Assessment of Intraoperative Scoring Systems for Predicting Cytoreduction Outcome in Peritoneal Metastatic Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Cytoreductive surgery (CRS) is a widely acknowledged treatment approach for peritoneal metastasis, showing favorable prognosis and long-term survival. Intraoperative scoring systems quantify tumoral burden before CRS and may predict complete cytoreduction (CC). This study reviews the intraoperative scoring systems for predicting CC and optimal cytoreduction (OC) and evaluates the predictive performance of the Peritoneal Cancer Index (PCI) and Predictive Index Value (PIV). METHODS: Systematic searches were conducted in Embase, MEDLINE, and Web of Science. Meta-analyses of extracted data were performed to compare the absolute predictive performances of PCI and PIV. RESULTS: Thirty-eight studies (5834 patients) focusing on gynecological (n = 34; 89.5%), gastrointestinal (n = 2; 5.3%) malignancies, and on tumors of various origins (n = 2; 5.3%) were identified. Seventy-seven models assessing the predictive performance of scoring systems (54 for CC and 23 for OC) were identified with PCI (n = 39/77) and PIV (n = 16/77) being the most common. Twenty models (26.0%) reinterpreted previous scoring systems of which ten (13%) used a modified version of PIV (reclassification). Meta-analyses of models predicting CC based on PCI (n = 21) and PIV (n = 8) provided an AUC estimate of 0.83 (95% confidence interval [CI] 0.79-0.86; Q = 119.6, p = 0.0001; I2 = 74.1%) and 0.74 (95% CI 0.68-0.81; Q = 7.2, p = 0.41; I2 = 11.0%), respectively. CONCLUSIONS: Peritoneal Cancer Index models demonstrate an excellent estimate of CC, while PIV shows an acceptable performance. There is a need for high-quality studies to address management differences, establish standardized cutoff values, and focus on non-gynecological malignancies.

Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases.

BACKGROUND: The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis. METHODS: Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005-2007 and 2013-2014). RFS, OS, and survival after recurrence were estimated using the Kaplan-Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated. RESULTS: A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06). CONCLUSION: In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.

Omentoplasty in Patients Undergoing Abdominoperineal Resection After Long-Course Chemoradiation for Locally Advanced and Locally Recurrent Rectal Cancer: A Comparative Single-Institution Cohort Study.

