Development of a prediction model for recurrence in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC. MATERIALS AND METHODS: For this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration. RESULTS: In total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044-1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550-0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities. CONCLUSION: We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC.

Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin.

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [111In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging. Primary study outcomes are safety and feasibility of this multimodal imaging approach. Secondary outcomes are determination of the optimal dose, correlation between tracer uptake and histopathology and effects on clinical strategy. Administration of [111In]In-DOTA-labetuzumab-IRDye800CW is well-tolerated and enables sensitive pre- and intraoperative imaging in patients who receive 10 or 50 mg of the tracer. Preoperative imaging revealed previously undetected lymph node metastases in one patient, and intraoperative fluorescence imaging revealed four previously undetected metastases in two patients. Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures.

Survival Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Patients with Synchronous Versus Metachronous Onset of Peritoneal Metastases of Colorectal Carcinoma.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases (PM) from colorectal carcinoma (CRC). Because of considerable morbidity, optimal patient selection is essential. This study was designed to determine the impact of the onset of PM (synchronous vs. metachronous) on survival outcomes after CRS-HIPEC. METHODS: Patients undergoing CRS-HIPEC for colorectal PM in two academic centers in the Netherlands between 2010 and 2020 were eligible for inclusion. Patients were classified as synchronous (s-PM, i.e., diagnosis at time of presentation, staging, or primary surgery) or metachronous onset (m-PM, i.e., diagnosis during follow-up) of colorectal PM. Survival outcomes were compared between groups by Kaplan-Meier survival and Cox regression analyses. RESULTS: Of 390 included patients, 179 (45.9%) had synchronous onset of colorectal PM. These patients more often presented with higher TN-stage and poor differentiation/signet cell histology. Treatment with perioperative chemotherapy was more common in s-PM patients. m-PM patients experienced more serious postoperative complications (Clavien-Dindo ≥ III). There was no significant difference in disease-free survival (DFS) between s-PM (median 9 months, interquartile range [IQR] 5-15) and m-PM patients (median 8 months, IQR 5-17). Overall survival (OS) was significantly shorter for s-PM (median 28 months, IQR 11-48) versus m-PM patients (median 33 months, IQR 18-66, p = 0.049). Synchronous onset of PM was not independently associated with OS in a multivariable analysis. CONCLUSIONS: Synchronous onset of colorectal PM was associated with poor tumor characteristics and more advanced disease, but was not an independent predictor of survival outcomes after CRS-HIPEC.

In Patients Undergoing CRS/HIPEC for Colorectal Adenocarcinoma with Peritoneal Metastases, Presence of Ascites on Computed Tomography Imaging is not a Prognostic Marker for Survival.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for patients with colorectal peritoneal metastases (CRPM). Patient selection is key to optimizing outcomes after CRS/HIPEC. The aim of this study was to determine the prognostic value of ascites diagnosed on preoperative imaging. METHODS: A prospective database of patients eligible for CRS/HIPEC between 2010 and 2020 was retrospectively analyzed. The presence of ascites, postoperative complications, overall survival (OS), disease-free survival (DFS), and completeness of cytoreduction were assessed. Univariable and multivariable logistic regression was performed to identify independent predictors for outcome. RESULTS: Of the 235 included patients, 177 (75%) underwent CRS/HIPEC while 58 (25%) were not eligible for CRS/HIPEC. In 42 of the 177 patients (24%) who underwent CRS/HIPEC, ascites was present on preoperative computed tomography (CT) imaging. Peritoneal Cancer Index (PCI) score was significantly higher in patients with preoperative ascites compared with patients without (11 [range 2-30] vs. 9 [range 0-28], respectively; p = 0.011) and complete cytoreduction was more often achieved in patients without ascites (96.3% vs. 85.7%; p = 0.007). There was no significant difference in median DFS and OS after CRS/HIPEC between patients with and without ascites {10 months (95% confidence interval [CI] 7.1-12.9) vs. 9 months (95% CI 7.2-10.8), and 25 months (95% 9.4-40.6) vs. 27 months (95% CI 22.4-31.6), respectively}. CONCLUSIONS: Ascites on preoperative imaging was not associated with worse survival in CRS/HIPEC patients with CRPM. Therefore, excluding patients from CRS/HIPEC based merely on the presence of ascites is not advisable.

Perioperative Systemic Therapy vs Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Alone for Resectable Colorectal Peritoneal Metastases: A Phase 2 Randomized Clinical Trial.

Importance: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). Objective: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. Design, Setting, and Participants: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. Interventions: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. Main Outcomes and Measures: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). Results: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. Conclusions and Relevance: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02758951.

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score-Matched Analysis of Centers in the Netherlands and Belgium.

