Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial.

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Symptoms of pre-treatment anxiety are associated with the development of chronic peripheral neuropathy among colorectal cancer patients.

PURPOSE: Identifying potentially modifiable predictors of chronic (chemotherapy-induced) peripheral neuropathy (PN) is important, especially in light of the limited treatment options. We aimed to examine pre-treatment anxiety and depressive symptoms as predictors of chronic PN symptom severity in colorectal cancer (CRC) patients up to 2 years after diagnosis. METHODS: Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 336) completed a questionnaire on anxiety and depressive symptoms (HADS) and sensory (SPN) and motor peripheral neuropathy (MPN) (EORTC QLQ-CIPN20) before initial treatment (baseline) and 1 and 2 years after diagnosis. Patients were included in the analyses if they either developed some level of SPN or MPN symptoms, or experienced a worsening of pre-treatment SPN or MPN symptoms. RESULTS: At 1-year follow-up, 115 patients (34%) reported SPN symptoms and 134 patients (40%) reported MPN symptoms. Of these patients, SPN and MPN symptoms had not returned to baseline level at 2-year follow-up in, respectively, 51% and 54% of patients. In multivariable regression analyses, neither pre-treatment anxiety symptoms nor pre-treatment depressive symptoms were associated with SPN or MPN symptom severity at 1-year follow-up. At 2-year follow-up, pre-treatment anxiety symptoms (ß = 0.44, p = 0.01), but not depressive symptoms, were associated with SPN symptom severity. CONCLUSIONS: Pre-treatment anxiety symptoms, but not depressive symptoms, were associated with SPN symptom severity 2 years after diagnosis. Future studies are needed that assess whether interventions targeted to reduce anxiety before and during treatment can reduce chronic PN severity or even prevent the persistence of PN.

Anxiety and depression mediate the association between chemotherapy-induced peripheral neuropathy and fatigue: Results from the population-based PROFILES registry.

OBJECTIVE: Chemotherapy-induced sensory peripheral neuropathy (CIPN) is common among colorectal cancer (CRC) survivors. The aim of this study was to examine whether CIPN is associated with both psychological distress (ie, anxiety and depression) and fatigue and whether the relationship between CIPN and fatigue can (partly) be explained by psychological distress. METHODS: All CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors completed questions on CIPN (EORTC QLQ-CIPN20), psychological distress (HADS), and fatigue (FAS) on average 5.6 years after diagnosis. Simple and multiple mediation analyses were performed to examine anxiety and depression as possible mediators in the association between CIPN and fatigue. RESULTS: Survivors with high (ie, upper 30% of scores) CIPN (n = 172) reported more anxiety and depressive symptoms and more fatigue compared with those with low CIPN (n = 299). Furthermore, among survivors with high CIPN, those who were anxious, depressed, or both reported more fatigue compared with those without psychological distress. These differences were clinically relevant. Finally, mediation analyses showed that while CIPN was directly associated with fatigue, the relationship between CIPN and fatigue was also significantly mediated by both anxiety and depression. CONCLUSIONS: CRC survivors with high CIPN report more fatigue, especially those who are also anxious and/or depressed. More research is needed on the direction of the relationship between CIPN, psychological distress, and fatigue. For now, the treatment of fatigue should also focus on addressing psychological distress, as treating fatigue alone might not be sufficient.

Ligation of the Intersphincteric Fistula Tract for High Transsphincteric Fistula Yields Moderate Results at Best: Is the Tide Turning?