BACKGROUND: Omentoplasty is a commonly performed procedure after abdominoperineal resection for rectal cancer, but its effectiveness to reduce pelviperineal complications is not firmly established. OBJECTIVE: This study aimed to assess the impact of omentoplasty on postoperative outcomes after long-course (chemo) radiotherapy and abdominoperineal resection in patients with locally advanced and locally recurrent rectal cancer. DESIGN: Retrospective cohort study. SETTINGS: Single center. PATIENTS: All patients with locally advanced and locally recurrent rectal cancer undergoing abdominoperineal resection after neoadjuvant (chemo)radiation in a tertiary referral center between 2008 and 2020 were retrospectively reviewed. MAIN OUTCOME MEASURES: Multivariable logistic and linear regression analyses were performed to analyze the association between omentoplasty and pelviperineal complications, duration of nasogastric tube drainage, and length of hospital stay. RESULTS: A total of 305 patients were analyzed, of whom 245 underwent omentoplasty (80%). Pelviperineal complications occurred in 151 patients (50%) overall, in 125 patients (51%) with omentoplasty, and in 26 patients (43%) without omentoplasty. Independent predictors of pelviperineal complications in multivariable analyses were smoking (OR 2.68; 95% CI, 1.46-4.94) and high BMI (OR 1.68; 95% CI, 1.00-2.83), but not omentoplasty (OR 1.36; 95% CI, 0.77-2.40). The mean duration of nasogastric tube drainage was longer after omentoplasty (6 vs 4 d) with a significant association in multivariable analysis (ß coefficient 1.97; 95% CI, 0.35-3.59). Patients undergoing omentoplasty had a significantly longer hospital stay (14 vs 10 d), and omentoplasty remained associated with a prolonged hospital stay after adjusting for confounding (ß coefficient 3.05; 95% CI, 0.05-5.74). LIMITATIONS: Retrospective design. CONCLUSION: Omentoplasty was not associated with a reduced risk of the occurrence of short-term pelviperineal complications after abdominoperineal resection in patients undergoing long-course (chemo)radiotherapy. Furthermore, in patients undergoing omentoplasty, prolonged duration of nasogastric tube drainage and hospital stay was observed. See Video Abstract at http://links.lww.com/DCR/C124 . OMENTOPLASTIA EN PACIENTES SOMETIDOS A RESECCIN ABDOMINOPERINEAL DESPUS DE QUIMIORRADIOTERAPIA DE CURSO LARGO PARA EL CNCER DE RECTO LOCALMENTE AVANZADO Y LOCALMENTE RECURRENTE ESTUDIO DE COHORTE COMPARATIVO DE UNA SOLA INSTITUCIN: ANTECEDENTES:La omentoplastía es un procedimiento que se realiza comúnmente después de la resección abdominoperineal por cáncer de recto, pero su efectividad para reducir las complicaciones pelvicoperineales no está firmemente establecida.OBJETIVO:Evaluar el impacto de la omentoplastía en las complicaciones pelvicoperineales a corto plazo y los resultados postoperatorios después quimioradioterapia de curso largo y resección abdominoperineal en pacientes con cáncer de recto localmente avanzado y localmente recurrente.DISEÑO:Estudio de cohorte retrospectivo.ESCENARIO:Centro único.PACIENTES:Se revisaron retrospectivamente todos los pacientes con cáncer de recto localmente avanzado y localmente recurrente sometidos a resección abdominoperineal después de quimioradiación neoadyuvante en un centro de referencia de tercer nivel entre 2008 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Se realizaron análisis de regresión lineal y logística multivariable para examinar la asociación entre la omentoplastía y las complicaciones pelvicoperineales (p. ej., problemas de heridas perineales y abscesos pélvicos), la duración del drenaje por sonda nasogástrica y la duración de la estancia hospitalaria.RESULTADOS:Se analizaron un total de 305 pacientes de los cuales 245 fueron sometidos a omentoplastía (80%). Las complicaciones pelvicoperineales ocurrieron en 151 pacientes (50%) en general, y en 125 (51%) y 26 (43%) de los pacientes con o sin omentoplastía, respectivamente. Los predictores independientes de complicaciones pelvicoperineales en análisis multivariable fueron el tabaquismo (OR 2.68, IC del 95% 1.46 a 4.94) y un IMC alto (OR 1.68, IC del 95% 1.00 a 2.83), pero no la omentoplastía (OR 1.36, IC del 95% 0.77 a 2.40) . La duración media del drenaje por sonda nasogástrica fue mayor después de la omentoplastía (6 frente a 4 días) con una asociación significativa en el análisis multivariable (coeficiente ß 1.97, IC del 95%: 0.35-3.59). Los pacientes que se sometieron a una omentoplastía tuvieron una estancia hospitalaria significativamente más larga (14 frente a 10 días), y la omentoplastía permaneció asociada con una estancia hospitalaria prolongada después de ajustar por factores de confusión (coeficiente ß 3.05, IC del 95%: 0.05-5.74).LIMITACIONES:Diseño retrospectivo.CONCLUSIÓN:La omentoplastía no se asoció con un riesgo reducido de aparición de complicaciones pelvicoperineales a corto plazo después de la resección abdominoperineal en pacientes sometidos a quimioradioterapia de larga duración. Adicionalmente, en los pacientes sometidos a omentoplastía se observó una duración prolongada del drenaje por sonda nasogástrica y la estancia hospitalaria. Consulte Video Resumen en http://links.lww.com/DCR/C124 . (Traducción-Dr. Jorge Silva Velazco ).

Morbidity and survival after laparoscopic versus open pancreatoduodenectomy: propensity score matched comparison.

