Chin-Fan Chen

Multiple genetic polymorphisms in the prediction of clinical outcome of metastatic colorectal cancer patients treated with first-line FOLFOX-4 chemotherapy.

Objectives The objective of the study is to investigate whether multiple chemotherapeutic agent-related genetic polymorphisms are associated with the clinical outcomes of Taiwanese metastatic colorectal cancers (mCRC) patients treated with the first-line FOLFOX-4 chemotherapy. Methods Consecutive mCRC patients were prospectively enrolled into this study. Peripheral blood samples were used for genotyping of polymorphisms in MTHFR, DPD, GSTP1, MDR1, TYMS, ERCC1, XRCC1, and ERCC2 genes by polymerase chain reaction–restriction fragment length polymorphism technique and DNA sequencing. The primary end point of the study was to investigate the association of each genetic polymorphism with progression-free survival and overall survival (OS). Results Favorable genotypes from polymorphisms in ERCC1 codon 118C/C [hazard ratio (HR)=0.061, 95% confidence interval (CI): 0.014–0.274, P<0.001] and XRCC1 codon 399G/G (HR=0.306, 95% CI: 0.103–0.905, P=0.032) that are associated with progression-free survival were identified. Furthermore, ERCC1 codon 118C/C (HR=0.065, 95% CI: 0.011–0.377, P=0.002) and XRCC1 codon 399G/G (HR=0.152, 95% CI: 0.041–0.568, P=0.005) were significantly associated with favorable OS. Combining ERCC1 and XRCC1 genetic polymorphisms, patients with both favorable genotypes of ERCC1 codon 118C/C and XRCC1 codon 399G/G were associated with the better OS than those with one or without any favorable genotypes (P<0.001). Conclusion The genetic polymorphisms of ERCC1 and XRCC1 may be useful in predicting clinical outcome in Taiwanese mCRC patients treated with FOLFOX-4. However, further prospective studies will be needed for the potential clinical implication.

Occult Colon Cancer in a Patient with Diabetes and Recurrent Klebsiella Pneumoniae Liver Abscess

Klebsiella pneumoniae (Kp) is a well‐known leading cause of liver abscess in patients with diabetes, but recurrent Kp liver abscess in such patients within a period of time is seldom seen. Here, we report a patient with diabetes who experienced three episodes of Kp liver abscess within 1 year. The patient was subsequently diagnosed to have an occult sigmoid cancer. The liver abscess did not recur after resection of the colonic tumor. Occult sigmoid colonic cancer may have played an important role in the recurrent Kp liver abscess in our case. Therefore, further investigation of gastrointestinal malignancies, particularly of the colonic tract, is necessary in patients with diabetes and Kp liver abscess.

Predictive value of vascular endothelial growth factor overexpression in early relapse of colorectal cancer patients after curative resection

BackgroundPreclinical and clinical studies have indicated that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor. Recently, there was a consistent trend of poorer survival rates in colorectal cancer (CRC) patients of earlier relapse. The purpose of this study was to investigate novel predictors of early relapse in stage I–III CRC and further to determine their correlation with disease outcomes.Materials and methodsWe retrospectively analyzed clinicopathological features and VEGF expression by immunohistochemical staining in 100 stage I–III CRC patients undergoing curative resection to identify predictors of postoperative early relapse.ResultsAmong 100 patients, 40 patients were classified into early relapse group, and 60 patients were categorized into non-early relapse group. A multivariate logistic regression analysis showed that vascular invasion (P = 0.048), perineural invasion (P = 0.042), VEGF overexpression (P = 0.023), and high postoperative carcinoembryonic antigen (CEA) levels (P = 0.004) were independent predictors of early relapse. Additionally, we found that with more predictors such as the combined incidence of vascular invasion, perineural invasion, VEGF overexpression, and postoperative CEA levels are involved, the incidence of early postoperative relapse increases. Moreover, VEGF overexpression predicted not only early postoperative relapse but also disease-free survival (P < 0.001) and overall survival (P = 0.002).ConclusionsThis study suggests that VEGF overexpression is an important predictor of early postoperative relapse in patients with stage I–III CRC and may help identify patients who would benefit from intensive follow-up and therapeutic programs.