BACKGROUND: Ligation of the intersphincteric fistula tract is a well-accepted and often used surgical procedure for perianal fistulas. OBJECTIVE: This study aims to confirm results of the ligation of the intersphincteric fistula tract in a specialized colorectal center. DESIGN: This is a retrospective cohort study. SETTING: This study took place in a large colorectal surgical department with a tertiary referral center for perianal fistulas. PATIENTS: Consecutive patients were operated on with ligation of the intersphincteric fistula tract for a transsphincteric perianal fistula between 2012 and December 2018. INTERVENTIONS: Patients underwent ligation of the intersphincteric fistula tract. MAIN OUTCOME MEASURES: The primary outcome measured was the healing rate. The secondary outcomes measured were conversion into an intersphincteric perianal fistula, risk of recurrence, complications, and postoperative continence status. RESULTS: Forty-six patients were treated with a ligation of intersphincteric fistula tract procedure. All patients (100%) had preoperative imaging in their workup. Forty patients (87%) had a high transsphincteric fistula. The primary healing rate was a disappointing 17 of 46 patients (37%). The median time until failure was 4.2 months (interquartile range, 3.5-6.5). Of the failures, 16 converted to an intersphincteric fistula (55% of failures and 35% of all patients). The mean duration of follow-up in patients without a recurrence was 9.5 months (SD 11.9). Four patients (9%) were lost to follow-up. The mean Fecal Incontinence Severity Index postoperatively was only 2.35 (SD 5.7; range, 0-30). This resulted in 9 patients (20%) having a newly impaired continence status postoperatively. Continence impairment was mild in all these patients. The risk of developing a recurrence 1 year after surgery is 64.2% (95% CI, 49%-80%). LIMITATIONS: This study was limited by its retrospective design and the small numbers with possible selection bias. CONCLUSIONS: Results with the ligation of intersphincteric fistula tract procedure were not as good as hoped. The effect on fecal continence, however, was minimal. The procedure might be more suitable for low transsphincteric fistulas. See Video Abstract at http://links.lww.com/DCR/A992. LA LIGADURA DEL TRACTO DE LA FÍSTULA INTERESFINTÉRICA PARA UNA FÍSTULA TRANSESFINTÉRICA ALTA, PRODUCE RESULTADOS MODERADOS EN EL MEJOR DE LOS CASOS: ¿ESTÁ CAMBIANDO LA MAREA?: La ligadura del tracto de la fístula interesfintérica es un procedimiento quirúrgico bien aceptado y de uso frecuente para las fístulas perianales. OBJETIVO: Confirmar los resultados de la ligadura del tracto de la fístula interesfintérica en un centro colorrectal especializado. DISEÑO:: Estudio de cohorte retrospectivo. AJUSTE: Gran departamento de cirugía colorrectal y con centro de referencia terciaria para fístulas perianales. PACIENTES: Pacientes consecutivos operados con ligadura del tracto de la fístula interesfintérica para una fístula perianal transesfintérica, entre 2012 y diciembre de 2018. INTERVENCIONES: Ligadura del tracto de fístula interesfintérica. PRINCIPALES MEDIDAS DE RESULTADO: Tasa de cicatrización, resultados secundarios: conversión a una fístula perianal interesfintérica, riesgo de recurrencia, complicaciones y estado de continencia postoperatoria. RESULTADOS: Cuarenta y seis pacientes fueron tratados con una ligadura del tracto de la fístula interesfintérica. Todos los pacientes (100 por ciento) tenían imagenología en su preparación preoperatoria. Cuarenta pacientes (87 por ciento) tenían una fístula transesfintérica alta. La tasa de cicatrización primaria fue decepcionante en 17 de 46 pacientes (37 por ciento). El tiempo medio hasta el fracaso fue de 4.2 meses (rango intercuartil 3.5-6.5). De los fracasos, 16 se convirtieron en una fístula interesfintérica (55 por ciento de los fracasos y 35 por ciento de todos los pacientes). La duración media del seguimiento en pacientes sin recurrencia fue de 9.5 meses (desviación estándar de 11.9). Se perdieron durante el seguimiento a cuatro pacientes (9 por ciento). Después de la operación, el promedio del índice de severidad de incontinencia fecal fue de solo 2.35 (desviación estándar de 5.7, rango 0-30). Esto resultó en que 9 pacientes (20 por ciento) tuvieran una continencia deteriorada postoperatoria. El deterioro de la continencia fue leve en todos estos pacientes. El riesgo de desarrollar una recurrencia a un año después de la cirugía es del 64.2 por ciento (intervalo de confianza del 95 por ciento: 49-80 por ciento). LIMITACIONES: Diseño retrospectivo, números pequeños con posible sesgo de selección. CONCLUSIONES: Los resultados del procedimiento con la ligadura del tracto de fístula interesfintérica no fueron tan buenos como se esperaba. El efecto sobre la continencia fecal, sin embargo, fue mínimo. El procedimiento podría ser más adecuado para las fístulas transesfintéricas bajas. Vea el Resumen del video en http://links.lww.com/DCR/A992.

