Carbohydrate Antigen 19-9 in Colorectal Cancer
Colorectal Cancer4,972 patients who underwent surgery for primary CRC between January 2004 and December 2015 at Seoul National University Hospital were retrospectively reviewed. CA19-9 is a valuable prognostic and diagnostic marker for CRC when used adjunctively with CEA and can be a supplementary marker with CEA to improve sensitivity, especially with elevated preoperative CA19-9.
A Novel Patent Platform of Detection of Circulating Tumor Cells to Early Detect Colorectal Cancer...
Colorectal Cancer (CRC)The best strategy to prevent colorectal cancer (CRC) death lies in early detection and early treatment at the local disease status of tumor. After curative resection of tumor, there are about 5~10% of stage I, 20~30% of stage II and 40~50% of stage III patients suffering metastasis during subsequent follow-up periods. Although carcinoembryonic antigen (CEA) is the most widely used biomarker for postoperative monitoring of recurrence on asymptomatic patients, it is difficult to use CEA as biological marker to identify the population with high recurrent risk in patients with early-stage cancer because lower than half of patients with early-stage cancer do not have CEA elevation. For improving the survival of patients with early-stage CRC, we need effort to search more useful biological markers to predict the risk of tumor recurrence and to select out patients with high recurrent risk to receive preventive adjuvant therapy. Circulating tumor cells (CTCs) in the blood play an essential role in cancer metastasis. Hence, the detection of CTCs and subsequent analysis can potentially revolutionize the cancer care ranging from screening, diagnosis, monitoring, to drug selection and so on. In the past decade, many methods using magnetic beads (CellSearch), filtration (RareCelletc), or flow cytometry have been developed but all of them have the shortcomings from low sensitivity, low purity, to unable to retrieve cells for downstream molecular analysis and cell culture. Recently, a biomimetic affinity based microfluidic platform has overcome abovementioned technical challenges. Importantly, by using only 2 ml of peripheral blood, Sinica's team has shown that the enumeration of CTCs increases with the CRC disease progression, where the mean CTC counts are 3, 15, 29 and 60 per ml for the stages I, II, III and IV, respectively. The results imply that monitoring CTC enumeration serially may serve as a prediction marker to identify the CRC patients with high probability of recurrence. The aims of this study are toestablishing CTC platform standard operation protocol (SOP) that leads to certification of ISO 13485 and to establish CTC criteria and evaluate its prediction power of early detection of colorectal cancer recurrence.
Incidence of Venous Thromboembolism Following Surgery in Patients With Colorectal Cancer
Symptomatic Venous ThromboembolismAsymptomatic Venous ThromboembolismVenous thromboembolism (VTE) has harmful effects on morbidity and mortality of cancer patients. In Western VTE guidelines, all solid cancer patients receiving abdominal major surgery are strongly recommended to receive pharmacologic prophylactic anticoagulation such as low molecular weight heparin (LMWH) in the perioperative periods. These recommendations are based on the high incidence of postoperative VTE development in Western cancer patients. However, there have been many cumulative data about the effect of different ethnicity on the VTE development and more and more investigators and clinicians admit that Asian ethnicity has lower incidence of VTE than Western ethnicity. Therefore, it may not be advisable to apply Western guidelines as it is to the clinical situation of Asian cancer patients. Although colorectal cancer (CRC) is one of the common cancers and the incidence is rapidly increasing in Asia, there have been few prospective data on the incidence of VTE development during the postoperative period in Asian CRC patients. To our knowledge, there have been a few small-sized prospective studies in Asia and thus clear conclusions could have not been drawn based on those studies. Most Korean colorectal surgeons think that the incidence of postoperative VTE development is very rare based on their own clinical experiences. They also have much concern about the complications such as bleeding that might be caused by routine use of pharmacologic thromboprophylaxis during the perioperative periods. Therefore, in most clinical situation, many Korean colorectal surgeons do not perform perioperative pharmacologic thromboprophylaxis using LMHW. Considering these clinical situations in Asia including Korea, the uncritical acceptance of Western guidelines may be inappropriate. The necessity of pharmacologic thrombo-prophylaxis can be answered only from our own prospective study on the incidence of postoperative VTE development after CRC surgery. Moreover, current surgical trend in cancer patients is minimally invasive approach such as laparoscopic surgery. However, the necessity of pharmacologic thromboprophylaxis in patients receiving laparoscopic cancer surgery has not been evaluated even in Western countries. Western guidelines also cannot exactly answer whether pharmacologic thromboprophylaxis is really necessary in cancer patients receiving laparoscopic cancer surgery. On above backgrounds, this study was designed.