Coexistence of perineural invasion and lymph node metastases is a poor prognostic factor in patients with locally advanced rectal cancer after preoperative chemoradiotherapy followed by radical resection and adjuvant chemotherapy.

Objective: To determine the role of lymph node metastases (ypN) and perineural invasion (PNI) in patients with locally advanced rectal cancer (LARC). Subjects and Methods: Eighty-eight LARC patients receiving preoperative chemoradiotherapy from April 2006 to November 2011 were enrolled in this study. Univariate and multivariate analyses were conducted to determine the association between clinicopathologic features and clinical outcome. Results: The presence of ypN (p = 0.011) and PNI (p = 0.032) was a significant adverse prognostic factor for disease-free survival (DFS). High histologic grade (p = 0.015), PNI+ (p = 0.043) and ypN+ (p = 0.041) were adverse prognostic factors for overall survival (OS). Positive PNI was significantly associated with a higher risk of distant failure (odds ratio = 6.09; 95% CI: 1.57-27.05; p = 0.008). Moreover, patients with a coexistence of ypN+ and PNI+ had the significantly worst DFS (p < 0.001) and OS rates (p < 0.001) compared with other phenotypes. Conclusions: The presence of either PNI or ypN was a significant prognostic factor for predicting poor survival rates in LARC patients, especially those with a coexistence of both factors. Accordingly, we recommend an intensive follow-up and therapeutic programs for LARC patients with simultaneous PNI+ and ypN+.

DPYD, TYMS, TYMP, TK1, and TK2 Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

This study is to investigate multiple chemotherapeutic agent- and radiation-related genetic biomarkers in locally advanced rectal cancer (LARC) patients following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response prediction. We initially selected 6 fluoropyrimidine metabolism-related genes (DPYD, ORPT, TYMS, TYMP, TK1, and TK2) and 3 radiotherapy response-related genes (GLUT1, HIF-1 α, and HIF-2 α) as targets for gene expression identification in 60 LARC cancer specimens. Subsequently, a high-sensitivity weighted enzymatic chip array was designed and constructed to predict responses following CCRT. After CCRT, 39 of 60 (65%) LARC patients were classified as responders (pathological tumor regression grade 2 ~ 4). Using a panel of multiple genetic biomarkers (chip), including DPYD, TYMS, TYMP, TK1, and TK2, at a cutoff value for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were obtained (AUC: 0.915; 95% CI: 0.840–0.991). Negative chip results were significantly correlated to poor CCRT responses (TRG 0-1) (P = 0.014, hazard ratio: 22.704, 95% CI: 3.055–235.448 in multivariate analysis). Disease-free survival analysis showed significantly better survival rate in patients with positive chip results (P = 0.0001). We suggest that a chip including DPYD, TYMS, TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT.

Helical Tomotherapy Combined with Capecitabine in the Preoperative Treatment of Locally Advanced Rectal Cancer

The aim of this study was to evaluate the efficacy of helical tomotherapy plus capecitabine as a preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Thirty-six LARC patients receiving preoperative CRT were analyzed. Radiotherapy (RT) consisted of 45 Gy to the regional lymph nodes and simultaneous-integrated boost (SIB) 50.4 Gy to the tumor, 5 days/week for 5 weeks. Chemotherapy consisted of capecitabine 850 mg/m2, twice daily, during the RT days. Patients underwent surgery 6–8 weeks after completion of CRT. Information was collected for patient characteristics, treatment response, and acute and late toxicities. Grade 3/4 (G3+) toxicities occurred in 11.1% of patients (4/36). Sphincter preservation rate was 85.2% (23/27). Five patients (14.3%) achieved pathological complete response. Tumor, nodal, and ypT0-2N0 downstaging were noted in 60% (21/35), 69.6% (16/23), and 57.1% (20/35). Tumor regression grade 2~4 was achieved in 28 patients (80%). After a median follow-up time of 35 months, the most common G3+ late morbidity was ileus and fistula (5.7%, 2/35). The study showed that capecitabine plus helical tomotherapy with an SIB is feasible in treatment of LARC. The treatment modality can achieve a very encouraging sphincter preservation rate and a favorable ypT0-2N0 downstaging rate without excessive toxicity.

Carcinoembryonic antigen in monitoring of response to cetuximab plus FOLFIRI or FOLFOX-4 in patients with metastatic colorectal cancer.

