Some pleural effusions labeled as idiopathic could be produced by the inhalation of silica

Objectives Exposure to silica nanoparticles has been associated with pleural effusions (PEs) in animal models and case series. We hypothesized that some PEs labelled as “idiopathic” could, in fact, be secondary to inhalation of silica. Methods A retrospective case control study was designed utilizing a prospectively maintained pleural database. Cases, represented by idiopathic PEs, were matched by age and gender to control patients who had been diagnosed with malignant, cardiac, or infectious PEs. A survey consisting of questions about occupational life and possibility of silica inhalation was conducted. In a subgroup of patients, pleural fluid concentrations of silica were quantified by plasma atomic emission spectrometry analysis. Also, the pleural biopsy of a silica-exposed case was subjected to an energy dispersive X-ray spectroscopy (EDX) to identify the mineral, the size of which was determined by electron microscopy. Results A total of 118 patients (59 cases and 59 controls) completed the survey. There were 25 (42%, 95% CI 31–55%) and 13 (22%, 95% CI 13–34%) silica-exposed workers in case and control groups, respectively. The exposure attributable fraction was 0.62 (95% CI 0.14–0.83). Four of eight exposed cases showed detectable levels of silica in the pleural fluid (mean 2.37 mg/L), as compared to none of 16 tested controls. Silica nanoparticles of 6–7 nm were identified in the pleural biopsy of an exposed case patient. Conclusions It is plausible that some idiopathic PEs could actually be caused by occupational silica inhalation.

Characteristics of early pleural effusions after orthotopic heart transplantation: comparison with coronary artery bypass graft surgery

Objectives Pleural effusions appearing within the first 30 postoperative days following coronary artery bypass grafting (CABG) are classified as early and believed to be directly related to the surgery. The characteristics of such effusions are well-described. Orthotopic heart transplantation is also known to be complicated by pleural effusions; however, their characteristics have not been systematically reported. We assessed the features of early postoperative pleural effusions after heart transplantation and compared them to those of early effusions following CABG. Methods We retrospectively collected demographic, clinical, and laboratory data for patients who underwent either orthotopic heart transplantation (study group) or CABG (comparison group) at our institution and whose postoperative course within 30 days was complicated by new or worsening pleural effusion that prompted drainage. Patients subjected to analysis consisted only of those with sufficiently complete laboratory profiles to permit adequate characterization of the nature of their pleural fluid. Results Out of 251 orthotopic heart transplant recipients, seven (2.8%) were found to have sufficiently complete pleural fluid results to be included in the study group. Out of 1,506 patients who underwent CABG, 32 (2.1%) had sufficiently complete pleural fluid results and formed the comparison group. The radiological appearance of pleural effusions in both groups was similar: bilateral in at least half and exclusively moderate to large. Effusions complicating both surgeries were exudative in close to 90% of cases. For those with available leukocyte differential counts, the pleural fluid of the post-orthotopic heart transplantation group was more often neutrophilic (3/5, 60%), whereas the fluid of the post-coronary artery bypass grafting group was more often lymphocytic (22/32, 69%) and tended to be hemorrhagic (median RBC count 33,000 cells/µL vs. 10,000 cells/µL). None of the comparisons of pleural fluid characteristics between the two groups reached statistical significance. Conclusions This small, descriptive study is the first to systematically report the fluid characteristics of pleural effusions complicating orthotopic heart transplantation within the first 30 postoperative days and to compare this group to those who developed effusions after CABG. Our findings revealed both similarities and differences in the pleural fluid characteristics between these two types of patients.

Risk factors and clinical outcomes in patients undergoing cytoreductive surgery with concomitant ureteric reimplantation

Objectives There are currently scarce data exploring ureteric reimplantation (UR) during cytoreductive surgery (CRS). Methods We identified patients undergoing CRS for peritoneal surface malignancies (PSM) of any origin at a single high-volume unit. UR was defined as ureteroureterostomy, transureterouretostomy, ureteroneocystostomy, ureterosigmoidostomy or ileal conduit performed during CRS. Peri-operative outcomes, long-term survival and risk factors for requiring UR were analysed. Results Seven hundred and sixty-seven CRSs were identified. Twenty-three (3.0%) procedures involved UR. Bladder resection and colorectal cancer (CRC) were associated with increased risk of UR (bladder resection: OR 12.90, 95% CI 4.91–33.90, p<0.001; CRC: OR 2.51, 95% CI 1.05–6.01, p=0.038). UR did not increase the risk of Grade III–IV morbidity or mortality. The rate of ureteric leak was 3/23 (13.0%) in the UR group. Mean survival was equivocal in patients with CRC (58.14 vs. 34.25 months, p=0.441) but significantly lower in those with high-grade appendiceal mucinous neoplasm (HAMN) undergoing UR (73.98 vs. 30.90 months, p=0.029). Conclusions UR during CRS does not increase major morbidity or mortality for carefully selected patients, and is associated with low rates of urologic complications. Whilst decreased survival was apparent in patients with HAMN undergoing UR, it is unclear whether this relationship is causal.

