Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

Small bowel obstruction, incisional hernia and survival after laparoscopic and open colonic resection (LAFA study).

BACKGROUND: Short-term advantages to laparoscopic surgery are well described. This study compared medium- to long-term outcomes of a randomized clinical trial comparing laparoscopic and open colonic resection for cancer. METHODS: The case notes of patients included in the LAFA study (perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care) were reviewed 2-5 years after randomization for incisional hernia, adhesional small bowel obstruction (SBO), overall survival, cancer recurrence and quality of life (QoL). The laparoscopic and open groups were compared irrespective of fast-track or standard perioperative care. RESULTS: Data on incisional hernias, SBO, survival and recurrence were available for 399 of 400 patients: 208 laparoscopic and 191 open resections. These outcomes were corrected for duration of follow-up. Median follow-up was 3·4 (i.q.r. 2·6-4·4) years. Multivariable regression analysis showed that open resection was a risk factor for incisional hernia (odds ratio (OR) 2·44, 95 per cent confidence interval (c.i.) 1·12 to 5·26; P = 0·022) and SBO (OR 3·70, 1·07 to 12·50; P = 0·039). There were no differences in overall survival (hazard ratio 1·10, 95 per cent c.i. 0·67 to 1·80; P = 0·730) or in cumulative incidence of recurrence (P = 0·514) between the laparoscopic and open groups. There were no measured differences in QoL in 281 respondents (P > 0·350 for all scales). CONCLUSION: Laparoscopic colonic surgery led to fewer incisional hernia and adhesional SBO events. REGISTRATION NUMBER: NTR222 (http://www.trialregister.nl).

Surgical stress response and postoperative immune function after laparoscopy or open surgery with fast track or standard perioperative care: a randomized trial.

OBJECTIVE: To evaluate the effect of laparoscopic or open colectomy with fast track or standard perioperative care on patient's immune status and stress response after surgery. METHODS: Patients with nonmetastasized colon cancer were randomized to laparoscopic or open colectomy with fast track or standard care. Blood samples were taken preoperatively (baseline), and 1, 2, 24, and 72 hours after surgery. Systemic HLA-DR expression, C-reactive protein, interleukin-6, growth hormone, prolactin, and cortisol were analyzed. RESULTS: Nineteen patients were randomized for laparoscopy and fast track care (LFT), 23 for laparoscopy and standard care (LS), 17 for open surgery and fast track care (OFT), and 20 for open surgery and standard care (OS). Patient characteristics were comparable. Mean HLA-DR was 74.8 in the LFT group, 67.1 in the LS group, 52.8 in the OFT group, and 40.7 in the OS group. Repeated-measures 2-way analysis of variance (ANOVA) showed this can be attributed to type of surgery and not aftercare (P = 0.002). Interleukin-6 levels were highest in the OS group. Repeated-measures 2-way ANOVA showed this can be attributed to type of surgery and not aftercare (P = 0.001). C-reactive protein levels were highest in the OS group. Following repeated-measures 2-way ANOVA, this can be attributed to type of surgery and not aftercare (P = 0.022). Growth hormone was lowest in the LFT group. Following repeated-measures 2-way ANOVA, this can be attributed to type of aftercare and not to type of surgery (P = 0.033). No differences between the groups were seen regarding prolactin or cortisol. No differences in (infectious) complication rates were observed between the groups. CONCLUSIONS: This randomized trial showed that immune function of HLA-DR in patients undergoing laparoscopic surgery with fast track care remains highest. This can be attributed to type of surgery and not aftercare. These results may indicate a reason for the accelerated recovery of patients treated laparoscopically within a fast track program as described in the LAparoscopy and/or FAst track multimodal management versus standard care (LAFA-Trial) (www.trialregister.nl, protocol NTR222).

Which fast track elements predict early recovery after colon cancer surgery?

