ABSTRACT
BACKGROUND/AIM: This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies. PATIENTS AND METHODS: This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m2 body surface area, respectively. The primary outcome measures were feasibility and perioperative complications. RESULTS: The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (Trec) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with Trec ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications. CONCLUSION: In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.
Subject(s)
Aerosols , Feasibility Studies , Peritoneal Neoplasms , Humans , Middle Aged , Female , Aged , Male , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/therapy , Retrospective Studies , Hyperthermia, Induced/methods , Hyperthermia, Induced/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hyperthermic Intraperitoneal Chemotherapy/methods , Hyperthermic Intraperitoneal Chemotherapy/adverse effects , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Oxaliplatin/therapeutic useABSTRACT
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.
Subject(s)
Aerosols , Nebulizers and Vaporizers , Humans , Antineoplastic Agents/administration & dosage , Pressure , Particle Size , Equipment DesignABSTRACT
OBJECTIVE: The aim of this study was to evaluate the feasibility and perioperative safety of high-pressure/high-dose pressurized intraperitoneal aerosol chemotherapy (HP/HD-PIPAC) to manage peritoneal surface malignancies (PSM). METHODS: Retrospective analysis of a prospective database of about 130 consecutive patients scheduled for HP/HD-PIPACs for PSM. Doxorubicin plus cisplatin (PIPAC-C/D) or oxaliplatin (PIPAC-Ox) were nebulized into a constant capnoperitoneum of 20 mmHg at doses of 6, 30, or 120 mg/m2 of body surface area (BSA). Outcome criteria were perioperative complications (Clavien-Dindo). RESULTS: The median age of patients was 62 years (range 9-82), and the primary tumor site was of colorectal (CRC), upper gastrointestinal tract (UGI), unknown primary (CUP), malignant epithelioid mesothelioma of the peritoneum (MPM), hepato-pancreatic-biliary tract (HPB), and other origin in 30 (23.1%), 27 (20.8%), 16 (12.3%), 16 (12.3%), 6 (4.6%), and 35 (26.9%) patients, respectively. Abdominal access failed for a first, second, third, and fourth or more HP/HD-PIPAC in 12/130 (9.2%), 4/64 (6.3%), 6/40 (15.0%), and 2/33 (6.1%) patients. A total of 243 procedures were performed in 118 patients. No intraoperative complications related to increased capnoperitoneal pressure occurred, but an intraoperative bleeding complication was observed in 1/243 (0.4%) patients. The overall rate of postoperative procedure-related complications was 19.3% (47/243), while 15.3% (37/243), 1.6% (6/243), 1.6% (1/243), 0.4% (1/243), and 0.4% (1/243) were Grade I, II, III, IV, and V complications, respectively. CONCLUSIONS: Perioperative complications of HP/HD-PIPAC are comparable with standard pressure/dose PIPAC treatment protocols. Prospective studies are warranted to examine potential improvement in therapy outcomes.
Subject(s)
Mesothelioma, Malignant , Peritoneal Neoplasms , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Retrospective Studies , Feasibility Studies , Respiratory Aerosols and DropletsABSTRACT
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.
Subject(s)
Colonic Neoplasms , Peritoneal Neoplasms , Aerosols , Animals , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/drug therapy , Fluorodeoxyglucose F18 , Humans , Nebulizers and Vaporizers , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/secondary , RatsABSTRACT
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.
Subject(s)
Laparoscopy , Rectal Neoplasms , Aged , Conversion to Open Surgery , Female , Humans , Logistic Models , Male , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The aim of this study was to retrospectively investigate the impact of intersphincteric resection (ISR) and Enhanced Recovery After Surgery (ERAS) protocols for rectal cancer. PATIENTS AND METHODS: Since we implemented rectal ERAS protocol and ISR in 2016, we retrospectively assessed and compared clinical, pathological and survival outcomes of two groups of patients: group 1, treated 2000-2015 (n=242); and group 2, treated 2016-2020 (n=108). Propensity score matching using nearest-neighbor method was used to match each patient of group 1 to a patient of group 2. RESULTS: Before and after matching, the American Society of Anesthesiology score for patients in group 1 was significantly lower than in group 2 (score of 3: 9.9% vs. 25.9%, p<0.0001) as were grade I-II complications (27.7% vs. 45.4% p<0.001). Before and after matching, the quality of the mesorectum excision was significantly lower in group 1 (complete in 31% vs. 59.2% p<0.0001). After matching, 3-year overall survival for groups 1 and 2 were similar (88.2% vs. 92.6%; p=0.988). CONCLUSION: ERAS and ISR had no negative impact on the oncological outcome of our patients and increased the preservation of bowel continuity.
