Background: Cystic lesions of the pancreas (PCLs) may be inflammatory or proliferative and making an accurate and timely pre-operative diagnosis remains a significant clinical challenge. This is principally due to the heterogeneity of the pathological processes involved. PCLs constitute an entity with diverse histology and although infrequent, the possible potential for malignant transformation of these lesions and the opportunity for curative surgery mandates that our diagnostic approaches are up to date and evidence based. In addition, improved diagnostic accuracy is crucial to prevent unnecessary surgical procedures with the inevitable associated morbidity. Methods: This narrative review examines the current diagnostic benchmarks and identifies novel diagnostic techniques that warrant further consideration, a number of which are beginning to be included in routine clinical practice when these PCLs are being investigated. A computerized search was made of MEDLINE, EMBASE and PubMed using the search words 'diagnostic approaches to pancreatic cystic lesions'. All relevant articles in English language or with an English abstract were retrieved and additionally cross referenced. Conclusion: The increasing accuracy of available imaging techniques together with the wider availability of endoluminal ultrasound and the development of additional novel methods to assess PCLs presents an opportunity to significantly improve the pre-operative diagnosis rate. This is essential to classify the type of PCL and hence guide the management particularly with lesions where there is a likelihood of progression to more serious pathology. We have highlighted the need for a comprehensive and standardized algorithm for the diagnosis and management of PCLs.
Background:Resection margin status is associated with oncologic outcomes following liver resection for colorectal liver metastases(CLM). Previous studies however, did not differentiate between true local recurrence at the resection margin versus recurrence elsewhere in the liver. This study aimed to determine if resection margin represents only a surrogate of advanced disease while not causally determining overall survival(OS). Methods: Clinicopathological data of patients who underwent curative resection for CLM between 2012-2017 at the Inselspital Bern were assessed. Follow-up crosssectional imaging following hepatectomy was reviewed by an independent radiologist to identify the presence and location of recurrence. Location of intrahepatic recurrence was distinguished in true local recurrence(only at resection margin) versus intrahepatic recurrence elsewhere. The association between surgical margin status and location and frequency of tumor recurrence was evaluated and the impact of true local recurrence on OS was analyzed.Results: During the study period, 91 patients underwent liver resection for CLM with curative intent. Surgical margins were positive for tumor cells(R1) in 10 patients(11%). After a median follow-up time of 47 months, tumor recurrence was identified in 54 patients(59%). Location of recurrence was independent from the R1 status(p=0.063). True local recurrence was not associated with worse OS among patients with recurrent disease(true local recurrence vs. elsewhere: 3-year OS: 73% vs. 65%, p=0.729). Main determinants of survival were no recurrence, any intrahepatic recurrence, and extrahepatic recurrence(p=0.012). Conclusions: R1 margin status was not associated with more frequent true local recurrence compared to other locations of recurrent disease. Additionally, the impact of true local recurrence on OS was not significantly different from that of any intrahepatic recurrent disease. Thus, based on our findings, R1 status should be considered as a surrogate parameter of extensive disease and potentially aggressive tumor biology. It should be used as an indicator for the need of intensive systemic treatment and close postoperative surveillance.
Background There is a well-documented scarcity of the availability of healthy human livers for transplantation. The majority of discarded donor livers are used for organ preservation studies in the context of liver transplantation. Hemi-hepatectomies are a common procedure performed in tertiary hepatobiliary units. The specimen, also consisting of healthy liver, is eventually discarded despite the presence of healthy human liver tissue which would be invaluable for research. In 1959, Russel and Burch described the “3Rs” of animal research as replacement, reduction, and refinement (Flecknell, 2002). Optimising the use of hemi-hepatectomy human liver tissue for research would reduce the need for live animals and provide a more economical and physiological model to study invasive hepatic disease. Ex vivo perfusion of human hepatic segments has enormous potential and we are currently investigating this tool to be used as a translational model for invasive disease, including macrophage response to the earliest phases of infection, as demonstrated in porcine organs by Wanford et al (2021). Methods This retrospective service evaluation project was registered locally with audit registration numbers 11852 and 11852a. All liver resections booked electronically over a six month period, between 1/10/20 and 31/3/21, were assessed. Patient records, including intra-operative notes, were reviewed to identify which patients had a partial hepatectomy (left hemi-hepatectomy, right hemi-hepatectomy, or left lateral segmentectomy). The data was then compared against histology reports to identify which segments from the specimen were pathological and which segments were disease-free. A prospective Research Ethics Committee-approved clinical trial was registered by the name of “Tissue Models for Liver Disease” or TIMOLD (ClinicalTrials.gov Identifier: NCT05255042; 8/9/2021). Patients recruited were those aged eighteen or over undergoing elective liver resections. Exclusion criteria included those with acute invasive infection, children and vulnerable groups. A re-audit was performed following implementation of the TIMOLD study for the same time period the following year, between 1/10/21 and 31/3/22. Data analysis was performed using GraphPad Prism. Results Between 1/10/20 and 31/3/21, 43 liver resections were listed. Intra-operatively, 3/43 patients had inoperable disease and 2/43 did not require a resection. Of the 38 liver resections performed, 30 (79%) were for colorectal liver metastases (CRLM), 4/38 (11%) were for hepatocellular carcinoma (HCC), and the remainder for cholangiocarcinoma, neuroendocrine tumours and adenomas. 19/38 (50%) liver resections were a hemi-hepatectomy or left lateral segmentectomy. Histology review found that 11/19 (58%) specimens contained at least one healthy liver segment which was eventually discarded. Between 1/10/21 and 31/3/22, following implementation of the TIMOLD study, 57 liver resections were listed. 6/57 patients were found to have inoperative disease and 1/57 did not require a resection. Of 50 liver resections, 32/50 (64%) were for CRLM, 9/50 (18%) were for HCC and the remainder for cholangiocarcinoma, neuroendocrine tumours, IPMN and benign disease. 27/50 (54%) had a hemi-hepatectomy or left lateral segmentectomy. 17/27 (63%) partial hepatectomies were found to contain at least one healthy liver segment with potential for research use. As part of the TIMOLD trial, 8/17 healthy liver segments were retrieved and used for research during a six-month period, in comparison to none the previous year (p<0.05; Chi-Squared). Conclusions We demonstrate that at least 50% of patients undergoing liver resection at a tertiary HPB unit require a hemi-hepatectomy or left lateral segmentectomy over 12 months. Furthermore, at least half of these partial resections involve healthy anatomical liver segments as part of the specimen. Over six months, eight disease-free human liver segments, which would otherwise have been discarded, were perfused ex vivo in an attempt to develop a model representing human hepatic physiology at the organ level. Expanding this research model to other hepatobiliary units provides scientists an invaluable model for pre-clinical research, negating the need for live animal experimentation.
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