Cheng-Chou Lai

Preoperative carcinoembryonic antigen elevation in colorectal cancer.

UNLABELLED BACKGROUND /AIMS: The aim of this study was to calculate the prevalence of elevated carcinoembryonic antigen (CEA) among colorectal cancer (CRC) patients and to evaluate the prognostic value of preoperative serum CEA levels in them. METHODOLOGY Between 1995 and 2005, 8,861 consecutive patients were enrolled from a prospective database. CEA =5ng/mL was defined as elevated CEA. RESULTS In the multivariate analysis, elevated preoperative CEA correlated with higher ages, circumferential tumors, colon tumors, large tumors, liver metastasis and high-stage (AJCC) tumors. After a 44-month median follow-up, elevated CEA was found to be an independent prognostic factor (odds ratio = 1.61) for overall survival in all 4 stages of the disease. The survival among patients with stage I tumors and elevated CEA (5-year survival rate = 74.7%) was not greater than that among patients with stage II tumors and no CEA elevation (5-year survival rate = 80.8%). CONCLUSIONS Elevated preoperative CEA correlated with a higher age, circumferential tumors, colon tumors, large tumors, liver metastasis, and high-stage (AJCC) tumors. Elevated preoperative CEA indicates a potential poor prognosis even in early stage tumors. This poorer prognosis in the patients with stage I tumors and elevated preoperative CEA was not cancer specific.

Neuroendocrine Carcinomas of the Colon and Rectum: Result of a 15-year Experience

Purpose. The experience of the uncommon malignancy, neuroendocrine carcinomas of the colon and rectum with emphasis on the pathology and clinical characteristics at a single hospital was reviewed. Methods. Of more than 11,000 colon or rectal cancers removed from July 1992 to June 2007 at Chang Gung Medical Center in Taipei, 11 cases diagnosed as colon or rectal neuroendocrine carcinoma were evaluated. Pathology was reviewed by a single pathologist. Medical records were retrospectively reviewed and patients were analyzed in terms of clinicopathologic and demographic characteristics including neuroendocrine type, tumor location, tumor stage, responses to treatment (operative procedure, chemotherapy or radiotherapy), metastases, and survival. Results. Five patients had distant metastasis at the time of diagnosis. Palliative chemotherapy or radiotherapy did not seem to offer a modest improvement in survival for these patients, with an overall survival of less than 11 months after diagnosis. Lymph node metastasis was found in 75%, and the distant metastasis in 45% of the 11 patients at the time of diagnosis. Overall survival rates for six-month, one-year, and three-year survival were 73 percent, 45 percent, 20 percent, respectively. These findings are in accordance with other publications, which demonstrate that the neuroendocrine carcinomas behave aggressively and are associated with worse prognosis than that of conventional adenocarcinomas of the same stage. Unexpectedly, improved results were found for two stage IIA and IIIB rectal small cell neuroendocrine carcinoma patients administered with adjuvant chemotherapy treatment with cisplatin and etoposide at our hospital. They were alive without evidence of disease at more than 10 years after treatment. Conclusions. Neuroendocrine malignancies are rare but behave aggressively in the colon or rectum, accounting for less than 0.1 percent of all colorectal cancers at our institution. Aggressive adjuvant chemotherapy with cisplatin and etoposide might offer a better chance of long-term survival for patients with stage Ⅱ and Ⅲ neuroendocrine carcinomas in the colon and rectum, which deserves further investigation.

Impact of Diabetes Status on Long Term Oncological Outcome of Stage II Colorectal Cancer

