Numerical and experimental evaluation of nasopharyngeal aerosol administration methods in children with adenoid hypertrophy.

Administering aerosol drugs through the nasal pathway is a common early treatment for children with adenoid hypertrophy (AH). To enhance therapeutic efficacy, a deeper understanding of nasal drug delivery in the nasopharynx is essential. This study uses an integrated experimental, numerical modelling approach to investigate the delivery process of both the aerosol mask delivery system (MDS) and the bi-directional delivery system (BDS) in the pediatric nasal airway with AH. The combined effect of respiratory flow rates and particle size on delivery efficiency was systematically analyzed. The results showed that the nasopharyngeal peak deposition efficiency (DE) for BDS was approximately 2.25-3.73 times higher than that for MDS under low-flow, resting and high-flow respiratory conditions. Overall nasopharyngeal DEs for MDS were at a low level of below 16 %. For each respiratory flow rate, the BDS tended to achieve higher peak DEs (36.36 % vs 9.74 %, 37.80 % vs 14.01 %, 34.58 % vs 15.35 %) at smaller particle sizes (15 µm vs 17 µm, 10 µm vs 14 µm, 6 µm vs 9 µm). An optimal particle size exists for each respiratory flow rate, maximizing the drug delivery efficiency to the nasopharynx. The BDS is more effective in delivering drug aerosols to the nasal cavity and nasopharynx, which is crucial for early intervention in children with AH.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review.

BACKGROUND: PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. METHODS: We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. RESULTS: This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). CONCLUSION: This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.

Lidocaine aerosol sprayed on oral and/or nasal mucosa for the rescue of acute trigeminal neuralgia exacerbations: A retrospective study.

INTRODUCTION: Acute trigeminal neuralgia exacerbation is a common reason for frequent emergency department visits, that often occurs while waiting for surgery, but evidence on effective drugs for acute trigeminal neuralgia is scant. Whether lidocaine aerosol could be a rescue option for the treatment of acute trigeminal neuralgia exacerbations is worth exploring. Positive predictors of the analgesic effects of lidocaine aerosol also warrant further investigation. METHODS: This is a retrospective study with a total of 152 patients. We analyzed the efficacy of lidocaine aerosol for the treatment of acute trigeminal neuralgia exacerbations. A positive response was considered a decrease in the VAS score of at least 50% at 30 min of treatment. Multivariable logistic analyses were performed to identify predictive factors for lidocaine aerosol response. RESULTS: In the group of 109 responders, the VAS score decreased from 8.3 ± 1.1 cm to 0.8 ± 1.0 cm at 15 min, and 1.7 ± 1.0 cm at 30 min. The effective rate at 15 min and 30 min were 77.6% and 70.4%, respectively. Multivariate logistic analyses showed the treatment may provide better clinical outcomes in V2 trigeminal neuralgia (OR 0.01, 95%Cl 0.001-0.15, p < 0.001), V3 trigeminal neuralgia (OR 0.02, 95%Cl 0.001-0.16, p = 0.001), and V2 + V3 trigeminal neuralgia (OR 0.01, 95%Cl 0.001-0.13, p < 0.001), patients who were taking carbamazepine or oxcarbazepine with a maximum dose (OR 6.15, 95%Cl 2.11-17.93, p = 0.001) were less likely to experience immediate pain relief. CONCLUSION: Lidocaine aerosol sprayed on oral and/or nasal mucosa is beneficial for immediate pain relief in patients with acute trigeminal neuralgia exacerbations. It is expected to become a promising treatment option for patients with V2 and/or V3 trigeminal neuralgia.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal surface malignancies (PSM): a prospective single-center registry study.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new, palliative approach for patients with peritoneal surface malignancies (PSMs). Its main goals are to control symptoms and ascites. For this experimental procedure, treatment efficacy and patient safety need to be closely monitored. METHODS: We performed a prospective registry study for patients with PSMs. Cisplatin (C) (7.5 mg/m2 body surface) and doxorubicin (D) (1.5 mg/m2) were administered laparoscopically via PIPAC. RESULTS: Between November 2015 and June 2020, we recorded data from 108 patients and 230 scheduled procedures. Tumor burden, patient fitness, quality of life, operating time and in-hospital stay remained stable over consecutive procedures. We recorded 21 non-access situations and 14 intraoperative complications (11 intestinal injuries, and three aspirations while inducing anesthesia). Three or more previous abdominal surgeries or cytoreductive surgery (CRS) with intraperitoneal hyperthermic chemoperfusion (HIPEC) were risk factors for non-access and intestinal injuries (χ2, p ≤ 0.01). Five Grade IV and three Grade V postoperative complications according to the Clavien-Dindo Classification (CDC) occurred. Median overall survival was 264 days (interquartile range 108-586). Therapies were primarily discontinued because of death (34%), progressive (26%), or regressive (16%) disease. CONCLUSION: PIPAC is effective in stabilizing PSMs and retaining quality of life in selected patients. Earlier abdominal surgeries and CRS with HIPEC should be considered when determining the indication for PIPAC. Randomized controlled studies are needed to evaluate PIPAC's therapeutic benefits compared to systemic chemotherapy (sCHT) alone. TRIAL REGISTRATION: NCT03100708 (April 2017).

