Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such.

Complicated colorectal cancer in nonagenarian patients: is it better not to perform anastomosis in emergency?

BACKGROUND: Colorectal cancer (CRC) is predominantly a disease of elderly people. Cancer in nonagenarian patients presents an ethical dilemma for surgeons and oncologists, and management of this group of patients in emergency for complicated CRC is debated. Presently described is retrospective study reporting experience of 6 departments of emergency surgery with management of nonagenarian patients sent to emergency surgery for CRC complications. METHODS: Data concerning patients aged over 90 years hospitalized from January 2011 to June 2015 in 6 departments of emergency surgery for complicated CRC were retrospectively analyzed. Data were collected in a dedicated database. Statistical analysis was conducted using IBM software SPSS 22 (IBM Corp., Armonk, NY, USA); statistical significance was set at p=0.05. RESULTS: In the period of study, 19 patients aged over 90 underwent surgery in emergency department for complicated CRC. Of the total, 52.63% were female, with sex ratio F:M of 1.11:1. Mean age was 92.52 years (range: 90-97 years; SD 1.49). Preoperative assessment of surgical risk was made using American Society of Anesthesiologists (ASA) score. There was no statistically significant difference in terms of in-hospital mortality between patients with ASA score ≤ 3 and patients with an ASA score >3. Primary anastomosis was performed in 6 of 19 patients (31.57%), all of whom had right-side colon cancer. Diverting stoma was created for 12 of 19 patients (63.15%). There was a statistically significant difference in incidence of postoperative complications between patients with right-side colon cancer and patients with left-side colon cancer (p=0.0498). Mean length of hospital stay was 12.78 days (range: 2-31 days; SD 6.31). In-hospital mortality rate was 21.05% (n=4). At follow up, overall survival was 47.36% (n=9). CONCLUSION: Elective surgery is the best way to manage CRC in all patients affected. Emergency surgery for CRC complications in patients over 90 is feasible with careful preoperative selection and evaluation of the patient. One-stage surgery is the best choice, in selected patients. Two- and three-stage surgery is indicated in case of peritonitis, for frail patients, for hemodynamically unstable patients. If there is high risk of anastomotic leakage, decompressive stoma is suggested as bridge to elective surgery, and in advanced neoplastic disease, as palliative procedure. In emergency setting, diverting stoma is a good surgical option in nonagenarian patients to decrease surgical risk, morbidity, and mortality; however, clinical randomized controlled trials are necessary to confirm this.

Rectovaginal Fistula: What Is the Optimal Strategy?: An Analysis of 79 Patients Undergoing 286 Procedures.

OBJECTIVES: The aim of this study was to assess results of surgery for rectovaginal fistula (RVF) and prognostic factors for success. BACKGROUND DATA: Management of RVF remains challenging and numerous surgical options are available. Few large reports of RVF are available and success prognostic factors remain unknown. METHODS: All patients operated for RVF from 1996 to 2014 were included. RESULTS: Seventy-nine patients presented RVF due to Crohn disease in 34 (43%), postoperative in 25 (32%), obstetrical in 7 (9%), radiation proctitis in 4 (5%), and miscellaneous in 9 (11%). A total of 286 procedures (132 with associated stoma, 46%) were performed including 217 conservative (76%) [seton drainage (n = 59; 21%), vaginal (n = 49, 17%) or rectal advancement flap (n = 46; 16%), diverting stoma only (n = 27; 9%), plug (n = 15; 5%), glue (n = 13; 5%), or others (n = 8, 3%)]; and 69 major procedures (24%) [gracilis muscle interposition (n = 32; 11%), coloanal or colorectal anastomosis (n = 19; 7%) including 11 delayed anastomosis with colonic pull-through, biomesh interposition (n = 9, 3%), and abdominoperineal resection (n = 9; 3%)]. After a mean follow-up of 33 months, overall success rate was 57 of 79 (72%). Per-procedure-based multivariate analysis identified major procedure [odds ratio (OR): 6.4 (2.9-14.2); P < 0.001], diverting stoma [OR: 3.5 (1.4-8.7); P = 0.009], less than 9 months between diagnosis and first surgery [OR: 2.3 (1.1-5.3); P = 0.046], and first surgery in our institution [OR: 3.2 (1.5-6.9); P = 0.003], as independent factors for success. CONCLUSIONS: Our study suggested that aggressive surgical treatment of RVF, including early use of temporary stoma and major procedure in case of failure of previous local treatment, leads to high success rates.