目的 糖尿病與大腸直腸癌有相似的飲食及生活因子。目前許多研究均顯示糖尿病病患有較高的大腸直腸癌發生率及較差的總存活率，但是長期存活率及癌症相關存活率的研究卻相對有限且無一致的結論。方法 挑選本院1999 年至2002 年第二期大腸直腸癌接受根除性切除但排除接受放射治療之病患。比較糖尿病及非糖尿病病患之臨床病理表現、長期總存活率及癌症相關存活率，另外則比較不同糖尿病治療方式之癌症相關存活率之異同。結果 在大腸直腸癌病患中，罹患糖尿病的病患有較高的年齡、BMI、慢性腎衰竭 (19%vs. 7.5%, p ＜ 0.001)、心肌梗塞 (16.7% vs. 5.7%, p = 0.043)、心衰竭病史 (4.8% vs. 1.2%, p= 0.008) 及癌胚抗原數值 (CEA ＞ 5 ng/ml, 55.2 vs. 33.6%, p ＜ 0.001)。兩組間總體存活率並無顯著差異，但糖尿病病患比非糖尿病病患有顯著較高的5 年癌症相關存活率 (91%vs. 81%, p = 0.025) 及3 年疾病無復發率 (88% vs. 78%, p = 0.015)。在多變數分析中排除metformin 使用及其他因子後糖尿病仍有顯著較低之疾病復發率風險 (HR = 0.192, p =0.023)，然而多變數分析中糖尿病之癌症死亡率風險卻達邊緣性統計顯著 (HR = 0.258, p= 0.064)。結論 糖尿病在第二期大腸直腸癌病患中雖有較高的癌胚抗原值，但排除metformin 使用後糖尿病對於第二期大腸直腸癌之癌症預後為明顯保護因子。

Reasonable Follow Up Interval of Colonoscopy for Resected Stage I Colorectal Cancer Patient

目的 目前針對第一期大腸癌術後的病人，對於追蹤的準則並沒有統一的共識。在我們的研究中，我們嘗試著去尋找關於異時性大腸癌的嚴重程度的危險因子，以及合理的大腸鏡追蹤時間間格。方法 從1995 年1 月到2015 年12 月，在台灣林口長庚醫院總共有17025 個病人被診斷大腸癌，其中有2258 位病人是第一期並且接受治癒性手術。在之後的追蹤裡，我們總共發現了31 個病人有異時性大腸癌做進一步的分析。結果 在我們的資料庫裡，異時性大腸癌的嚴重度跟家族癌症史、年齡、性別、合併症如高血壓心臟病及糖尿病、第一次切除大腸癌時的CEA 數值、切除方式、T1 或T2、以及原始大腸癌的位置沒有統計學上顯著的相關。結論 大腸鏡追蹤的時間間格跟異時性大腸癌的嚴重程度有顯著相關，並且我們算出一條回歸曲線，根據這條曲線方程式，我們可以預測如果預期在發現異時性大腸癌時仍在可治癒的程度 (第三期以內)，合理的大腸鏡追蹤間格為75 個月。

Neoadjuvant Long Course CCRT Significantly Increases Disease Free Survival among Pathological Stage III Rectal Cancer Patients as Compared to Short Course RT Alone

目的 對於局部晚期直腸癌的病患，為了達到更好的局部控制及存活率，無論是術前短程放射治療或是長程同步放化療皆被使用中。然而，如何選擇這兩個治療方法仍無定論。方法 我們蒐集了2002 年1 月1 日至2006 年12 月31 日於林口長庚醫院診斷為局部晚期直腸癌的病患，所有病患皆接受完整術前短程放射治療或是長程同步放化療並接受根除性手術，術後追蹤日期至2009 年12 月31 日。變異項目如病患的性別、年齡、術前CEA 濃度及腫瘤位置皆被收集分析。總生存率，無病生存率，局部復發率和遠處轉移率也由統計分析比較。結果 在臨床病理特徵方面，腫瘤位置是短程治療及長程治療唯一的差異項 (低位直腸63.4% vs. 81.0%, p = 0.049)。針對淋巴結轉移與否的次族群分析存在許多統計上的差異。對於沒有淋巴結轉移的次族群，短程治療有較好的總生存率 (五年存活率89.3% vs. 62.2,p = 0.009)。對於有淋巴結轉移的次族群，長程同步放化療則有較好的無病生存率 (五年存活率27.8% vs. 64.7%, p = 0.018)，較低的遠處轉移率 (Metastasis free rate 26.8% vs.76.5%, p = 0.003) 及趨向有較好的總生存率 (p = 0.059)。對於局部復發率，兩者並無顯著差異 (83.0% vs. 87.5%, p = 0.557)。結論 基於我們的研究，對於中低位直腸癌且有淋巴結轉移的病患，為了達到更好的無病生存率，術前長程同步放化療是可以考慮的治療方式。對於沒有淋巴結轉移的病患，術前短程放療則與術前長程同步放化療有同樣的疾病控制。

