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ObjectiveTechnical ex-vivo comparison of commercial nebulizer nozzles used for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).MethodsThe performance of four different commercial nebulizer nozzles (Nebulizer; HurriChemTM; MCR-4 TOPOL®; QuattroJet) was analysed concerning: i) technical design and principle of operation, ii) operational pressure as function of the liquid flow rate, iii) droplet size distribution via laser diffraction spectrometry, iv) spray cone angle, spray cone form as well as horizontal drug deposition by image-metric analyses and v) chemical resistance via exposing to a cytostatic solution and chemical composition by means of spark optical emission spectral analysis.ResultsThe Nebulizer shows quasi an identical technical design and thus also a similar performance (e.g., mass median droplet size of 29 μm) as the original PIPAC nozzles (MIP/ CapnoPen). All other nozzles show more or less a performance deviation to the original PIPAC nozzles. The HurriChemTM has a similar design and principle of operation as the Nebulizer, but provides a finer aerosol (22 μm). The principle of operation of MCR-4 TOPOL® and QuattroJet differ significantly from that of the original PIPAC nozzle technology. The MCR-4 TOPOL® offers a hollow spray cone with significantly larger droplets (50 μm) than the original PIPAC nozzles. The QuattroJet generates an aerosol (22 μm) similar to that of the HurriChemTM but with improved spatial drug distribution.ConclusionThe availability of new PIPAC nozzles is encouraging but can also have a negative impact if their performance and efficacy is unknown. It is recommended that PIPAC nozzles that deviate from the current standard should be subject to bioequivalence testing and implementation in accordance with the IDEAL-D framework prior to routine clinical use.

Abstract Background Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, mainly due to skeletal muscle wasting, resulting in a decrease in patients' quality of life, response to cancer treatments, and survival. Our objective was to investigate skeletal muscle alterations in cachectic cancer patients. Methods This is a prospective study of patients managed for pancreatic or colorectal cancer with an indication for systemic chemotherapy (METERMUCADIG ‐ NCT02573974). One lumbar CT image was used to determine body composition. Patients were divided into three groups [8 noncachectic (NC), 18 with mild cachexia (MC), and 19 with severe cachexia (SC)] based on the severity of weight loss and muscle mass. For each patient, a pectoralis major muscle biopsy was collected at the time of implantable chamber placement. We used high‐resolution oxygraphy to measure mitochondrial muscle oxygen consumption on permeabilized muscle fibres. We also performed optical and electron microscopy analyses, as well as gene and protein expression analyses. Results Forty‐five patients were included. Patients were 67% male, aged 67 years (interquartile range, 59–77). Twenty‐three (51%) and 22 (49%) patients were managed for pancreatic and colorectal cancer, respectively. Our results show a positive correlation between median myofibres area and skeletal muscle index (P = 0.0007). Cancer cachexia was associated with a decrease in MAFbx protein expression (P

Abstract Introduction This study aimed to externally evaluate the accuracy of four predictive scores for conversion to open surgery after rectal laparoscopic resection. None of the four scores achieved external validation previously. Methods This was a retrospective analysis of two prospectively maintained databases from two academic centers in France and Morocco. All consecutive patients who underwent laparoscopic resection for rectal adenocarcinoma between 2005 and 2020 were included. Logistic regression was used to assess the association between the factors present in the four scores and conversion. The accuracy of each score was assessed using the area under the curve (AUC). Observed and predicted conversion rates were compared for each score using the Chi-square goodness-of-fit test. Results Four hundred patients were included. There were 264 men (66%) with a mean age of 65.95 years (standard deviation 12.2). The median tumor height was 7 cm (quartiles 4–11) and 29% of patients had low rectal tumors. Conversion rate was 21.75%. The accuracy to predict conversion was low with an AUC lower than 0,62 for the four models. The observed conversion rates were significantly different from the predicted rates, except for one score. Conclusions The four models had low accuracy in predicting the conversion to open surgery for laparoscopic rectal resection. There is a need for new well-designed studies, analyzing more specific variables, in a multicentric design to ensure generalizability of the results for daily surgical practice.

