Computer-assisted Individualized Hemodynamic Management Reduces Intraoperative Hypotension in Intermediate- and High-risk Surgery: A Randomized Controlled Trial.

BACKGROUND: Individualized hemodynamic management during surgery relies on accurate titration of vasopressors and fluids. In this context, computer systems have been developed to assist anesthesia providers in delivering these interventions. This study tested the hypothesis that computer-assisted individualized hemodynamic management could reduce intraoperative hypotension in patients undergoing intermediate- to high-risk surgery. METHODS: This single-center, parallel, two-arm, prospective randomized controlled single blinded superiority study included 38 patients undergoing abdominal or orthopedic surgery. All included patients had a radial arterial catheter inserted after anesthesia induction and connected to an uncalibrated pulse contour monitoring device. In the manually adjusted goal-directed therapy group (N = 19), the individualized hemodynamic management consisted of manual titration of norepinephrine infusion to maintain mean arterial pressure within 10% of the patient's baseline value, and mini-fluid challenges to maximize the stroke volume index. In the computer-assisted group (N = 19), the same approach was applied using a closed-loop system for norepinephrine adjustments and a decision-support system for the infusion of mini-fluid challenges (100 ml). The primary outcome was intraoperative hypotension defined as the percentage of intraoperative case time patients spent with a mean arterial pressure of less than 90% of the patient's baseline value, measured during the preoperative screening. Secondary outcome was the incidence of minor postoperative complications. RESULTS: All patients were included in the analysis. Intraoperative hypotension was 1.2% [0.4 to 2.0%] (median [25th to 75th] percentiles) in the computer-assisted group compared to 21.5% [14.5 to 31.8%] in the manually adjusted goal-directed therapy group (difference, -21.1 [95% CI, -15.9 to -27.6%]; P < 0.001). The incidence of minor postoperative complications was not different between groups (42 vs. 58%; P = 0.330). Mean stroke volume index and cardiac index were both significantly higher in the computer-assisted group than in the manually adjusted goal-directed therapy group (P < 0.001). CONCLUSIONS: In patients having intermediate- to high-risk surgery, computer-assisted individualized hemodynamic management significantly reduces intraoperative hypotension compared to a manually controlled goal-directed approach.

What is the Best Therapeutic Strategy for Metachronous Resectable Colorectal Liver Metastases After Adjuvant Oxaliplatin-Based Chemotherapy? A Multidisciplinary Inter-Group Survey.

BACKGROUND: To report the current clinical practice of French physicians for metachronous resectable liver metastasis (LM) occurring after a FOLFOX adjuvant chemotherapy for primary cancer. METHODS: Twenty four clinical situations were proposed to a panel of experts via 4 learned societies. Clinical situations varied according time of recurrence (early between 6 and 12 month or > 12 month), extension of LM (limited ≤ 2 or extended > 2 lesions), presence of a neuropathy or not, and of a RAS or BRAF mutation. RESULTS: A total of 157 physicians participated in this study. A consensus was reached in 17 (71%) clinical situations. For an early limited recurrence, whatever presence of neuropathy, the preferred therapeutic approach (45%) was upfront surgery. For an early extended recurrence, whatever presence of neuropathy, there was a consensus (64%) for a preoperative chemotherapy by FOLFIRI + biologic agent. For a late recurrence without neuropathy, there was a consensus (50%) for a preoperative FOLFOX chemotherapy, whatever the extension of LM. For a late recurrence with neuropathy, upfront surgery was chosen (52%) for limited LM, and preoperative chemotherapy by FOLFIRI + biologic agent (73%) for extended LM. No response was influenced by the RAS mutation status. There was a strong consensus for intensified preoperative chemotherapy in all clinical situations for BRAF-mutated LM. CONCLUSIONS: This national survey provides an overview of the practice patterns in the treatment of LM occurring after adjuvant FOLFOX for primary. It could be a basis to establish expert's recommendations for the clinical practice.

What is the Prognostic Value of a Discordant Radiologic and Pathologic Response in Patients Undergoing Resection of Colorectal Liver Metastases After Preoperative Chemotherapy?