AIM: It is questioned whether all separate fast track elements are essential for enhanced postoperative recovery. We aimed to determine which baseline characteristics and which fast track elements are independent predictors of faster postoperative recovery in patients undergoing resection for colon cancer. METHOD: Data from the LAFA trial database were used. In this trial, fast track care was compared with standard perioperative care in 400 patients undergoing laparoscopic or open surgery for colonic cancer. During admission 19 fast track elements per patient were prospectively evaluated and scored whether or not they were successfully applied. To identify predictive factors six baseline characteristics and those fast track items that were successfully achieved were entered in a univariate and multivariate linear regression analysis with total postoperative hospital stay (THS) as the primary outcome. RESULTS: In 400 patients, two baseline characteristics and two fast track elements were found to be significant independent predictors of THS: female sex [B = 0.85; 95% CI 0.75-0.96; reduction of 15% (CI 14-25%) in THS], laparoscopic resection [B = 0.85; 95% CI 0.75-0.96; reduction of 15% (CI 14-25%) in THS], 'normal diet at postoperative days 1, 2 and 3' [B = 0.70; 95% CI 0.61-0.81; reduction of 30% (CI 19-39%) in THS] and 'enforced mobilization at postoperative days 1, 2 and 3' [B = 0.68; 95% CI 0.59-0.80; reduction of 32% (CI 20-41%) in THS]. CONCLUSION: Evaluating only those fast track elements that were successfully achieved, enforced advancement of oral intake, early mobilization, laparoscopic surgery and female sex were independent determinants of early recovery.

The prevalence of dysplasia in the ileoanal pouch following restorative proctocolectomy for ulcerative colitis with associated dysplasia.

AIM: A recent systematic review indicated that dysplasia present before restorative proctocolectomy is a predictor of subsequent dysplasia in the pouch. This prospective study was carried out to assess the prevalence of dysplasia in the ileal pouch in patients having RPC for ulcerative colitis with co-existing dysplasia in the operation specimen. METHOD: Eligible patients were invited for a surveillance endoscopy. The afferent and blind efferent ileal loop, ileoanal pouch and rectal cuff were examined by standard endoscopy using a dye-spray technique with methylene blue. Mucosal abnormalities were biopsied and random biopsies were taken from the afferent and blind ileal loop, pouch and rectal cuff. RESULTS: Fourty-four patients (25 male, mean 49 years) underwent pouch endoscopy at a mean interval from RPC of 8.6 years. Dysplasia was detected in two (4.5%) patients. In one, low-grade dysplasia was found in the rectal cuff and in the other low-grade dysplasia was detected in random biopsies from the pouch and the efferent ileal loop. CONCLUSION: This prospective pouch-endoscopy study detected dysplasia in < 5% of patients over nearly 10 years. The benefit of routine surveillance for dysplasia in the pouch is uncertain, as the significance of low-grade dysplasia in the pouch is not clear.

Decreased incidence of isolated tumor cells in lymph nodes after laparoscopic resection for colorectal cancer.

BACKGROUND: Laparoscopic surgery has potential for less tumor cell spread because of the no-touch technique. We assessed the effect of the surgical approach (open versus no-touch laparoscopic) on the presence of tumor cells in sentinel lymph nodes (SN) of patients with stage I and II colorectal cancer. METHODS: A single-center consecutive prospective series of patients operated on for colorectal cancer was analyzed. After conventional hematoxylin and eosin (H&E) staining, 107 patients without lymphatic metastases were included; 59 patients had open surgery, and 48 patients underwent laparoscopic resection. Patients in the laparoscopic group underwent a no-touch medial to lateral approach, whereas the conventional lateral to medial approach was applied in open surgery. A SN procedure was performed in all patients. The SNs were immunohistochemically analyzed for presence of occult tumor cells (OTC). According to the American Joint Committee on Cancer (AJCC) these tumor cells were divided into micrometastases (0.2-2 mm) or isolated tumor cells (ITC, < 0.2 mm). RESULTS: In ten patients micrometastases were found, equally distributed between the two groups. However, ITC were more often found after open surgery (18 versus 5 patients, p = 0.03). Presence of OTC was related to depth of tumor invasion and tumor diameter > 3.5 cm. Logistic regression analysis identified lymphovascular invasion as a predictor for micrometastases [odds ratio (OR) 18.4], whereas open resection was predictive for presence of ITC (OR 3.3). CONCLUSIONS: No-touch medial to lateral laparoscopic surgery results in less isolated tumor cells in lymph nodes compared with open lateral to medial surgery in patients with stage I and II colorectal cancer.

