Preclinical Model of Perianal Fistulizing Crohn's Disease.

BACKGROUND: Fistulizing anoperineal lesions (FAPLs) are common and severe complications of Crohn's disease (CD), exposing patients to the risk of anal sphincter alteration and permanent stoma. Due to the limited efficacy of current treatments, identifying new local therapies is mandatory. However, testing new treatments is currently limited because no relevant preclinical model of Crohn's-like FAPL is available. Thus, a reliable and reproducible experimental model of FAPLs is needed to assess new therapeutic strategies. METHODS: Twenty-one rats received a rectal enema of 2,4,6-trinitrobenzensulfonic acid (TNBS) to induce proctitis. Seven days later, a transsphincteric fistula tract was created with a surgical thread, instilled with TNBS twice a week until its removal at day 7 (group 1), day 14 (group 2), or day 28 (group 3). In each rat, pelvic MRI was performed just before and 7 days after thread removal. Rats were sacrificed 7 days after thread removal for pathological assessment of the fistula tract. RESULTS: The optimal preclinical model was obtained in group 3. In this group, 7 days after thread removal, all animals (9 of 9) had a persistent fistula tract visible on MRI with T2-hypersignal (normalized T2 signal intensity: 2.36 ± 0.39 arbitrary units [a.u.] [2.08-2.81]) and elevation of the apparent diffusion coefficient (1.33 ± 0.16 10-3 millimeter squared per seconds [1.18-1.49]). The pathological examination of the fistula tract revealed acute and chronic inflammation, granulations, fibrosis, epithelialization, and proctitis in the adjacent rectum. CONCLUSIONS: This reproducible preclinical model could be used to assess the effectiveness of innovative treatments in perianal fistulizing CD.

Anastomotic leakage after side-to-end anastomosis for rectal cancer: does leakage location matter?

AIM: To assess outcome according to location of anastomotic leakage (AL) after side-to-end stapler or manual low colorectal or coloanal anastomosis following laparoscopic total mesorectal excision (TME) for rectal cancer. METHODS: All patients presenting with symptomatic or asymptomatic AL after TME and side-to-end low anastomosis for rectal cancer performed from 2005 to 2014 were identified from our prospective database. CT-scans with contrast enema were reviewed to assess location of AL origin. RESULTS: Among 279 patients who underwent TME with side-to-end anastomosis from 2005 to 2014, 70 patients presented with AL and were included: 43 (61%) patients with AL on the circular anastomosis (CAL) were compared to 27 (39%) with AL on the transverse stapling line of the colonic stump (TAL). CAL and TAL were associated with similar rates of symptomatic AL (63% versus 48%, respectively; p=0.339), severe postoperative morbidity rate (33% versus 18%; p=0.313), and long-term outcomes, including definitive stoma rate (10 versus 11%; p=0.622), and major low anterior resection syndrome rate (56% vs 57%; p=0.961). CONCLUSION: Our study showed that whatever the location of AL on a side-to-end low colorectal or coloanal anastomosis after TME for cancer, both short and long-term outcomes are similar. This article is protected by copyright. All rights reserved.

Feasibility and Safety of Laparoscopic Colon Surgery Performed Under Intravenous Sedation and Local Anesthesia Using Microinvasive (<3 mm) Instruments: An Acute and Survival Study on Porcine Model.

PURPOSE: The purpose of the study was to evaluate the feasibility and safety of performing laparoscopic intestinal surgery using local anesthesia and intravenous sedation with instruments <3 mm in diameter. METHODS: Porcine model with acute (n = 2) and the survival studies (n = 8): all female pigs, weight (median 36.4 kg, range 33.2-38.4 kg). Surgeries were performed using only intravenous sedation with ketamine-midazolam and local anesthetic infiltration at the sites of trocar insertion, with airway protection. CO2 pneumoperitoneum was maintained using pressure of 3 to 5 mm Hg. Commercially available instruments, sizes <3 mm in diameter were used. Surgical steps were as follows: (a) exploration of all quadrants of the abdomen and pelvis, (b) "running" the entire length of small bowel, (c) dissection of bowel attachments to the peritoneal sidewall, and (d) creating a 2.5 cm enterotomy in the colon and suture repair of this defect. RESULTS: All 10 surgeries were completed successfully. Animals tolerated the procedure well, with no requirement of intubation. There were no decrements in vital signs during pneumoperitoneum or surgery. Despite spontaneous respiration movements, all planned surgical maneuvers were feasible. The median length of operations was 74 minutes (range 56-165 minutes). All survival animals had an uneventful recovery; there were no infectious complications, oral intake and bowel function returned within 24 hours. CONCLUSIONS: It appears feasible and safe to perform simple laparoscopic intestinal procedures using instruments <3 mm in diameter and low CO2 insufflation pressure under local anesthesia and intravenous sedation. This methodology holds promise in the development of new approaches to intestinal surgery and disease diagnosis.