BACKGROUND: The clinical significance of discordant radiological and pathological response to preoperative chemotherapy of colorectal liver metastases (CLM) is unknown. METHODS: From 2011 to 2016, all eligible patients undergoing resection for CLM after preoperative chemotherapy were included at two centres. Patients were categorized according to radiologic response using RECIST as Rad-responders (complete/partial response) or Rad-non responders (stable disease) and according to Blazer et al. pathologic response grade as Path-responders (complete/major response) or Path-non responders (minor response). Survival outcome was analysed according to radiologic and pathologic response. RESULTS: Among 413 patients undergoing resection of CLM, 119 fulfilled the inclusion criteria. Among these, 52 (44%) had discordant radiologic and pathologic response including 27 Rad-non responders/path responders and 25 Rad-responders/Path-non responders. Rad-non responders/path responders and Rad-responders/Path-non responders had similar characteristics except for the proportion receiving more than 6 cycles of preoperative chemotherapy (7/27 vs 16/25; P = 0.017). Median disease-free survival was not different in patients with or without discordant radiologic and pathologic responses (P = 0.195) but the type of discordance had an impact on oncologic outcome as median disease-free survival was 13.9 months (95% CI 5.7-22.2 months) in Rad-non responders/Path responders and 8.6 (6.2 - 10.9 months) in Rad-responders/Path-non responders (P = 0.034). Univariate and multivariate analysis showed that major pathologic response was associated with improved disease-free survival (OR 0.583, 95% CI 0.36-0.95, P = 0.031). CONCLUSION: A discordant radiologic and pathologic response is common after preoperative chemotherapy for CLM. In these patients, pathologic response drives oncologic outcome.

Short-term and Long-term Outcome of Endoluminal Vacuum Therapy for Colorectal or Coloanal Anastomotic Leakage: Results of a Nationwide Multicenter Cohort Study From the French GRECCAR Group.

BACKGROUND: The indications and efficacy of endoluminal vacuum therapy for the management of colorectal/coloanal anastomotic leakage are not well defined. OBJECTIVE: This study aimed to evaluate the efficacy and to define adequate indications of endoluminal vacuum therapy to treat colorectal/coloanal anastomotic leakage. DESIGN: The retrospective cohort evaluated in this study is based on a prospectively maintained database. SETTINGS: This study was conducted in 8 centers from the French GRECCAR study group. PATIENTS: Patients with colorectal/coloanal anastomotic leakage treated with endoluminal vacuum therapy were included. MAIN OUTCOME MEASURES: The primary outcome measured was the success rate of endoluminal vacuum therapy defined by the complete healing of the perianastomotic sepsis and a functional anastomosis. The predictive factors of success of endoluminal vacuum therapy and long-term functional result (low anterior resection syndrome score) were also analyzed. RESULTS: Among 62 patients treated for an anastomotic leakage of colorectal/coloanal anastomosis from 2012 to 2017, 47 fulfilled the inclusion criteria. The patients had a mean of 6.6 (±5.8) replacements for a total of 27 (±34) days treatment duration, associated with diverting stoma in 81%. After 37 months median follow-up, a successful treatment of anastomotic leakage using endoluminal vacuum therapy could be achieved in 26 patients (55%). The success rate was improved in patients undergoing primary endoluminal vacuum therapy compared to salvage endoluminal vacuum therapy (73% vs 33%, p = 0.006) and when endoluminal vacuum therapy was initiated within 15 days compared to more than 15 days after the diagnosis of anastomotic leakage (72.4% vs 27.8%, p = 0.003). At 12 months, 53% of patients who responded had minor low anterior resection syndrome and only 3 necessitated anastomotic stricture dilation. LIMITATIONS: This was a noncomparative cohort study. CONCLUSION: Endoluminal vacuum therapy appears to be effective to treat colorectal anastomotic leakage especially when it is used as primary treatment of the fistula. Long-term functional outcome of patients undergoing conservative management of anastomotic leakage may be improved with endoluminal vacuum therapy. See Video Abstract at http://links.lww.com/DCR/B103. RESULTADOS A CORTO Y LARGO PLAZO DE LA TERAPIA DE VACÍO ENDOLUMINAL PARA LA FUGA ANASTOMÓTICA COLORRECTAL O COLOANAL: RESULTADOS DE UN ESTUDIO DE COHORTE MULTICÉNTRICO A NIVEL NACIONAL DEL GRUPO FRANCÉS GRECCAR: Las indicaciones y la eficacia de la terapia de vacío endoluminal para el tratamiento de la fuga anastomótica colorrectal / coloanal no están bien definidas.Evaluar la eficacia y definir indicaciones adecuadas de la terapia de vacío endoluminal para tratar la fuga anastomótica colorrectal / coloanal.Cohorte retrospectivo basada en una base de datos mantenida prospectivamente.Este estudio se realizó en 8 centros del grupo de estudio Francés GRECCAR.Se incluyeron pacientes con fuga anastomótica colorrectal / coloanal tratados con terapia de vacío endoluminal.Tasa de éxito de la terapia de vacío endoluminal definida por la curación completa de la sepsis perianastomótica y una anastomosis funcional. También se analizaron los factores predictivos del éxito de la terapia de vacío endoluminal y el resultado funcional a largo plazo (puntaje bajo del síndrome de resección anterior).Entre 62 pacientes tratados por una fuga anastomótica de anastomosis colorrectal / coloanal de 2012 a 2017, 47 cumplieron los criterios de inclusión. Los pacientes tuvieron una media de 6.6 (±5.8) reemplazos para un total de 27 (±34) días de duración del tratamiento, asociado con estoma de desvio en el 81%. Después de una mediana de seguimiento de 37 meses, se pudo lograr un tratamiento exitoso de la fuga anastomótica usando terapia de vacío endoluminal en 26 pacientes (55%). La tasa de éxito mejoró en pacientes sometidos a terapia de vacío endoluminal primaria en comparación con la terapia de vacío endoluminal de rescate (73% frente a 33%, p = 0.006) y cuando la terapia de vacío endoluminal se inició dentro de los 15 días en comparación con más de 15 días después del diagnóstico de fuga anastomótica (72.4% vs 27.8%, p = 0.003). A los 12 meses, el 53% de los pacientes que respondieron tenían síndrome de resección anterior baja leve y solo 3 necesitaban dilatación de estenosis anastomótica.Estudio de cohorte no comparativo.La terapia de vacío endoluminal parece ser efectiva para tratar la fuga anastomótica colorrectal, especialmente cuando se usa como tratamiento primario de la fístula. El resultado funcional a largo plazo de los pacientes sometidos a un tratamiento conservador de la fuga anastomótica puede mejorarse con la terapia de vacío endoluminal. Consulte Video Resumen en http://links.lww.com/DCR/B103.