The Immunoscore as a Prognostic Marker for Patients With a Colorectal Cancer
Colorectal CancerSurgical Resection of the Colorectal TumorMedical and Scientific Background: Colorectal cancers (CRC) are the leading cancers in both genders. This cancer is of prognostic severity. The prognosis of this cancer has not been significantly improved. The treatment of colonic cancer is primarily based on surgery. Adjuvant chemotherapy is proposed for metastatic cancers (stages III and IV). However nearly 30% of patients with localized cancer (stage II) will present a recurrence. Despite intense research efforts, no markers of sufficient prognostic value (independent of TNM) are available to identify this group of patients and justify intensified therapy. The natural history of cancer involves interactions between the tumor and the immune system of the host. The immune infiltration at the tumor site may be indicative of host response. We showed that the density of intratumor memory T cells (CD45RO) and cytotoxic T cells (CD8) in tumor regions (the core and the invasive margin) influenced the occurrence of early events of metastasis (tumor emboli) and was strongly associated with prognosis of patients with CRC (Pagès et al, NEJM-2005). This immune criterion was a better predictor of survival than the "gold standard" histoprognostic data of tumor invasion (T stage and N) and allowed to identify a group of patients at high risk of recurrence (*2). The availability of this immune criterion in clinical practice could improve the prognostic assessment of patients and better guide the therapeutic. A dedicated platform has been implemented in our hospital to speed up the transfer of this immune investigation into the clinic. The investigation takes into account the density of immune cell populations in tumor regions (the core and the invasive front of the tumor). This methodology has been validated for the markers CD45RO, CD3 and CD8 and leads to the creation of an immune score ("immunoscore" ranging from IO to I4). We validated the prognostic impact of the immunoscore in a retrospective series of 250 colorectal cancers. The main objective of this multicentric prospective clinical study is to assess in clinical practice the "immunoscore" and measure its prognostic value. The cohort study will include 400 patients with CRC stage I to IV (6 centers for inclusion; Paris-HEGP, Dijon, Bobigny-Avicenne, Besancon, Poitiers, Rouen). Two years of inclusion and a follow-up of 3 years for each patient will be performed (co-financing for data collection during the 4th and 5th year planned). For each patient, the pathologist of the center will send to the immunomonitoring platform of HEGP tissue sections from a paraffin block containing the tumor regions. The investigations will combine a step of immunostaining for CD3, CD8, and CD45RO (Ventana automate) markers, high-resolution scanning of the stained slides and quantification of digital images by an imaging module developed by our group from the program of Developer XD of Définiens company. The immunoscore will be calculated and the score will be correlated to the clinical data for the relapse and the survival. The secondary objective of this program is to evaluate the prognostic performance of the immune infiltrate on the biopsies performed for diagnostic purposes. This study will be conducted on patients of the cohort whose biopsies were performed in the same hospital than surgery and whose samples are available in pathology laboratories involved (representing 50% of cases). For the same patients will be conducted a genetic investigation of the tumor to assess the MSI status, the presence of a K-Ras and BRAF mutations. This investigation will be performed on tumor sections from the same tumor block selected for the immunohistochemical analyses. The sections will be processed by the Department of Biology, Hôpital Européen Georges Pompidou. The prognostic performance of the immune investigations performed on tumor sections and biopsies will be compared to that of genetic features of the tumor. Finally, a questionnaire will be sent every six months along the monitoring of the patients to obtain information concerning (i) the emergence of an immune disorder (such as allergy, autoimmunity, inflammatory process) and (ii) the psychological status of the patients. The potential impact of such parameters during the course of the disease on the prediction of the relapse and survival obtained with the immunoscore performed at the time of surgery will be evaluated. Expected results : This prospective study is an indispensable step for the clinical validation of the prognostic value of the immunoscore. The secondary objectives should help to precise the benefit of a concomitant analysis of the biopsy, the genetic features of the tumor. The questionnaire should help to identify the clinical parameters to track along the monitoring
NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
Colorectal CancerSurgical resection is the best treatment option for colorectal cancer. Despite this radical approach, recurrences within five years are still common. Several authors have proposed that the immunosuppressive state surrounding the perioperative period was a key element of cancer cells spread. A particular subtype of T lymphocytes, the Natural Killer cells (NKs), is the main actor of the innate immune system. Several factors of the perioperative period can reduce activity of NKs such as stress, pain, opioids and general anaesthetics. Lidocaine is a local anaesthetic that has been widely used intravenously for abdominal surgeries. Intravenous lidocaine has been shown to reduce pain scores, morphine consumption, ileus time and length of stay in major colorectal surgeries. It reduced markers of systemic inflammation as well. The authors hypothesize that the use of intravenous lidocaine during laparoscopic surgeries for colorectal cancer resection will preserve NKs activity.
Mutational Profiling in Colorectal Tumors to Determine Its Role in the Diagnosis, Prognostic Significance...