Perineal or Abdominal Approach First During Intersphincteric Resection for Low Rectal Cancer: Which Is the Best Strategy?

BACKGROUND: Intersphincteric resection during total mesorectal excision for low rectal cancer can be performed through a primary abdominal or a primary perineal approach. OBJECTIVE: The purpose of this study was to compare the results of a primary perineal approach with those of a primary abdominal approach in patients undergoing laparoscopic total mesorectal excision for low rectal cancer. DESIGN: This was a case-matched retrospective study from a prospectively maintained database. SETTING: The study was conducted at a tertiary colorectal surgery referral center. PATIENTS: From 2005 to 2013, among 138 patients with low rectal cancer who underwent total mesorectal excision with intersphincteric resection, 34 patients with a primary abdominal approach (abdominal group) were matched with 51 identical patients with a primary perineal approach (6-cm perineal dissection along the mesorectal plane; perineal group), according to TNM stage, sex, BMI, and age. MAIN OUTCOMES MEASURES: Postoperative morbidity, oncologic outcomes, and 3-year overall and disease-free survivals were measured. RESULTS: The operative time was significantly shorter in the perineal group (269 minutes in perineal vs 240 minutes in abdominal group; p = 0.01). Overall morbidity (47% vs 47%; p = 1.00), severe morbidity (16% vs 15%; p = 0.90), and clinical anastomotic leakage (24% vs 12%; p = 0.17) rates showed no differences when comparing the 2 groups. The overall R1 resection rate was similar in the 2 groups (16% vs 9%; p = 0.36), including a 10% vs 9% positive circumferential margin (p = 0.88) and a 8% vs 0% positive distal margin (p = 0.15). After a median follow-up of 39 months, 3-year overall (100% vs 93% (95% CI, 88%-98%); p = 0.26) and disease-free (63% (95% CI, 56%-71%) vs 62% (95% CI, 53%-71%); p = 0.58) survival rates showed no differences between the 2 groups. LIMITATIONS: The study was limited by its nonrandomized nature and limited sample size. CONCLUSIONS: In cases of laparoscopic total mesorectal excision with intersphincteric resection for low rectal cancer, the primary perineal approach appears to reduce operative time and is associated with similar short- and long-term outcomes as compared with the primary abdominal approach. The primary perineal approach should thus be considered as the standard strategy.

Redo-surgery by transanal colonic pull-through for failed anastomosis associated with chronic pelvic sepsis or rectovaginal fistula.

PURPOSE: Redo-surgery with new colorectal (CRA) or coloanal (CAA) anastomosis for failed previous CRA or CAA is exposed to failure and recurrent leakage, especially in case of rectovaginal fistula (RVF) or chronic pelvic sepsis (CPS). In these two situations, transanal colonic pull-through and delayed coloanal anastomosis (DCAA) could be an alternative to avoid definitive stoma. This study aimed to assess results of such redo-surgery with DCAA for failed CRA or CAA with CPS and/or RVF. METHODS: All patients who underwent DCAA for failed CRA or CAA with CPS and/or RVF were reviewed. Success was defined as a patient without any stoma at the end of follow-up. Long-term functional results were assessed using the low anterior resection syndrome (LARS) score. RESULTS: 24 DCAA were performed after failed CRA or CAA with CPS (n = 15) or RVF (n = 9). Sixteen (67%) patients had a diverting stoma at the time (n = 5) or performed during DCAA (n = 11). After a mean follow-up of 29 ± 19 months, success rate was 79% (19/24): 5 patients had a permanent stoma because of recurrent sepsis (n = 2), anastomotic stricture (n = 1), or poor functional outcomes (n = 2). Functional outcomes were satisfactory (no or minor LARS) in 82% of the successful patients. CONCLUSION: In case of failed CRA or CAA with CPS or RVF, DCAA was associated with a 79% success rate. It could therefore be proposed as an alternative to standard redo-CRA or CAA when the risk of recurrent sepsis and failure with subsequent definitive stoma is thought to be high.