What are the risk factors of failure of enhanced recovery after right colectomy? Results of a prospective study on 140 consecutive cases.

PURPOSE: Nausea and vomiting is the main cause of failure of enhanced recovery protocol (ERP) after right hemicolectomy. METHODS: From January 2013 to January 2018, all patients undergoing right hemicolectomy were prospectively included. Patients undergoing emergency surgery, additional complex procedure or temporary stoma, nasogastric tube (NGT) maintenance, or abdominal drainage were excluded. Failure of ERP was defined as nausea/vomiting precluding oral feeding after POD3 and/or the occurrence of postoperative ileus requiring NGT and/or length of stay (LOS) ≥ 8 days except for patients awaiting admission in rehabilitation unit. Risk factors of failure of ERP were identified using univariate and multivariate analysis. RESULTS: Among 306 patients undergoing right hemicolectomy, 140 fulfilled the inclusion criteria. Postoperative morbidity was 31%, and the mortality rate was nil. The mean postoperative hospital stay was 7 days (range 2-30). Successful ERP was achieved in 83 patients (59%). Causes of failure were major nausea/vomiting precluding oral feeding after POD3 in 36, postoperative ileus requiring NGT in 16 and LOS ≥ 8 days in 36. On multivariate analysis, preoperative anemia (OR 5.2; CI 95%, 1.3-21.1, p = 0.02) and platelet anti-aggregant/anti-coagulant (OR 4.5; CI 95%, 1.7-12.1, p = 0.003) were associated with the risk of failure of ERP. CONCLUSION: This study shows that anemia and medication with antiplatelet/anticoagulation therapy increase the risk of failure of ERP after right hemicolectomy that translates most of the time by nausea/vomiting and postoperative ileus. The presence of these factors should lead to adapt the strategy to improve outcome rather than be considered as contraindication to ERP.

Prognostic Value of Sterilized Lymph Nodes After Preoperative Chemoradiotherapy for Patients with ypN0 Rectal Cancer.

BACKGROUND: Patients with ypN0 rectal cancer who have received preoperative chemoradiotherapy can be divided into those who initially were node negative and those whose positive nodes have been sterilized by preoperative therapy. The long-term prognosis for ypN0 patients with sterilized lymph nodes (LNS) is unknown. This study aimed to assess the prognostic value of LNS after preoperative chemoradiotherapy for patients with ypN0 rectal cancer. METHODS: From January 2007 to March 2014, 206 patients with ypN0 tumors of the mid or lower rectum treated by chemoradiotherapy and radical surgery were enrolled in the study. Of these 206 patients, 49 had ypN0 tumors with LNS (LNS+ group), and 157 had ypN0 tumors without LNS (LNS- group). The patients in both groups were comparable in terms of tumor characteristics, type of chemoradiotherapy, type of surgery, R0 resection rate, and postoperative complication rate. RESULTS: The mean follow-up period was 40.5 ± 27 months. The 1- and 3-year OS rates in the LNS+ group were respectively 100 and 95.5% versus 99.4 and 91.6% in the LNS- group (P = 0.549). The 1- and 3-year DFS rates in the LNS+ group were respectively 100 and 94.2% versus 94.7 and 87.1% in the LNS- group (P = 0.117). The multivariate analysis showed that the presence of LNS did not affect OS (P = 0.918) or DFS (P = 0.209). CONCLUSIONS: The prognosis is excellent for patients with ypN0 rectal cancer who have LNS after preoperative chemoradiotherapy. The presence of LNS in ypN0 rectal cancer patients after chemoradiotherapy should not be considered a factor for a poor prognosis.