PURPOSE: Technical challenges and a perceived higher risk of complications hinder a wide adoption of minimally invasive pancreatoduodenectomy. We aim to further define the place of minimally invasive pancreatoduodenectomy by comparison with the traditional open approach. METHODS: A comparison of the surgical outcomes and survival after laparoscopic (LPD) versus open pancreatoduodenectomy (OPD) was retrospectively performed from a prospectively kept database. To reduce the effect of bias and confounding, baseline characteristics of both groups were matched using propensity score matching (NCT05110573; Nov 8, 2021; retrospectively registered). RESULTS: From a total of 67 LPD and 105 OPD patients, propensity score matching resulted in two balanced groups of 38 patients. In both groups, 87% of surgeries were performed for cancer. In the LPD group, conversion rate was 22.4%. Mean operative time was significantly longer after LPD versus OPD (320.1 ± 53.8 vs. 277.7 ± 63.8 min; p = .008). Hospital stay was significantly shorter after LPD versus OPD (median 13.5 vs. 17.0 days; p = .039). No significant differences were observed in blood loss, total complication rate (73.7% vs. 86.8%; p = .249), major complication rate (26.5% vs. 10.5%; p = .137), postoperative pancreatic fistula rate (13.2% vs. 7.9%; p = .711), 90-day mortality rate (5.3% vs. 0%; p = .493), R0 resection rate (85.4% vs. 85.8%), or number of lymph nodes (median 10.0 vs. 8.5; p = .273). In cancer patients, no significant differences were observed in overall survival (median 27.1 vs. 23.9 months; p = .693), disease-free survival, or recurrence rate. CONCLUSION: LPD provided acceptable short-term and oncological outcomes. Compared to OPD, we noted a higher major complication rate, without compromising surgical safety or oncological outcomes.

Patient-reported outcomes after pelvic exenteration for colorectal cancer: A systematic review.

AIM: Pelvic exenteration (PE) carries high morbidity. Our aim was to analyse the use of patient-reported outcome measures (PROMs) in PE patients. METHOD: Search strategies were protocolized and registered in PROSPERO. PubMed, Embase, Cochrane Library, Google Scholar, Web of Science and ClinicalTrials.gov were searched with the terms 'patient reported outcomes', 'pelvic exenteration' and 'colorectal cancer'. Studies published after 1980 reporting on PROMs for at least 10 PE patients were considered. Study selection, data extraction, rating of certainty of evidence (GRADE) and risk of bias (ROBINS-I) were performed independently by two reviewers. RESULTS: Nineteen of 173 studies were included (13 retrospective, six prospective). All studies were low to very low quality, with an overall moderate/serious risk of bias. Studies included data on 878 patients with locally advanced rectal cancer (n = 344), recurrent rectal cancer (n = 411) or cancer of unknown type (n = 123). Thirteen studies used validated questionnaires, four used non-validated measures and two used both. Questionnaires included the Functional Assessment of Cancer Therapy-Colorectal questionnaire (n = 6), Short Form Health Survey (n = 6), European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 (n = 6), EORTC-CR38 (n = 4), EORTC-BLM30 (n = 1), Brief Pain Inventory (n = 2), Short Form 12 (n = 1), Assessment of Quality of Life (n = 1), Short Form Six-Dimension (n = 1), the Memorial Sloan Kettering Cancer Center Sphincter Function Scale (n = 1), the Cleveland Global Quality of Life (n = 1) or other (n = 4). Timing varied between studies. CONCLUSIONS: Whilst the use of validated questionnaires increased over time, this study shows that there is a need for uniform use and timing of PROMs to enable multicentre studies.

Clinical utility of near-infrared perfusion assessment of the gastric tube during Ivor Lewis esophagectomy.

