Impact of primary endoscopic resection on oncological outcomes after esophagectomy for cancer: a retrospective propensity score-based cohort study.

BACKGROUND: Esophageal cancer posed significant global health challenges, particularly due to poor survival rates, especially in advanced stages. Primary endoscopic resection had emerged as an alternative treatment for early esophageal cancer, aiming to preserve organ function and reduce surgical morbidity. METHODS: This retrospective multicenter cohort study included 334 patients with early esophageal cancer (T1a-b, N0) from 30 French-speaking European centers between 2000 and 2010. Patients underwent either primary endoscopic resection followed by esophagectomy (E group, n = 36) or esophagectomy alone (S group, n = 298). Cox proportional hazards models adjusted for TNM stage and propensity score weighting were used to assess the impact of primary endoscopic resection on recurrence-free survival (RFS), overall survival (OS), and postoperative complications. RESULTS: Primary endoscopic resection did not significantly influence RFS (adjusted HR 0.92, 95% CI 0.31 to 2.68, p = 0.88) or OS (adjusted HR 1.06, 95% CI 0.35 to 3.13, p = 0.92) compared to esophagectomy alone. Initial higher thromboembolic complications in the endoscopic resection group were not significant after adjustment (adjusted OR 4.73, 95% CI 0.34 to 64.27, p = 0.24). CONCLUSIONS: Primary endoscopic resection followed by esophagectomy for early esophageal cancer did not alter oncological outcomes or overall survival in this retrospective cohort. These findings supported the role of primary endoscopic resection as a safe initial treatment strategy, warranting validation in larger prospective studies. REGISTRATION: Our study was registered retrospectively on the Clinicaltrials.com website under the identifier NCT01927016. We acknowledge the importance of prospective registration and regret that this was not done before the commencement of the study.

[Surgical management of gastrointestinal stromal tumors of gastric origin]. / Prise en charge chirurgicale des tumeurs stromales gastro-intestinales d'origine gastrique.

Gastrointestinal Stromal Tumors (GISTs) account for 1 to 2% of gastrointestinal malignant tumors. They are characterized by overexpression of the tyrosine kinase (KIT). 60% of GISTs originate in the stomach. Managing them remains complex and varies depending on several factors such as location, size, molecular biology, type of clinical presentation, and the risks/benefits of surgical treatment. Surgery remains the only curative treatment, while tyrosine kinase inhibitors have demonstrated their efficacy as systemic treatment in the perioperative context. Risk stratification for recurrence guides the choice of adjuvant treatment, with a recommended duration of 3 years for high-risk patients.

Les tumeurs stromales gastro-intestinales (GIST) constituent entre 1 et 2 % des tumeurs malignes gastro-intestinales. Elles se caractérisent par une surexpression de la tyrosine kinase (KIT). 60 % des GIST sont d'origine gastrique. Leur prise en charge reste complexe et varie selon plusieurs facteurs tels que la localisation, la taille, la biologie moléculaire, le type de manifestation clinique et les risques/bénéfices du traitement chirurgical. La chirurgie demeure le seul traitement curatif, tandis que les inhibiteurs de tyrosine kinase ont démontré leur efficacité comme traitement systémique dans le contexte périopératoire. La stratification du risque de récidive guide le choix du traitement adjuvant, avec une durée recommandée de 3 ans pour les patients à haut risque.

Prognostic value of tumor regression grade (TRG) after oncological gastrectomy for gastric cancer.

PURPOSE: Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS). METHODS: Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted. RESULTS: Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance. CONCLUSIONS: TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS.

Functional results after hiatal repair and gastropexy without fundoplication in patients with paraoesophageal hernia.