Preoperative oral polymeric diet enriched with transforming growth factor-beta 2 (Modulen) could decrease postoperative morbidity after surgery for complicated ileocolonic Crohn's disease.

OBJECTIVE: Exclusive polymeric diet enriched with transforming growth factor-beta 2 (ANS-TGF-ß2) has been used for remission induction and maintenance in pediatric Crohn's disease (CD). Its use in the preoperative setting has never been evaluated. The aim of this study was to evaluate preoperative ANS-TGF-ß2 to decrease postoperative complications after surgery for complicated ileocolonic CD. METHODS: From 2011 to 2015, data of all consecutive patients who underwent elective surgery for ileocolonic CD were collected prospectively. Preoperative, exclusive ANS-TGF-ß2 was administered in high-risk patients with complicated CD. Complicated CD was defined by the presence of obstructive symptoms, and/or steroid treatment, and/or preoperative weight loss >10% and/or perforating CD. Outcomes of high-risk patients receiving preoperative ANS-TGF-ß2 were compared to those of low-risk patients with no complicated CD who underwent upfront surgery. RESULTS: Fifty-six patients underwent surgery for ileocolonic CD. Among them, 35 high-risk patients received preoperative ANS-TGF-ß2 and 21 low-risk patients underwent upfront surgery. Preoperative full-dose ANS-TGF-ß2 was feasible in 34/35 high-risk patients. Discontinuation of steroids during preoperative ANS-TGF-ß2 could be achieved in 10/16 patients (62.5%). Postoperative complications rates were 8/35 (23.8%) and 5/21 (22.9%) in high-risk and low-risk patients, respectively (p = 1). Temporary ileocolostomy rates in high-risk patients and in low-risk patients were 4/35 (11%) and 0/21, respectively (p = 0.286) Conclusion: Preoperative ANS-TGF-ß2 is feasible in most high-risk patients with complicated ileocolonic CD and could limit the deleterious effects of risk factors of postoperative morbidity. These results need to be confirmed in a large randomized controlled trial.

The small height of an anastomotic colonic doughnut is an independent risk factor of anastomotic leakage following colorectal resection: results of a prospective study on 154 consecutive cases.

PURPOSE: The aim of this prospective study was to assess the influence of morphological characteristics of anastomotic doughnuts on the risk of anastomotic leakage (AL) after double-stapled colorectal anastomosis. METHODS: This single-center prospective study enrolled all patients undergoing double-stapled colorectal anastomosis between December 2012 and December 2015. Maximal diameter and minimal and maximal heights and widths of both colonic and rectal doughnuts were measured by surgeons in the operating room. Their influence on the risk of AL was analyzed on uni- and multivariate models. RESULTS: One hundred fifty-four patients were included; 92 (59.7%) were operated on for malignancy. Colorectal anastomoses > and <10 cm above the anal verge were performed in 96 (62.3%) and 58 (37.7%) patients, respectively. AL occurred in 17 (11.0%). The minimal height of the colonic doughnut (CD) was the only measurement significantly associated with an increased risk of AL (p = 0.026). A cutoff value of 4.5 mm for the CD determined on the ROC curve (AUC 0.685, p = 0.013) yielded the best sensitivity (61.4%) and specificity (82.4%) to predict AL. On multivariate analysis, a height of the CD <4.5 mm (OR 5.743, 95% IC 1.476-22.346, p = 0.012), malignant disease (OR 8.821, 95% IC 1.051-74.006, p = 0.045), and American Society of Anesthesiologists score >2 (OR 3.408, 95% IC 1.017-11.418, p = 0.047) were the only independent risk factors of AL. CONCLUSION: The CD's minimal height influences the risk of AL. Its routine measurement during operation, along with other risk factors, could help to decide which patients could benefit from a diverting stoma or the creation of a new anastomosis.

Sigmoid resection with primary anastomosis and ileostomy versus laparoscopic lavage in purulent peritonitis from perforated diverticulitis: outcome analysis in a prospective cohort of 40 consecutive patients.

