Treatment Of Early-stage Colorectal Cancer Research Articles

Current Status of Diagnosis and Treatment of Colorectal Cancer in Asian Countries: A Questionnaire Survey

Introduction: Diagnostic and therapeutic methods for colorectal cancer (CRC) have advanced; however, they may be inaccessible worldwide, and their widespread use is challenging. This questionnaire survey investigates the current status of diagnosis and treatment of early-stage CRC in Asian countries. Methods: Responses to the questionnaire were obtained from 213 doctors at different institutions in 8 countries and regions. The questionnaire consisted of 39 questions on the following four topics: noninvasive diagnosis other than endoscopy (6 questions), diagnosis by magnification and image-enhanced endoscopy (IEE) including artificial intelligence (AI) (10 questions), endoscopic submucosal dissection (ESD), proper use among other therapeutic methods (11 questions), and pathologic diagnosis and surveillance (12 questions). Results: Although 101 of 213 respondents were affiliated with academic hospitals, there were disparities among countries and regions in the dissemination of advanced technologies, such as IEE, AI, and ESD. The NICE classification is widely used for the diagnosis of colorectal tumors using IEE, while the JNET classification with magnification was used in countries such as Japan (65/70, 92.9%) and China (16/22, 72.7%). Of the 211 respondents, 208 (98.6%) assumed that en bloc resection should be achieved for carcinomas, and 180 of 212 (84.9%) believed that ESD was the most suitable in cases with a diameter larger than 2 cm. However, colorectal ESD is not widespread in countries such as Thailand, the Philippines, and Indonesia. Conclusion: The promotion of advanced technologies and education should be continual to enable more people to benefit from them.

S242 Observations in Therapy Interventions for Stage III and Stage IV Colon Cancer From 2010 to 2019

Introduction: Colorectal cancer (CC) treatment options range from surgery, radiation therapy, systemic chemotherapy (CH), targeted immunotherapy (IM), or a combination of these. Surgical resection is the standard of care for cases with curative intent. CH is recommended in all cases of stage III cancer after surgery. Combination CH and IM have been FDA approved for use in recent years. With the advent of IM and the major breakthroughs in its curative ability, we intended to assess the shift in treatment of stage III and stage IV CC. Methods: The 2022 National Cancer Database Public Benchmark reports from the American College of Surgeons from 1391 hospitals was utilized. IRB approval was not required as the database contains de-identified information. This study analyzed CC cases with first line course of treatment for AJCC stage III-IV. 15,897 patients in 2010 and 20,060 in 2019 with stage IV cancer were evaluated, respectively. For stage III CC, 20,036 and 21,954 were evaluated in 2010 and 2019, respectively. A two-sample proportion z-test for significance was used. Results: Changes in trends were examined with stage III CC comparing the years 2010 and 2019 [Figure 1b]. Surgery in patients decreased (32.3% vs 29.9%, p< 0.001). Surgery in combination with CH did not change significantly (63.5% vs 64.4%, p= 0.006). CH only also did not change significantly (0.2% vs 0.3%, p= 0.039). IM combined with CH was limited (0% vs 0.1%). However, combination IM, surgery and CH increased use of IM (0.1% vs 1.9%, p< 0.001), and decreased treatment with surgery or CH alone. CH alone was used in 18.6% of cases in 2010 compared to 15.1% in 2019 for stage IV CC (p< 0.001) [Figure 1b]. Surgical treatment decreased over the years from 18.8% to 13% (p< 0.001). Surgery and CH combination also decreased (38.9% vs 19.3%, p< 0.001). In contrast, treatment with IM and CH increased (0.2% vs. 12.7%, p< 0.001). IM in combination with surgery and CH also increased significantly in stage IV CC (0.2% vs 14.4%, p< 0.001). Conclusion: Treatment options between 2010 and 2019 were compared for stage III and stage IV CC. Stage IV CC treatment regimens have changed with increased use of IM and decreased sole use surgery and CH. However, stage III CC treatment regimens have largely been unchanged comparing 2010 to 2019. With the major successes of IM in treatment of early stage CC, there should be more work and studies to support its use in late stage.Figure 1.: a. Stage III colorectal cancer treatment distribution for 2010 and 2019 Figure 1b. Stage IV colorectal cancer treatment distribution for 2010 and 2019

