Benoit Romain

Long-term survival after liver resection for colorectal liver metastases in patients with hepatic pedicle lymph nodes involvement in the era of new chemotherapy regimens.

Summary and Background:Survival benefit, in patients with colorectal liver metastases (CLM) and hepatic pedicle lymph nodes (HPLN) involvement along the common hepatic artery and celiac axis (area 2 or distal) has not been observed. However, these results are based on historical series, using suboptimal chemotherapy drugs. Objective:The aim of the present study is to investigate the impact of HPLN involvement on survival after resection for CLM in the era of the new chemotherapy regimens. Patients and Methods:Between January 2000 and June 2006, 45 high risk consecutive patients presenting all with pathologically proven HPLN metastases were identified from a prospectively maintained database. Prognostic factors for survival and recurrence were analyzed. Results:The mean follow-up was 25.5 months. HPLN involvement was located in area 1 in 17 patients, area 2 in 10, and both area 1 and 2 were involved in 18 patients. The overall 3- and 5-year survival rates were 29.7% and 17.3%, respectively. The median survival was 20.9 months. Three patients are alive and disease-free at 32.4, 33.5, and 46.9 months, respectively. The multivariate analysis showed that the carcinoembryonic antigen blood level before hepatectomy, a curative intent R0 liver resection, the ratio of involved/total resected HPLN, and an adjuvant chemotherapy after liver resection were independent risk factors for overall survival. Conclusions:This study showed that the localization of HPLN metastases within area 1 or 2 does not anymore affect survival after CLM resection. Furthermore, this study provides a support to perform a routine HPLN dissection in high risk patients undergoing liver resection for CLM to recognize HPLN involvement, to improve the ratio of involved/total resected lymph nodes, and to assign the patients for an adjuvant chemotherapy. Finally, these results indicate that curative intent R0 liver resection with HPLN dissection can offer the only potential cure for patients with CLM who present with HPLN involvement.

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer

Background:We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.Methods:Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.Results:Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.Conclusions:mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.

To Drain or Not to Drain Infraperitoneal Anastomosis After Rectal Excision for Cancer: The GRECCAR 5 Randomized Trial.

Objective: To assess the effect of pelvic drainage after rectal surgery for cancer. Background: Pelvic sepsis is one of the major complications after rectal excision for rectal cancer. Although many studies have confirmed infectiveness of drainage after colectomy, there is still a controversy after rectal surgery. Methods: This multicenter randomized trial with 2 parallel arms (drain vs no drain) was performed between 2011 and 2014. Primary endpoint was postoperative pelvic sepsis within 30 postoperative days, including anastomotic leakage, pelvic abscess, and peritonitis. Secondary endpoints were overall morbidity and mortality, rate of reoperation, length of hospital stay, and rate of stoma closure at 6 months. Results: A total of 494 patients were randomized, 25 did not meet the criteria and 469 were analyzed: 236 with drain and 233 without. The anastomotic height was 3.5 ± 1.9 cm from the anal verge. The rate of pelvic sepsis was 17.1% (80/469) and was similar between drain and no drain: 16.1% versus 18.0% (P = 0.58). There was no difference of surgical morbidity (18.7% vs 25.3%; P = 0.83), rate of reoperation (16.6% vs 21.0%; P = 0.22), length of hospital stay (12.2 vs 12.2; P = 0.99) and rate of stoma closure (80.1% vs 77.3%; P = 0.53) between groups. Absence of colonic pouch was the only independent factor of pelvic sepsis (odds ratio = 1.757; 95% confidence interval 1.078–2.864; P = 0.024). Conclusions: This randomized trial suggests that the use of a pelvic drain after rectal excision for rectal cancer did not confer any benefit to the patient.

Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases

Background:Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC).Methods:We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012.Results:mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS: 43 months; TTR: 19 months) compared with mEGFR (OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS: KRAS G12V: 26 months vs Cohort: 60 months; DFS: KRAS G12V: 15 months vs Cohort: 24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28–0.65), P<0.0001 for OS; HR: 0.67 (0.48–0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR: 0.01, (0.001–0.08), P<0.0001).Conclusions:mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.

Complex abdominal wall defect reconstruction using a latissimus dorsi free flap with mesh after malignant tumor resection.