Colorectal CancerThe aim of this study is to investigate mutational changes occurring in colorectal tumors, from benign polyps, malignant cancer and metastatic tumors. The investigators also plan to establish the clinical correlation, emphasizing on aspects such as the diagnosis and prognosis of disease and the specific treatment outcome. For the purpose, the investigators plan to obtain specimens from patients with colorectal tumors to extract DNA material. The specimens include tissues from either primary (mostly endoscopic biopsies specimens) or metastatic tumors (obtained from sonogram or other imaging modalities guided biopsy), as well as other humors including blood (for serum), malignant ascites, pleural effusions or other body fluids that could be related to CRCs. These patients would receive detailed explanations with regard to the investigations before signing IRB consent. At the initial stage, Wanfang Medical Center would be the only medical institution where endoscopic specimens would be collected. The project would eventually be extended to the Taipei Medical University Hospital and Shuan-Ho Hospital.
Influence of Neoadjuvant Therapy on the Resectability of Hepatic Metastases From Colorectal Cancers...
Colorectal CancerMore and more colorectal surgeons believe that surgical resections of hepatic metastases from colorectal cancer is the only chance for cure of patients. The five-year survival for patients with hepatic metastasis from colorectal cancer after surgical resection is approximately 30 %. However, most hepatic metastases from colorectal cancer were inoperable. With the progress of chemotherapy, for example, the combination of the 5-Fu, leucovorin, and oxaliplatin, some surgeons advocated that approximately 20% of inoperable liver metastases will be converted to operable case, thus providing the long-term survival for patients. In this study, we made a phase Ⅱ clinical trial regarding the use of the Folfox-4 regimens in the neo-adjuvant treatment of inoperable hepatic metastases. Our aims is to evaluate the tumor response rate for this regimen, the rate of resectability of liver metastases, progression free survival and overall survival of patients. In addition, the difference between the reports from Western and Oriental countries will be analyzed. We believe this study will provide new perspectives regarding the most beneficial treatment modalities for the patients with hepatic metastases from colorectal cancer.
Comparison of Laparoscopic Colectomy Versus Open Colectomy for Colorectal Cancer: … A Prospective...
Colorectal CancerThe laparoscopic colectomy has been enthusiastically used by many colorectal surgeons in Taiwan, Japan, Europe, and USA, for around 10 years. Further clarification of the controversies cited above will be based on the evidence-based medicine, i.e., the randomized, well-controlled, prospective clinical trials. Actually, a handful of randomized prospective data regarding the laparoscopic colectomy has been appeared in USA and Europe. However, we still do not have this kind of data in Taiwan, and therefore this study is important and mandatory. In this project, we assumed that a difference in cancer-related survival of less then 15% between treatments indicates an equivalent efficacy. Assuming a 70% 5-year, cancer-related survival of stage II and III colorectal cancer patients in the open colectomy group, a minimum of 100 patients per group was required to showed that both surgical techniques were equivalent with an α-level of 0.20 and a β error of 0.05. Only patients with stage II and III disease undergoing curative resection will be enrolled onto this study. The patients will be randomly allocated to either treatment group by block randomization method. Postoperatively, the patients will be prospectively evaluated regarding the following parameters including operative stress, such as erythrocyte sedimentation rate, serum interleukin-6, WBC counts and classification, CD-4 to CD-8 ratio, postoperative life quality, such as wound size, degree of pain, time to have flatus passage and feeding, time to resume daily activity and work, and the oncological outcomes, such as recurrence patterns of tumor, and 5-year patient survival. The evaluation of above-mentioned parameters will be single-blindly done by our research assistant, who has no idea of both surgical techniques. We hope this study will promote the level of surgical research in Taiwan.
Colorectal Cancer Immunomonitoring Combined With Radiofrequency ablatIon
Colorectal CancerRadiofrequency ablatIonThe primary objective of the study aims to compare soluble CD154 (CD40L) levels before and after radiofrequency ablation (RFA) in patients with colorectal cancer (CRC) liver metastases. The secondary objectives aims: to compare soluble CD154 (sCD40-L) levels before and after treatment by RFA or surgery alone in patients with CRC liver metastases; to study the feasibility and reliability of soluble CD154 (sCD40-L) levels to detect and quantify the induction of immun response in CRC liver metastases patients after RFA; to study the impact of surgery on plasma soluble CD154 levels; to study association between CD154 expression level before and after RFA in CRC liver metastases patients and relapses rate at 1 year.
Outcomes of Patients Who Had an Incomplete Colonoscopy After a Positive Fecal Immunological Test...
Colorectal CancerIn France, colorectal cancer (CRC) is the second leading cause of cancer death. Its organized screening (Organized ColoRectal Cancer Screening: DOCCR), now carried out by immunological test for occult blood in the stool, has proven its effectiveness. When the immunological test is positive, the Haute Autorité de Santé recommends a total colonoscopy. In 5 to 10% of cases, this colonoscopy is incomplete. The renewal of the endoscopic procedure or the performance of additional second-line examinations are then recommended. At present, however, the respective place of second-line examinations to be performed in this situation is not the subject of specific and validated recommendations.