Subject(s)
Rectal Neoplasms , Cohort Studies , Humans , Neoplasm Grading , Rectal Neoplasms/surgery , Rectum/surgery , Retrospective StudiesABSTRACT
BACKGROUND/AIM: Impact of neoadjuvant chemoradiotherapy (CRT) in locally advanced upper rectal adenocarcinoma (LAURC) is debated. The aim of this study was to compare outcomes between LAURC and locally advanced sigmoid and recto-sigmoid junction cancer (LASC). PATIENTS AND METHODS: This retrospective study included 149 consecutive patients [42 CRT/LAURC, 16 upfront surgery (US/LAURC) and 91 LASC]. Partial mesorectum excision (PME) was performed for all LAURC. Pathology results as well as short-and-long-term outcomes were compared between the three groups. RESULTS: Overall mortality was nil. Morbidity was comparable (CRT/LAURC 23.8% vs. LASC: 20.8% vs. US/LAURC: 37.5%, p=0.2354). CRT was associated with a reduced risk of positive circumferential margin (CRT/LAURC: 9.5% vs. US/LAURC: 18.7%, p<0.0001). Recurrence rate, 5-year disease-free survival and overall survival were similar between the three groups. CONCLUSION: CRT and PME did not improve LAURC oncological outcomes but were associated with improved margins. CRT for LAURC was not associated with increased morbidity.
Subject(s)
Adenocarcinoma/surgery , Rectal Neoplasms/surgery , Adenocarcinoma/mortality , Humans , Prognosis , Progression-Free Survival , Rectal Neoplasms/mortality , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to manage gastric cancer peritoneal metastasis (GCPM). METHODS: This study analyzed a prospective database of GCPM patients treated with cisplatin and doxorubicin PIPAC (PIPAC-C/D). The outcome criteria were adverse events, pathologic response [peritoneal regression grading score (PRGS)], and overall survival (OS). RESULTS: The PIPAC-C/D procedure was scheduled for 144 patients with a median age of 57 years (range 22-88 years). Access to the abdominal cavity for the first PIPAC failed in 11 patients (7.7 %). A total of 296 procedures were performed for 131 patients. Of the 144 patients, 52 (36.1%) underwent one PIPAC, 32 (22.2%) underwent two PIPACs, 24 (16.7%) underwent three PIPACs, and 21 (14.6%) underwent four or more PIPACs. The overall morbidity/mortality was grade 1 for 22 patients (15.3%), grade 2 for 32 patients (22.2%), grade 3 for 7 patients (4.9%), grade 4 for no patients (0%), and grade 5 for 2 patients (1.4%). Of the 37 patients who had three or more PIPACs eligible for histopathologic response analysis, 27 (73%) had major or complete regression (PRGS 1/2). A median OS of 11 months (range 0-61 months) for the total study population and 16 months (range 2-61 months) for the patients with three or more PIPACs was observed. For 10 patients (7%) who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, the median OS was 15 months (minimum, 4 months; maximum, 27 months). Multivariate analysis showed three or more PIPACs to be an independent prognostic factor for improved OS (hazard ratio, 0.36; p < 0.0001). CONCLUSIONS: Repetitive PIPAC-C/D ± systemic chemotherapy is associated with low morbidity and mortality rates. Prospective randomized trials are needed to confirm whether three or more PIPAC-C/Ds improve clinical outcome.
Subject(s)
Peritoneal Neoplasms , Stomach Neoplasms , Adult , Aerosols , Aged , Aged, 80 and over , Cisplatin , Doxorubicin , Humans , Middle Aged , Peritoneal Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Young AdultABSTRACT
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a promising approach with a high optimization potential for the treatment of peritoneal carcinomatosis. To study the efficacy of PIPAC and drugs, first rodent cancer models were developed. But inefficient drug aerosol supply and knowledge gaps concerning spatial drug distribution can limit the results based on such models. To study drug aerosol supply/deposition, computed tomography scans of a rat capnoperitoneum were used to deduce a virtual and a physical phantom of the rat capnoperitoneum (RCP). RCP qualification was performed for a specific PIPAC method, where the capnoperitoneum is continuously purged by the drug aerosol. In this context, also in-silico analyses by computational fluid dynamic modelling were conducted on the virtual RCP. The physical RCP was used for ex-vivo granulometric analyses concerning drug deposition. Results of RCP qualification show that aerosol deposition in a continuous purged rat capnoperitoneum depends strongly on the position of the inlet and outlet port. Moreover, it could be shown that the droplet size and charge condition of the drug aerosol define the deposition efficiency. In summary, the developed virtual and physical RCP enables detailed in-silico and ex-vivo analyses on drug supply/deposition in rodents.
