Role Of Ovarian Metastases In Colorectal Cancer (ROMIC): a Dutch study protocol to evaluate the effect of prophylactic salpingo-oophorectomy in postmenopausal women.

BACKGROUND: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients. METHODS: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy. DISCUSSION: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC. TRIAL REGISTRATION: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 . PROTOCOL VERSION: 1.0, date 2021 June 8.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

Outcomes on diverting ostomy formation and reversal after low anterior resection in the older more advanced rectal cancer patient.

BACKGROUND: To decrease morbidity caused by anastomotic leakages after a low anterior resection (LAR) with primary anastomosis, a diverting ostomy is often created. Reversal of a diverting ostomy is associated with morbidity, which may result in non-reversal, particularly in the elderly. This study aimed to describe the diverting ostomy-related outcomes in elderly patients with more advanced rectal cancer after LAR. MATERIALS AND METHODS: All rectosigmoid and rectal cancer patients ≥70 years who underwent LAR with primary anastomosis between 2006 and 2019 in the Catharina Hospital (Eindhoven, The Netherlands) were included for analyses. Reversal rates, ostomy-related complications, morbidity and mortality after ostomy reversal, and definitive ostomy rates were evaluated. RESULTS: In total 164 patients were included, of which 150 (91.5%) underwent primary or secondary ostomy creation. Ostomy-related complications were reported in 34.7% (95%-CI 27.1-42.9%). In total, 72.5% (95%-CI 64.2-79.7%) reversed their diverting ostomy. Non-reversal was mostly due to relapsing disease (52.6%). Median time to ostomy reversal was 3.2 months (IQR 2.3-5.0). No or minor complications after ostomy reversal were observed in 84.0% (95%-CI 75.3-90.6%). Over time, ostomy recreation was performed in 15.0% (95%-CI 8.6-23.5%), and ultimately 65.8% (95%-CI 57.8-73.2%) were ostomy-free after the median follow-up of 3.8 years. CONCLUSION: Although most elderly successfully reversed their diverting ostomy after LAR with limited morbidity, attention should be paid for the risk of non-reversal and ostomy recreation over time. Preoperative patient counselling is important in every individual to be able to decide if LAR with primary anastomosis or a permanent end colostomy is preferred.

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study.

INTRODUCTION: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. METHODS: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics. RESULTS: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). CONCLUSION: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.

Prospective multicentre study of a new bowel obstruction treatment in colorectal surgery: Reduced morbidity and mortality.

INTRODUCTION: Bowel obstruction patients are at increased risk of emergency surgery and have poor nutritional and physical conditions. These patients could benefit from prehabilitation and prevention of emergency surgery. This study assessed the effect of a multimodal obstruction treatment for bowel obstruction patients in colorectal surgery on the risk of emergency surgery and postoperative morbidity and mortality. MATERIALS AND METHODS: This multicenter observational cohort study included all consecutive bowel obstruction patients who received obstruction treatment (obstruction protocol) in the period 2019-2020 in two Dutch hospitals. Benign and malignant causes of bowel obstruction were included. Treatment consisted of 1. dietary adjustments, 2. postponing surgery for three weeks, 3. laxatives, and 4. prehabilitation. We compared emergency surgery and postoperative morbidity and mortality rates to known rates from the literature. RESULTS: Eighty-nine patients were included: obstruction treatment was successful in 77 patients (87%) who underwent elective surgery and unsuccessful in 12 patients (13%) who underwent emergency surgery. Sixty-six (74%) had colorectal cancer, and 22 (25%) had benign disease. Thirty-day mortality of 0% in our study was significantly lower than the national average of 4% in colorectal cancer patients in the Netherlands (p = 0.049). Anastomotic leakage rate was 3%, severe complications (Clavien-Dindo ≥ III) 8%, and bowel perforation 0%. These rates did not differ significantly from rates reported in literature. CONCLUSION: The obstruction treatment prevented emergency surgery in most patients with bowel obstruction and reduced postoperative morbidity and mortality. The obstruction treatment seems to be a safe and efficient alternative to emergency surgery.

Combined transverse thoracis plane and pectoral nerve blocks for breast surgery under sedation.

The pectoral nerves 2 (pecs 2) block is widely used as adjunct to general anaesthesia for breast surgery. There are a few case reports and a single case series that describe regional anaesthesia as a single technique or supplemented by light to moderate sedation. Here we describe the management of a 91-year-old ASA physical status 4 patient who presented with a T4 breast malignancy. She was considered unfit for general anaesthesia due to significant valvular heart disease. A wide local excision was successfully performed under a pecs 2 block and a transverse thoracis plane block, supplemented with light sedation. We consider this technique to be a good option for selected patients who are considered unfit for general anaesthesia.

Age-related differences in morbidity and mortality after surgery for primary clinical T4 and locally recurrent rectal cancer.