Intestinal barrier function in patients undergoing colectomy.

AIM: The aim of this pilot study was to determine whether the type of approach (open or laparoscopic) and the order of devascularization during laparoscopic colectomy affect intestinal barrier function, local inflammatory response and clinical outcome. METHOD: Twenty-two patients undergoing elective colectomy from April 2006 to July 2008 were randomized to two sequences of vascular ligation, starting with either the inferior mesenteric artery or the ileocolic artery. Eighteen patients scheduled for open surgery served as a prospective control group. To assess the intestinal barrier function, release of intestinal fatty-acid binding protein (I-FABP; a marker of mucosal injury and ischaemia) was measured pre- and postoperatively. Mesenteric lymph nodes were harvested to assess the expression of inflammatory mediator-related genes using multiplex ligation probe amplification. The study was registered under NTR1025. RESULTS: Laparoscopic devascularization starting at the ileocolic artery resulted in a significantly increased excretion of I-FABP over time (P = 0.002). In this group, the I-FABP levels were significantly increased on postoperative days 1 and 3 compared with preoperative values (P = 0.011 and P = 0.001, respectively). There were no differences in expression of inflammatory mediator-related genes or postoperative morbidity among the groups. CONCLUSIONS: In this pilot study, devascularization commencing at the ileocolic artery during laparoscopic colectomy was associated with prolonged intestinal mucosal ischaemia.

Systematic review of laparoscopic vs open colonic surgery within an enhanced recovery programme.

BACKGROUND: Fast track surgery accelerates recovery, reduces morbidity and shortens hospital stay. It is unclear what the effects are of laparoscopic or open surgery within a fast track programme. The aim of this systematic review was to review the existing evidence. METHOD: A systematic review was performed of all randomized (RCTs) and controlled clinical trials (CCTs) on laparoscopic and open surgery within a fast track setting. Primary endpoints were primary and overall hospital stay, readmission rate, morbidity and mortality. Study selection, quality assessment and data extraction were performed independently by two observers. RESULTS: Only two RCTs and three CCTs were eligible for final analysis, which reported on 400 patients. Data could not be pooled because of clinical heterogeneity. One RCT and one CCT stated a shorter primary hospital stay in the laparoscopic group of 3 and 2 days, respectively. In one RCT, the readmission rate was lower in the laparoscopic group; absolute risk reduction (ARR) 21.4% [95% confidence interval (CI): 6-42.3%] resulting in a number needed to treat (NNT) of 4.7 patients (95% CI: 2.4-176). Another study showed a 23% difference in favour of the laparoscopic group with regard to morbidity (95% CI: 6.3-39.1%), i.e. an NNT of 4.4 patients (95% CI: 2.6-15.9). There were no significant differences in mortality rates. CONCLUSION: Due to the present lack of data, no robust conclusions can be made. A large randomized controlled trial is required to compare laparoscopic with open surgery within a fast track setting.

Effect of vaginal delivery on long-term pouch function.

BACKGROUND: The optimal method of childbirth for women with a restorative proctocolectomy (RP) has yet to be determined. Little is known about long-term ileal pouch function after vaginal delivery, especially when childbirth occurred before RP. The aim of this study was to evaluate the effect of vaginal delivery before or after RP on long-term pouch function. METHODS: All 267 women who underwent RP between January 1985 and November 2004 were invited to participate. Functional outcome was assessed by colorectal functional outcome questionnaire, and patients were asked about their pregnancies and risk factors for obstetric injury. Linear regression analysis was performed to study potential risk factors for poor pouch function. RESULTS: The response rate was 82.6 per cent. Median follow-up after pouch surgery was 7.2 (range 1.0-19.7) years. One hundred patients had at least one delivery. Fifty-two (60 per cent) of the 86 patients who attempted a vaginal delivery had an increased risk of obstetric injury according to predefined risk factors. In these patients ageing and longer follow-up were significant risk factors for impaired incontinence. CONCLUSION: Women who had RP and vaginal delivery with a high risk of obstetric injury had impaired continence with ageing and longer follow-up. Patients with RP should be informed about the considerable risk of vaginal delivery on long-term ileal pouch function.