BACKGROUND: Anastomotic leakage (AL) after Ivor Lewis esophagectomy with intrathoracic anastomosis carries a significant morbidity. Adequate perfusion of the gastric tube (GT) is an important predictor of anastomotic integrity. Recently, near infrared fluorescent (NIRF) imaging using indocyanine green (ICG) was introduced in clinical practice to evaluate tissue perfusion. We evaluated the feasibility and efficacy of GT indocyanine green angiography (ICGA) after Ivor Lewis esophagectomy. METHODS: This retrospective analysis used data from a prospectively kept database of consecutive patients who underwent Ivor Lewis (IL) esophagectomy with GT construction for cancer between January 2016 and December 2020. Relevant outcomes were feasibility, ICGA complications and the impact of ICGA on AL. RESULTS: 266 consecutive IL patients were identified who matched the inclusion criteria. The 115 patients operated with perioperative ICGA were compared to a control group in whom surgery was performed according to the standard of care. ICGA perfusion assessment was feasible and safe in all 115 procedures and suggested a poorly perfused tip in 56/115 (48.7%) cases, for which additional resection was performed. The overall AL rate was 16% (43/266), with 12% (33/266) needing an endoscopic our surgical intervention and 6% (17/266) needing ICU support. In univariable and multivariable analyses, ICGA was not correlated with the risk of AL (ICGA:14.8% vs non-ICGA:17.2%, p = 0.62). However, poor ICGA perfusion of the GT predicted a higher AL rate, despite additional resection of the tip (ICGA poorly perfused: 19.6% vs ICG well perfused: 10.2%, p = 0.19). CONCLUSIONS: ICGA is safe and feasible, but did not result in a reduction of AL. The interpretation and necessary action in case of perioperative presence of ischemia on ICGA have yet to be determined. Prospective randomized trials are warranted to analyze its benefit on AL in esophageal surgery. Trial registration Ethical approval for a prospective esophageal surgery database was granted by the Ethical committee of the Ghent University Hospital. Belgian registration number: B670201111232. Ethical approval for this retrospective data analysis was granted by our institutional EC. REGISTRATION NUMBER: BC-09216.

An International Registry of Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PURPOSE: Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry. METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed. RESULTS: The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p < 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications. CONCLUSION: CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology.

Quality of Life after Minimally Invasive Esophagectomy: A Cross-Sectional Study.

INTRODUCTION: Surgery remains essential in the curative treatment of esophageal cancer (EC), but it is known for its high morbidity and impaired health-related QoL. Minimally invasive esophagectomy (MIE) was introduced to reduce surgical trauma and improve QoL. METHODS: This cross-sectional study aimed to evaluate long-term HRQoL after MIE in comparison with the general population. HRQoL assessment was based on three questionnaires: the European Organisation for Research and Treatment of Cancer (EORTC) Core 30 (QLQ-C30, version 3), the EORTC QLQ Oesophago Gastric 25 (QLQ-OG25), and the Supportive Care Needs Survey-Short Form 34 (SCNS-SF34). Results were compared to a healthy reference population. RESULTS: One hundred and forty eligible MIE patients were identified, of whom met the inclusion criteria, and 49 completed all questionnaires. Patients reported a significantly better mean score on the global health status and QoL than the healthy reference population (71.5 ± 15.1 vs. 66.1 ± 21.7; p = 0.016). However, patients scored significantly worse about functioning (physical, role, and social) (p < 0.05), fatigue (p = 0.021), eating, dysphagia, pain and discomfort, reflux, appetite loss, weight loss, coughing, and taste (p < 0.001). DISCUSSION/CONCLUSION: EC survivors can reach a high global health status and QoL at least 1 year after MIE, despite long-term functional, nutritional, and gastrointestinal complaints. Patients provided written informed consent, and the study protocol was approved by the Ethics Committee of Ghent University Hospital (identifier: ID B670201940737).

The impact of molecular profile on the lymphatic spread pattern in stage III colon cancer.

The anatomical spread of lymph node (LN) metastasis is of practical importance in the surgical management of colon cancer (CC). We examined the effect of KRAS, BRAF, and microsatellite instability (MSI) on LN count and anatomical spread pattern in stage III CC. We determined KRAS, BRAF, and MSI status from stage III CC patients. Biomarker status was correlated with LN count and anatomical spread pattern, which was classified as sequential or skipped. Relapse-free survival (RFS) was estimated using Kaplan-Meier method, and correlations were assessed using log-rank and Cox regression analyses. We analyzed 369 stage III CC patients. The proportion of KRAS mutant (mt), BRAF mt, and MSI-high (H) were 44.2% (163/344), 6.8% (25/344), and 6.8% (25/344), respectively. The mean number of metastatic LN was higher in microsatellite-stable (MSS) compared with MSI patients (3.5 vs. 2.7, P = .0406), although no differences were observed in accordance with KRAS or BRAF status. Interestingly, patients with BRAF mt and MSI-H were less likely to harbor skipped metastatic LN (9.3% vs 20% and 4% vs 10.5% compared with BRAF wild-type (wt) and MSS, respectively), but KRAS status did not predict anatomical spread pattern. Patients with KRAS wt and MSI-H showed superior RFS compared with KRAS mt and MSS patients, respectively, whereas BRAF status did not affect RFS. Differences exist in the anatomical pattern of invaded LN in accordance with the molecular status of stage III CC. Patients with MSI-H CC have less invaded and skipped LN, suggesting that a tailored surgical approach is possible.