PIPAC nebulizer: How to test the new devices in the market, expert recommendations.

Pressurized intraperitoneal aerosol chemotherapy, named PIPAC, is now used in many centers around the world and as an intraperitoneal drug delivery system for treatment of peritoneal carcinomatosis. Recently, many of us have encountered problems during PIPAC procedures due to changes in material and production features of the original PIPAC nebulizer. Concomitantly, new PIPAC nebulizers proposed by other manufacturers are being launched on the market; which claim that they are the same as the original device in delivering PIPAC. However, these new devices are all different in terms of materials, technical characteristics and costs. We have considered that, to maintain the acquired results of PIPAC, we must ensure that the new systems are equivalent. The characteristics deemed essential by the expert group are as follows: 1: The nebulizer must be able to create droplets through an injector pressure between 10 and 20 bars, 2: The mean droplet size must be 3 micrometers, with 95% of the droplets between 0 and 10 micrometers, 3: The diffusion angle must be 70 degrees, which is the minimum.

Oncological Outcomes After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in the Treatment of Peritoneal Carcinomatosis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of initially unresectable peritoneal carcinomatosis (PC). Our objective was to assess its oncological outcomes. METHODS: Between July 2016 and September 2020, data from 100 PIPAC procedures with oxaliplatin or doxorubicin-cisplatin in 49 patients with PC (all etiologies) were analyzed. We studied the evolution of the peritoneal cancer index (PCI), the need for radical surgery (R0), and overall survival (OS). RESULTS: The patients' median age was 65 (59; 71) years, and 55.1% were women. Median PIPAC procedures per patient were 2 (1-3), and 28 (57.1%) underwent more than one PIPAC procedure. Median PCI at the first PIPAC was 19 (15-22). PCI decreased for 37%, remained stable for 29.6%, and increased for 33.4% patients. Four (8.3%) underwent radical R0 surgery after PIPAC. After a median follow-up of 16.1 months (1.5-90.1), the median overall survival from PC diagnosis was 29.1 months (14.8-34.3), with a median gastric and colorectal PC survival of 11.3 (7.2-34.3) and 29.1 months (16.1-31) respectively. Overall survival after the first PIPAC session was 11.6 months (6-17.3), with median survival after gastric and colorectal PCs being 6 (2.9-15.5) and 13.3 months (5-17.6), respectively. Stratification of patients according to the number of lines of systemic chemotherapy, PIPAC procedures, and the chronology of PC onset did not result in a significant difference in survival. CONCLUSION: The OS was in line with the literature. PIPAC could delay oncological progression and improve survival. These encouraging results justify the ongoing and future evaluations of PIPAC by prospective randomized trials.

Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for gastric cancer with peritoneal metastases: A systematic review by the PIPAC UK collaborative.

INTRODUCTION: Gastric cancer with peritoneal metastases (GCPM) carries a poor prognosis. Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) offers pharmacokinetic advantages over intravenous therapy, resulting in higher chemotherapy concentrations in peritoneal deposits, and potentially reduced systemic absorption/toxicity. This review evaluates efficacy, tolerability and impact on quality of life (QOL) of PIPAC for GCPM. METHODS: Following registration with PROSPERO (CRD42021281500), MEDLINE, EMBASE and The Cochrane Library were searched for PIPAC in patients with peritoneal metastases, in accordance with PRISMA standards RESULTS: Across 18 included reports representing 751 patients with GCPM (4 prospective, 11 retrospective, 3 abstracts, no phase III studies), median overall survival (mOS) was 8 - 19.1 months, 1-year OS 49.8-77.9%, complete response (PRGS1) 0-35% and partial response (PRGS2/3) 0-83.3%. Grade 3 and 4 toxicity was 0.7-25% and 0-4.1% respectively. Three studies assessing QOL reported no significant difference. CONCLUSION: PIPAC may offer promising survival benefits, toxicity, and QOL for GCPM.

