Irreversible Electroporation for Liver Metastases from Colorectal Cancer: A Systematic Review.

BACKGROUND: Irreversible electroporation (IRE) is a non-thermal form of ablation based on the delivery of pulsed electrical fields. It has been used to treat liver lesions, particularly those in proximity to major hepatic vasculature. The role of this technique in the portfolio of treatments for colorectal hepatic metastases has not been clearly defined. This study undertakes a systematic review of IRE for treatment of colorectal hepatic metastases. METHODS: The study protocol was registered with the PROSPERO register of systematic reviews (CRD42022332866) and reports in compliance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Ovid MEDLINE®, EMBASE, Web of Science and Cochrane databases were queried in April 2022. The search terms 'irreversible electroporation', 'colon cancer', 'rectum cancer' and 'liver metastases' were used in combinations. Studies were included if they provided information on the use of IRE for patients with colorectal hepatic metastases and reported procedure and disease-specific outcomes. The searches returned 647 unique articles and the exclusions left a total of eight articles. These were assessed for bias using the methodological index for nonrandomized studies (MINORS criteria) and reported using the synthesis without meta-analysis guideline (SWiM). RESULTS: One hundred eighty patients underwent treatment for liver metastases from colorectal cancer. The median transverse diameter of tumours treated by IRE was <3 cm. Ninety-four (52%) tumours were adjacent to major hepatic inflow/outflow structures or the vena cava. IRE was undertaken under general anaesthesia with cardiac cycle synchronisation and with the use of either CT or ultrasound for lesion localisation. Probe spacing was less than 3.2 cm for all ablations. There were two (1.1%) procedure-related deaths in 180 patients. There was one (0.5%) post-operative haemorrhage requiring laparotomy, one (0.5%) bile leak, five (2.8%) post-procedure biliary strictures and a zero incidence of post-IRE liver failure. CONCLUSIONS: This systematic review shows that IRE for colorectal liver metastases can be accomplished with low procedure-related morbidity and mortality. Further prospective study is required to assess the role of IRE in the portfolio of treatments for patients with liver metastases from colorectal cancer.

Venous thromboembolism (VTE) after open hepatectomy compared to minimally invasive liver resection: a systematic review and meta-analysis.

BACKGROUND: Even though the risk of postoperative venous thromboembolism (VTE) after liver resection is well recognized, the association between surgical approach and VTE risk is unknown. This study aims to compare VTE rates following open liver resection (OLR) and minimally invasive liver resection (MILR). METHODS: MEDLINE, Web Of Sciences and EMBASE databases were interrogated to identify eligible studies published between February 2016 and August 2022. Studies were considered suitable if they reported a comparison between OLR and MILR (including laparoscopic liver resection [LLR] or robotic liver resection [RLR]). RESULTS: Fourteen studies including 11 356 patients met the inclusion criteria. 5622 patients underwent OLR and 5734 patients underwent MILR. The VTE rate was higher among patients who underwent OLR compared to MILR (2.8% vs 1.4%, OR (95% CI) = 1.84, p=<00001). Similarly, the subgroup analysis showed a higher rate of deep venous thrombosis (DVT) (1.4% vs 0.7%, OR (95% CI) = 1.98, p = 0.02) and pulmonary embolism (PE) (1.3% vs 0.7%, OR (95% CI) = 1.88, p = 0.002) in patients who underwent OLR compared to MILR. DISCUSSION: Patients who undergo open hepatectomy have a higher incidence of postoperative VTE when compared to those undergoing minimally invasive liver resection. This finding was consistent for both DVT and PE.

A procalcitonin-based algorithm to guide antibiotic use in patients with acute pancreatitis (PROCAP): a single-centre, patient-blinded, randomised controlled trial.

BACKGROUND: Differentiating inflammation from bacterial infection in patients with acute pancreatitis can be difficult. Procalcitonin can distinguish infection from inflammation, and algorithms based on procalcitonin measurement can differentiate bacterial sepsis from a systemic inflammatory response. We aimed to test the hypothesis that a procalcitonin-based algorithm to guide initiation, continuation, and discontinuation of antibiotics could lead to reduced antibiotic use without an adverse effect on outcome in acute pancreatitis. METHODS: PROCAP was a single-centre, patient-blinded, randomised controlled trial done at the Manchester Royal Infirmary (Manchester, UK). Eligible participants were aged 18 years or older and had a clinical diagnosis of acute pancreatitis. Participants were randomly assigned (1:1) to procalcitonin-guided care or usual care using web-based randomisation software. The randomisation sequence was stratified by disease severity and admission pathway, using variable block sizes of 4, 6, or 8. Patients, but not clinicians, were masked to group assignment. In the procalcitonin-guided care group, procalcitonin testing was conducted on days 0, 4, 7, and weekly thereafter. Guidance was to stop or not start antibiotics following a test value of less than 1·0 ng/mL and to start or continue antibiotics following a test value of 1·0 ng/mL or more. In the intervention group, any empirical clinical decision to use antibiotics was preceded by measurement of procalcitonin. Otherwise, both groups received standard care. The primary outcome was use of antibiotics during the index admission to hospital. All analyses were done in the intention-to-treat population. This study was registered with the International Standard Randomised Controlled Trial registry, ISRCTN 50584992. FINDINGS: Between July 29, 2018, and Nov 13, 2020, 369 patients were screened, of whom 260 were enrolled and randomly assigned to a treatment group (132 to procalcitonin-guided care and 128 to usual care). 59 (45%) of patients in the procalcitonin-guided care group were prescribed antibiotics compared with 79 (63%) in the usual care group (adjusted risk difference -15·6% [95% CI -27·0 to -4·2]; p=0·0071). The odds ratio for the treatment effect was 0·49 (95% CI 0·29 to 0·83; p=0·0077). There was no significant difference between groups in terms of the number of clinical infections or hospital-acquired infections per patient. Four (3%) patients in the procalcitonin-guided care group and three (2%) patients in the usual care group died; all deaths were related to underlying severe pancreatitis. There was no difference in adverse events between the groups. INTERPRETATION: Our findings suggest that procalcitonin-guided care can reduce antibiotic use without increasing infection or harm in patients with acute pancreatitis. Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis. FUNDING: None.