Consensus statement on safety measures for pressurized intraperitoneal aerosol chemotherapy

Objectives Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising treatment for peritoneal cancer that entails, however, potential risks for the caregivers in the operating room (OR). This study aimed to reach a consensus within the PIPAC community on a comprehensive safety protocol. Methods Active PIPAC centers were invited to participate in a two-round Delphi process on 43 predefined items: concise summaries of the existing evidence were presented together with questions formulated using the population, intervention, comparator, and outcome framework. According to the Grading of Recommendations Assessment, Development, and Evaluation, the strength of recommendation was voted by panelists, accepting a consensus threshold of ≥50% of the agreement for any of the four grading options, or ≥70% in either direction. Results Forty-seven out of 66 invited panelists answered both rounds (response rate 76%). The consensus was reached for 41 out of 43 items (95.3%). Strong and weak recommendations were issued for 30 and 10 items, respectively. A positive consensual recommendation was issued to activate laminar airflow without specific strength, neither strong nor weak. No consensus was reached for systematic glove change for caregivers with a high risk of exposure and filtering facepiece mask class 3 for caregivers with low risk of exposure. Conclusions A high degree of consensus was reached for a comprehensive safety protocol for PIPAC, adapted to the risk of exposure for the different caregivers in the OR. This consensus can serve as a basis for education and help reach a high degree of adherence in daily practice.

Acute respiratory distress syndrome (ARDS) after pressurized intraperitoneal aerosol chemotherapy with oxaliplatin: a case report

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method for intraabdominal cavity chemotherapy. It combines the benefits of a minimally invasive approach (low morbidity and easy to repeat) with the pharmacokinetic advantages of intraperitoneal administration and tolerance seems excellent. We would like to report one case of a serious adverse event, acute respiratory distress syndrome, which is likely related to oxaliplatin administration; all signs disappeared within a few days.

Can pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-O+) be added to standard treatment for resectable high-risk gastric cancer patients? a study protocol

Objectives Gastric cancer remains one of the most fatal cancers, despite an intensive treatment regime of chemotherapy–surgery–chemotherapy. Peritoneal metastatic disease is commonly diagnosed post treatment regime and once established, patients are likely to die in 3–9 months. Systemic chemotherapy does not increase survival for these patients due to the poor vascularisation of this area. We are proposing the addition of pressurised intraperitoneal aerosol chemotherapy (PIPAC) to the treatment regime for curative patients as a preventive measure to reduce the risk of peritoneal metastases occurring. Methods This is a prospective, single centre, non-randomised, open-label pilot trial evaluating the addition of PIPAC to the standard multimodal treatment pathway. Patients will undergo standard neoadjuvant chemotherapy with four cycles of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT), then PIPAC, followed by gastrectomy. Four cycles of FLOT will be administered post-surgery. Primary outcome is safety and feasibility, assessed by perioperative morbidity and possible interruptions of the standard multimodal treatment pathway.

Influence of pre-analytical sample preparation on drug concentration measurements in peritoneal tissue: an ex-vivo study

Objectives Biopsy morphology (surface/depth ratio) and sample processing might affect pharmacological measurements in peritoneal tissue. Methods This is an ex-vivo study on inverted bovine urinary bladders (IBUB). We compared cisplatin (CIS) and doxorubicin (DOX) concentration in 81 standardized transmural punch biopsies of different diameters (6 and 12 mm). Then, we assessed the effect of dabbing the peritoneal surface before analysis. After automatized tissue homogenization with ceramic beads followed by lyophilisation, DOX concentration was quantified by high-performance liquid chromatography (HPLC), CIS concentration by atomic absorption spectroscopy. Experiments were performed in triplicate; the analysis was blinded to the sample origin. Comparisons were performed using non-parametric tests. Results Concentrations are given in mean (CI 5–95%). Results were reproducible between experiments (for CIS p=0.783, for DOX p=0.235) and between different localizations within the IBUB (for CIS p=0.032, for DOX p=0.663). Biopsy diameter had an influence on CIS tissue concentration (6 mm biopsies: 23.2 (20.3–26.1), vs. 12 mm biopsies: 8.1 (7.2–9.2) ng/mg, p<0.001) but not on DOX: (0.46, 0.29–0.62) vs. 0.43 (0.33–0.54) ng/mg respectively, p=0.248). Dabbing the peritoneal surface reduced DOX tissue concentration (dry biopsies: 0.28 (0.12–0.43) vs. wet biopsies: 0.64 (0.35–0.93) ng/mg, p=0.025) but not CIS (23.5 (19.0–28.0) vs. 22.9 (18.9–26.9) ng/mg, respectively, p=0.735). Conclusions Measurements of drug concentration in peritoneal tissue can be influenced by the biopsy’s surface/depth ratio and after drying the biopsy’s surface. This influence can reach a factor three, depending on the drug tested. The biopsy technique and the pre-analytical sample preparation should be standardized to ensure reliable pharmacological measurements in peritoneal tissue.