Incidentally found mucinous epithelial tumors of the appendix with or without pseudomyxoma peritonei: diagnostic and therapeutic algorithms based on current evidence.

Mucinous appendiceal tumors with or without the pseudomyxoma peritonei (PMP) syndrome are rare, but often present as an incidental finding. The confusing histology and lack of large prospective trials result in a considerable diagnostic and therapeutic challenge in these patients. We propose treatment algorithms in patients with incidentally found mucinous epithelial appendiceal tumors, with or without PMP, based on the currently available evidence. The therapeutic approach should take into account the histology and grade of the primary appendix tumor, as well as those of the associated peritoneal disease.

The role of the peritoneal microenvironment in the pathogenesis of colorectal peritoneal carcinomatosis.

Recent insights have implicated mesothelial-to-mesenchymal transition (MMT) as a mechanism by which mesothelial cells can transdifferentiate into cancer-associated fibroblasts (CAFs) in several cancers metastasizing to the peritoneum. However, this was not evaluated extensively in colorectal cancer. We examined the presumed mesothelial origin of CAFs in three types of colorectal carcinoma: conventional type adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma. We evaluated the expression of mesothelial, mesenchymal, angiogenesis and colorectal cancer-related markers in peritoneal samples of twelve colorectal cancer patients with peritoneal carcinomatosis and four control patients by immunohistochemistry. We observed morphological and immunohistochemical changes in the vicinity of tumor implants in all studied colorectal cancer types. Mesothelial cells acquired a spindle-shaped myofibroblast-like morphology, lost expression of mesothelial markers, and gained expression of mesenchymal markers. Analysis of consecutive tissue sections and double staining for mesothelial and mesenchymal markers revealed overlap in expression of mesothelial and CAF markers. These findings are highly suggestive of a mesothelial origin of CAFs in peritoneal carcinomatosis in colorectal cancer. Interfering with the process of MMT might be a valuable approach in treating and preventing peritoneal carcinomatosis. Differences observed between colorectal cancer types suggest that one single strategy might not be applicable.

Heating technology for malignant tumors: a review.

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 °C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC).

BACKGROUND: pressurized intraperitoneal aerosol chemotherapy (PIPAC), with or without electrostatic precipitation (ePIPAC), was recently introduced in the treatment of peritoneal metastases (PM) from ovarian cancer (OC). Preliminary clinical data are promising, but several methodological issues as well the anticancer efficacy of PIPAC remain unaddressed. Here, we propose a rat ePIPAC model that allows to study these issues in a clinically relevant, reproducible, and high throughput model. METHODS: laparoscopy and PIPAC were established in healthy Wistar rats. Aerosol properties were measured using laser diffraction spectrometry based granulometric analyses. Electrostatic precipitation was accomplished using a commercially available generator (Ultravision™). A xenograft model of ovarian PM was created in athymic rats using intraperitoneal (IP) injection of SKOV-3 luciferase positive cells. Tumor growth was monitored weekly by in vivo bioluminescence imaging. RESULTS: PIPAC and electrostatic precipitation were well tolerated using a capnoperitoneum of 8 mmHg. All rats survived the (e)PIPAC procedure and no gas or aerosol leakage was observed over the entire procedure. With an injection pressure of 20 bar, granulometry showed a mean droplet diameter (D(v,0.5)) of 47 µm with a flow rate of 0.5 mL/s, and a significantly lower diameter (30 µm) when a flow rate of 0.8 mL/s was used. Experiments using IP injection of SKOV-3 luciferase positive cells showed that after IP injection of 20 × 106 cells, miliary PM was observed in all animals. PIPAC was feasible and well supported in these tumor bearing animals. CONCLUSIONS: we propose a reproducible and efficient rodent model to study PIPAC and ePIPAC in OC xenografts with widespread PM. This model allows to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPAC treatment.