Worse Survival in Rectal Cancer Patients with Preoperative Radiotherapy Compared to without Radiotherapy in Same Postoperative Pathologic pN1 Classification

Purpose. In this study, we compared the rectal cancer patients with and without preoperative radiotherapy, to evaluate the change of pathologic characteristics and prognosis. Patients and Methods. From 2002 to 2007, the cases of primary rectal cancer and receiving curative resection were selected. Totally, there were 1544 cases including 239 cases preoperative radiotherapy enrolled. Results. After preoperative radiotherapy, the significant change of pathologic characteristics included more percentage of smaller tumor size, ulcerative morphologic type and poor differentiation histological grade in patients with preoperative RT than those of not (all p ＜ 0.05). The recurrent incidence, 3-year disease-free and 5-year cancer-specific survival rates of patients with preoperative radiotherapy vs. no radiotherapy were 60.0 vs. 42.8% (p = 0.04), 45.0 vs. 59.7% (p = 0.04) and 47.6 vs. 64.3% (p = 0.056) in pT4 patients, and were 48.1 vs. 30.7% (p = 0.01), 52.8 vs. 72.9% (p ＜ 0.01) and 51.8 vs. 75.1% (p = 0.03) in pN1 patients, respectively. After curative resection of tumor, the prognosis of pN1 patients with preoperative radiotherapy was worse than those without radiotherapy. There was no difference in survival rate of pN0 and pN2 classification between the patients with and without preoperative RT. Conclusion. Downstage effect of preoperative RT has beneficial impact on long term survival of patients with rectal cancer, but our findings showed that the worse survival rates of pathologic ypN1 classification of patients with preoperative RT then pathologic pN1 classification without preoperative RT. This may be resulted from change of characteristics of cancer cell behavior or insufficient response to show benefits. Further study is necessary to more precisely select suitable patients for receiving preoperative RT.

Is the Tegafur/uracil and Leucovorin Adjuvant Chemotherapy Overused in Low-risk Group Stage II Colorectal Cancer Patients?

Purpose. Colorectal cancer is one of the most common cancers and the third leading cause of cancer-related death in Taiwan. Because of the nationwide biennial fecal immunochemical screening, the number of colorectal cancer cases detected at an early stage is increasing. According to the National comprehensive cancer network (NCCN) clinical practice guidelines, adjuvant chemotherapy is suggested for patients with high-risk group stage II colorectal cancer; research in the low-risk group stage II colorectal cancer has been less specific. We aimed to review our hospital database to evaluate the effect of uracil-tegafur (UFT) and leucovorin adjuvant chemotherapy on low-risk group stage II colorectal cancer patients. Materials and Methods. Between January 2004 and August 2009, 1273 stage II colorectal cancer patients underwent standard curative operations at the Linkou and Keelung Branch of Chang Gung Memorial Hospital in Taiwan. After excluding the patients with early recurrence within 6 months after the operation, and those who received intravenous adjuvant chemotherapy, the remaining 1107 patients were enrolled in the study. After analyzing the pathological and clinical characteristics of the patients, 515 were identified to have low-risk group stage II colorectal cancer. All patients in this group were followed up for at least 5 years postoperatively or until the date of patient death. Statistical analysis was performed with SPSS ver. 20. Results. In our database, patients in the high-risk group (n = 592) had significantly worse overall survival and 5-year disease-free survival compared to those in the low-risk group (n = 515). In the low-risk group stage II colorectal cancer patients, 70 patients received UFT and leucovorin adjuvant chemotherapy, while 445 patients did not receive adjuvant chemotherapy. Comparing the two groups revealed that UFT and leucovorin adjuvant chemotherapy did not improve the overall survival or 5-year disease- free survival in the low-risk group stage II colorectal cancer patients. Conclusion. Our data showed that low-risk group stage II colorectal cancer patients who received the UFT and leucovorin adjuvant chemotherapy might be overtreated. We should aim to avoid exposing these patients to the side effects of unnecessarily administered chemotherapy, and control its impact on the economy.