BACKGROUND: The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs. PATIENTS AND METHODS: Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018. RESULTS: After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings. CONCLUSION: CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.

Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery.

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

Can [18F]F-FDG PET/CT be used to assess the pre-operative extent of peritoneal carcinomatosis in patients with colorectal cancer?

PURPOSE: To evaluate whether PET/CT could be used to assess the extent of colorectal peritoneal metastases. METHODS: All patients who underwent a PET/CT scan before a CRS-HIPEC procedure between January 1, 2010 and December 31, 2013 were retrospectively included (n = 35). Two nuclear medicine physicians (observer 1 and observer 2) separately reviewed the scans on intraperitoneal abnormalities. A simplified PCI was used to compare the extent of rPCI versus sPCI. RESULTS: Included patients had a median age of 60.6 years. Histology of primary tumors were 51.5% adenocarcinomas, 37.1% mucinous adenocarcinoma, and 11.4% SRCC. Median sPCI was 9.5 (5.0-11.8) and median rPCI was 5.0 (3.0-7.0) for observer 1 and 4.0 (3.0-6.0) for observer 2 (p = 0.02 and p = 0.01, respectively). When compared to the surgical data, PET/CT showed a poor correlation for assessing the extent of PC for both adenocarcinoma (observer 1 rho - 0.17, p = 0.51 and observer 2 rho 0.13, p = 0.61) as well as mucinous carcinoma or SRCC (observer 1 rho 0.44, p = 0.08 and observer 2 rho 0.38, p = 0.14). CONCLUSION: PET/CT underestimates the extent of PC during surgery in both mucinous and non-mucinous CRC and is not recommended for intraperitoneal tumor scoring.

Retrospective Analysis of Non-Surgical Treatment of Acute Cholecystitis.

Background: Worldwide, acute cholecystitis is a common disease. The current standard of treatment is according to the Tokyo Guidelines established in 2018. Conservative management with various combinations of analgesics, anti-inflammatory drugs, and percutaneous drainage are sometimes used to avoid or delay surgery, especially in frail patients, but little is known about the efficacy and safety of these strategies. Therefore, we evaluated the effect of antibiotic agents, with or without gallbladder drainage, or symptomatic treatment alone in patients with acute cholecystitis who were considered unfit for acute surgery. Patients and Methods: All patients whose initial treatment for cholecystitis was conservative who were admitted between 2014 and 2016 were included in this study. Patients were divided into three groups: those treated with antibiotic agents, those who received antibiotic agents in combination with percutaneous gallbladder drainage and those whose treatment was only symptomatic. Demographic characteristics, comorbidities, Tokyo Severity Classification, length of stay, re-admission rates, secondary treatment (delayed drainage or surgery), and complication rates were retrieved from their medical records. Results: Initially 33 were treated with conservative methods in this period. Fifteen patients were treated initially with antibiotic agents, 12 patients with antibiotic agents in combination with percutaneous drainage, and 6 patients received symptomatic treatment only. One patient had mild cholecystitis (Tokyo Severity Classification grade I) and the other 32 patients had moderate to severe (grade II or III) cholecystitis. Eventually, 25 patients (76%) underwent cholecystectomy, 2 of whom (8%) were emergency operations because of disease progression. Twelve patients (36%) were re-admitted, of whom the majority (83%) was re-admitted before cholecystectomy. Conclusion: Treatment of cholecystitis with antibiotic agents, drainage, or analgesic agents is feasible. However, it should be regarded as a bridge to surgery rather than a definitive solution because of frequent recurrence. Occasionally, an emergency operation could not be avoided as a result of disease progression under conservative treatment.

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6)

BACKGROUND: Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. METHODS: This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. DISCUSSION: This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. TRIAL REGISTRATION: Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016-001865-99 .

Comparison of 2 Perioperative Management Protocols and Their Influence on Postoperative Recovery after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Standard Parenteral Nutrition, Selective Bowel Decontamination and Suprapubic Catheters?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with considerable postoperative morbidity, including ileus and infectious complications. Perioperative care is believed to be an important factor for the development and treatment of postoperative morbidity. PATIENTS AND METHODS: Data on case-matched patients from a retrospective database of 2 Dutch HIPEC centres was compared. Patient selection and procedures were identical in both hospitals although perioperative management items differ slightly. In centre B, immediate total parenteral nutrition (TPN), suprapubic urine bladder catheter placement (SPCs) and selective decontamination of the digestive-tract are standard care for CRS-HIPEC patients, while in centre A, they are not. RESULTS: From a total of 223 patients, 68 consecutive patients from centre B were compared to 68 matched patients from centre A. TPN was administered to 54.4% of patients in centre A because of prolonged ileus, whereas it was standard of care in centre B. In all, 105 (77.2%) patients experienced postoperative complications including 17.6% who had a grades III-IV complication. The incidence of grade III-V complications was 18 (26.4%) in centre A and 8 (11.8%) in centre B (p = 0.03). Median hospital stay was 12 days (7-84) in A and 11(6-80) in centre B (p = 0.546). CONCLUSIONS: Gastrointestinal recovery after CRS-HIPEC seems to take longer as compared to other surgical procedures. Between the 2 centres, a significant difference in severe complications was found, while standard TPN, selective bowel decontamination and SPCs were the only identified differences in perioperative care.