Subject(s)
Antineoplastic Agents/administration & dosage , Peritoneal Neoplasms/drug therapy , Peritoneum/diagnostic imaging , Aerosols , Animals , Antineoplastic Agents/pharmacokinetics , Computer Simulation , Computer-Aided Design , Humans , Hydrodynamics , Injections, Intraperitoneal/instrumentation , Injections, Intraperitoneal/methods , Models, Animal , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/metabolism , Peritoneum/metabolism , Phantoms, Imaging , Pressure , Rats , Tomography, X-Ray Computed , User-Computer InterfaceABSTRACT
BACKGROUND: The benefit of repetitive PIPAC specifically in CPM patients has yet to be demonstrated in terms of oncological and functional outcomes. OBJECTIVE: The aim of this study was to evaluate the outcome of patients with non-resectable colorectal peritoneal metastases (CPM) treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: We conducted an analysis of a prospective single-center database of all CPM patients who underwent PIPAC with oxaliplatin 92 mg/m2 body surface (PIPAC-Ox). The outcome criteria were adverse events (Common Terminology Criteria for Adverse Events version 4.0), Peritoneal Regression Grading Score (PRGS), and survival. RESULTS: Overall, 102 patients with a median age of 64 years (33-88) were scheduled for PIPAC-Ox. Access to the abdominal cavity for the first application failed in 22/102 (21.6%) patients. A total of 185 PIPACs were performed, with 26/102 (25.5%), 20/102 (19.6%), 17/102 (16.7%), and 17/102 (16.7%) patients undergoing one, two, three, and four or more PIPACs, respectively. Perioperative overall morbidity/mortality Grade I-V occurred in 14 (7.6%), 29 (15.8%), 6 (3.2%), 1 (0.5%), and 1 (0.5%) patient without significant differences between each cycle. Of 27 patients who underwent three or more PIPACs, 20/102 (19.6%) had major/complete CPM regression (PRGS 1-2). In a multivariate analysis, independent predictive factors for > 12 months' survival following the first PIPAC-Ox administration were three or more PIPACs (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.35-15.2; p = 0.014) and younger patient age (OR 1.058, 95% CI 1.00-1.12; p = 0.039). CONCLUSIONS: Repetitive PIPAC-Ox for CPM patients, alone or combined with perioperative systemic chemotherapy, is feasible. Our data suggest that three or more consecutive PIPAC-Ox cycles for advanced CPM can improve survival.
Subject(s)
Colorectal Neoplasms , Peritoneal Neoplasms , Adult , Aerosols , Aged , Aged, 80 and over , Colorectal Neoplasms/drug therapy , Humans , Middle Aged , Oxaliplatin , Peritoneal Neoplasms/drug therapy , Prospective StudiesABSTRACT
Intraperitoneal chemotherapy (IPC) is a locoregional treatment option in patients with peritoneal metastases (PM). Here, we present an ovarian cancer (OC)-derived PM mouse model for the study of different forms of IPC. Xenograft cell proliferation (luciferase-transfected OVCAR3 and SKOV3 clones) and growth kinetics were assessed using PET scan, bioluminescence imaging (BLI), and histological tumor analysis. Liquid IPC was achieved by intraperitoneal injection with/without capnoperitoneum (6-7 mmHg). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was mimicked using an intratracheal drug aerosol administration system (micro-nozzle), which, as demonstrated by ex vivo granulometric analysis using laser diffraction spectrometry, produced a polydisperse, bimodal aerosol with a volume-weighted median diameter of (26.49 ± 2.76) µm. Distribution of Tc-99m-labeled doxorubicin in mice was characterized using SPECT and was dependent on the delivery mode and most homogeneous when the micro-nozzle was used. A total of 2 mg doxorubicin per kg body weight was determined to be the optimally effective and tolerable dose to achieve at least 50% tumor reduction. Repeated PIPAC (four times at seven-day-intervals) with doxorubicin in SKOV3-luc tumor-bearing mice resulted in halted tumor proliferation and tumor load reduced after the second round of PIPAC versus controls and the number of tumor nodules was significantly reduced (27.7 ± 9.5 vs. 57.3 ± 9.5; p = 0.0003). Thus, we established the first mouse model of OC PM for the study of IPC using a human xenograft with SKOV3 cells and an experimental IPC setup with a miniaturized nozzle. Repeated IPC was feasible and demonstrated time-dependent anti-tumor activity.