Does single port improve results of laparoscopic colorectal surgery? A propensity score adjustment analysis.

BACKGROUND: The benefit of single-incision laparoscopy (SIL) over conventional multiport laparoscopy (ML) is not demonstrated in colorectal surgery, mainly because of potentially biased reports. The objective of this study was to compare SIL to ML for colorectal resection, using a propensity score (PS) adjusted analysis. METHODS: From July 2009 to April 2013, 764 patients who underwent 799 colorectal resections by SIL or ML were analyzed. PS was estimated using a logistic regression model. RESULTS: Eighty-four colorectal resections were performed using SIL: 43 ileocolic resections, 15 right-sided colectomies, 14 left-sided colectomies, 5 rectal resections, 4 subtotal colectomies, and 3 total proctocolectomies. Intra-operative complications occurred in 3 procedures (4 %), and conversion laparotomy in 10 (12 %). Postoperative mortality was nil and overall morbidity rate was 25 %, including 7 % of major complications. Mean postoperative length of hospital stay was 8 ± 6 (4-47) days. Outcomes of SIL, when compared to those of 715 ML and after PS adjustment, showed no difference in terms of intra-operative complication (p = 0.315), conversion to open surgery (p = 0.387), overall morbidity (p = 0.393), major morbidity (p = 0.381), or length of postoperative hospital stay (p = 0.080). However, the length of hospital stay was significantly shorter after SIL in the right colectomy subgroup (p = 0.001). CONCLUSIONS: In colorectal surgery, SIL appears to be safe and effective as compared to ML. It can also reduce hospital stay after right colectomy. These results, if confirmed by randomized trials, would validate SIL in colorectal surgery.

Risk factors for circumferential R1 resection after neoadjuvant radiochemotherapy and laparoscopic total mesorectal excision: a study in 233 consecutive patients with mid or low rectal cancer.

PURPOSE: This study aimed to identify risk factors for circumferential R1 resection (R1c) after neoadjuvant radiochemotherapy (RCT) and laparoscopic total mesorectal excision (TME) for mid or low rectal cancer. Better knowledge of pre- or intraoperative risk factors could possibly help for the management of these patients. METHODS: Between 2005 and 2013, 233 consecutive patients undergoing laparoscopic TME for low or mid rectal cancer after RCT were included. R1c resection was defined as a circumferential margin ≤ 1 mm. Univariate and multivariate analyses were performed to identify independent risk factors for R1c. RESULTS: Twenty-five patients had R1c resection (11%). In univariate analysis, low rectal cancer, anterior tumour, T4 on pretherapeutic magnetic resonance imaging (MRI), T4 and/or N+ on post-RCT MRI and operative time > 240 min were associated with a significantly increased risk of R1c resection. In multivariate analysis, only T4 on post-RCT MRI (odds ratio (OR) = 6.02 [1.06-33]; p = 0.043) and operative time >240 min. (OR = 5.4 [1.01-28.9]; p = 0.049) were identified as independent risk factors for R1c resection. The risk of R1c resection was 3% (n = 3/88), 10% (n = 5/51) or 38% (n = 3/8) when 0, 1 or 2 risk factors were present in the same patient, respectively. CONCLUSION: Patients with T4 on MRI after RCT and/or operative time >240 min. seems to be at higher risk for R1c resection. In a pragmatic approach, we consider that systematic second MRI after RCT could help the surgeon, especially in area where circumferential margin is too short, in order to reduce this risk of R1 resection.