Intraperitoneal chemotherapy in the management of pancreatic adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer represents one of the leading causes of cancer-related death worldwide. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proven with curative intent mainly for other tumors and there is a lack of consensus regarding possible benefits also in pancreatic cancer. The present systematic review and meta-analysis aim to provide an up-to-date overview of the effectiveness and safety of intraperitoneal treatments in the management of pancreatic cancer. METHODS: A systematic review of articles was conducted according to PRISMA and AMSTAR-2 guidelines. 11 studies were included in the analysis. RESULTS: We included in our analysis 212 patients subdivided in three groups: 64 in the HIPEC group (57 with prophylactic intent and 7 with curative intent), 55 in the PIPAC group and 93 in the NIPEC group. Primary outcomes were represented by survival rates; we evidenced at an observation time of three years a survival of 24% in the HIPEC group (25.5% in the prophylactic arm and 6.2% in the curative arm), 5.3% in the PIPAC group and 7.9% in the NIPEC group. CONCLUSIONS: HIPEC could be considered as a promising technique for prophylaxis and treatment of peritoneal metastasis (PM) in case of borderline resectable and locally advanced disease. Increased survival rates emerged without additional morbidity when surgical resection and CRS are possible. In addition, our data about PIPAC and NIPEC as palliative treatment in unresectable disease seems to identify more favorable survival rates compared to literature.

Assessment of postoperative pain after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of peritoneal metastasis.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique, for the treatment of initially unresectable peritoneal metastasis (PM). Our objective was to assess postoperative pain and morbidity. METHODS: Between July 2016 and September 2020, data from 100 consecutive PIPAC procedures with oxaliplatin (PIPAC Ox) or doxorubicin-cisplatin (PIPAC C/D) in 49 patients with PM (all etiologies) were analyzed. Pain was self-assessed using a visual analog scale (VAS) of 0-10. RESULTS: The median PIPAC procedures per patient were 2 [1-3]. Patients indicated greatest pain at 4 pm on the day of the procedure (D0) and on postoperative D1 at 8 am and 4 pm. Postprocedural moderate-to-severe pain (VAS 4-10) was more frequent with PIPAC Ox than with PIPAC C/D, respectively 14 (36.8%) vs 7 (13.5%); p = 0.010. Hospitalization was longer for patients with moderate-to-severe pain than for others (median 4 days [3-7] vs 3 days [2-4], p = 0.004). Multivariate analysis identified oxaliplatin as a factor associated with greater pain (OR [95% CI], 2.95 [1.10-7.89]. Opiate administration was similar after PIPAC Ox and PIPAC C/D procedures, p = 0.477. CONCLUSION: PIPAC was well-tolerated, and pain was well-controlled in the majority of patients. Pain was greatest at 4 pm on D0 and 8 am and 4 pm on D1. PIPAC Ox is associated with greater pain than PIPAC C/D, independently of opiate treatment. Moderate-to-severe pain was associated with longer hospital stays.

Feasibility and safety of PIPAC combined with additional surgical procedures: PLUS study.

BACKGROUND: PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery. METHODS: PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis. RESULTS: the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p < 0.001), length of stay (p < 0.001) and medical complication rate (p < 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported. CONCLUSIONS: these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available.

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.

Controlled inhalation improves central and peripheral deposition in cystic fibrosis patients with moderate lung disease.

AIM: With progressive impairment of lung function, deposition of inhaled drug in the lungs becomes progressively more central, limiting its effectiveness. This pilot study explored the possibility that long slow inhalations might improve delivery of aerosol to the lung periphery in cystic fibrosis patients with moderate lung disease. METHODS: Five subjects aged 12-18 years (mean FEV1 72%; range 63-80%) inhaled a radiolabelled aerosol from a jet nebuliser on two occasions. Two inhalation techniques were compared: breathing tidally from a standard continuous output nebuliser and using long slow inhalations from the AKITA® JET system. RESULTS: Long slow breaths resulted in much lower oropharyngeal deposition with higher lung doses. Importantly, the peripheral lung increased proportionately. The increased lung dose is attributable to more of the larger inhaled droplets passing into the lower airways. This would be expected to increase the central deposition unless significantly more of the smaller droplets were able to penetrate deeper into the lungs. The data support improved delivery of drug to the distal lung when compared with tidal breathing. CONCLUSION: These pilot data suggest that this approach may prove to be clinically relevant in improving the efficacy of inhaled medication in those with moderate-severe lung disease.