Inherited bowel cancer: a review from a surgeon’s perspective

Colorectal cancer (CRC) is the second most deadly cancer affecting globally. Although most CRCs seen in young adults are sporadic, hereditary cancer syndromes should be considered as an essential factor. Screening for colorectal cancer aids in the early detection and treatment of early-stage CRC; which reduces mortality rates. This review article aimed to present neoplastic and non-neoplastic polyps and their management from a surgeon's perspective while describing screening protocols in high-risk groups. It also highlighted the etiology, clinical features, diagnosis and management of adenomatous polyps and hereditary bowel cancer syndromes like Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), Cowden syndrome (CS), Lynch syndrome (LS) and familial adenomatous polyposis (FAP). The article summarized the importance of these syndromes as a risk factor in colorectal cancer and identifies these as high-risk group patients in colorectal screening protocols. A summary of the management of these risk factors has been described from a surgeon's point of view.

Tips for difficult colorectal endoscopic submucosal dissection

Colorectal endoscopic submucosal dissection (ESD) is now widely performed and firmly established in the treatment of early-stage colorectal cancer. In particular, there have been many studies on difficult cases of colorectal ESD. Difficult cases can be divided into two groups: difficult dissection of the lesions and difficult approach to the lesion. In most cases, a combination of strategies can solve the problem. Challenging lesions such as those in the anal canal and ileum can also be treated from an anatomical perspective. In the rectum, there are no limits to size or circumference. In addition, the indications for ESD in patients without risk of metastasis other than deep invasion are being considered. Therefore, when ESD is performed on difficult lesions, it is necessary to ensure the quality of dissection.

How to Perform a High-Quality Endoscopic Submucosal Dissection

How to Perform a High-Quality Endoscopic Submucosal Dissection

Usefulness of serum opsonic activity measured by chemiluminescence method to assess the invasiveness of colorectal endoscopic mucosal dissection

Endoscopic sub-mucosal dissection (ESD) is considered as a low-invasive treatment for early-stage colorectal cancer, but the degree of invasiveness has not been well investigated. The aim of this study was to evaluate the physical stress due to colorectal ESD based on changes in serum opsonic activity (SOA). SOA was examined by measuring reactive oxygen species (ROS) produced by neutrophils using lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL). Sixty-nine patients were enrolled into the study and examined SOA in the morning of the day of ESD, the next day, and at four days after ESD. The peak height (PH) and area under the curve (AUC) of LgCL showed no significant difference between the day and the next day, whereas the PH and AUC for LgCL were significantly higher four days after ESD than on the day of ESD (p < .05). In contrast, the PH and AUC of LmCL showed no significant changes during the ESD perioperative period. This difference suggests that SOA changes during the colorectal ESD perioperative period involved minor increases in the production of lower-toxicity ROS. This finding supports the position that ESD is a technique that does not generate a great deal of physical stress. On the other hand, a significant increase in SOA at four days after colorectal ESD suggests that care is needed with postoperative management even after the patient has started to eat meals again.

Survivorship care for early‐stage colorectal cancer: a national survey of general surgeons and colorectal surgeons

Few data are available on the optimal long-term care of early-stage colorectal cancer survivors, termed survivorship care. We aimed to investigate current practice in the management of patients following treatment for early-stage colorectal cancer. We performed an internet survey of members of the American Society for Colon and Rectal Surgeons about several aspects of long-term care, including allocation of clinician responsibility, challenges with transitions to primary care physicians (PCPs), long-term care plan provision and recommended surgical follow-up duration. Overall, 251 surgeons responded. Surgeons reported taking primary responsibility for managing adverse surgical effects (93.2%) and surveillance testing (imaging and laboratories 68.6%, endoscopy 82.4%). Barriers to PCP handoffs included patient preference for surgical follow-up (endorsed by 76.6%) and inadequate communication with PCPs (endorsed by 36.9%). Approximately one-third of surgeons routinely provide survivorship care plans to PCPs; surgeons who received formal survivorship training were more likely to do so compared to those without such training (OR 3.29, 95% CI 1.57, 6.92). Although only 20.4% of surgeons follow their patients beyond 5years, individuals in practice longer were more likely to continue long-term follow-up than those with ≤10years of experience. This is the largest survey of surgeons regarding long-term management for early-stage colorectal cancer and highlights the potential for improved coordination with PCPs and increased implementation of survivorship care plans.