Extended and full‐thickness abdominal wall defects are commonly reconstructed using free flaps. Published surgical outcomes involving the latissimus dorsi (LD) free flap procedure are limited and are less numerous than those with free flaps involving the thigh. The aim of this report was to describe the immediate and long‐term evaluation of complex abdominal wall reconstruction using a LD free flap with mesh.

KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer

Introduction The utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC). Results KRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61–82.56) vs 56 months (95% CI: 68.71–127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93–59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17–0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14–1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations. Materials and Methods We retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations. Conclusions KRAS exon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†

OBJECTIVES The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status. METHODS We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known. RESULTS A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001]. CONCLUSION Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.

Impact of weekday surgery on application of enhanced recovery pathway: a retrospective cohort study

Objective To compare the enhanced recovery after surgery (ERAS) protocol compliance and clinical outcomes depending on the weekday of surgery. Settings Cohort of consecutive non-selected patients undergoing elective colorectal surgery from January 2012 to March 2015. This retrospective analysis of our prospective database compared patients operated early in the week (Monday and Tuesday) with patients operated in the second half (late: Thursday, Friday). Primary outcome measures Compliance with the ERAS protocol, functional recovery, complications and length of stay. Results Demographic and surgical details were similar between the early (n=352) and late groups (n=204). Overall compliance with the ERAS protocol was 78% vs 76% for the early and late groups, respectively (p=0.009). Significant differences were notably prolonged urinary drainage and intravenous fluid infusion in the late group. Complication rates and length of stay, however, were not different between surgery on Monday or Tuesday and surgery on Thursday or Friday. Conclusions Application of the ERAS protocol showed only minor differences for patients operated on early or late during the week, and clinical outcomes were similar. A fully implemented ERAS programme appears to work also over the weekend.

The Added Diagnostic Value of 18 F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors

BackgroundThe precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs.MethodsBetween January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology.ResultsThere were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003).Conclusion18F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

Avoiding delayed diagnosis of significant blunt bowel and mesenteric injuries: Can a scoring tool make the difference? A 7-year retrospective cohort study

INTRODUCTION Significant blunt bowel and mesenteric injuries (sBBMI) are frequently missed despite the widespread use of computed tomography (CT). Early treatment improves the outcome related to these injuries. The aim of this study was to assess the prevalence of sBBMI, the incidence of delayed diagnosis and to test the performance of the Bowel Injury Prediction Score (BIPS), determined by the white blood cell (WBC) count, presence or absence of abdominal tenderness and CT grade of mesenteric injury. PATIENTS AND METHODS Single-centre, registry-based retrospective cohort study, screening all consecutive trauma patients admitted to Lausanne University Hospital Trauma Centre from 2008 to 2015 after a road traffic accident. All patients with reliable information about the presence or absence of sBBMI who underwent abdominal CT and for whom calculation of the BIPS was possible were included for analysis. The incidence of delayed (>24h after admission) diagnosis in the patient group with sBBMI was determined and the diagnostic performance of the BIPS for sBBMI was assessed. RESULTS For analysis, 766 patients with reliable information about the presence or absence of sBBMI were included. The prevalence of sBBMI was 3.1% (24/766). In 24% (5/21) of stable trauma patients undergoing CT, a diagnostic delay of more than 24h occurred. Abdominal tenderness (p<0.0001) and CT grade ≥4 (p<0.0001) were associated with sBBMI, whereas CT grade 4 alone (p=0.93) and WBC count ≥17G/l (p=0.30) were not. A BIPS ≥2 had a sensitivity of 89% (95% CI, 67-99), specificity of 89% (95% CI, 86-91), positive likelihood ratio of 8 (95% CI, 6.1-10), negative likelihood ratio of 0.12 (95% CI, 0.03-0.44), positive predictive value (PPV) of 19% (95% CI, 15-24) and negative predictive value (NPV) of 99.7% (95% CI, 98.7-99.9). CT alone identified 79% (15/19) and the BIPS 89% (17/19) of patients with sBBMI (p=0.66). CONCLUSIONS Diagnostic delays in patients with sBBMI are common (24%), despite the routine use of abdominal CT. Application of the BIPS on the present cohort would have led to a high number of non-therapeutic abdominal explorations without identifying significantly more sBBMI early than CT alone.