Next-generation sequencing and histological response assessment in peritoneal metastasis from pancreatic cancer treated with PIPAC.

BACKGROUND: Peritoneal metastasis from pancreatic cancer (PM-PC) may be treated with repeated pressurised intraperitoneal aerosol chemotherapy (PIPAC). Utility of next-generation sequencing (NGS) to detect cancer-related mutations in peritoneal quadrant biopsies (QBs) and peritoneal fluid (PF) after systemic and PIPAC treatment has not been evaluated. Around 90% of pancreatic cancers (PCs) harbour a KRAS mutation, making PC ideal for the evaluation of this aspect. AIMS: Evaluation of PM-PC in terms of (1) histological response to PIPAC using Peritoneal Regression Grading Score (PRGS), (2) clinical characteristics and (3) frequency of mutations in QBs and PF before and after PIPAC. METHODS: Peritoneal QBs and PF were obtained prior to each PIPAC. NGS for 22 cancer-related genes was performed on primary tumours, QBs and PFs. Response was assessed by the four-tiered PRGS. RESULTS: Sixteen patients treated with a median of three PIPAC procedures were included. The mean PRGS was reduced from 1.91 to 1.58 (p=0.02). Fifty-seven specimens (13 primary tumours, 2 metastatic lymph nodes, 16 PFs and 26 QB sets) were analysed with NGS. KRAS mutation was found in 14/16 patients (87.50%) and in QBs, primary tumours and PF in 8/12 (66.67%), 8/13 (61.53%) and 6/9 (66.67%). The median overall survival was 9.9 months (SE 1.5, 95% CI 4.9 to 13.9). CONCLUSION: PIPAC induces histological response in the majority of patients with PM-PC. KRAS mutation can be found in PM-PC after PIPAC at a frequency similar to the primaries. NGS may be used to detect predictive mutations in PM-PC of various origins, also when only post-PIPAC QBs or PFs are available.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)-directed treatment of peritoneal metastasis in end-stage colo-rectal cancer patients.

BACKGROUND: Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) represents a novel approach to intraperitoneal chemotherapy. Hereby results, obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from colorectal cancer (CRC), are presented. METHODS: Data from CRC patients (n = 24) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 trials are reported. Oxaliplatin 92 mg/m2 was administered at 4-6-week intervals. A CE certified nebulizer was used to aerosolize the chemotherapeutics. Outcome criteria were objective tumor response, survival and adverse events. RESULTS: Retrospective analysis of 74 PIPAC procedures carried out in 24 consecutive patients with PM from CRC included from October 2015 to February 2019. Five patients had still the primary tumor in situ, and 22 patients had received palliative systemic chemotherapy. Nineteen patients completed more than two PIPAC procedures, and objective tumor response according to the histological Peritoneal Regression Grading Score (PRGS) was observed in 67% of the patients, while 21% had stable disease. Four patients (21%) had complete response (mean PRGS = 1 and negative cytology). We recorded a median survival of 37.6 (range 7.3-48.9) months from the time of PM diagnosis, whereas it was 20.5 (range 0.13-34.7) months following the first PIPAC session. Minor postoperative complications were noted, and few were considered causally related to the PIPAC treatment. However, two cases of severe postoperative complications were recorded (urosepsis and iatrogenic bowel perforation). CONCLUSIONS: PIPAC with low-dose oxaliplatin can induce objective tumor regression in selected patients with advanced PM from colorectal cancer.

Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible, but the histological tumor response in peritoneal metastasis is insufficient.

INTRODUCTION: Electrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM). MATERIALS AND METHODS: Patients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE. RESULTS: Sixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1-6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC. CONCLUSION: One minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.

Peritoneal microdialysis as a tool for detecting anastomotic leakage in patients after left-side colon and rectal resection. A systematic review.

OBJECTIVE: The objective was to evaluate peritoneal microdialysis in the detection of clinical anastomotic leakage after left-sided colon and rectal resection through a systematic review. METHODS: A systematic review (PRISMA guidelines) based on a systematic search through PubMed, Cochrane Library, and EMBASE (1 February 2017) was performed. Methodological index of non-randomised studies score was selected to assess the methodological quality. Patient demographics and raw data for intraperitoneal microdialysis concentrations of glucose, lactate, glycerol and pyruvate for 5 d postoperative were obtained from the respective study groups. RESULTS: Ten studies with a total of 128 patients were included. Thirty (23%) patients developed clinical anastomotic leakage. The area under the curve for intraperitoneal lactate concentration was significant higher in patients with anastomotic leakage (58.2; 95% CI 39.2, 77.2) compared with the no leakage group (41.0; 95% CI 35.2, 46.1; p = .007). Receiver operating characteristic curve analysis of the maximum measured lactate concentration demonstrated 25% sensitivity, 88% specificity and 74% accuracy for AL at a cut-off value of 9.8 mmol/L. The odds ratio for a 5 mmol/L increase in lactate in relation to the risk of AL was 2.9 (CI 1.1, 8.0). CONCLUSIONS: Increased intraperitoneal lactate concentration within the first 5 d postoperative was significantly associated with clinical anastomotic leakage, but with low predictive values. The microdialysis method is not yet ready for clinical implication before large prospective studies have defined cut off values for a biologic marker in the setting of a clear definitions of leakage.