Endoscopic non-ablative fractional laser therapy in an orthotopic colon tumour model

Colorectal cancer is one of the leading causes of cancer-related deaths. Although several therapeutic management strategies are available at the early colon cancer stages, such as endoscopic mucosal or submucosal dissection, associated complications often include bleeding or bowel perforations. As an alternative approach, we investigated endoscopic non-ablative fractional laser (eNAFL) irradiation as a minimally invasive therapeutic modality for the treatment of early-stage colorectal cancer. By implanting SL4-DsRed colon cancer cells into the colons of the C57BL/6 mice, we developed an orthotopic colon tumour mouse model and demonstrated the early-stage tumour growth delay following the eNAFL irradiation. Additionally, we evaluated the temperature changes in the eNAFL-irradiated area using numerical simulations, and induced inflammation using histological analysis. Our results indicate a minimal thermal damage confined to the irradiated spot, sparing the adjacent tissue and alteration in the tumour microenvironment. eNAFL irradiation may be clinically useful as a minimally invasive therapeutic intervention at the early stage of tumourigenesis. In future, an optimal eNAFL therapeutic dose should be determined, in order to increase the efficacy of this approach.

Exploiting a novel miR-519c–HuR–ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment for early stage CRC, adjuvant chemotherapy is usually given to reduce the risk of recurrence after colectomy. Overexpression of a multidrug resistance (MDR) transporter ABCG2 in vitro has been shown to cause resistance to 5-fluorouracil (5-FU) and irinotecan, components of the most commonly adopted regimens for treating CRC. Both anticancer drugs are known ABCG2 substrates. An effective way to predict drug response may provide guidance for better cancer treatment. We investigated the effect of ABCG2 dysregulation on cancer cell sensitivity to chemotherapy using pairs of snap-frozen paraffin-embedded archival blocks of human colorectal cancer tissues and their matched non-cancerous colon tissues from CRC patients. In CRC patients responding to chemotherapy, the tumors were found to have remarkable lower ABCG2 expression than the adjacent normal colon tissues. On the contrary, the tumors from patients not responding to 5-FU-based chemotherapy have higher ABCG2 level than the adjacent normal tissues. The high ABCG2 expression in the tumor is associated with the concomitant overexpression of the mRNA binding protein HuR but a low expression of miR-519c because miR-519c is known to target both ABCG2 and HuR. Further investigation in CRC cell lines revealed that the ABCG2 overexpression was caused by an interplay between miR-519c, HuR and the length of the 3′ untranslated region (UTR) of ABCG2. These parameters may be further developed as useful biomarkers to predict patient response to adjuvant chemotherapy. Besides being predictive biomarkers, the microRNAs and mRNA binding protein identified may also be potential drug targets for modulating ABCG2 to combat resistance in CRC chemotherapy.

Therapeutic strategy in unresectable metastatic colorectal cancer.

While surgery is the cornerstone treatment for early-stage colorectal cancer, chemotherapy is the first treatment option for metastatic disease when tumor lesions are frequently not fully resectable at presentation. Mortality from colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic colorectal cancer is a global treatment strategy, which applies several lines of therapy, salvage surgery, maintenance, and treatment-free intervals. The individualization of cancer treatment is based on the evaluation of prognostic factors for survival (serum lactate dehydrogenase level, performance status), and predictive factors for treatment efficacy [Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status]. The available treatment modalities for metastatic colorectal cancer are chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), anti-angiogenic agents (e.g. bevacizumab), and anti-epidermal growth factor agents (cetuximab, panitumumab). The increasing number of active compounds dictates the strategy of trials evaluating these treatments either in combination or sequentially. Alternative outcomes that can be measured earlier than overall survival are needed to shorten the duration and reduce the size and cost of clinical trials.