Work-Up and Outcome of Hepatic Resection for Peri-Hilar Cholangiocarcinoma (PH-CCA) without Staging Laparoscopy.

Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy in the work-up algorithm. During the 13 years from 1 January 2009 to 1 January 2022, 32 patients underwent laparotomy for planned surgical resection of PH-CCA. Data were collected on demographic profile, admission biochemistry, radiology, pre-operative intervention, operation and outcome, together with post-operative complications and disease-free and overall survival. Results: All patients underwent pre-operative contrast-enhanced CT. Twenty-four (75%) underwent pre-operative MR. Twenty-three (72%) underwent pre-operative biliary drainage. Twenty-nine patients (91%) had either type III or IV peri-hilar cholangiocarcinoma. One patient (3%) in this series underwent a non-resectional laparotomy. Twenty-nine (91%) had a final histopathological diagnosis of PH-CCA. One further patient had a final diagnosis of an intraductal papillary neoplasm of the biliary tree (IPNB) with high-grade dysplasia but no invasive cancer. Eleven patients (36%) received chemotherapy after surgery. The median (95% CI) time to recurrence was 14 (7-31) months. The median survival was 25 (18-upper limit not reached) months. Conclusion: This cohort of 32 patients undergoing attempted resection for PH-CCA without the use of staging laparoscopy in the work-up algorithm indicates that with careful attention to patient fitness and cross-sectional and interventional radiologic/endoscopic imaging, a very low non-therapeutic laparotomy rate of 3% can be achieved and sustained.

Reporting of longitudinal pancreatojejunostomy with partial pancreatic head resection (the Frey procedure) for chronic pancreatitis: A systematic review.

BACKGROUND: Longitudinal pancreatojejunostomy with partial pancreatic head resection (the Frey procedure) is accepted for surgical treatment of painful chronic pancreatitis. However, conduct and reporting are not standardized and thus, making comparisons difficult. This study assesses the reporting standards of this procedure. DATA SOURCES: A systematic literature review was performed between January 1987 and January 2020. The keyword and Medical Subject Heading "chronic pancreatitis" was used together with the individual operation term "Frey pancreatojejunostomy". Reports were included if they provided original information on conduct and outcome. Thirty-three papers providing information on 1205 patients constituted the study population. Risk of bias in included reports was assessed. RESULTS: Etiology of chronic pancreatitis (alcohol) was reported in 26 of 28 (93%) studies, duration of symptoms prior to surgery in 19 (58%) studies and pre-operative opiate use in 12 (36%) studies. In terms of morphology, pancreatic duct diameter was reported in 17 (52%) studies and diameter of the pancreatic head in 13 (39%) studies. In terms of technique, three (9%) studies reported weight of excised parenchyma. There were 9 (0.7%) procedure-related deaths. Post-operative follow-up ranged from 6 to 82.5 months. No studies reported post-operative portal hypertension. CONCLUSIONS: There is substantial heterogeneity between studies in reporting of clinical baseline, morphology of the diseased pancreas, operative detail and outcome after longitudinal pancreatojejunostomy with partial pancreatic head resection. This critically compromises the comparison between centers and between surgeons. Structured reporting is necessary for clinicians to assess choice of procedure and for patients to make informed choices when seeking treatment for painful chronic pancreatitis.

Endovascular Hepatic Artery Stents in the Modern Management of Postpancreatectomy Hemorrhage.