The value of contrast-enhanced laparoscopic ultrasound during robotic-assisted surgery for primary colorectal cancer.

AIM: The aim of this study was to assess the potential clinical value of contrast enhanced laparoscopic ultrasonography (CE-LUS) as a screening modality for liver metastases during robotic assisted surgery for primary colorectal cancer (CRC). METHOD: A prospective, descriptive (feasibility) study including 50 consecutive patients scheduled for robotic assisted surgery for primary CRC. CE-LUS was performed by 2 experienced specialists. Only patients without metastatic disease were included. Follow-up was obtained with contrast-enhanced CT imaging at 3 and 12 months postoperatively. RESULTS: Fifty patients were included; 45 patients were available for final analysis. The patients were equally distributed between stage I, II, and III according to the TNM classification system. No liver metastasis was detected during LUS and CE-LUS. CE-LUS was easy to perform and there was no complication. Follow-up revealed no liver metastasis in any of the patients. CONCLUSION: CE-LUS did not increase the detection rate of occult liver metastasis during robotic assisted primary CRC surgery. The use of CE-LUS as a screening modality for detection of liver metastasis cannot be recommended based on this study, but larger controlled studies on high-risk patients seem relevant.

Intraoperative Ultrasound as a Screening Modality for the Detection of Liver Metastases during Resection of Primary Colorectal Cancer - A Systematic Review.

Colorectal cancer (CRC) is one of the most common cancer diseases worldwide. One in 4 patients with CRC will have a disseminated disease at the time of diagnosis and often in the form of synchronous liver metastases. Studies suggest that up to 30% of patients have non-recognized hepatic metastases during primary surgery for CRC. Intraoperative ultrasonography examination (IOUS) of the liver to detect liver metastases was considered the gold standard during open CRC surgery. Today laparoscopic surgery is the standard procedure, but laparoscopic ultrasound examination (LUS) is not performed routinely. Aim To perform a systematic review of the test performance of IOUS and LUS regarding the detection of synchronous liver metastases in patients undergoing surgery for primary CRC. Method The literature was systematically reviewed using the search engines: PubMed, Cochrane, Embase and Google. 21 studies were included in the review and the key words: intraoperative ultrasound, laparoscopic ultrasound, staging colon and rectum cancer. Results Intraoperative ultrasound showed a higher sensitivity, specificity, positive predictive value and overall accuracy for the detection liver metastases during surgery for primary CRC, compared to preoperative imaging modalities (ultrasound, computed tomography (CT) and contrast-enhanced computed tomography (CE-CT)). LUS showed a higher detection rate for liver metastases compared to CT, CE-CT and magnetic resonance imaging (MRI). Conclusion This systematic review found that both IOUS and LUS had a higher detection rate regarding liver metastases during primary CRC surgery, especially liver metastases<10 mm in diameter, when compared to US, CT, CE-CT and MRI.

[Laparoscopic ultrasound imaging in colorectal cancer resection may increase the detection rate of small liver metastases].

Up to 20% of the patients with colorectal cancer (CRC) will have liver metastases at the time of the diagnosis, and some of these metastases may be missed during preoperative evaluation. While intraoperative ultrasound is considered the gold standard for liver evaluation during primary open CRC surgery, laparoscopic ultrasound (LUS) is not performed routinely during laparoscopic CRC surgery. Based on the available literature LUS had a higher detection rate for especially small liver metastases compared to preoperative imaging modalities, but better prospective trials are needed.

[Perivascular epithelioid cell tumours in the liver]. / Perivaskulær epiteloidcelletumor i leveren

The PEComa family is a group of tumours having perivascular epithelioid cells (PEC) as the predominating component. PEComas occur in various organs and are considered to be benign tumours. However, rare cases showing pleomorphic morphology, atypical mitoses or necrosis should be considered malignant sarcomas. The precise incidence is unknown but PEComas are reported with increasing frequency. Standard treatment is surgery but there are no guidelines on further follow-up or treatment. PEComa in the liver is a rare tumour, and to our knowledge this is the first published case from Denmark.