ABSTRACT
BACKGROUND: Peritoneal metastasis (PM) in patients with breast (BC) and endometrial cancer (EC) is rare and treatment options are limited. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has demonstrated efficacy against PM from various cancers, but its efficacy in BC/EC patients is unknown. METHODS: Retrospective cohort study of patients with PM from BC/EC undergoing PIPAC with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were collected within an international prospective PIPAC registry. Study outcomes were microscopic tumor regression grade (TRG), survival, adverse events (CTCAE), and quality of life (QoL). RESULTS: 150 PIPAC procedures in 44 patients (BC/EC = 28/16; mean age 58.8 ± 10.1 and 63.2 ± 10.1 years, respectively) were analyzed. The mean number of PIPACs per patient was 3 (range 0-9) and 3.5 (range 0-10), respectively. Primary/secondary non-access occurred in 4/3 of 150 (5%) procedures. PIPAC induced objective tumor regression as demonstrated by repetitive PM biopsies in 73% (32/44) of patients. Peri- and postoperative CTCAE grade 3 and 4 complications were observed in 12/150 (8%) of procedures. No grade 5 event was observed. After a median follow up of 5.7 (IQR 2.7-13.0) months, overall median survival was 19.6 (95% CI: 7.8-31.5) months (from first PIPAC). QoL indicators (general health, nausea, fatigue, constipation, pain, dyspnea, social, cognitive, emotional, and physical functioning) all improved or were maintained throughout PIPAC treatments. CONCLUSIONS: Repetitive intraperitoneal chemotherapy with PIPAC is feasible and safe in patients with PM from BC and EC. PIPAC induces significant histological regression of PM while maintaining QoL.
Subject(s)
Breast Neoplasms/drug therapy , Endometrial Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Aerosols , Cohort Studies , Female , Humans , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: In the COVID-19 crisis, laparoscopic surgery is in focus as a relevant source of bioaerosol release. The efficacy of electrostatic aerosol precipitation (EAP) and continuous aerosol evacuation (CAE) to eliminate bioaerosols during laparoscopic surgery was verified. STUDY DESIGN: Ex-vivo laparoscopic cholecystectomies (LCs) were simulated ± EAP or CAE in Pelvitrainer equipped with swine gallbladders. Release of bioaerosols was initiated by performing high-frequency electrosurgery with a monopolar electro hook (MP-HOOK) force at 40 watts (MP-HOOK40) and 60 watts (MP-HOOK60), as well as by ultrasonic cutting (USC). Particle number concentrations (PNC) of arising aerosols were analyzed with a condensation particle counter (CPC). Aerosol samples were taken within the Pelvitrainer close to the source, outside the Pelvitrainer at the working trocar, and in the breathing zone of the surgeon. RESULTS: Within the Pelvitrainer, MP-HOOK40 (6.4 × 105 cm-3) and MP-HOOK60 (7.3 × 105 cm-3) showed significantly higher median PNCs compared to USC (4.4 × 105 cm-3) (p = 0.001). EAP led to a significant decrease of the median PNCs in all 3 groups. A high linear correlation with Pearson correlation coefficients of 0.852, 0.825, and 0.759 were observed by comparing MP-HOOK40 (± EAP), MP-HOOK60 (± EAP), and USC (± EAP), respectively. During ex-vivo LC and CAE, significant bioaerosol contaminations of the operating room occurred. Ex-vivo LC with EAP led to a considerable reduction of the bioaerosol concentration. CONCLUSIONS: EAP was found to be efficient for intraoperative bioaerosol elimination and reducing the risk of bioaerosol exposure for surgical staff.