PURPOSE: This prospective study aimed to compare outcomes after laparoscopic peritoneal lavage (LPL) and sigmoid resection with primary colorectal anastomosis (RPA). METHODS: From June 2010 to June 2015, 40 patients presenting with Hinchey III peritonitis from perforated diverticulitis underwent LPL or RPA. Patients with Hinchey II or IV peritonitis and patients who underwent an upfront Hartmann procedure were excluded. Primary endpoint was overall 30-day or in-hospital postoperative morbidity after surgical treatment of peritonitis. RESULTS: Twenty-five patients underwent RPA and 15 LPL. Overall postoperative morbidity and mortality rates were not significantly different after RPA and LPL (40 vs 67 %, p = 0.19; 4 vs 6.7 %, p = 1, respectively). Intra-abdominal morbidity and reoperation rates were significantly higher after LPL compared to RPA (53 vs 12 %, p < 0.01; 40 vs 4 %, p = 0.02, respectively). Multivariate analysis showed that LPL (p = 0.028, HR = 18.936, CI 95 % = 1.369-261.886) was associated with an increased risk of postoperative intra-abdominal septic morbidity. Among 6 patients who underwent reoperation after LPL, 4 had a Hartmann procedure. All surviving patients who had a procedure requiring stoma creation underwent stoma reversal after a median delay of 92 days after LPL and 72 days after RPA (p = 0.07). CONCLUSION: LPL for perforated diverticulitis is associated with a high risk of inadequate intra-abdominal sepsis control requiring a Hartmann procedure in up to 25 % of patients. RPA appears to be safer and more effective. It may represent the best option in this context.

Publication Fate of Research Works Achieved During Master's Degree in Surgical Science in a French Survey.

The aim of this study was to assess the publication fate of research projects performed during the research year by students enrolled in a Master's degree (MSc) of surgical science and to identify factors associated with subsequent publication. An anonymous online survey of 35 questions was sent to students enrolled in MSc of surgical science between 2013 and 2020. The questionnaire included student's characteristics, topic, and supervision of the research projects developed during the research year and dissemination of the research work. Data regarding publication was collected using PubMed database. Factors associated with publication were identified by univariate analysis. Among 361 students, 26% completed the survey. Among respondents, the publication rate of research projects was 53.7%. The median time interval between the end of the research year and the date of publication was 2 (1-3) years. The student was listed as a first author in 70.6% of publications. Factors associated with publication of the research work completed during the research year were student's previous publications (P = 0.041) and presentation of the research work in academic conferences (P = 0.005). The most mentioned cause for non-publication was the absence of completion of the research work. Among respondents, the publication rate of research works performed during the MSc was high, which emphasizes the quality of the work carried out by the students and their involvement. Significant efforts must be undertaken to encourage the enrollment of residents in scientific research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01973-y.

Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease.

BACKGROUND: E-cadherin, a major actor of cell adhesion in the intestinal barrier, is encoded by the CDH1 gene associated with susceptibility to Crohn Disease (CD) and colorectal cancer. Since epigenetic mechanisms are suspected to contribute to the multifactorial pathogenesis of CD, we studied CpG methylation at the CDH1 locus. The methylation of the CpG island (CGI) and of the 1st enhancer, two critical regulatory positions, was quantified in surgical specimens of inflamed ileal mucosa and in peripheral blood mononuclear cells (PBMC) of 21 CD patients. Sixteen patients operated on for a non-inflammatory bowel disease, although not normal controls, provided a macroscopically normal ileal mucosa and PBMC for comparison. RESULTS: In ileal mucosa, 19/21 (90%) CD patients vs 8/16 control patients (50%) (p < 0.01) had a methylated CDH1 promoter CGI. In PBMC, CD patients with methylated CGI were 11/21 (52%) vs 7/16 controls (44%), respectively. Methylation in the 1st enhancer of CDH1 was also higher in the CD group for each of the studied CpGs and for their average value (45 ± 17% in CD patients vs 36 ± 17% in controls; p < 0.001). Again, methylation was comparable in PBMC. Methylation of CGI and 1st enhancer were not correlated in mucosa or PBMC. CONCLUSIONS: Methylation of several CpGs at the CDH1 locus was increased in the inflamed ileal mucosa, not in the PBMC, of CD patients, suggesting the association of CDH1 methylation with ileal inflammation. Longitudinal studies will explore if this increased methylation is a risk marker for colorectal cancer.

Levels of gemcitabine transport and metabolism proteins predict survival times of patients treated with gemcitabine for pancreatic adenocarcinoma.