PURPOSE: Paraoesophageal hernias (PEH) are associated with a high complication rate and often occur in elderly and fragile patients. Surgical gastropexy without fundoplication is an accepted alternative procedure; however, outcomes and functional results are rarely described. Our study aims to evaluate short-term outcomes and the long-term quality of life after gastropexy as treatment for PEH. METHODS: Single center cohort analysis of all consecutive patients who underwent gastropexy for PEH without fundoplication. Postoperative outcomes and functional results were retrospectively collected. Reflux symptoms developed postoperatively were reported using the validated quality of life questionnaire: GERD-Health Related Quality of Life Qestionnaire (GERD-HRQL). RESULTS: Thirty patients (median age: 72 years (65-80)) were included, 40% classified as ASA III. Main PEH symptoms were reflux (63%), abdominal/thoracic pain (47%), pyrosis (33%), anorexia (30%), and food blockage (26%). Twenty-six laparoscopies were performed (86%). Major complications (III-IVb) occurred in 9 patients (30%). Seven patients (23%) had PEH recurrence, all re-operated, performing a new gastropexy. Median follow-up was 38 (17-50) months. Twenty-two patients (75%) reported symptoms resolution with median GERD-HRQL scale of 4 (1-6). 72% (n = 21) reported operation satisfaction. GERD-HRQL was comparable between patients who were re-operated for recurrence and others: 5 (2-19) versus 3 (0-6), p = 0.100. CONCLUSION: Gastropexy without fundoplication was performed by laparoscopy in most cases with acceptable complications rates. Two-thirds of patients reported symptoms resolution, and long-term quality-of-live associated to reflux symptoms is good. Although the rate of PEH recurrence requiring a new re-intervention remained increased (23%), it does not seem to affect long-term functional results.

Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma.

BACKGROUND: Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy. METHODS: A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS. RESULTS: The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34). CONCLUSIONS: At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.

Gastro-Intestinal Disorders and Micronutrient Deficiencies following Oncologic Esophagectomy and Gastrectomy.

Primary surgical indications for the esophagus and stomach mainly involve cancer surgeries. In recent years, significant progress has been made in the field of esogastric surgery, driven by advancements in surgical techniques and improvements in perioperative care. The rate of resectability has increased, and surgical strategies have evolved to encompass a broader patient population. However, despite a reduction in postoperative mortality and morbidity, malnutrition remains a significant challenge after surgery, leading to weight loss, muscle mass reduction, and deficiencies in essential nutrients due to digestive complications. Malnutrition worsens quality of life and increases the risk of tumor recurrence, significantly affecting prognosis. Nevertheless, the nutritional consequences following surgery are frequently overlooked, mainly due to a lack of awareness regarding their long-term effects on patients who have undergone digestive surgery, extending beyond six months. Micronutrient deficiencies are frequently observed following both partial and total gastrectomy, as anticipated. Surprisingly, these deficiencies appear to be similarly prevalent in patients who have undergone esophagectomy with iron, vitamins A, B1, B12, D, and E deficiencies commonly observed in up to 78.3% of the patients. Recognizing the distinct consequences associated with each type of intervention underscores the importance of implementing preventive measures, early detection, and prompt management.

The role of cytology in patients undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC) treatment for peritoneal carcinomatosis.

Objectives: Cytology of ascites or peritoneal washing is a routine part of staging of peritoneal metastases (PM). We aim to determine value of cytology in patients undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods: Single-center retrospective cohort study included consecutive patients having PIPAC for PM of different primary between January 2015 and January 2020. Results: A total of 75 patients (median 63 years (IQR 51-70), 67 % female) underwent a total of 144 PIPAC. At PIPAC 1 59 % patients had positive and 41 % patients had negative cytology. Patients with negative and positive cytology only differed in terms of symptoms of ascites (16% vs. 39 % respectively, p=0.04), median ascites volume (100 vs. 0 mL, p=0.01) and median PCI (9 vs. 19, p<0.01). Among 20 patients who completed 3 PIPACs (per protocol), cytology changed in one from positive to negative, and in two from negative to positive. Median overall survival was 30.9 months in the per protocol group and 12.9 months in patients having <3 PIPACs (=0.519). Conclusions: Positive cytology under PIPAC treatment is more frequently encountered in patients with higher PCI and symptomatic ascites. Cytoversion was rarely observed and cytology status had no impact on treatment decisions in this cohort.