Long-term Oncological and Functional Outcomes of Chemoradiotherapy Followed by Organ-Sparing Transanal Endoscopic Microsurgery for Distal Rectal Cancer: The CARTS Study.

Importance: Treatment of rectal cancer is shifting toward organ preservation aiming to reduce surgery-related morbidity. Short-term outcomes of organ-preserving strategies are promising, but long-term outcomes are scarce in the literature. Objective: To explore long-term oncological outcomes and health-related quality of life (HRQL) in patients with cT1-3N0M0 rectal cancer who underwent neoadjuvant chemoradiotherapy (CRT) followed by transanal endoscopic microsurgery (TEM). Design, Setting, and Participants: In this multicenter phase II feasibility study, patients with cT1-3N0M0 rectal cancer admitted to referral centers for rectal cancer throughout the Netherlands between February 2011 and September 2012 were prospectively included. These patients were to be treated with neoadjuvant CRT followed by TEM in case of good response. An intensive follow-up scheme was used to detect local recurrences and/or distant metastases. Data from validated HRQL questionnaires and low anterior resection syndrome questionnaires were collected. Data were analyzed from February 2011 to April 2017. Main Outcomes and Measures: The primary study outcome of the study was the number of ypT0-1 specimens by performing TEM. Secondary outcome parameters were locoregional recurrences and HRQL. Results: Of the 55 included patients, 30 (55%) were male, and the mean (SD) age was 64 (39-82) years. Patients were followed up for a median (interquartile range) period of 53 (39-57) months. Two patients (4%) died during CRT, 1 (2%) stopped CRT, and 1 (2%) was lost to follow-up. Following CRT, 47 patients (85%) underwent TEM, of whom 35 (74%) were successfully treated with local excision alone. Total mesorectal excision was performed in 16 patients (4 with inadequate responses, 8 with completion after TEM, and 4 with salvage for local recurrence). The actuarial 5-year local recurrence rate was 7.7%, with 5-year disease-free and overall survival rates of 81.6% and 82.8%, respectively. Health-related quality of life during follow-up was equal to baseline, with improved emotional well-being in patients treated with local excision (mean score at baseline, 72.0; 95% CI, 67.1-80.1; mean score at follow-up, 86.9; 95% CI, 79.2-94.7; P = .001). Major, minor, and no low anterior resection syndrome was experienced in 50%, 28%, and 22%, respectively, of patients with successful organ preservation. Conclusions and Relevance: In early-stage rectal cancer (cT1-3N0M0), CRT enables organ preservation with additional TEM surgery in approximately two-thirds of patients with good long-term oncological outcome and HRQL. This multimodality treatment triggers a certain degree of bowel dysfunction, and one-third of patients still undergo radical surgery and are overtreated by CRT.

Value of macrobiopsies and transanal endoscopic microsurgery in the histological work-up of rectal neoplasms: A retrospective study.

AIM: To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology. METHODS: Patients with a rectal neoplasm who underwent flexible endoscopy and biopsies were included. In case of benign biopsies rigid rectoscopy and macrobiopsies were employed. If this failed to prove malignancy, transanal endoscopic microsurgery (TEM) was used in a final effort to establish a certain preoperative diagnosis. The preoperative results were compared with the findings after surgical excision and follow up to calculate the reliability of this algorithm. RESULTS: One hundred and thirty-two patients were included. One hundred and ten patients with a carcinoma and 22 with an adenoma. Seventy-five of 110 carcinomas were proven malignant after flexible endoscopy. With the addition of rigid endoscopy and taking of macrobiopsies, this number increased to 89. Performing TEM excision biopsies further enlarged the number of proven malignancies to 100. CONCLUSION: The step-up approach includes taking macrobiopsies through the rigid rectoscope and performing excision biopsies using transanal endoscopic microsurgery in addition to flexible endoscopy. This approach, reduced the number of missed preoperative malignant diagnoses from 32% to 9%.

The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery.

BACKGROUND: The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer. METHODS/DESIGN: Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol. DISCUSSION: The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051).