Does pathologic response of rectal cancer influence postoperative morbidity after neoadjuvant radiochemotherapy and total mesorectal excision?

BACKGROUND: A pathologic complete response (pCR) can be observed in up to 25% of patients after preoperative chemoradiotherapy for rectal cancer and is associated with an improved long-term prognosis. However, few data are available regarding the effect of pCR on postoperative morbidity. This study aimed to assess the impact of the pCR on postoperative outcomes after laparoscopic total mesorectal excision (TME). METHODS: A prospectively maintained database (2006-2011) was reviewed for all consecutive patients (n = 143) undergoing laparoscopic TME for mid or low rectal cancer after neoadjuvant chemoradiotherapy. Postoperative data were compared for pCR-group and non-pCR-group. A pCR was defined as the absence of gross and microscopic tumor in the specimen, irrespective of the nodal status (ypT0). RESULTS: Thirty-three patients (23%) had a pCR. Median operating time was greatly shorter in the pCR-group (230 minutes, 180-360), compared with the non-pCR-group (240 minutes, 130-420, P = .02). Lymph node involvement was noted for 12% of the patients in the pCR-group and 33% of the patients in the non-pCR-group (P = .91). Clavien Dindo grade 3 and 4 complications (6% vs 22%, P = .04), infection related morbidity (47% vs 76%, P = .04), and clinical anastomotic leakage rates (9% vs 29%, P = .02) were lesser in the pCR group compared with the non-pCR group. Mean duration of hospital stay was lesser in the pCR-group (9 vs 12 days, P = .01). CONCLUSION: This study showed that Clavien Dindo grade 3 and 4 complications, including anastomosis leakage, and infection related complications rates were lesser in patients with pathologic complete response after RCT and laparoscopic TME for rectal cancer.

Bilobar colorectal liver metastases: a new model for preclinical studies.

SUMMARY: This study aimed to develop a new model of colorectal liver metastases (LM) in the rat. Both single macroscopic and multiple bilobar microscopic LM were investigated, as this closely resembled the human situation, before right hepatectomy was performed for 'single' right LM. The single macroscopic LM was elicited by direct injection of DHD/K12 colorectal cancer cells under the capsule of the median liver lobe in immunocompetent BDIX rats. The bilobar micrometastases were elicited by intraportal injection of DHD/K12 cells. A preliminary protocol was conducted to assess the dose of cells required to inject in to the portal vein, using 10(6) , 2 × 10(6) and 3 × 10(6) DHD/K12 cells (n = 15 rats). The resultant protocol for the experimental model used intraportal injection of 10(6) DHD/K12 cells and direct injections of 0.5 × 10(6) , 10(6) and 1.5 × 10(6) DHD/K12 cells (n = 15 rats). For both protocols, BDIX rats were sacrificed at day 30 after injection. The preliminary protocol showed that intraportal injection of 10(6) DHD/K12 cells was associated with bilobar micrometastases of 0.8 mm mean diameter at day 30. The main protocol assessed that direct injection of 0.5 × 10(6) under the liver median lobe capsule and intraportal injection of 10(6) DHD/K12 cells were associated at day 30 with a single macroscopic metastasis confined to a liver lobe and bilobar micrometastases, without peritoneal carcinomatosis or lung metastasis. Thus we have developed a new experimental model of bilobar colorectal LM including both macro- and microscopic colorectal LMs, which mimics the human situation and which will be useful in preclinical studies.

Staged laparoscopic adjuvant intraperitoneal chemohyperthermia after complete resection for locally advanced colorectal or gastric cancer: a preliminary experience.

BACKGROUND: Cytoreductive surgery followed by intraperitoneal chemohyperthermia (IPCH) is a promising treatment for patients with peritoneal carcinomatosis, a disease with dismal prognosis. METHODS: We describe our preliminary experience with staged adjuvant laparoscopic IPCH after complete resection in patients with locally or regionally advanced colorectal or gastric cancer. RESULTS: Twenty-one patients underwent resection for colorectal (N = 16) or gastric cancer (N = 5) followed by staged laparoscopic IPCH. No conversion to laparotomy was required. No major operative incident occurred. Mean duration of hospital stay was 12 days (range 9-23 days). No mortality occurred in the 30-day postoperative period. Four patients developed major complications (19%). One patient (5%) was reoperated. Mean follow-up period was 15.5 months (range 9-29 months). Three patients died, including two of cancer-related causes. No patient developed peritoneal carcinomatosis during the follow-up period. CONCLUSION: Staged laparoscopic adjuvant IPCH after open or laparoscopic resection in selected patients with colorectal or gastric cancer is feasible and reasonably safe. However, additional data are required to determine the effect on long-term survival.