A Comprehensive Review of Prognostic Factors in Patients with Gastric Adenocarcinoma.

Gastric adenocarcinoma remains associated with a poor long-term survival, despite recent therapeutical advances. In most parts of the world where systematic screening programs do not exist, diagnosis is often made at advanced stages, affecting long-term prognosis. In recent years, there is increasing evidence that a large bundle of factors, ranging from the tumor microenvironment to patient ethnicity and variations in therapeutic strategy, play an important role in patient outcome. A more thorough understanding of these multi-faceted parameters is needed in order to provide a better assessment of long-term prognosis in these patients, which probably also require the refinement of current staging systems. This study aims to review existing knowledge on the clinical, biomolecular and treatment-related parameters that have some prognostic value in patients with gastric adenocarcinoma.

[Surgery: what's new in 2022]. / Chirurgie : ce qui a changé en 2022.

During 2022 a lot of efforts were developed to reduce health-costs by reducing complications and length of hospital stay. Same-day surgery is becoming the standard for all patients scheduled for elective surgery in CHUV. Outpatient colectomy also become a new standard. During 2022, endoscopic bariatric surgery became increasingly used. Not widely performed yet in Switzerland, these treatments deserve to be recognized and considered in various situations. Finally, 2022 saw a promising development of robotic surgery with the acquisition of Da Vinci and Dexter robots after allowing various high-precision surgical procedures.

2022 a été marquée par les efforts déployés pour réduire les coûts de la santé en diminuant les complications et en raccourcissant les durées d'hospitalisation. L'admission le jour même (Same Day Surgery (SDS)) va à moyen terme devenir le nouveau standard pour tous les patients admis pour une chirurgie en électif au CHUV, il en va de même avec le concept de la colectomie en ambulatoire. 2022 est aussi marquée par le développement de la chirurgie endoscopique bariatrique à l'échelle globale. Non encore pratiqués largement en Suisse, ces traitements méritent d'être connus et considérés dans certaines situations particulières. Finalement, 2022 voit aussi le développement de la chirurgie robotique à la suite de l'acquisition des robots Da Vinci et Dexter, permettant la réalisation de nombreuses interventions chirurgicales de haute précision.

Neoadjuvant Chemoradiotherapy versus Chemotherapy for Gastroesophageal Junction Adenocarcinoma; Which Is the Optimal Treatment Option?

Background: Locally advanced gastroesophageal junction adenocarcinoma (GEJ) is treated with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. The aim of this study was to compare pathologic response and long-term outcomes in junction adenocarcinoma treated with neoadjuvant RCT versus CT. Methods: All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 were retrospectively analyzed. Results: A total of 94 patients were included, 67 (71.2%) RCT and 27 (28.8%) CT. Complete pathologic response was more frequent in RCT patients (13.4% vs. 7.4%, p = 0.009) with a trend to better lymph node control (ypN0) (55.2% vs. 33.3%; p = 0.057). RCT offered no benefit in R0 resection (66.7% vs. 72.1% CT, p = 0.628) and was related to higher postoperative cardiovascular complications (35.8% vs. 11.1%; p = 0.017). Long-term overall and disease-free survival were similar (5-year OS 61.1% RCT vs. 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs. 22.8% CT; p = 0.763). NAT type was neither independently associated with pathologic response nor long-term survival. Discussion: Patients with locally advanced GEJ adenocarcinoma treated with RCT had more postoperative cardiovascular complications but higher rates of complete pathologic response and a trend to superior locoregional lymph node control. This did not translate in a survival or recurrence benefit.

Histological regression of peritoneal metastases of recurrent tubo-ovarian cancer after systemic chemotherapy.