Effect of Pressurized Intraperitoneal Aerosol Chemotherapy on the Survival Rate of Patients with Peritoneal Carcinomatosis of Gastric Origin.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of initially unresectable peritoneal carcinomatosis (PC). Our objective was to compare the results of PIPAC associated with systemic chemotherapy (PIPAC_CHEM) with those of systemic chemotherapy alone (ONLY_CHEM) in patients with gastric PC without metastasis other than peritoneal, and the WHO performance status < 3. METHODS: This was a retrospective, single center, comparative non-randomized study. Seventeen PIPAC_CHEM patients were compared to 29 ONLY_CHEM patients. The primary endpoint was overall survival at 6 months from diagnosis of PC. RESULTS: Ninety-eight patients were screened and 46 were included (PIPAC_CHEM, n = 17; ONLY_CHEM, n = 29). The PIPAC_ CHEM population was significantly younger (median 64 years [56; 68] vs 74 years [61; 79]; p = 0.0054). Median PIPAC session per patient is 2 [1-3]. Six-month survival was significantly higher in the PIPAC_CHEM group than in the ONLY_CHEM group 16/17 (94.1% [65-99.2]) vs 19/29 (65.5% [45.4-79.7]), respectively; p = 0.029. Over the entire follow-up, median survival [95% CI] was 12.8 months [7.2-34.3] with PIPAC vs 9.1 months [5.4-11.5] without, p = 0.056. At 6 months, median length of additional hospitalization was significantly less for PIPAC_CHEM (median 2 days [2-7]) than without PIPAC (median 11 days [3-21]) (p = 0.045). CONCLUSION: The overall survival at 6 months after the diagnosis of carcinomatosis was significantly better for PIPAC_CHEM patients. This difference appears to continue until at least 18 months. At 6 months, days of additional hospitalization was significantly less in the PIPAC_CHEM group. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT 04,879,953.

Consensus guidelines for pressurized intraperitoneal aerosol chemotherapy: Technical aspects and treatment protocols.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to treat patients with peritoneal cancer. A recent survey demonstrated considerable diversification of current practice of PIPAC raising issues of concern also regarding safety and efficacy. The study aim was to reach consensus on best practice of PIPAC treatment. METHODS: Current practice was critically discussed during an expert meeting and the available evidence was scrutinized to elaborate a 33-item closed-ended questionnaire. All active PIPAC centers were then invited to participate in an online two-round Delphi process with 3 reminders at least. Consensus was defined a priori as >70% agreement for a minimal response rate of 70%. RESULTS: Forty-nine out of 57 invited PIPAC centers participated in Delphi 1 and 2 (86%). Overall, there was agreement for 21/33 items. Consensus was reached for important aspects like advanced OR ventilation system (91.8%), remote monitoring (95.9%), use of the PRGS (85.7%) and use of a safety checklist (98%). The drug regimens oxaliplatin (87.8%) and cisplatin/doxorubicin (81.6%) were both confirmed by the expert panel. Important controversies included number and location of Biopsies during repeated PIPAC and the combination of PIPAC with additional surgical procedures. CONCLUSION: This consensus statement aims to allow for safe and efficacious PIPAC treatment and to facilitate multi-center analyses of the results. Additional preclinical and clinical studies are needed to resolve the remaining controversies.

The Clinical Desire for Pressurized Intraperitoneal Aerosol Chemotherapy in South Korea: An Electronic Survey-based Study.

BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.

Patient-reported outcomes during repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for isolated unresectable colorectal peritoneal metastases in a multicenter, single-arm, phase 2 trial (CRC-PIPAC).

BACKGROUND: CRC-PIPAC prospectively assessed repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) as a palliative monotherapy (i.e., without concomitant systemic therapy in between subsequent procedures) for unresectable colorectal peritoneal metastases (CPM). The present study explored patient-reported outcomes (PROs) during trial treatment. METHODS: In this single-arm phase 2 trial in two tertiary centers, patients with isolated unresectable CPM received 6-weekly PIPAC-OX (92 mg/m2). PROs (calculated from EQ-5D-5L, and EORTC QLQ-C30 and QLQ-CR29) were compared between baseline and 1 and 4 weeks after the first three procedures using linear mixed modeling with determination of clinical relevance (Cohen's D ≥ 0.50) of statistically significant differences. RESULTS: Twenty patients underwent 59 procedures (median 3 [range 1-6]). Several PROs solely worsened 1 week after the first procedure (index value - 0.10, p < 0.001; physical functioning - 20, p < 0.001; role functioning - 27, p < 0.001; social functioning - 18, p < 0.001; C30 summary score - 16, p < 0.001; appetite loss + 15, p = 0.007; diarrhea + 15, p = 0.002; urinary frequency + 13, p = 0.004; flatulence + 13, p = 0.001). These PROs returned to baseline at subsequent time points. Other PROs worsened 1 week after the first procedure (fatigue + 23, p < 0.001; pain + 29, p < 0.001; abdominal pain + 32, p < 0.001), second procedure (fatigue + 20, p < 0.001; pain + 21, p < 0.001; abdominal pain + 20, p = 0.002), and third procedure (pain + 22, p < 0.001; abdominal pain + 22, p = 0.002). Except for appetite loss, all changes were clinically relevant. All analyzed PROs returned to baseline 4 weeks after the third procedure. CONCLUSIONS: Patients receiving repetitive PIPAC-OX monotherapy for unresectable CPM had clinically relevant but reversible worsening of several PROs, mainly 1 week after the first procedure. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03246321; Netherlands trial register: NL6426.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): The First Reported Case in Brazil Using Standardized Technique with the Capnopen® Nebulizer Device.