BACKGROUND & AIMS: Patients who undergo surgery for pancreatic ductal adenocarcinoma (PDAC) frequently receive adjuvant gemcitabine chemotherapy. Key determinants of gemcitabine cytotoxicity include the activities of the human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit 1 (RRM1). We investigated whether tumor levels of these proteins were associated with efficacy of gemcitabine therapy following surgery. METHODS: Sequential samples of resected PDACs were retrospectively collected from 434 patients at 5 centers; 142 patients did not receive adjuvant treatment (33%), 243 received adjuvant gemcitabine-based regimens (56%), and 49 received nongemcitabine regimens (11%). We measured protein levels of hENT1, dCK, and RRM1 by semiquantitative immunohistochemistry with tissue microarrays and investigated their relationship with patients' overall survival time. RESULTS: The median overall survival time of patients was 32.0 months. Among patients who did not receive adjuvant treatment, levels of hENT1, RRM1, and dCK were not associated with survival time. Among patients who received gemcitabine, high levels of hENT1 and dCK were significantly associated with longer survival time (hazard ratios of 0.34 [P < .0001] and 0.57 [P = .012], respectively). Interaction tests for gemcitabine administration and hENT1 and dCK status were statistically significant (P = .0007 and P = .016, respectively). On multivariate analysis of this population, hENT1 and dCK retained independent predictive values, and those patients with high levels of each protein had the longest survival times following adjuvant therapy with gemcitabine. CONCLUSIONS: High levels of hENT1 and dCK in PDAC predict longer survival times in patients treated with adjuvant gemcitabine.

Evaluation of predictive models in daily practice for the identification of patients with Lynch syndrome.

The optimal strategy for identifying patients with Lynch syndrome among patients with newly diagnosed colorectal cancer (CRC) is still debated. Several predictive models (e.g., MMRpredict, PREMM1,2 and MMRpro) combining personal and familial data have recently been developed to quantify the risk that a given patient with CRC carries a Lynch syndrome-causing mutation. Their clinical applicability to patients with CRC from the general population requires evaluation. We studied a consecutive series of 214 patients with newly diagnosed CRC characterized for tumor microsatellite instability (MSI), somatic BRAF mutation, MLH1 promoter methylation and mismatch repair (MMR) gene germline mutation status. The performances of the models for identifying MMR mutation carriers (8/214, 3.7%) were evaluated and compared to the revised Bethesda guidelines and a molecular strategy based on MSI testing in all patients followed by the exclusion of MSI-positive sporadic cases from mutational testing by screening for BRAF mutation and MLH1 promoter methylation. The sensitivities of the three models, at the lowest thresholds proposed, were identical (75%), with similar numbers of probands eligible for further MSI testing (almost half the patients). In our dataset, the prediction models gave no better discrimination than the revised Bethesda guidelines. Both approaches failed to identify two of the eight mutation carriers (the same two patients, aged 67 and 81 years, both with no family history). Thus, like the revised Bethesda guidelines, predictive models did not identify all patients with Lynch syndrome in our series of consecutive CRC. Our results support systematic screening for MMR deficiency in all new CRC cases.

Preservation of genital innervation in women during total mesorectal excision: which anterior plane?

BACKGROUND: Erectile dysfunction, principally related to injury of the autonomic nerve fibers in men, is a major cause of postoperative morbidity after anterolateral dissection during total mesorectal excision (TME) for rectal adenocarcinoma. However, the autonomic innervation of erectile bodies is less known in women, and the anterolateral plane of dissection during TME remains unclear. The existence of the rectovaginal septum(RVS) is controversial. The purpose of the present study was to identify the RVS in the human fetus and adult female by dissection, immunohistochemistry, and three-dimensional reconstruction, and to define its relationship with erectile nerve fibers so as to determine the anterolateral plane of dissection during TME, which could reduce postoperative sexual dysfunction in women. METHOD: Macroscopic dissection, histologic studies, and immunohistochemistry examination with 3D reconstruction were performed in six fresh female adult cadavers and six female fetuses. RESULTS: The RVS was clearly definable in all adult specimens. It was composed of multiple connective tissue, with smooth muscle fibers originating from the uterus and the vagina. It is closely applied to the vagina and has a relationship with the neurovascular bundles (NVBs) that contain erectile fibers intended for the clitoris. The NVBs are situated anteriorly to the posterior extension of rectovaginal septum. This posterior extension protects the NVBs during the anterior and anterolateral dissection for removal of rectal cancer. CONCLUSIONS: To reduce the risk of postoperative sexual dysfunction in women undergoing TME for rectal cancer, we recommend careful dissection to the anterior mesorectum to develop a plane of dissection behind the posterior extension of the RVS if oncologically reasonable.

Neural supply to the clitoris: immunohistochemical study with three-dimensional reconstruction of cavernous nerve, spongious nerve, and dorsal clitoris nerve in human fetus.

