Volume 7, Issue 4

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/m 2 ) 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.

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.