Abstract Background Traditionally, patients with peritonitis Hinchey III and IV due to perforated diverticulitis were treated with Hartmann’s procedure. In the past decade, resection and primary anastomosis have gained popularity over Hartmann’s procedure and recent guidelines recommend Hartmann’s procedure in two situations only: critically ill patients and in selected patients with multiple comorbidity (at high risk of complications). The protective stoma (PS) is recommended after resection with primary anastomosis, however its interest has never been studied. The aim of this trial is to define the role of systematic PS after resection and primary anastomosis for peritonitis Hinchey III and IV due to perforated diverticulitis. Methods/design This DIVERTI 2 trial is a multicenter, randomized, controlled, superiority trial comparing resection and primary anastomosis with (control group) or without (experimental group) PS in patients with peritonitis Hinchey III and IV due to perforated diverticulitis. Primary endpoint is the overall 1 year morbidity according to the Clavien–Dindo classification of surgical complications. All complications occurring during hospitalization will be collected. Late complications occurring after hospitalization will be collected during follow-up. In order to obtain 80% power for a difference given by respective main probabilities of 67% and 47% in the protective stoma and no protective stoma groups respectively, with a two-sided type I error of 5%, 96 patients will have to be included in each group, hence 192 patients overall. Expecting a 5% rate of patients not assessable for the primary end point (lost to follow-up), 204 patients will be enrolled. Secondary endpoints are postoperative mortality, unplanned reinterventions, incisional surgical site infection (SSI), organ/space SSI, wound disruption, anastomotic leak, operating time, length of hospital stay, stoma at 1 year after initial surgery, quality of life, costs and quality-adjusted life years (QALYs). Discussion The DIVERTI 2 trial is a prospective, multicenter, randomized, study to define the best strategy between PS and no PS in resection and primary anastomosis for patients presenting with peritonitis due to perforated diverticulitis. Trial registration ClinicalTrial.gov: NCT04604730 date of registration October 27, 2020. https://clinicaltrials.gov/ct2/show/NCT04604730?recrs=a&cond=Diverticulitis&draw=2&rank=12 .

Abstract Background/aim To develop and validate a nebulizer device for anti-cancer research on pressurized intraperitoneal aerosol supply in a preclinical peritoneal metastases (PM) rat model. Material and methods For aerosol generation, an ultrasonic nebulizer (USN) was modified. Aerosol analyses were performed ex-vivo by laser diffraction spectrometry (LDS). Intraperitoneal (IP) 99mtechnetium sodium pertechnetate (99mTc) aerosol distribution and deposition were quantified by in-vivo single photon emission computed tomography (SPECT/CT) and compared to liquid IP instillation of equivalent volume/doses of 99mTc with and without capnoperitoneum. PM was induced by IP injection of HCT116-Luc2 human colon cancer cells in immunosuppressed RNU rats. Tumor growth was monitored by bioluminescence imaging (BLI), 18F-FDG positron emission tomography (PET) and tissues examination at necropsy. Results The USN was able to establish a stable and reproducible capnoperitoneum at a pressure of 8 to 10 mmHg. LDS showed that the USN provides a polydisperse and monomodal aerosol with a volume-weighted diameter of 2.6 μm. At a CO2 flow rate of 2 L/min with an IP residence time of 3.9 s, the highest drug deposition efficiency was found to be 15 wt.-%. In comparison to liquid instillation, nebulization showed the most homogeneous IP spatial drug deposition. Compared to BLI, 18F-FDG-PET was more sensitive to detect smaller PM nodules measuring only 1–2 mm in diameter. BLI, 18F-FDG PET and necropsy analyses showed relevant PM in all animals. Conclusions The USN together with the PM rat model are suitable for robust and species-specific preclinical pharmacological studies regarding intraperitoneal delivery of pressurized aerosolized drugs and cancer research.

Abstract Background Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15–25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. Methods We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. Results There were 70 patients (55/15 males, female respectively) with median age 60 (54–68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). Conclusions Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

The long-term tolerability of linezolid is low because of mitochondrial toxicity, whereas tedizolid may represent a better option for suppressive therapy. We report a first presumed case of tedizolid-associated optic neuropathy after a very prolonged (18-month) intake and believe that screening for optic neuropathy should be considered for patients undergoing tedizolid suppression. [ABSTRACT FROM AUTHOR]

Abstract Background Colorectal cancer is a major public concern, being the second deadliest cancer in the world. Whereas survival is high for localized forms, metastatic colorectal cancer has showed poor prognosis, with a 5-year survival barely surpassing 11%. Conventional chemotherapies against this disease proved their efficiency and remain essential in first-line treatment. However, the large number of authorized protocols complexifies treatment decision. In common practice, such decision is made on an empirical basis, by assessing benefits and risks for the patient. In other words, there is currently no efficient means of predicting the efficacy of any chemotherapy protocol for metastatic colorectal cancer. Methods/design The use of a chemosensitivity assay, the Oncogramme®, should help clinicians administer the best chemotherapy regimen to their patients. We hypothesize it would ultimately improve their survival. In this multicentred, prospective trial (ONCOGRAM), eligible patients with metastatic colorectal cancer are randomized to determine whether they will receive an Oncogramme®. For clinicians whose patients benefited from the assay (arm A), results are used as a decision support tool. Patients not undergoing the Oncogramme® procedure are treated according to current practice, without the assistance of the assay (arm B). Primary outcome is 1-year progression-free survival. Secondary outcomes include response rates, as well as 6-month and 1-year survival rates. Discussion This study aims at investigating the clinical utility of the Oncogramme® as a decision support tool for the treatment of patients with metastatic colorectal cancer. If the Oncogramme® positively influenced patient overall survival and/or progression-free survival, it would be of great value for clinicians to implement this assay within the current landscape of personalized medicine tools, which include genomics and biomarker assays. Trial registration ClinicalTrials.gov identifier NCT03133273 . Registered on April 28, 2017.

