Pleura and Peritoneum最新文献

Objectives: Pseudomyxoma peritonei (PMP) is a rare cancer currently affecting over 11,736 patients across Europe. Since PMP is so uncommon, collaboration between scientific centers is key to discovering the mechanisms behind the disease, efficient treatments, and targets pointing to a cure. To date, no consensus has been reached on the minimum data that should be collected during PMP research studies. This issue has become more important as biobanking becomes the norm. This paper begins the discussion around a minimum data set that should be collected by researchers through a review of available clinical trial reports in order to facilitate collaborative efforts within the PMP research community.

Content: A review of articles from PubMed, CenterWatch, ClinicalTrials.gov and MedRxiv was undertaken, and clinical trials reporting PMP results selected.

Summary: There is a core set of data that researchers report, including age and sex, overall survival, peritoneal cancer index (PCI) score, and completeness of cytoreduction, but after this, reports become variable.

Outlook: Since PMP is a rare disease, it is important that reports include as large of a number of standardised data points as possible. Our research indicates that there is still much ground to cover before this becomes a reality.

Objectives: The aim of this study is to analyze the prevalence of somatic mutations in BRCA1 and BRCA2 in malignant mesothelioma and their putative impact on protein properties.

Methods: Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of BRCA1 and BRCA2 genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server.

Results: BRCA2 variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02).

Conclusions: BRCA2 somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.

Objectives: Up to one quarter of the patients with colorectal cancer (CRC) develop peritoneal carcinomatosis (PM). The aims of this retrospective study were to characterize the histological response of the PM of CRC to preoperative chemotherapy and evaluate the potential prognostic value, in terms of survival.

Methods: This retrospective unicentric study evaluated a group of 30 patients treated between 2010 and 2020 at the São João University Hospital Center with preoperative chemotherapy, followed by cytoreduction surgery plus hyperthermic intraperitoneal chemotherapy. The evaluation of the histological response was done using two scores: the tumor regression grading (TRG) and the peritoneal regression grading score (PRGS).

Results: Mean post-procedure survival is higher in the PRGS 1-2 group (74.19 months) vs. the PRGS 3-4 group (25.27 months) (p=0.045), as well as in the TRG 1-2 group (74.58 months) vs. TRG 4-5 (25.27 months) (p=0.032). As for progression-free survival (PFS), the PRGS 1-2 group had a mean value of 58.03 months vs. PRGS 3-4 which had 11.67 months (p=0.002). Similar was observed with the TRG 1-2 group, which had a mean PFS of 61.68 months vs. TRG 4-5 with 11.67 months (p=0.003).

Conclusions: A better histological response to preoperative chemotherapy, represented as a lower PRGS and TRG value, is associated with longer post-procedure survival and progression-free survival in this group of patients. That is, these two scores have prognostic value.

Objectives: Appendiceal cancer is a rare malignancy, occurring in roughly 1.2 per 100,000 per year. Low grade appendiceal neoplasams (LAMN) in particular can lead to pseudomyxoma peritonei (PMP), and respond poorly to systemic chemotherapy. Standard treatment includes cytoreduction surgery (CRS) with addition of heated intraoperative peritoneal chemotherapy (HIPEC). Several centres include early postoperative intraperitoneal chemotherapy (EPIC) however; the literature is mixed on the benefits. We aim to examine the benefits of additional EPIC through a propensity-matched analysis.

Methods: Patients with LAMN with PMP who underwent cytoreductive surgery at St George hospital between 1996 and 2020 were included in this retrospective analysis. Propensity score matching was performed with the following used to identify matched controls; sex, age, American Society of Anesthesiologists (ASA) grade, peritoneal cancer index (PCI) and morbidity grade. Outcomes measured included length of stay and survival.

Results: A total of 224 patients were identified of which 52 received HIPEC alone. Propensity matching was performed to identify 52 matched patients who received HIPEC + EPIC. Those receiving HIPEC + EPIC were younger at 54.3 vs. 58.4 years (p=0.044). There was a median survival benefit of 34.3 months for HIPEC + EPIC (127.3 vs. 93.0 months, p=0.02). Median length of stay was higher in those who received EPIC (25.0 vs. 23.5 days, p=0.028).

Conclusions: In LAMN with PMP, the addition of EPIC to HIPEC with CRS improves overall survival in propensity score matched cases but results in prolonged hospitalisation. The use of EPIC should still be considered in selected patients.

Objectives: Erector spinae plane (ESP) blocks are a regional anaesthetic technique used for pain relief in thoracic procedures. Our centre has recently begun using ESP blocks pre-medical thoracoscopy for analgesia.

Methods: Nine patients undergoing MT from September 2021 to February 2022 were included. Opioid use and depth of required sedation was recorded. Pre and post pain scores and at home were recorded by interview and review of charts. A functional pain questionnaire was administered via telephone.

Results: Average greatest depth of sedation using propofol was 1.92 (standard error of mean [SEM] 0.27), with remifentanil 2.52 (SEM 0.46). 78% required oral analgesia on day 0 post discharge. 55% required oral analgesia on post-op day 1. Patients used an average of 3.33 mg oral morphine (SEM 2.35) in hospital, and 3 mg (SEM 2) on post-op day 1. Periprocedural pain scores were 0.66 (SEM 0.27). Pain scores in recovery were 1.56 (SEM 0.76). Pain scores 3-12 h post discharge were 3.56 (SEM 0.7), while pain scores on post-op day 1 were significantly higher at 5.56 (SEM 0.90) (Figure 1). Functional pain scoring showed patients doing activities of daily living well with a good ability to breathe and cough. All felt that their pain was well controlled on the day of the procedure and at home. No complications were reported.