Subject(s)
Aerosols , Cholecystectomy, Laparoscopic/methods , Electrosurgery/methods , Infection Control/methods , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Models, Animal , Static Electricity , Aerosols/analysis , Air Microbiology , Animals , COVID-19/prevention & control , COVID-19/transmission , Cholecystectomy, Laparoscopic/instrumentation , Electrosurgery/instrumentation , In Vitro Techniques , Infection Control/instrumentation , Occupational Exposure/analysis , Occupational Exposure/prevention & control , Pilot Projects , SwineABSTRACT
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 < 0.001). The mean wexner continence grading scale was significantly different between AAL (11,4 ± 3,8), SAL (10,3 ± 0,6) and WAL (6,4 ± 4,7) groups (p = 0.049). The 3 and 5-year overall and disease-free survival rates were similar between the 3 groups (86.6% /84% vs 100%/100% vs 76%/70 and 82.9%/77% vs 100%/100% vs 94.7%/88.3% for patients with SAL, AAL, and WAL, p = 0.480 and p = 0.527). CONCLUSION: The permanent stoma rate was significant higher in patients with SAL or AAL compared to WAL patients. AL did not impair long-term oncological outcome.
Subject(s)
Anastomotic Leak/epidemiology , Neoplasm Recurrence, Local/epidemiology , Proctectomy/adverse effects , Rectal Neoplasms/therapy , Aged , Anastomosis, Surgical/adverse effects , Anastomotic Leak/diagnosis , Anastomotic Leak/etiology , Asymptomatic Diseases/epidemiology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/prevention & control , Proctectomy/methods , Prognosis , Radiotherapy, Adjuvant , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Rectum/pathology , Rectum/surgery , Retrospective Studies , Risk Factors , Surgical Stomas/adverse effects , Surgical Stomas/statistics & numerical dataABSTRACT
BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new technology for delivering intraperitoneal chemotherapy. It is generally assumed that with PIPAC, the ratio of peritoneal to systemic drug concentration is superior to liquid hyperthermic intraperitoneal chemotherapy (HIPEC). To date, no direct comparative data are available supporting such an assumption. MATERIALS AND METHODS: Twelve 65-day-old pigs were randomly separated into three groups of four pigs each, all of which received intraperitoneal chemotherapy using the following administration methods: PIPAC with oxaliplatin 92 mg in 150 ml dextrose 5% (Group 1); PIPAC with electrostatic aerosol precipitation (ePIPAC; Group 2); or laparoscopic HIPEC (L-HIPEC) with oxaliplatin 400 mg in 4 L dextrose 5% at 42 °C (Group 3). Serial blood and peritoneal tissue concentrations of oxaliplatin were determined by spectrometry. RESULTS: In all three groups, the maximum concentration of oxaliplatin in blood was detected 50-60 min after onset of the chemotherapy experiments, with no significant differences among the three groups (p = 0.7994). Blood oxaliplatin concentrations (0-30 min) were significantly higher in the L-HIPEC group compared with the ePIPAC group (p < 0.05). No difference was found for the overall systemic oxaliplatin absorption (area under the curve). Overall concentrations in the peritoneum were not different among the three groups (p = 0.4725), but were significantly higher in the visceral peritoneum in the PIPAC group (p = 0.0242). CONCLUSIONS: Blood and tissue concentrations were comparable between all groups; however, depending on the intraperitoneal area examined and the time points of drug delivery, the concentrations differed significantly between the three groups.
Subject(s)
Hyperthermia, Induced , Oxaliplatin/administration & dosage , Oxaliplatin/pharmacokinetics , Aerosols/administration & dosage , Aerosols/pharmacokinetics , Animals , Laparoscopy , Peritoneum/metabolism , Swine , Tissue DistributionABSTRACT
BACKGROUND/AIM: The aim of this study was to determine the clinical impact of low tie ligation (LT) of the inferior mesenteric artery (IMA) below the left colic artery versus high tie ligation (HT) at the origin of the IMA in patients undergoing rectal cancer surgery. PATIENTS AND METHODS: Between January 2005 and December 2017, all consecutive patients who underwent rectal resection for non-metastatic cancer were retrospectively included. Patients who had LT were compared to those who had HT. RESULTS: Overall, 200 patients were identified (101 HT and 99 LT). Postoperative 30-day mortality rate was nil in both groups. There were significantly higher severe postoperative complications in HT versus LT patients (Clavien-Dindo III-IV) (18.8% vs. 9.1%, p=0.048). Median follow-up was 38.5 months and overall survival at 5 years was 91.5% and there was no difference between the two groups (90.1% vs. 92.9%; HT vs. LT p=0.640). CONCLUSION: LT ligation of IMA significantly decreased the severe postoperative complication rate without affecting recurrence-free or overall survival.