INTRODUCTION: Little detailed information is available concerning autonomic and somatic nerve supply to the clitoris, potentially causing difficulties for nerve preservation during pelvic and perineal surgery. AIM: To identify the location and type (nitrergic, adrenergic, cholinergic and sensory) of nerve fibers in the clitoris and to provide a three-dimensional (3D) representation of their structural relationship in the human female fetus. METHODS: Serial transverse sections were obtained from five human female fetuses (18-31 weeks of gestation) and subjected to histological and immunohistochemical investigations; digitized serial sections were used to construct a 3D representation of the pelvis. MAIN OUTCOME MEASURES: Pelvic-perineal nerve location and type were evaluated qualitatively. RESULTS: The female neurovascular bundle (NVB) is the anteroinferior terminal portion of the inferior hypogastric plexus that runs along the postero-lateral then lateral face of the vagina and is rich in nNOS-positive fibers. The cavernous nerve (CN) is a thin ventrocaudal collateral projection of the NVB, and this projection does not strictly follow the NVB course. The CN runs along the lateral surface of the vagina and urethra and penetrates the homolateral clitoral crus. The CN provides adrenergic, cholinergic, and nitrergic innervation to the clitoris, but not sensory innervation. The spongious nerve (SN) is the terminal and main projection of the NVB and provides nitrergic innervation to the vestibular bulbs. The dorsal clitoris nerve (DCN), somatic branche of the pudendal nerve, runs along the superior surface of the clitoral crus and body and has a segmental proerectile nitrergic activity related to communicating branches with the CN. CONCLUSIONS: "Computer-assisted anatomic dissection" allowed the identification of the precise location and distribution of the autonomic and somatic neural supply to female erectile bodies, providing an anatomical basis for nerve-sparing surgical techniques, and participating to the understanding of neurogenic female sexual dysfunction.

A model of primary culture of colorectal cancer and liver metastasis to predict chemosensitivity.

BACKGROUND: Prediction of chemosensitivity is a major goal of modern oncology. The aim of this study was to establish a simple and effective model of primary culture of colorectal cancer fragments and to test whether it allows prediction of chemosensitivity. METHODS: Colorectal cancer fragments (primary tumors or liver metastases) of 94 consecutive and previously untreated patients were obtained, prepared, and cultured in polyHEMA. For each fragment cultured, a proliferative index (PI) was calculated after immunostaining at d 0 and after 7 d in culture with media alone or supplemented for 24h with the topoisomerase I inhibitor metabolite SN-38. The correlation between in vitro response (decrease in PI after exposure to the drug) and in vivo response (RECIST criteria) was studied in a subset of patients who had measurable metastases and were treated with a topoisomerase I inhibitor. RESULTS: PolyHEMA allowed three-dimensional culture of tumor fragments up to 7 d without fibroblastic invasion and with a slight but significant decrease of PI (59% at d 0 versus 51% after 7 d in culture, P < 0.001). In vitro drug efficacy was tested in 67 fragments, the mean PI after culture with SN-38 dropped to 22% (P < 0.001). In a subset of 12 patients, there was no statistically significant correlation between in vitro and in vivo response (P = 0.13). CONCLUSION: Primary culture in polyHEMA was easy to perform successfully in 71% of cases. On this model, the antiproliferative effect of SN-38 could be measured and results correlated to clinical data.

Female pelvic autonomic neuroanatomy based on conventional macroscopic and computer-assisted anatomic dissections.

PURPOSE: To confront nerve dissection, tissue staining, nerve immunolabelling and Computer-Assisted Anatomic Dissection (CAAD) in identifying the precise location and origin of intrapelvic autonomic nerve fibers and to provide a three-dimensional (3D) representation of their relationship to other anatomical structures. METHODS: Serial transverse sections of the pelvic portion of five human female fetuses (18-31 weeks of gestation) were studied histologically (with hematoxylin/eosin and Masson trichrome) and immunohistochemically (anti-protein S100 antibody) digitized and reconstructed three-dimensionally with Surf driver software for Windows (Winsurf 4.3). Three fresh female adult cadavers were macroscopically dissected to individualize the inferior hypogastric plexus afferences and efferences and their anatomical relationships. RESULTS: This combined investigation including the CAAD technique allowed identifying the precise location and distribution of the pelvic nerve elements and their relationships to female pelvic organs. Hypogastric nerves (HN) were located in the retrorectal multilaminar structure and joined the homolateral inferior hypogastric plexus (IHP) at the lateral border of the recto-uterine pouch. The intersection of the ureter with the posterior wall of the uterine artery precisely located the junction of HN and IHP. Antero-inferior branches supplying female sexual and continence organs originated from the antero-inferior angle of IHP and were bundled at the posterolateral vaginal wall. CONCLUSIONS: CAAD is an encouraging anatomical method for the development of anatomical and surgical research and teaching. Complementary to traditional anatomical studies, it may provide useful anatomical data for the comprehension of postoperative sexual and urinary dysfunction and the development of nerve-sparing surgical techniques.

Impact of the COVID-19 pandemic on oncological and functional robotic-assisted surgical procedures.