Conclusions: ESP blocks provide good analgesia. Pain scores showed significant analgesic effect lasting several hours. The project showed pain outcomes and patient acceptability were good for the use of regional anaesthesia.

Objectives: Small bowel adenocarcinoma (SBA) with peritoneal metastasis (PM) is rare and despite treatment with systemic chemotherapy, the prognosis is poor. However, there is emerging evidence that cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a survival benefit over systemic therapy alone. This systematic review will assess the effectiveness of CRS-HIPEC for SBA-PM.

Content: Three databases were searched from inception to 11/10/21. Clinical outcomes were extracted and analysed.

Summary: A total of 164 cases of SBA-PM undergoing CRS-HIPEC were identified in 12 studies. The majority of patients had neoadjuvant chemotherapy (87/164, 53%) and complete cytoreduction (143/164, 87%) prior to HIPEC. The median overall survival was 9-32 months and 5-year survival ranged from 25 to 40%. Clavien-Dindo grade III/IV morbidity ranged between 19.1 and 50%, while overall mortality was low with only 3 treatment-related deaths.

Outlook: CRS-HIPEC has the potential to improve the overall survival in a highly selected group of SBA-PM patients, with 5-year survival rates comparable to those reported in colorectal peritoneal metastases. However, the expected survival benefits need to be balanced against the intrinsic risk of morbidity and mortality associated with the procedure. Further multicentre studies are required to assess the safety and feasibility of CRS-HIPEC in SBA-PM to guide best practice management for this rare disease.

Objectives: Peritoneal metastasis (PM) from appendiceal cancer or colorectal cancer (CRC) has significant morbidity and limited survival. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a minimally invasive approach to treat PM. We aim to conduct a dose-escalation trial of mitomycin C (MMC)-PIPAC combined with systemic chemotherapy (FOLFIRI) in patients with PM from appendiceal cancer or CRC.

Methods: This is a multicenter Phase I study of MMC-PIPAC (NCT04329494). Inclusion criteria include treatment with at least 4 months of first- or second-line systemic chemotherapy with ineligibility for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Exclusion criteria are: progression on chemotherapy; extraperitoneal metastases; systemic chemotherapy intolerance; bowel obstruction; or poor performance status (ECOG>2). Escalating MMC-PIPAC doses (7-25 mg/m²) will be administered in combination with standard dose systemic FOLFIRI. Safety evaluation will be performed on 15 patients (dose escalation) and six expansion patients: 21 evaluable patients total.

Results: The primary endpoints are recommended MMC dose and safety of MMC-PIPAC with FOLFIRI. Secondary endpoints are assessment of response (by peritoneal regression grade score; Response Evaluation Criteria in Solid Tumors [RECIST 1.1], and peritoneal carcinomatosis index), progression free survival, overall survival, technical failure rate, surgical complications, conversion to curative-intent CRS-HIPEC, patient-reported outcomes, and functional status. Longitudinal blood and tissue specimens will be collected for translational correlatives including pharmacokinetics, circulating biomarkers, immune profiling, and single-cell transcriptomics.

Conclusions: This Phase I trial will establish the recommended dose of MMC-PIPAC in combination with FOLFIRI. Additionally, we expect to detect an early efficacy signal for further development of this therapeutic combination.

Objectives: The four-tied peritoneal regression grading score (PRGS) is increasingly used to evaluate the response of peritoneal metastases (PM) to chemotherapy. The minimal number of peritoneal biopsies needed for PRGS determination remains unclear.

Methods: A prospective cohort of 89 PM patients treated with 210 pressurized intraperitoneal aerosol chemotherapy (PIPAC) cycles was investigated. Four biopsies from every abdominal quadrant were recommended. Histological tumor response was defined as a stable or decreasing mean PRGS between therapy cycles, progression increasing. We compared the diagnostic uncertainty induced by missing biopsies to the histological response.

Results: A total of 49 patients had at least two PIPAC and were eligible for therapy response assessment. Mean PRGS decreased from 2.04 (CI 5-95% 1.85-2.27) to 1.79 (CI 5-95% 1.59-2.01), p=0.14, as a proof of therapy effectiveness. 35 (71.4%) patients had a stable or decreasing PRGS (therapy response), 14 (28.6%) a PRGS increase (disease progression). Histology showed agreement between four biopsies in 42/210 laparoscopies (20%), between ≥3 biopsies in 103 (49%), and between ≥2 biopsies in 169 laparoscopies (81%). Mean loss of information with one missing biopsy was 0.11 (95% CI=0.13) PRGS points, with two missing biopsies 0.18 (95% CI 0.21). In 9/49 patients (18.3%), the loss of information with one less biopsy exceeded the change in PRGS under therapy.

Conclusions: A minimum of three biopsies is needed to diagnose PM progression with an accuracy superior to 80%. Missing biopsies often result in a false diagnosis of tumor progression.