Subject(s)
Mesenteric Artery, Inferior/surgery , Neoplasm Recurrence, Local/surgery , Postoperative Complications/pathology , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Ligation/methods , Lymph Node Excision , Male , Mesenteric Artery, Inferior/pathology , Mesenteric Artery, Inferior/radiation effects , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoplasm Recurrence, Local/radiotherapy , Postoperative Complications/epidemiology , Postoperative Complications/radiotherapy , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Rectum/pathology , Rectum/radiation effects , Rectum/surgeryABSTRACT
PURPOSE: Adhesions following major colorectal surgery can be responsible for bowel obstruction, mostly occurring in the small intestine. Published data for long-term survival following major colorectal surgery complicated with intestinal obstruction are limited. The aim of this study was to identify the mortality rates and mortality risk factors in patients with primary colorectal surgery (PMCS) complicated with surgical small bowel obstruction (SBO). METHODS: This was a retrospective analysis of a prospective national registry of patients who underwent PMCS in 2008. RESULTS: Of 15,640 patients who underwent PMCS, 2900 required further surgery for SBO with a median follow-up of 42 months (until the end of 2014). Re-hospitalization mortality rate was 10.1%, and 65% of deaths were obstruction-related. No differences were found in SBO incidence between patients who had undergone laparoscopic or open procedures. Hospital mortality was significantly higher in patients who underwent open PMCS compared with those who underwent a laparoscopic procedure (11% vs. 2%, p = 0.0006). Overall 1- and 5-year survival rates in patients who underwent surgical SBO treatment were significantly lower when the initial surgery was an open procedure compared with a laparoscopy (96.8% vs. 99.4% and 86.6% vs. 95.1%, respectively, p = 0.0016). Multivariate analysis revealed that age, sex, a history of diabetes, cancer, and heart disease were mortality risk factors. CONCLUSIONS: The surgical incidence and mortality rate of PMCS complicated with SBO were elevated. Laparoscopy clearly reduced long-term postoperative mortality in patients with and without abdominal adhesions.
Subject(s)
Colorectal Surgery/adverse effects , Hospital Mortality , Intestinal Obstruction/etiology , Intestine, Small/pathology , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Patient Readmission , Risk Factors , Survival Analysis , Time FactorsABSTRACT
BACKGROUND: Adhesive small bowel obstruction (SBO) represents a heavy burden in healthcare systems worldwide and is associated with significant morbidity and mortality. Although conservative treatment alone can lead to SBO resolution in most cases, its optimal duration is still a matter of debate. The aim of this study was to analyze different SBO evolution patterns in order to further determine when to switch to surgical treatment. STUDY DESIGN: All patients who were admitted for adhesive SBO between 2011 and 2016 were reviewed. Patients who had immediate surgery (IS), a successful medical treatment (SMT), and a failed medical treatment (FMT) were compared in terms of overall morbidity, mortality, and SBO recurrence. RESULTS: Overall 154 patients were identified, including 23 (14.9%) in IS, 27 (17.5%) in FMT, and 104 (67.6%) in SMT groups. In terms of comorbidities, patients were similar in all groups. Overall morbidity rates were highest in IS and FMT groups (30% and 33%, respectively, vs. 4% in the SMT group, p < 0.001) whereas mortality rate was highest in the FMT group (22% vs. 0% and 0% in IS and SMT groups, respectively, p < 0.001). SBO recurrence rate was highest in the SMT group (22% vs. 4% and 7% in IS and FMT groups, respectively, p = 0.042). CONCLUSION: FMT seems to be associated with similar overall morbidity compared with IS but with increased postoperative mortality. Patient frailty seems to be worsened by prolonged inefficient medical treatment.
ABSTRACT
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new approach to deliver intraperitoneal chemotherapy as a pressurized aerosol in patients with advanced peritoneal metastases (PM). Although this treatment has rapidly been adopted into clinical practice, most surgeons are not familiar with the basics and principles of this technology. The purpose of this article is to review patient selection criteria, as well as highlighting important operative and technical details regarding PIPAC technology with a focus on "how to do it." To this end, safety and feasibility data from a series of 1200 consecutive PIPAC procedures performed by two pioneers of PIPAC treatment are presented.