Does anastomotic leakage impair functional results and quality of life after laparoscopic sphincter-saving total mesorectal excision for rectal cancer? A case-matched study.

PURPOSE: Anastomotic leakage (AL) after total mesorectal excision (TME) for rectal cancer is suspected to alter function. However, very few reports have been devoted to this problem. The aim of this study was to assess the influence of AL on function and quality of life (QoL) after laparoscopic TME for cancer. METHODS: A total of 170 patients who underwent laparoscopic TME and sphincter-saving surgery for mid and low rectal cancer were included (67 % after neoadjuvant chemoradiotherapy). Twenty-one patients with AL were assessed for function and QoL (Short Form 36 (SF-36), Fecal Incontinence Quality of Life (FIQL), CR-29, and Wexner's score) at the most recent follow-up. These patients were matched to 42 patients without AL according to sex, body mass index, ypTNM, radiotherapy, and type of anastomosis. RESULTS: After a median follow-up of 30 months, AL significantly impaired physical activity (SF-36) (p = 0.004), self-respect (FIQL) (p = 0.029), wear pad's score (Wexner's score) (p = 0.043), and blood and mucus in stool score (CR-29) (p = 0.001). Overall Wexner's score did not show any significant difference in the two groups, 8.9 in AL patients vs. 11.6 in patients without AL (p = 0.1). CONCLUSION: AL significantly impairs both functional results and quality of life after laparoscopic sphincter-saving TME for rectal cancer. However, the observed difference was only limited, leading to similar outcomes on most of the tested scores. Patients with AL should be warned that if they initially experience severely impaired results, outcomes tend with time to become similar to those observed in noncomplicated patients.

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.

Laparoscopic resection of retrorectal tumors: a feasibility study in 12 consecutive patients.

BACKGROUND: Surgical approaches for retrorectal tumors (RRT) are either abdominal, dorsal trans-sacrococcygeal, or perineal. Very few cases have been reported so far concerning a laparoscopic approach. The aim of this study was to assess the results of laparoscopy for the treatment of RRT. METHODS: All patients who underwent laparoscopy for RRT between 2003 and 2012 were reviewed. Data included patient and tumor characteristics, surgical morbidity, and mortality. RESULTS: A total of 12 consecutive women with a median age of 55 years underwent laparoscopy for RRT. Median operative time was 145 min (range 70-215). Two conversions in laparotomy occurred, and one patient needed a temporary diverting ileostomy for rectal injury. Postoperatively, two patients presented urinary tract infections. Median length of stay was 8 days (range 4-16). Pathological examinations showed complete resections (R0) for ten benign tumors and one malignant tumor (Ewing sarcoma). One lesion was incompletely resected, a colloid sarcoma (R1 status), and was re-operated on by laparotomy after neoadjuvant chemoradiation. No local recurrence was observed after a median follow-up of 34 months (range 12-79) for benign lesions, and 28 and 71 months for the two patients who underwent resection of Ewing and colloid sarcoma, respectively. CONCLUSIONS: Laparoscopic resection for RRT seems feasible and safe. It allows complete excision of tumors located in the retrorectal space with low morbidity. Thus, this approach can be a valid alternative to standard Kraske or open abdominal approaches for the treatment of RRT.

Effects of a multimodal management strategy for acute mesenteric ischemia on survival and intestinal failure.