Introduction: Post-treatment histological regression of peritoneal metastases (PM) is a new and potentially important predictor of oncological outcomes. Histology of PM from adnexal origin is usually evaluated by the Chemotherapy Response Score (CRS). The aim of this preliminary study was to quantify the response of PM of recurrent tubo-ovarian cancer (TOVC) after systemic chemotherapy by using the recently validated Peritoneal Regression Grading System (PRGS) and compare it with CRS. Correlation with per operative evaluation through Peritoneal Cancer Index (PCI) was performed. Material and methods: Retrospective cohort study of all consecutive patients with recurrent PM from TOVC undergoing surgery after prior systemic chemotherapy from January 2015 to March 2019. Biopsies were assessed with the four-scale PRGS. Results: Thirty-eight patients were included. Patients had a median of 2 (range 1-2) lines and 12 (range 3-18) cycles of prior systemic chemotherapy. Overall mean (SD) PRGS was 2.3 (±1.1). Of the patients, 26% (10) had complete response (PRGS 1), 40% (15) had major response (PRGS 2), 26% (10) minor response (PRGS 3), and 8% (3) had no response (PRGS 4). Mean PRGS was positively correlated with the Peritoneal Cancer Index (ρ = 0.5302, p = 0.0003) and inversely correlated with CRS (ρ = -0.8403, p < 0.0001). No correlation was highlighted between mean PRGS and overall survival (ρ = -0.0195, p = 0.9073). Conclusion: CRS and mean PRGS correlated with each other. Histological response of PM after systemic chemotherapy was quantifiable and variable. The role of PRGS for the evaluation of treatment response and as potential surrogate marker for oncological outcomes is part of ongoing and planned research.

Assessment of Treatment Response after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) for Appendiceal Peritoneal Metastases.

Background The aim of this study was to analyse survival and surrogates for oncological response after PIPAC for appendiceal tumours. Methods This retrospective cohort study included consecutive patients with appendiceal peritoneal metastases (PM) treated in experienced PIPAC centers. Primary outcome measure was overall survival (OS) from the date of diagnosis of PM and from the start of PIPAC. Predefined secondary outcome included radiological response (RECIST criteria), repeat laparoscopy and peritoneal cancer index (PCI), histological response assessed by the Peritoneal regression grading system (PRGS) and clinical response. Results Final analysis included 77 consecutive patients (208 PIPAC procedures) from 15 centres. Median OS was 30 months (23.00-46.00) from time of diagnosis and 19 months (13.00-28.00) from start of PIPAC. 35/77 patients (45%) had ≥3 procedures (pp: per protocol). Objective response at PIPAC3 was as follows: RECIST: complete response 4 (11.4%), 11 (31.4%) partial/stable; mean PRGS at PIPAC3: 1.8 ± 0.9. Median PCI: 21 (IQR 18-27) vs. 22 (IQR 17-28) at baseline (p = 0.59); 21 (60%) and 18 (51%) patients were symptomatic at baseline and PIPAC3, respectively (p = 0.873). Median OS in the pp cohort was 22.00 months (19.00-NA) from 1st PIPAC. Conclusion Patients with PM of appendiceal origin had objective treatment response after PIPAC and encouraging survival curves call for further prospective evaluation.

Selection Criteria for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Treatment in Patients with Peritoneal Metastases.

