Band 5, Heft 4

Pressurised IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a novel surgical technique to administer aerosolized chemotherapy into the abdominal cavity as treatment for peritoneal metastasis from various cancers. As the surgery is unique and there are concerns about occupational hazards, specific anaesthetic setup and techniques are required. Notably, our institution’s experience with PIPAC has enlightened us that anaesthesia requirements during PIPAC are generally uncomplicated and that the majority of the patients undergoing PIPAC do not require invasive monitoring, advanced intra or postoperative analgesia like epidurals or PCA. The need for postoperative intensive unit care is also not required in routine PIPAC cases. We describe the anaesthetic considerations involved and the detailed preparation of staff, space, anaesthetic equipment and drugs to facilitate the appropriate modifications for anaesthesia monitoring and maintenance for an elective set up as well as our standard operating procedure for an emergency situation should it arise.

Objectives Local anesthetic medical thoracoscopy (LAT) is a well-established diagnostic, therapeutic, and preventative intervention in undiagnosed pleural effusions with a high diagnostic sensitivity and low complication rates. There is a large variability in practice. We describe a nine-year experience in a large district general hospital in England. Methods Two hundred seventy-five patients had LAT between January 2010 and December 2018. Data on outcomes and complications were obtained from the patients’ notes, electronic records, laboratory, and radiographic findings. Results The main diagnoses were malignant pleural mesothelioma (MPM) (n=110, 40%), chronic inflammation/fibrinous pleuritis (77, 28%), lung cancer (26, 9.5%), and breast cancer (16, 6%). LAT failed to diagnose cancer in 7/275 patients (false-negative rate 2.5%, diagnostic sensitivity 97.5%). Out of the 105 patients with chronic inflammation/fibrinous pleuritis or atypical proliferative processes, 21 (20%) were subsequently diagnosed with malignancy. Talcum pleurodesis was performed in 146 patients, and was successful in 86%. Seventy eight (28%) patients had trapped lung; 27 of those had a repeat procedure. The median length of stay was 3.96 days. There was one hospital death (0.3% mortality). Complications of LAT included pleural (3, 1%) and wound infections (4, 1.4%), persistent air leaks (9, 3.2%), subcutaneous emphysema (10, 3.6%), and tumor extension to the access port (1, 0.3%). Conclusions In this cohort, LAT was safe, effective, and enabled high diagnostic sensitivity. Further areas of study include optimal sedation and anesthetic pathways and combining LAT with indwelling pleural catheters (IPC).

Objectives Malignant pleural effusion (MPE) is a devastating evolution of several malignancies. Pressurized intrathoracic aerosol chemotherapy (PITAC) might be a novel therapy option in MPE. Methods PITAC is considered for patients with MPE with a performance status <2 and without other metastatic sites. General anesthesia is administered and a double-lumen bronchial tube is inserted. The patient is placed in a lateral decubitus position, and the operation is performed after ipsilateral lung exclusion. Two 12-mm balloon trocars are inserted—one in the seventh intercostal space in the mid-axillary line and one in the fifth intercostal space in the anterior axillary line. Extent of pleural disease and volume of MPE are documented. MPE is removed and parietal pleural biopsy are performed. An intrathoracic pressure of 12 mmHg CO 2 is established, and a combination of Cisplatin (10.5 mg/m 2 in a total volume of 150 cc NaCl 0.9%) and Doxorubicin (2.1 mg/m 2 in a total volume of 50 cc NaCl 0.9%) are aerosolized via nebulizer in the pleural cavity. Vital signs and nebulization are remote-controlled. After 30 min, the remaining toxic aerosol is exhausted using a closed surgical smoke evacuation system. A 24Fr chest tube is inserted in postero-apical position with continuous negative pressure of 20 cm H 2 O. When needed, PITAC may be repeated every six weeks in alternate with systemic chemotherapy. Results In our hands, the technique above has shown to be feasible and safe. Conclusions Further studies are needed to assess the potential symptomatic and oncological benefits of PITAC in MPE.

Objectives Carboplatin is frequently used in various doses for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of epithelial ovarian cancer (EOC) although its pharmacokinetics, including focus on the perfusion time, has not been evaluated when used in modern era cytoreductive surgery (CRS). The aim was to evaluate the pharmacokinetics and hematological toxicity of carboplatin used for HIPEC with a perfusion time of 90 min. Methods Fifteen patients with stage III–IV primary EOC received CRS and 90 min of HIPEC with carboplatin at dose 800 mg/m 2 . For the pharmacokinetic analysis, perfusate and blood samples were obtained during HIPEC and up to 48 h after HIPEC (blood only). Hematological toxicity within 30 days was graded according to Common Terminology Criteria for Adverse Events. Severe toxicity (grades 3–5) is reported. Results Mean maximum concentration of carboplatin was 12 times higher in perfusate than plasma (mean CmaxPF=348 µg/mL (range: 279–595 µg/mL) versus mean CmaxPL=29 µg/mL (range: 21–39 µg/mL)). Mean terminal half-life of carboplatin in perfusate was 104 min (range: 63–190 min) and mean intraperitoneal-to-plasma area under the concentration-time curve (AUC) ratio was 12.3 (range: 7.4–17.2). Two patients (13%) had grade 3 neutropenia within 30 days. No grade 4–5 hematological toxicities were identified. Conclusions Carboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m 2 . Large interindividual differences were found in the pharmacokinetic parameters, making risk of systemic exposure difficult to predict.

Objectives To study the expression of growth factors in the regulation of tissue repair after peritoneal damage tissue response to peritoneal damage. Methods Experimental study in 35 male Wistar rats determining the evolution over time of the tissue response to aseptic peritoneal damage. A standardized bowel and peritoneal lesions were created in the right lower quadrant by laparotomy. Then, tissular expression of growth factors was evaluated by multiplex polymerase chain reaction at seven timepoints between 6 h and 30 days, postoperatively. Results Tissular responses of granulocyte-stimulating factors (Csf2, Csf3), connective tissue growth factor (Ctgf), epidermal growth factors and receptor (Egf, Egfr), fibroblast growth factors (Fgf2, 7 and 10), heparin binding EGF-like growth factor (Hbegf), hepatocyte growth factor (Hgf), insulin-like growth factor-1 (Igf1), mitogenic transforming growth factors (Tgfa, Tgfb1, Tgfbr3), and vascular endothelial growth factor A (Vegfa) were biphasic with a first expression peak at day 3, followed by a more pronounced peak at day 14. Conclusions We observed a long-lasting, widespread response of tissular growth factors for at least two weeks after peritoneal damage. To be clinically effective, the prophylaxis of postoperative adhesions might be needed for an extended period of time.

Peritoneal metastases from signet ring cell adenocarcinoma may be overlooked at laparoscopy, resulting in problematic false-negative diagnoses. Conversely, false-positive diagnoses are rarely reported. For the surgeon, cachexia may rise suspicion for peritoneal metastases by exhibiting a worrisome micronodular appearance of the peritoneum, and atrophic adipocytes looks like signet ring cells at the microscopical level. Being aware of this underdiagnosed condition may help avoiding unfortunate false-positive diagnoses of peritoneal metastases during intraoperative consultation.