The COVID-19 pandemic led to a decrease in surgical activity to avoid nosocomial contamination. Robotic-assisted surgery safety is uncertain, since viral dissemination could be facilitated by gas environment. We assessed the impact and safety of the COVID-19 pandemic on robotic-assisted surgery. Data were collected prospectively during lockdown (March 16th-April 30th 2020) in 10 academic centres with robotic surgical activity and was compared to a reference period of similar length. After surgery, patients with suspected COVID-19 were tested by RT-PCR. During the COVID-19 lockdown we evidenced a 60% decrease in activity and a 49% decrease in oncological procedures. However, the overall proportion of oncological surgeries was significantly higher during the pandemic (p < 0.001). Thirteen (7.2%) patients had suspected COVID-19 contamination, but only three (1.6%) were confirmed by RT-PCR. The COVID-19 pandemic resulted in a significant decrease in robotic-assisted surgery. Robotic approach was safe with a low rate of postoperative COVID-19 contamination.

Evidence of heterogeneity within colorectal liver metastases for allelic losses, mRNA level expression and in vitro response to chemotherapeutic agents.

A goal of oncology is to predict chemosensitivity of tumors. This approach assumes that in a patient all tumor deposits are homogeneous. We have tested the heterogeneity between several samples of the same liver metastasis (LM; intrametastatic heterogeneity) or between multiple LM (intermetastatic heterogeneity) from colorectal cancer in a single patient. In 16 untreated patients, several fragments of LM and nontumorous liver were collected. Heterogeneity to anticancer drug treatment was assessed in vitro on primary tissue cultures on poly-HEMA-coated surface with or without the topoisomerase-I inhibitor metabolite SN-38. Heterogeneity of response to SN-38 was observed in 55% of cases from one fragment to another in the same LM and in 64% of cases from one LM to another in the same patient. Allelic losses were characterized on 5q, 8p, 17p, 18q, 22q using 29 microsatellites markers. Seven patients (58%) had a perfect homogeneity for allelic losses in their LM whereas 3 (21%) had intrametastatic and 2 (18%) had intermetastatic heterogeneity. The analysis of gene expression was carried out by real time RT-PCR quantification using specific probes for TS, TOPO1, ERCC1, and CES2. Level expression of genes tested appeared heterogeneous with average variations of 57(+ or - 23)%, 52(+ or - 18)%, 53(+ or - 18)%, 56(+ or - 16)% for TS, TOPO1, ERCC1, and CES2 respectively for intermetastatic variability and 47(+ or - 26)%, 36(+ or - 14)%, 38(+ or - 19)%, and 56(+ or - 29)%, respectively for intrametastatic variability. Our results demonstrate intermetastatic and intrametastatic heterogeneity suggesting that pretherapeutic analysis of a single tumor biopsy is likely to lead to a misinterpretation of sensitivity to anticancer treatment.

Impaired mobility, ASA status and administration of tramadol are risk factors for postoperative delirium in patients aged 75 years or more after major abdominal surgery.

OBJECTIVE: The aim of this prospective study was to determine incidence, duration, and risk factors for postoperative delirium (PD) in elderly patients undergoing major abdominal surgery. SUMMARY BACKGROUND DATA: The incidence and risk factors of PD after major abdominal surgery in elderly patients are not well documented. METHODS: From May 2006 to May 2008, 118 patients aged 75 years or more without severe preoperative cognitive dysfunction (mini mental state examination score >10/30) and undergoing major elective abdominal surgery were included. The preoperative geriatric assessment battery consisted of 4 tests evaluating physical (instrumental activities of daily living and timed get up and go test score) and cognitive function (mini mental state examination score), and detecting the presence of an underlying depression (Short-GDS). After the operation, geriatric patients were assessed for PD by the Confusion Assessment Method. Univariate and multivariate analyses were used to determine risk factors for PD. RESULTS: Overall, PD occurred in 28 patients (24%). Multivariate analysis showed that an American Society of Anesthesiologists status of 3-4 (P = 0.02), impaired mobility (timed get up and go test score >20 seconds) (P = 0.009) and postoperative tramadol administration (P = 0.0009) were risk factors for PD. The mortality rate was 14% in 28 patients with PD and 3.3% in 90 patients without PD (P = 0.051). The morbidity rate was 35.5% in 28 patients with PD and 32% in 90 patients without PD (NS). The mean hospital stay was 19 +/- 11 days for patients with PD and 14 +/- 8 for patients without PD (P = 0.01). Fifteen of 24 (62.5%) surviving patients with PD and 28 of 87 (32%) surviving patients without PD were discharged to geriatric rehabilitation unit (P = 0.007). CONCLUSIONS: PD is a frequent and severe postoperative event in elderly patients after major abdominal surgery. A perioperative geriatric assessment should be recommended to patients with an American Society of Anesthesiologists status of 3-4 and preoperative impaired mobility to facilitate the management of PD. In these patients, the postoperative administration of tramadol should be avoided.