Background: The standard treatment protocol for PIPAC consists of three procedures. Completion of treatment has been shown to be prognostic of improved survival. The aim of this study was to identify predictors for completion of treatment. Methods: Retrospective multicentric cohort study of patients with peritoneal metastases undergoing PIPAC in three PIPAC expert centers. Per protocol (PP) treatment was defined as patients receiving ≥3 PIPACs and was compared to patients receiving <3. Results: Overall, 183 patients had 517 PIPACs. The main reasons for stopping PIPAC were disease progression in 50% patients, bowel obstruction in 15%, patient's refusal to pursue in 10%, conversion to cytoreductive surgery in 7%, and medical reasons in 8%. Overall, 95 patients (52%) had PP treatment. The PP median OS was 17 vs. 7 months, p = 0.001. PP patients had r ascites (410 ± 100 mL vs. 960 ± 188 mL, p = 0.001), no prior history of bowel obstruction (12% vs. 24%, p = 0.028), and more bimodal treatment (39% vs. 13%, p < 0.001). After multiple regression, bimodal treatment was found as an independent predictive factor for completing PP (OR = 4.202, 95%CI [1.813, 10.630], p < 0.001), along with prior bowel obstruction (OR = 0.389, 95%CI [0.153, 0.920], p = 0.037). Conclusion: The absence of ascites and prior bowel obstruction can help to select patients suitable for PIPAC. Best results seem to be achieved when PIPAC is combined with systemic chemotherapy.

Early postoperative outcomes of staging laparoscopy for peritoneal metastases with or without pressurized intra-peritoneal aerosol chemotherapy (PIPAC).

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for palliative treatment of peritoneal surface malignancies (PSM) and is currently tested also in the neoadjuvant and prophylactic setting. The aim was therefore to compare safety and tolerance of staging laparoscopy with or without PIPAC. METHODS: This retrospective analysis compared consecutive patients undergoing staging laparoscopy alone for oesogastric cancer with patients having PIPAC for suspected PSM of various origins from January 2015 until January 2020. Safety was assessed by use of the Clavien classification for complications and CTCAE for capturing of adverse events. Pain and nausea were documented by use of a visual analogue scale (VAS: 0-10: maximal intensity). RESULTS: Overall, 25 PIPAC procedures were compared to 24 staging laparoscopies. PIPAC procedures took a median of 35 min (IQR: 25-67) longer. Four patients experienced at least one complication in either group (p = 0.741). No differences were noted for postoperative nausea (p = 0.961) and pain levels (p = 0.156). Median hospital stay was 2 (IQR: 1-3) for PIPAC and 1 (IQR: 1-2) for the laparoscopy group (p = 0.104). CONCLUSIONS: The addition of PIPAC did not jeopardize safety and postoperative outcomes of staging laparoscopy alone. Further studies need to clarify its oncological benefits.

Feasibility and Safety of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy With or Without Intraoperative Intravenous 5-Fluorouracil and Leucovorin for Colorectal Peritoneal Metastases: A Multicenter Comparative Cohort Study.

BACKGROUND: This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L). METHODS: Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group). RESULTS: In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group (p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group (p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups. CONCLUSIONS: The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies.

Immunotherapy for Esophageal Cancer: State-of-the Art in 2021.

The management of esophageal cancer (EC) has experienced manifold changes during the last decades. Centralization of EC treatment has been introduced in many countries, subsequently allowing the development of specialized high-volume centers. Minimal invasive surgery has replaced open surgery in many centers, whereas more potent systemic treatments have been introduced in clinical practice. Newer chemotherapy regimens increase long-term survival. Nevertheless, the overall survival of EC patients remains dismal for advanced tumor stages. In this direction, a wide range of targeted biologic agents (immunotherapy) is currently under assessment. Anti- Human Epidermal Growth Factor Receptor-2 (HER-2) monoclonal antibodies are used in HER2 (+) tumors, predominantly well-differentiated adenocarcinomas, and are currently assessed in the neoadjuvant setting (TRAP, INNOVATION trials). Immune checkpoint inhibitors Nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181), have demonstrated a survival benefit compared with conventional chemotherapy in heavily pre-treated progressive disease. More recently, CheckMate-577 showed very promising results for nivolumab in a curative adjuvant setting, improving disease-free survival mainly for esophageal squamous cell carcinoma. Several ongoing trials are investigating novel targeted agents in the preoperative setting of locally advanced EC. In addition, other immunomodulatory approaches such as peptide vaccines and tumor infiltrating lymphocytes (TILs) are currently under development and should be increasingly integrated into clinical practice.