First-line treatment of metastatic colorectal cancer with combinations of cetuximab and irinotecan-based or oxaliplatin-based chemotherapy has shown promising efficacy. The clinical response to such treatment is generally assessed by tumor measurement through imaging. This study was performed to evaluate the correlation between serial changes in imaging results and carcinoembryonic antigen (CEA) levels. In 64 patients with metastatic colorectal cancer receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy we retrospectively analyzed the relationship between changes in serum CEA and changes in imaging results throughout the treatment course. Response in terms of serum CEA change was defined as a >/=50% drop in CEA level for more than 4 weeks. The sensitivity and specificity of serum CEA changes after targeted chemotherapy in relation to imaging results were 80.5% (33/41) and 73.9% (17/23), respectively, with a diagnostic accuracy of 78.1% (50/64). The progression-free survival time of responders assessed by serum CEA change was significantly longer than that of nonresponders (p=0.0091). Our results highlight the importance of serum CEA monitoring in assessing the response to targeted chemotherapy and in predicting the prognosis of patients with metastatic colorectal cancer.

Adult Intussusception Secondary to Lymphangioma of the Cecum: A Case Report

We report the case of a patient with ileocolic intussusception caused by cecal lymphangioma. A 45‐year‐old man visited our hospital with a 2‐month history of frequent episodes of watery diarrhea (≥ 5 times/day) and intermittent abdominal pain. A cecal submucosal tumor with mucosal ulceration and partial obstruction of the colonic lumen was identified by colonoscopy. He was admitted to our hospital 2 days later due to aggravation of his abdominal pain. Physical examination revealed tenderness over the right abdomen with no peritoneal signs. A double‐contrast lower gastrointestinal series showed a right‐side colonic lesion with indentation and a peripheral, beak‐like sign. Abdominal computed tomography scanning revealed an intra‐abdominal mass with the characteristic sausage sign, highly suggestive of intussusception. The patient subsequently underwent right hemicolectomy. The final diagnosis was ileocolic intussusception with cecal lymphangioma, which was confirmed by histopathology. He had an uneventful recovery with follow‐up in our hospital. This case highlights the possibility of colonic lymphangioma as the leading point of adult intussusception, and this should be taken into consideration as a possible diagnosis in this uncommon clinical condition.

Successful Management of Perforated Duodenal Diverticulitis With Intra-abdominal Drainage and Feeding Jejunostomy: A Case Report and Literature Review

We report the clinical experience of one patient with perforated duodenal diverticulitis who was successfully treated by intra‐abdominal drainage and feeding jejunostomy. A 53‐year‐old male patient visited our hospital due to acute onset of abdominal pain and distension. Physical examination revealed tenderness over the epigastric area and right‐lower quadrant of the abdomen without obvious rebound tenderness or muscle guarding. Duodenal diverticulitis with a retroperitoneal abscess was identified by abdominal computed tomography scan. Surgical intervention was performed after the failure of conservative treatment. The operative findings were compatible with perforated duodenal diverticulitis, and intra‐abdominal drainage of retroperitoneal abscess with simultaneous feeding jejunostomy was undertaken. The patient was doing well at the 4‐month postoperative follow‐up visit. We suggest the use of a conservative operative method, as opposed to conventional diverticulectomy and duodenorrhaphy, as an alternative approach for the management of this disorder, especially when conservative treatment has failed.

FOLFIRI combined with bevacizumab as first-line treatment for metastatic colorectal cancer patients with hyperbilirubinemia after UGT1A1 genotyping.

Objective: To report a metastatic colorectal cancer patient with hyperbilirubinemia treated with a combination of bevacizumab and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) using uridine diphosphate glucuronosyl transferase (UGT1A1) genotyping. Clinical Presentation and Intervention: A 46-year-old male was diagnosed with rectosigmoid colon cancer with liver metastases and hyperbilirubinemia presenting with severe jaundice. UGT1A1 genotyping was used before therapy to ascertain whether genotype-adjusted dosages of irinotecan plus bevacizumab could alleviate the toxicity. Then, the patient was treated with FOLFIRI. Conclusion: The FOLFIRI regimen was successfully used in this patient without concerns regarding toxicity.