Reversal of Hartmann's procedure utilizing single-port laparoscopy: an attractive alternative to laparotomy.

BACKGROUND: Complications after restoration of intestinal continuity (RIC) following Hartmann's procedure occur frequently and are often serious. These complications result in a reported morbidity of 4-30 % and a reported mortality of 10-14 %. Reducing the amount of surgical trauma accompanying abdominal access seems an attractive tool to reduce perioperative morbidity. This possibility is offered by single-port Hartmann's reversal (SPHR) through the colostomy site. METHODS: The purpose of the present prospective study was to compare outcome of SPHR to a retrospectively collected historical control group of conventional open Hartmann's reversal (OHR). All patients undergoing RIC between January 1, 2009, and January 1, 2014, were included in the present study. Operation time, morbidity and hospital stay were assessed. Postoperative surgical results of SPHR and OHR were the main outcome of the study. RESULTS: During the study period, 41 patients (M/F = 23:18; median age 58 (26-85) years) were included in the present study. Sixteen patients underwent OHR; 25 patients underwent SPHR. No mortality was observed in the present series. Median operation time was similar between groups [184 (29-377) vs. 153.5 (73-332) min]. Hospital stay was significantly shorter in the SPHR group [16 (4-74) vs. 4 (1-34) days, p < 0.05]. The number of complications was significantly lower in the SPHR group (33 vs. 10, p < 0.05); furthermore, significantly less patients had severe complications (Clavien-Dindo III or higher) in the SPHR group (7/33 vs. 1/10). Less wound-related complications occurred in the SPHR group (12 vs. 5, p < 0.05). CONCLUSION: This study confirms recent findings in the literature regarding the safety and feasibility of SPHR. SPHR seems to be an attractive alternative to OHR.

Sex differences in health-related quality of life and psychological distress among colorectal cancer patients: a 2-year longitudinal study.

PURPOSE: While sex differences in the incidence and mortality of colorectal cancer (CRC) are well documented, less is known about sex differences in patients' health-related quality of life (HRQoL) and psychological distress. To enhance patient-tailored care, we aimed to longitudinally examine sex differences in HRQoL and psychological distress among CRC patients from diagnosis up until 2-year follow-up. METHODS: Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 334) completed questions on HRQoL (EORTC QLQ-C30) and psychological distress (HADS) before initial treatment (baseline), 4 weeks after surgery, and at 1 and 2 years after diagnosis. Also, HRQoL and psychological distress were assessed in a sex- and age-matched reference population. RESULTS: When directly comparing female (N = 126, 38%) and male (N = 208, 62%) CRC patients, female patients reported significantly worse HRQoL, such as more insomnia at baseline, worse physical and role functioning 4 weeks after surgery, more diarrhea at 1 year, and more pain and constipation at 2-year follow-up. However, a comparison with the reference population revealed larger differences between patients and reference in males than in females. For example, at 1- and 2-year follow-up, male patients reported significantly worse cognitive and social functioning, more insomnia, and more anxiety compared with a reference population. CONCLUSIONS: Especially male CRC patients reported worse HRQoL and more psychological distress when compared with a reference population. IMPLICATIONS FOR CANCER SURVIVORS: Knowledge of sex-specific differences in HRQoL and psychological distress among CRC patients may help healthcare providers anticipate and appropriately address patients' unique healthcare needs.

The course of peripheral neuropathy and its association with health-related quality of life among colorectal cancer patients.

PURPOSE: To gain more insight into the course of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on health-related quality of life (HRQoL) in a population-based sample of colorectal cancer (CRC) patients up to 2 years after diagnosis. METHODS: All newly diagnosed CRC patients from four hospitals in the Netherlands were eligible for participation in an ongoing prospective cohort study. Patients (n = 340) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis. RESULTS: Among chemotherapy-treated patients (n = 105), a high sensory peripheral neuropathy (SPN) level was reported by 57% of patients at 1 year, and 47% at 2-year follow-up, whereas a high motor peripheral neuropathy (MPN) level was reported by 47% and 28%, at years 1 and 2, respectively. Linear mixed model analyses showed that SPN and MPN symptoms significantly increased from baseline to 1-year follow-up and did not return to baseline level after 2 years. Patients with a high SPN or MPN level reported a worse global quality of life and a worse physical, role, emotional, cognitive, and social functioning compared with those with a low SPN or MPN level. CONCLUSIONS: Future studies should focus on understanding the mechanisms underlying CIPN so targeted interventions can be developed to reduce the impact of CIPN on patient's lives. IMPLICATIONS FOR CANCER SURVIVORS: Patients need to be informed of both CIPN and the impact on HRQoL.

