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.
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
InIn-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
InIn-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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC.
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