Treatment Response After Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastases of Colorectal Originf.

The objective of this study is to analyze oncological outcomes of patients with peritoneal metastases (PM) of colorectal origin treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Background: PIPAC has been demonstrated to be a feasible and safe novel treatment for patients with PM of various origins. Only small series reports on survival after PIPAC by disease entity. Methods: International retrospective cohort study of consecutive patients with PM of colorectal origin. Outcome measures were overall survival (OS), radiological response according to Response Evaluation Criteria in Solid Tumors (RECIST), histological response (peritoneal regression grading score [PRGS]: complete response: 1-4: no response), change of peritoneal cancer index (PCI), and symptom control. Results: Seventeen eligible centers compiled 256 non-selected patients (mean age 61 [50.6-69.2], 43% female) and 606 procedures. Sixty-three percent were treated after 2 lines of chemotherapy, median PCI at PIPAC1 was 18 (interquartile range [IQR] = 10-27). Median OS was 19.00 months (IQR = 12.9-29.8) from diagnosis and 9.4 months (IQR = 4.5-16.8) from PIPAC1. One hundred and four of 256 patients (40.6%) had ≥3 procedures (per protocol [pp]) with the following outcomes at PIPAC3: RECIST: 59.3% partial response/stable, 40.7% progression; mean PRGS: 2.1 ± 0.9. Median PCI was 21 (IQR = 15-29) at baseline and 20 (IQR = 12-27) at PIPAC3 (P = 0.02). Fifty-six (54%) and 48 (46%) patients were symptomatic at baseline and PIPAC3, respectively (P = 0.267). Median OS for the pp cohort was 11.9 months (IQR = 10.7-15.0) from PIPAC1. Independent predictors for survival were radiological response (HR = 3.0; 95% CI = 1.6-5.7) and no symptoms (HR = 4.5, 95% CI = 2.2-9.1) at PIPAC3. Conclusions: Objective treatment response and encouraging survival were demonstrated after PIPAC for colorectal PM. Prospective registry data and comparative studies are now needed in to confirm these data.

Histological regression of gastrointestinal peritoneal metastases after systemic chemotherapy.

OBJECTIVES: Peritoneal metastases (PM) are relatively resistant to systemic chemotherapy, and data on histological response to therapy is rare. The aim of this study was to quantify the treatment response of PM after systemic chemotherapy. METHODS: Retrospective monocentric cohort study of 47 consecutive patients with PM from gastrointestinal origin undergoing surgery (cytoreduction: CRS + Hyperthermic IntraPEritoneal Chemotherapy [HIPEC] or Pressurized IntraPeritoneal Aerosol Chemotherapy [PIPAC]) after prior systemic chemotherapy from 1.2015 to 3.2019. Tumor response was assessed using the 4-scale Peritoneal Regression Grading System (PRGS) (4: vital tumor to 1: complete response). RESULTS: Patients had a median of 2 (range: 1-7) lines and 10 (3-39) cycles of prior systemic chemotherapy. A median of four biopsies (range: 3-8) was taken with a total of 196 analyzed specimens. Twenty-four biopsies (12%) showed no histological regression (PRGS4), while PRGS 3, two and one were diagnosed in 37 (19%), 39 (20%), and 69 (49%) specimens, respectively. A significant heterogeneity was found between peritoneal biopsies in 51% patients. PRGS correlated strongly with peritoneal spread (PCI, p<0.0001), and was improved in patients with more than nine cycles of systemic chemotherapy (p=0.04). Median survival was higher in patients with PRGS < 1.8 (Quartiles one and 2) than higher (Q3 and Q4), but the difference did not reach significance in this small cohort. CONCLUSIONS: PRGS is an objective too to describe histological response of PM of GI origin after systemic chemotherapy. This response differs significantly between patients, allowing to distinguish between chemosensitive and chemoresistant tumors.