Transanal Local Excision Versus Radical Surgery for T1N0 Lower Rectal Adenocarcinoma

Background. The aim of this study was to compare surgical outcomes including survival in T1N0 rectal adenocarcinoma patients undergoing transanal local excision or radical surgery. Methods. We retrospectively reviewed 87 and 176 patients who underwent transanal local excision and radical surgery, respectively, for T1N0 rectal adenocarcinoma without neoadjuvant chemotherapy or radiotherapy between May 1995 and January 2013. Results. The mean age, sex distribution, and carcinoembryonic antigen level were similar between the 2 groups. The mean duration of hospital stay was 4.66 days in the local resection group and 12.32 days in the radical surgery group (p＜0.05). The overall survival rate at 5 years was 91% in the local resection group and 83% in the radical surgery group (p=0.928). The disease-free survival rate at 5 years was 87% in the local resection group and 93% in the radical surgery group (p=0.037). The disease- free survival rate at 5 years in the local resection group was significantly poorer than in the radical surgery group. Conclusion. Local excision is an alternative method of treatment for early lower rectal adenocarcinoma. With selection, the oncologic outcomes for local excision are similar to that of radical surgery. Advantages of local excision include early bowel function recovery, shorter hospital length of stay, lower morbidity, and avoidance of colostomy.

Prognosis of Stage IIIA Colorectal Cancer Patients with or without Postoperative Adjuvant Chemotherapy

Introduction. The new definition of stage IIIA colorectal cancer (CRC) was introduced in the Seventh Edition of the American Joint Committee on Cancer (AJCC 7th). Because the outcomes of patients with stage IIIA CRC are not worse than those of patients with stage II disease, we evaluated whether chemotherapy would also benefit this group of patients.Patients and Methods. Patients who received curative surgery and were diagnosed with stage IIIACRC between 1995 and 2006 were enrolled and analyzed.Results. Total 149 patients diagnosed stage IIIA colorectal cancer were enrolled. In these patients, 31 were T1 stage with only one found recurrence. Whether adjuvant therapy performed or not, there was no significant meaning for their prognosis. For T2 patients, higher recurrence rate was noted with N1b patients. Though no statistical meaning achieved, for those without chemotherapy, mucinous type, insufficient lymph node exam, higher recurrent rate were noted. The new AJCC 7th made difference in T1N2a group. Though only 5 patients collected in this study, none was found tumor recurrence, and the result was compatible with the new staging system.Conclusion. Adjuvant therapy is recommended for stage IIIA CRC patients with T2 disease. However, adjuvant chemotherapy may not be beneficial for stage IIIA CRC patients with T1 disease.

Adequacy of Lymph Node Retrieval in Laparoscopic Surgery for Colorectal Cancer

Purpose. The aim of this study was to compare laparoscopic colorectal cancer resection to conventional colorectal cancer resection with regard to the number of lymph nodes retrieved. Methods. Between November 2007 and October 2009, we retrospectively investigated 1252 patients with colorectal cancer who underwent curative resection at Lin Kou Chang Gung Memorial Hospital. The patients were divided into two groups: those who underwent laparoscopic surgery and those who underwent open surgery. The clinicopathologic variables of two groups were analyzed and compared, including age, gender, body mass index (BMI), tumor location, tumor size, neoadjuvant therapy, tumor stage, and the number of lymph nodes retrieval. Results. Group 1 comprised 1091 patients who underwent open surgery, and group 2 comprised 161 patients who underwent laparoscopic colorectal surgery. There was no difference in age, gender, BMI, tumor location, and tumor stage between the two groups. However, there was a significant difference in tumor size between group 1 and group 2 (4.5±2.1 vs. 3.8±1.7 cm, p＜0.001). Further, there was no significant difference in the number of lymph nodes retrieved between group 1 and group 2 (27.2±14.5 vs. 25.8±14.2, p=0.248). Conclusion. For selected patients, lymph node retrieval during laparoscopic colorectal cancer resection was adequate in the surgical cases at Lin Kou Chang Gung Memorial Hospital. However, long-term follow-up examinations are required to show if there is any difference in local recurrence and survival between patients who undergo laparoscopic colorectal cancer resection and those who undergo conventional colorectal cancer resection.