High Pressure Nebulization (PIPAC) Versus Injection for the Intraperitoneal Administration of mRNA Complexes.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering drugs into the abdominal cavity as an aerosol under high pressure. It is hypothesized to have advantages such as enhancing tissue uptake, distributing drugs homogeneously within the closed and expanded abdominal cavity and higher local concentration of drugs in the peritoneal cavity. However, the clinical trials of PIPAC so far are limited to liquid chemotherapeutic solution, and the applicability of biomolecules (such as mRNA, siRNA and oligonucleotide) is not known. We aimed to investigate the feasibility of administrating mRNA lipoplexes to the peritoneal cavity via high pressure nebulization. METHODS: We firstly investigated the influences of nebulization on physicochemical properties and in vitro transfection efficiency of mRNA lipoplexes. Then, mRNA lipoplexes were delivered to healthy rats through intravenous injection, intraperitoneal injection and PIPAC, respectively. RESULTS: mRNA lipoplexes can withstand the high pressure applied during the PIPAC procedure in vitro. Bioluminescence localized to the peritoneal cavity of rats after administration by IP injection and nebulization, while intravenous injection mainly induced protein expression in the spleen. CONCLUSION: This study demonstrated that local nebulization is feasible to apply mRNA complexes in the peritoneal cavity during a PIPAC procedure.

Effect of treatment sequence on survival in stage IV rectal cancer with synchronous and potentially resectable liver metastases.

BACKGROUND AND OBJECTIVES: The optimal treatment sequence in stage IV rectal cancer (RC) with synchronous liver metastases (SLM) remains undefined. Here, we compared outcomes between patients treated with the bowel-first approach (BFA) or the liver-first approach (LFA). METHODS: Consecutive patients diagnosed with stage IV RC with SLM and who underwent complete resection were included. Both groups were matched using propensity scores. Differences in postoperative outcome, local control, and long-term survival were studied. In addition, a decision analysis (DA) model was built using TreeAge Pro to define the approach that results in the highest treatment completion rate. RESULTS: During a 12-year period, 52 patients were identified, 21 and 31 of whom underwent the BFA and the LFA, respectively. Twenty-eight patients were matched; patients treated with the BFA experienced a longer median OS (50.0 vs 33.0 months; P = .40) and higher 5-year OS (42.9% vs 28.6%). The DA defined the BFA to be superior when the failure threshold (ie, no R0 resection, treatment discontinuation regardless of cause) for colectomy is less than 28.6%. CONCLUSIONS: In stage IV rectal cancer with SLM, either the BFA or the LFA result in similar long-term outcomes. Treatment should be tailored according to clinicopathological variables.

Intraoperative radiation therapy for rectal cancer and recurrent intra-abdominal sarcomas.

PURPOSE: The aim of this study was to evaluate the effect of high-dose-rate intraoperative radiation therapy (HDR-IORT) in a multimodality treatment on the local control (LC) and the overall survival (OS) rate in locally advanced rectal cancer (LARC), locally recurrent rectal cancer (LRRC) and recurrent intra-abdominal sarcomas (RS). MATERIALS AND METHODS: A retrospective analysis was performed on 27 patients who were treated with radical resection and HDR-IORT between April 2007 and January 2017. Patient, tumor and surgical characteristics were analyzed and the perioperative (<30 days) and long-term complications (>30 days) were assessed and graded. RESULTS: None of the patients with LARC (n = 4) developed a local recurrence and all patients were still alive at the end of the follow-up. The LC rates of LRRC (n = 17) after one and three years were respectively 48% and 40% and the one, three and five years OS were respectively 93%, 62% and 44%. For RS (n = 6), the LC rates after one and three years were both 33% and the one and three years OS rate were respectively 83% and 46%. CONCLUSIONS: The results of our study show that HDR-IORT could be a valuable asset in the multimodality management of LARC, LRRC and RS.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience.

BACKGROUND: The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA). METHODS: A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC. RESULTS: Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS. CONCLUSION: The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.