The observed increase in the incidence of complicated diverticulitis may lead to the performance of more emergency surgeries. This study aimed to assess the rate and risk factors of emergency surgery for sigmoid diverticulitis. The primary outcomes were the rate of emergency surgery for sigmoid diverticulitis and its associated risk factors. The urgent or elective nature of the surgical intervention was provided by the surgeon and in accordance with the indication for surgical treatment. A mixed logistic regression with a random intercept after multiple imputations by the chained equation was performed to consider the influence of missing data on the results. Between 2010 and 2021, 6,867 patients underwent surgery for sigmoid diverticulitis in the participating centers, of which one-third (n = 2317) were emergency cases. In multivariate regression analysis with multiple imputation by chained equation, increasing age, body mass index <18.5 kg/m2, neurologic and pulmonary comorbidities, use of anticoagulant drugs, immunocompromised status, and first attack of sigmoid diverticulitis were independent risk factors for emergency surgery. The likelihood of emergency surgery was significantly more frequent after national guidelines, which were implemented in 2017, only in patients with a history of sigmoid diverticulitis attacks. The present study highlights a high rate (33%) of emergency surgery for sigmoid diverticulitis in France, which was significantly associated with patient features and the first attack of diverticulitis. [ABSTRACT FROM AUTHOR]

Objective: Technical ex-vivo comparison of commercial nebulizer nozzles used for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Methods: The performance of four different commercial nebulizer nozzles (Nebulizer; HurriChemTM; MCR-4 TOPOL®; QuattroJet) was analysed concerning: i) technical design and principle of operation, ii) operational pressure as function of the liquid flow rate, iii) droplet size distribution via laser diffraction spectrometry, iv) spray cone angle, spray cone form as well as horizontal drug deposition by image-metric analyses and v) chemical resistance via exposing to a cytostatic solution and chemical composition by means of spark optical emission spectral analysis. Results: The Nebulizer shows quasi an identical technical design and thus also a similar performance (e.g., mass median droplet size of 29 μm) as the original PIPAC nozzles (MIP/ CapnoPen). All other nozzles show more or less a performance deviation to the original PIPAC nozzles. The HurriChemTM has a similar design and principle of operation as the Nebulizer, but provides a finer aerosol (22 μm). The principle of operation of MCR-4 TOPOL® and QuattroJet differ significantly from that of the original PIPAC nozzle technology. The MCR-4 TOPOL® offers a hollow spray cone with significantly larger droplets (50 μm) than the original PIPAC nozzles. The QuattroJet generates an aerosol (22 μm) similar to that of the HurriChemTM but with improved spatial drug distribution. Conclusion: The availability of new PIPAC nozzles is encouraging but can also have a negative impact if their performance and efficacy is unknown. It is recommended that PIPAC nozzles that deviate from the current standard should be subject to bioequivalence testing and implementation in accordance with the IDEAL-D framework prior to routine clinical use. [ABSTRACT FROM AUTHOR]

Abstract Background The influence of anastomotic leakage (AL) on local recurrence rates and survival in rectal cancer remains controversial. The aim of this study was to analyze the effect of asymptomatic anastomotic leakage (AAL) and symptomatic anastomotic leakage (SAL) on short- and long-term outcome after curative rectal cancer resection. Methods All patients who underwent surgical resection of non-metastatic rectal cancer with curative intent from January 2005 to December 2017 were retrospectively analyzed. Short-term morbidity, long-term functional and oncological outcomes were compared between patients with SAL, AAL and without AL (WAL). Results Overall, 200 patients were included and AL was observed in 39 (19.5%) patients (10 AAL and 29 SAL) with a median follow-up of 38.5 months. Rectal cancer location and preoperative neoadjuvant treatment was similar between the three groups. Postoperative 30-day mortality rate was nil. The permanent stoma rate was higher in patients with SAL or AAL compared to WAL patients (44.8 and 30% vs 9.3%, p