BACKGROUND & AIMS: Acute mesenteric ischemia (AMI) is an emergency with a high mortality rate; survivors have high rates of intestinal failure. We performed a prospective study to assess a multidisciplinary and multimodal management approach, focused on intestinal viability. METHODS: In an Intestinal Stroke Center, we developed a multimodal management strategy involving gastroenterologists, vascular and abdominal surgeons, radiologists, and intensive care specialists; it was tested in a pilot study on 18 consecutive patients with occlusive AMI, admitted to a tertiary center from July 2009 to November 2011. Patients with left ischemic colitis, nonocclusive AMI, chronic mesenteric ischemia, and other emergencies were excluded. Patients received specific medical management: revascularization of viable small bowel and/or resection of nonviable small bowel; 12 patients received arterial revascularization. We evaluated the percentages of patients who survived for 30 days or 2 years, the number with permanent intestinal failure, and morbidity. Lengths and rates of intestinal resection were compared with or without revascularization, and in patients with early or late-stage disease. RESULTS: Patients were followed up for a mean of 497 days (range, 7-2085 d); 95% survived for 30 days, 89% survived for 2 years, and 28% had morbidities within 30 days. Intestinal resection was necessary for 7 cases (39%), with mean lengths of intestinal resection of 30 cm and 207 cm, with or without revascularization, respectively (P = .03). Among patients with early or late-stage AMI, rates of resection were 18% and 71%, respectively (P = .049). Patients with early stage disease had shorter lengths of intestinal resection than those with late-stage disease (7 vs 94 cm; P = .02), and spent less time in intensive care (2.5 vs 49.8; P = .02). CONCLUSIONS: A multidisciplinary and multimodal management approach might increase survival of patients with AMI and prevent intestinal failure.

Safety, feasibility, and short-term outcomes of single port access colorectal surgery: a single institutional case-matched study.

BACKGROUND: Feasibility of single port access (SPA) colorectal surgery has been established for various procedures from ileocecal resection to proctectomy. Nevertheless, its benefits compared to conventional laparoscopy still need to be assess. The aim of this study was to compare SPA to conventional colorectal laparoscopic surgery in a single institutional case-matched study. METHODS: From July 2009 to July 2010, 25 SPA colorectal resections were matched on main predictive risk factors of postoperative complications, in a one to two fashion, with patient having the same procedure for the same indication by conventional laparoscopy. RESULTS: Patient characteristics were comparable between both groups. SPA was successfully performed in 24 of 25 patients, with a need to conversion to standard laparoscopy in one case (4%). SPA was associated with a significantly shorter median operative time (130 vs 180 min, p = 0.04) and hospital stay (6 vs 7 days, p = 0.005). Postoperative morbidity rates were similar between the two groups (4% vs 16%, p = 0.25). CONCLUSION: SPA colorectal resection can be safely performed in selected patients with results comparable to those observed after conventional laparoscopic surgery. However, larger studies including randomized controlled trail are needed to demonstrate possible benefits of SPA colorectal resection over conventional colorectal laparoscopic surgery.

Redo surgery for failed colorectal or coloanal anastomosis: a valuable surgical challenge.

BACKGROUND: Redo surgery (RS) in patients with failed anastomosis is a rare procedure, and data about this surgery are lacking. The aim of this study was to examine the operative results and long-term outcomes of RS. METHODS: All patients who underwent RS between 1999 and 2008 were included. Data were analyzed from a prospective colorectal database. Failure of the procedure was defined as the inability to perform the RS or the inability to close the defunctioning stoma. RESULTS: Thirty-three patients (22 men) underwent the first surgery at a mean age of 53.4 years. Twenty-four had a colorectal anastomosis (CRA) and nine a coloanal anastomosis (CAA). The reasons for performing RS were stricture (n = 17), prior Hartmann procedure for complication on initial anastomosis (n = 6), chronic fistula (n = 5) or miscellaneous (n = 5). RS was impossible for 2 patients due to extensive adhesions. The mean operating time was 279 min (133-480) and the overall postoperative morbidity rate was 55%. The rate of anastomotic leakage and/or isolated pelvic abscess was 27%. After a mean delay of 3.9 months (0.3-16), 26 patients (79%) had a stoma closure. The mean number of stools per day was 3.2. The failure rates after new handsewn CAA and new stapled CRA were 33% (4/12) and 5% (1/19), respectively (P = .0385). The type of the former anastomosis influenced the success rate of restoring the intestinal continuity: failure rate after prior CAA was 56% and 8% after prior CRA (P = .0031). CONCLUSION: Redo surgery for failure of previous CRA or CAA is feasible but requires a demanding surgical procedure with high short-term morbidity.