiotherapy; Capecitabine