Surviving cancer treatment: An investigation of the experience of fear about, and monitoring for, recurrence in patients following treatment for colorectal cancer

Background It is known that many individuals worry about their cancer recurring after colorectal cancer treatment but the significance and specific manifestations of this problem require exploration. Purpose This paper reports upon the research findings of a qualitative study to explain how fears of recurrence can affect individuals recovering from curative colorectal cancer surgery. Methods A longitudinal, grounded theory study was conducted. Sixteen participants who had received curative treatment for colorectal cancer were interviewed on up to four occasions during the 12 months following their surgery, 62 interviews were conducted in total. Results Many participants expressed anxiety about if and when their cancer might return, despite the knowledge that they had had successful treatment for early-stage colorectal cancer. This fear led some to adopt new behaviours in a desire to achieve a more dependable and controllable body. Heightened monitoring and management of the body characterised a state of ‘guarding’ – a concept developed from the data. By contrast, other participants did not perceive the risk of cancer recurrence to be as personally threatening or were able to assume strategies to manage any such concerns and find a sense of resolution to their recovery. Conclusion The nature of an individual’s response to fears of recurrence and consequent impact on their recovery warrants greater clinical consideration. Providing opportunities to openly discuss the possibility of cancer recurrence, assessing individual fears and offering suggestions on possible coping strategies to lessen the associated distress, are essential supportive activities enabling transition to life beyond cancer.

Targeted Therapies as Adjuvant Treatment for Early-Stage Colorectal Cancer: First Impressions and Clinical Questions

The use of adjuvant chemotherapy has improved survival in early-stage colon cancer. Ongoing adjuvant clinical trials are evaluating the addition of targeted therapies to standard chemotherapy regimen. Preliminary results with bevacizumab were disappointing. Also, cetuximab added to chemotherapy does not seem to be better than chemotherapy alone, even in selected wild-type KRAS populations. A better understanding of mechanisms of action of drugs, tumor biology, and predictive biomarkers are needed to design future adjuvant trials.

Targeted Therapies as Adjuvant Treatment for Early-Stage Colorectal Cancer: First Impressions and Clinical Questions

Survival rates for metastatic colorectal cancer (CRC) have increased considerably over the years largely because of the application of optimized chemotherapy regimens. More recently, the addition of the targeted agents bevacizumab, cetuximab, and panitumumab in advanced disease has also demonstrated clinical benefit. Adjuvant chemotherapy is the standard of care in patients with early-stage CRC who are at high risk of recurrence. One challenge is how to apply targeted agents in early-stage CRC. Initial results from the NSABP-08 trial in CRC, the first report of bevacizumab in the adjuvant treatment of solid cancers, are disappointing. Nevertheless, the results of several important phase III trials of targeted adjuvant therapy are awaited. Until then, the use of targeted agents in early-stage CRC cannot be recommended. The identification of biomarkers to select patients who might derive clinical benefit is crucial in determining the full potential of targeted agents in the adjuvant setting. In this review, we discuss the biologic rationale for targeted therapies in early-stage CRC, the current clinical trials, and the clinical challenges facing the success of these agents in the adjuvant setting.

A novel prognostic index in colorectal cancer defined by serum carcinoembryonic antigen and plasma tissue inhibitor of metalloproteinases-1