BACKGROUND Peritoneal metastasis is a common progression of abdominal-pelvic cancers, and it is associated with poorer oncological prognosis when compared to other metastasis sites. Its treatment has limited results, mainly because of poor bioavailability of chemotherapy within the abdominal cavity after systemic administration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proposed as a novel method to deliver chemotherapy directly into the peritoneal surface; it combines the effectiveness and response of an intraperitoneal therapy with benefits of a minimally invasive approach. The laparoscopic capnoperitoneum is used to instill chemotherapy particles in a more efficient way for distribution and penetration when compared to peritoneal lavage. In the present study, we describe the first PIPAC performed in Brazil, according to the standard technique previously described with the Capnopen® nebulizer device, as well as technique details based on our literature review. CASE REPORT A 67-year-old man with pancreatic adenocarcinoma metastatic to the liver at first diagnosis underwent systemic treatment with the FOLFIRINOX protocol. After a major clinical response due to systemic treatment, pancreaticoduodenectomy was performed with resection and radiofrequency ablation of hepatic nodules. After 7 months of follow-up, the patient's condition evolved with symptomatic relapse in the peritoneum. Aiming at better control of this site, multiple PIPAC procedures were performed, showing excellent control of the peritoneal cavity disease. The patient had a sustained response in the peritoneal cavity and showed systemic disease progression 6 months after the first PIPAC procedure, which deceased at 20 months after the first PIPAC procedure and 42 months after the primary diagnosis. CONCLUSIONS This report shows that the PIPAC procedure is reproducible elsewhere, with safety and good functional results.

Effect of Respiratory Tract Disease on Particle Deposition.

This chapter describes the effects that respiratory disease has on particle deposition in the lungs. The geometry of airways, breathing patterns, and regional ventilation are all affected by various lung diseases, including COPD, asthma, and cystic fibrosis, and in turn modify total and regional deposition from normal. Total particle deposition in the lung is increased by airways obstruction and increased ventilation at rest compared to healthy individuals. Regional particle deposition is 1) shifted from distal to more proximal bronchial airways by airway obstruction, and 2) becomes more heterogeneous due to uneven lung ventilation. The net effect of the changes in total and regional particle deposition from normal is to greatly enhance bronchial airway surface doses for particle deposition while leaving unventilated lung regions inaccessible to the particles. As a result, both therapeutic aerosol delivery and the adverse effects of pollutant particles may be altered with progression of lung disease.

Pressurized Intraperitoneal Aerosol Chemotherapy-Related Clinical Trials in the Treatment of Peritoneal Metastases.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a treatment option for patients with peritoneal metastases. We evaluated the current status of ongoing prospective clinical trials investigating PIPAC to provide an overview and predict trends in this field. METHODS: All 367,494 records of clinical trials registered at ClinicalTrials.gov were searched for trials dealing with PIPAC. Active or unpublished trials were further analyzed. RESULTS: In total, 22 clinical trials were identified and selected for further analyses. Most trials had a single-arm design and were phase I or II. No phase III trials were registered. Academic centers were recorded as primary sponsors in the majority of trials (63.6%). Every year, between 2 and 5 new trials were initiated. In 17 trials (81.8%), PIPAC was used in a palliative setting only, 2 trials performed PIPAC in a neoadjuvant setting, and 2 trials performed PIPAC in an adjuvant setting. Six different drugs (doxorubicin, cisplatin, oxaliplatin, nab-paclitaxel, 5-fluorouracil, and docetaxel) were used in these clinical trials. Most trials investigated the efficacy (n = 15) or safety (n = 7) of PIPAC therapies. CONCLUSIONS: The results of ongoing clinical trials will bring specific information on indications for PIPAC as well as the impact of PIPAC on quality of life and overall survival.