Comparative Quality of Life in Patients Following Transanal Minimally Invasive Surgery and Healthy Control Subjects.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is considered the successor of transanal endoscopic microsurgery (TEMS). It makes use of more readily available laparoscopic instruments and single-port access platforms with similar perioperative, clinical and oncological outcomes. Little is known about quality of life (QoL) outcomes after the use of TAMIS. The aim of this study was to assess QoL after TAMIS in our patients and compare this with QoL in the healthy Dutch population. METHODS: All patients undergoing TAMIS for selected rectal neoplasms between October 2011 and March 2014 were included in this analysis. Patients were studied for a minimal period of 24 months. QoL outcomes were measured using the Short-Form 36 Health Survey (SF-36) questionnaire; faecal continence was measured using the Faecal Incontinence Severity Index questionnaire. Patient reported outcomes were compared to case-matched healthy Dutch control subjects. We hypothesise that undergoing TAMIS will subsequently result in a decreased quality of life in patients compared to healthy individuals. RESULTS: Thirty-seven patients (m:f = 17:20, median 67 years) were included in the current analysis. In four patients (10.8%), postoperative complications occurred. The median follow-up was 36 (range 21-47) months. Postoperative QoL scores are similar comparable to those reported by Dutch healthy controls. Patients reported a statistically significant better QoL score in the 'bodily pain' domain when compared to the controls (81.8 vs. 74.1 points) (p = 0.01). Significant worse QoL scores for the 'social functioning' domain were reported by patients after TAMIS (84.4 vs. 100 points) (p = 0.03). CONCLUSION: TAMIS seems to be a safe technique with postoperative QoL scores similar to that of healthy case matched controls in 3-year follow-up. There seems to be no association between faecal incontinence and reported QoL. Negative effects of TAMIS on social functioning of patients should not be underestimated and should be discussed during preoperative counselling.

Use of Epidural Analgesia in Sigmoidectomy: Is There Any Advantage in the Era of Minimally Invasive Surgery?

BACKGROUND: There is no consensus as to the effects of epidural analgesia on postoperative outcomes after laparoscopy in the context of the Enhanced Recovery Programs. The aim of this study was to evaluate the effects of epidural analgesia on postoperative outcomes after elective laparoscopic sigmoidectomy. METHODS: The use of epidural analgesia was discontinued in elective laparoscopic sigmoidectomy and substituted by the perioperative administration of systemic lidocaine. Data from patients undergoing elective laparoscopic sigmoidectomy between January 2014 and September 2016 was prospectively analysed. Patients with epidural analgesia were compared with patients without, in analgesics administrated postoperatively, length of stay, day of first defecation and mobilisation, and complication and reoperation rates. RESULTS: A total of 160 patients (male 85; female 75), median age 68 (30-92 years), were included. The groups consisted of 80 patients each. Mean length of stay (5.6 vs. 7.2 days, p = 0.03) and day of first mobilisation (mean 1.2 vs. 1.6 days, p = 0.004) were significantly shorter in the group without epidural analgesia. Reoperation rate (7.5 vs. 2.5%) was not statistically different. Complication rate was significantly lower (12.5 vs. 30%, p = 0.007) in the group without epidural. Day of first defecation was shorter in the epidural group (1.4 vs. 1.7 days, p = 0.04). Mean amount of analgesics administrated was not statistically different between groups, except for metamizole, that was administrated more in the group without epidural. CONCLUSIONS: Epidural analgesia did not offer benefits on postoperative analgesia or outcomes after elective laparoscopic sigmoidectomy, causing longer length of stay, later mobilisation and higher complication rate.