Objective. The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue inhibitor of metalloproteinases (TIMP)-1 as a prognostic index in patients with primary, curatively resected CRC. Material and methods. Blood samples were collected before surgery from 422 patients with CRC stage I–III (Dukes’ stage A–C). CEA was determined in serum by a routine analysis and TIMP-1 was determined in plasma using a validated in-house enzyme-linked immunosorbent assay. Disease-free survival (DFS) was registered and its associations with serum CEA and plasma TIMP-1 levels were studied using a Cox multivariate model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for DFS were calculated. Results. An event was recorded in 186 patients: 75 had local recurrence, 75 had distant metastases, 28 had both local recurrence and distant metastases, and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale, serum CEA and plasma TIMP-1 were statistically significant in a multivariate analysis with HR = 1.1 (95% CI 1.0–1.2) and HR = 1.5 (95% CI 1.1–2.0), respectively. The two serological markers could be combined to form a prognostic index adjusted for baseline variables. This index showed a 51% increase in HR for a given CEA level if the TIMP-1 level was doubled. Conclusions. Preoperative serum CEA and plasma TIMP-1 levels are independent predictors of DFS in patients with primary resectable CRC. In combination these two proteins could form an index for the assessment of risk of disease recurrence in early-stage CRC.

Current and emerging trends in the treatment of early-stage colorectal cancer: importance of a multidisciplinary approach

In 2006, an estimated 148,610 Americans will receive a diagnosis of colorectal cancer [1]. Colorectal cancer is the second most common cause of cancer-related mortality, causing an estimated 55,170 deaths in the United States annually. Five-year survival rates are 90% and 75% in patients with American Joint Committee on Cancer (AJCC) stage I and II colorectal cancer, respectively, compared with -50% for those with stage III disease. Chemotherapy improves survival in _<33% of patients with stage III disease [2,3] but does not improve survival in patients with early-stage disease [2], who are potentially cured by surgical resection alone. However, <30% of patients with tumor-negative lymph nodes will develop recurrent disease and die of colon cancer [2]. The United States has no standard guidelines for the extent of lymphadenectomy during colectomy, the pathologic assessment of nodes in the colectomy specimen, or the indications for chemotherapy in patients with earlystage colorectal cancer. Close communication between the surgeon, the pathologist, the medical oncologist, and other health care professionals is essential to improve the selection of patients for systemic chemotherapy and to avoid the toxicity and expense of chemotherapy in patients who can be cured by surgical resection alone. This review describes recent modifications in the staging systems for colon cancer, the quality of surgery as it relates to the number of lymph nodes retrieved in the resected specimen, the importance of the number of lymph nodes retrieved, and immunologic and molecular techniques that may improve the accuracy of staging. Finally, the role of adjuvant chemotherapy is reviewed, particularly as it pertains to the treatment of early-stage colorectal cancer. Preoperative evaluation The diagnosis of colon cancer is followed by a preoperative staging workup to determine the extent of disease. National Comprehensive Cancer Network guidelines for the preoperative staging of colon cancer recommend pathology review, colonoscopic evaluation of the cecum, computed tomography (CT) of the abdomen and pelvis, chest radiography, complete blood count to assess the severity of anemia, a chemistry panel, and a carcinoembryonic antigen (CEA) level to establish a baseline for monitoring of recurrence [4]. Preoperative abdominal and pelvic CT is common. Although it has not been validated by randomized clinical trials, results can be helpful: if liver metastases are discovered, hepatic resection can be undertaken at colectomy; if metastases are widespread, nonoperative management may be considered. Barton et al [5] reported that preoperative abdominal CT of 70 men undergoing colectomy provided information that was used in treatment planning and management in 26 (37%) cases. By contrast, chest radiography is not useful for identifying metastatic disease and cannot be recommended except for assessing specific pulmonary symptoms [6].

CME Test Answers Current and emerging trends in the treatment of early-stage colorectal cancer

CME Test Answers Current and emerging trends in the treatment of early-stage colorectal cancer

CME Test Questions Current and emerging trends in the treatment of early-stage colorectal cancer

CME Test Questions Current and emerging trends in the treatment of early-stage colorectal cancer

CME Test Answer Sheet and Evaluation Form for Current and emerging trends in the treatment of early-stage colorectal cancer

The ABCDE ring moiety of ciguatoxin CTX3C, a major causative agent of ciguatera poisoning, was stereoselectively synthesized. The key transformations are a chiral auxiliary-based asymmetric alkylation and an asymmetric aldol condensation, which controlled the formation of the C11 and C21-stereocenters, respectively. A highly practical and efficient route to the ABCD ring fragment, a common precursor for the divergent synthesis of the left wings of ciguatoxins, was also established.