AIM: Outcomes in elderly patients (≥75 years) with non-advanced colorectal cancer have improved. It is unclear whether this is also true for elderly patients with clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). We aimed to compare age-related differences in morbidity and mortality after curative treatment for cT4RC and LRRC. METHODS: All cT4RC and LRRC patients without distant metastasis who underwent curative surgery between 2005 and 2017 in the Catharina Hospital (Eindhoven, The Netherlands) were included. Morbidity and mortality were evaluated based on age (<75 and ≥75 years) and date of surgery (2005-2011 and 2012-2017). RESULTS: Overall, 72 of 474 (15.2%) cT4RC and 53 of 293 (18.1%) LRRC patients were ≥75 years. No significant differences in the incidence of Clavien-Dindo I-IV complications were observed between age groups. However, in elderly cT4RC patients, cerebrovascular accidents occurred more frequently (4.2% vs. 0.5%, P = 0.03). Between 2005-2011 and 2012-2017, 30-day mortality improved from 7.5% to 3.1% and from 10.0% to 0.0% in elderly cT4RC and LRRC patients, respectively. The 1-year mortality during 2012-2017 was worse in elderly than in younger patients (28.1% vs. 6.2%, P = 0.001 for cT4RC and 27.3% vs. 13.8%, P = 0.06 for LRRC). In elderly cT4RC and LRRC patients, 44.4% and 46.2% died due to non-cancer-related causes, while only 27.8% and 23.1% died due to disease recurrence, respectively. CONCLUSION: Although the 30-day mortality in elderly cT4RC and LRRC patients improved after curative treatment, the 1-year mortality in elderly patients continued to be high, which requires more awareness for the elderly after hospitalization.

Improved Outcomes for Responders After Treatment with Induction Chemotherapy and Chemo(re)irradiation for Locally Recurrent Rectal Cancer.

BACKGROUND: Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes. METHODS: All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS). RESULTS: A pathologic complete response was observed in 22 patients (17%), a "good" response (Mandard 2-3) in 74 patients (56%), and a "poor" response (Mandard 4-5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (p = 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (p = 0.004, p = 0.003, and p = 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (p = 0.020 and p = 0.028, respectively). CONCLUSIONS: Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.

Functional bowel complaints and quality of life after surgery for colon cancer: prevalence and predictive factors.

AIM: Low anterior resection syndrome (LARS) severely affects the quality of life (QoL) of patients after surgery for rectal cancer. There are very few studies that have investigated LARS-like symptoms and their effect on QoL after colon cancer surgery. The aim of this study was to investigate the prevalence of functional abdominal complaints and related QoL after colon cancer surgery compared with patients with similar complaints after rectal cancer surgery. METHOD: All patients who underwent colorectal cancer resections between January 2008 and December 2015, and who were free of colostomy for at least 1 year, were eligible (n = 2136). Bowel function was assessed by the LARS score, QoL by the EORTC QLQ-C30 and QLQ-CR29 questionnaires. QoL was compared between the LARS score categories and tumour height categories. RESULTS: A total of 1495 patients (70.0%) were included in the analyses, of whom 1145 had a colonic and 350 a rectal tumour. Symptoms of LARS were observed in 55% after rectal cancer resection compared with 21% after colon cancer resection. Female gender (OR 1.88, CI 1.392-2.528) and a previous diverting stoma (OR 1.84, CI 1.14-2.97) were independently associated with a higher prevalence of LARS after colon cancer surgery. Patients with LARS after colon cancer surgery performed significantly worse in most QoL domains. CONCLUSION: The results of this study highlight the presence of LARS-like symptoms after surgery for colonic cancer. Patients suffering from major LARS-like symptoms after colon resection reported the same debilitating effect on their QoL as patients with major LARS after rectal resection. This should be addressed by colorectal cancer specialists in order to adequately inform patients.

The low anterior resection syndrome in a reference population: prevalence and predictive factors in the Netherlands.

AIM: The low anterior resection syndrome (LARS) severely affects quality of life (QoL) after colorectal cancer surgery. There are no data about these complaints and the association with QoL in a reference population. The aim of this study was to assess LARS and the association with QoL in a reference population. METHODS: Six hundred patients who visited the outpatient clinic because of general or trauma surgical indications were asked to participate in this study. They received an invitation letter containing three validated questionnaires to assess LARS (assessed with the LARS score) and both general [European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30] and colorectal-specific (EORTC QLQ-CR29) QoL. RESULTS: Five hundred and one respondents could be included for the analyses. The median age at inclusion was 68 years and 47.3% were men. Major LARS was observed in 15% of patients (11.4% in men and 18.9% in women, P = 0.021). Women reported more urgency (P = 0.070) and incontinence for both flatus (P < 0.001) and stool (P = 0.063) compared to men. In univariate analyses, women reported major LARS significantly more often than men (OR 1.82; 95% CI 1.10-3.01). Patients with major LARS scored significantly worse in most QoL domains compared to patients with no/minor LARS. CONCLUSION: This is the first study demonstrating major LARS and the association with QoL in a reference population of patients without colorectal cancer. Our data can assist in the interpretation of LARS in past and future research about abdominal complaints after colorectal cancer surgery.