Background: Postoperative hemorrhage is a potentially lethal complication of pancreatoduodenectomy. This study reports on the use of endovascular hepatic artery stents in the management of postpancreatectomy hemorrhage. Methods: This is a retrospective analysis of a prospectively maintained, consecutive dataset of 440 patients undergoing pancreatoduodenectomy over 68 months. Data are presented on bleeding events and outcomes, and contextualized by the clinical course of the denominator population. International Study Group of Pancreatic Surgery terminology was used to define postpancreatectomy hemorrhage. Results: Sixty-seven (15%) had postoperative hemorrhage. Fifty (75%) were male and this gender difference was significant (P = 0.001; 2 proportions test). Postoperative pancreatic fistulas were more frequent in the postoperative hemorrhage group (P = 0.029; 2 proportions test). The median (interquartile range [IQR]) delay between surgery and postoperative hemorrhage was 5 days (2-14 days). Twenty-six (39%) required intervention comprising reoperation alone in 12, embolization alone in 5, and endovascular hepatic artery stent deployment in 5. Four further patients underwent more than 1 intervention with 2 of these having stents. Endovascular stent placement achieved initial hemostasis in 5 of 7 (72%). Follow-up was for a median (IQR) of 199 days (145-400 days) poststent placement. In 2 patients, the stent remained patent at last follow-up. The remaining 5 stents occluded with a median (IQR) period of proven patency of 10 days (8-22 days). Conclusions: This study shows that in the specific setting of postpancreatoduodenectomy hemorrhage with either a short remnant gastroduodenal artery bleed or a direct bleed from the hepatic artery, where embolization risks occlusion with compromise of liver arterial inflow, endovascular hepatic artery stent is an important hemostatic option but is associated with a high risk of subsequent graft occlusion.

Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review.

BACKGROUND: Treatment with neoadjuvant chemoradiotherapy followed by liver transplantation yields promising results in perihilar cholangiocarcinoma (PH-CCA). This study reviews the literature to assess whether there is evidence to justify modern phase II studies of neoadjuvant chemoradiotherapy prior to resection of PH-CCA. DATA SOURCES: A systematic review of the literature for reports of patients undergoing resection of PH-CCA after neoadjuvant chemoradiotherapy was performed using MEDLINE and EMBASE databases for the period between 1990 and 2019. The keywords and MeSH headings "hilar cholangiocarcinoma", "Klatskin", "chemoradiotherapy" and "chemotherapy" were used. Data were extracted on demographic profile, disease staging, chemoradiotherapy protocols, complications and outcome. Risks of bias were assessed using Cochrane methodology. RESULTS: There were seven reports on this topic, with median recruitment period of 14 (range 4-31) years. The total number of patients in these studies was 87. Interval from completion of neoadjuvant treatment to surgery varied from 3 days to 6 months. Resection was by hepatectomy with three studies reporting an R0 rate of 100%, 24% and 63%, respectively. Three studies reported histopathological evidence of prior treatment response. There were two treatment related deaths at 90 days. Median survival was 19 (95% CI: 9.9-28) months and 5-year survival 20%. CONCLUSIONS: There are potential benefits of treatment on both R0 rate and complete response in resected specimens. Scientific equipoise exists in relation to neoadjuvant chemoradiotherapy for PH-CCA.

Standards for reporting on surgery for chronic pancreatitis: a report from the International Study Group for Pancreatic Surgery (ISGPS).

BACKGROUND: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. METHODS: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. RESULTS: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. CONCLUSION: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

BACKGROUND: Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome. METHODS: This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles. DISCUSSION: When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

The Practical Management of Chronic Pancreatitis: A Multidisciplinary Symposium Held at the Annual Meeting of the Pancreatic Society of Great Britain and Ireland, Manchester 2016.

AIM: This study is about a questionnaire survey of delegates attending the chronic pancreatitis symposium at the 2016 meeting of the Pancreatic Society of Great Britain and Ireland and seeks a multidisciplinary "snapshot" overview of practice. METHODS: A questionnaire was developed with multidisciplinary input. Questions on access to specialist care, methods of diagnosis and treatment including specific scenarios were incorporated. Eighty-three (66%) of 125 delegates effectively participated in this survey. RESULTS: Twenty-four (29%) had neither a chronic pancreatitis MDT in their hospital nor a chronic pancreatitis referral MDT. Most frequently utilised diagnostic modalities were CT, MR and EUS with no respondents utilising duodenal intubation tests. Initial treatment was provided through non-opiate analgesia by 69 (93%), through the use of opiates by 56 (76%) and through the use of co-analgesics by 49 (66%). Fifty two (68%) routinely referred patients with alcohol-related disease for counselling. Preferred treatment for large duct disease without mass was endoscopic therapy. In older patients with a mass, pancreaticoduodenectomy was preferred. CONCLUSION: This is a small study likely to be skewed by sampling bias but is thought to be the first multidisciplinary survey of the management of chronic pancreatitis in the United Kingdom and Ireland. The results show a need for comprehensive access to specialist pancreatitis MDT care and there remains substantial variation in management.

Geographical variance in reporting of elective surgery for chronic pancreatitis.

The selection of optimum surgical procedure from the range of reported operations for chronic pancreatitis (CP) can be difficult. The aim of this study is to explore geographical variation in reporting of elective surgery for CP. A systematic search of the literature was performed using the Scopus database for reports of five selected procedures for CP: duodenum-preserving pancreatic head resection, total pancreatectomy with islet autotransplantation (TPIAT), Frey pancreaticojejunostomy, thoracoscopic splanchnotomy and the Izbicki V-shaped resection. The keyword and MESH heading 'chronic pancreatitis' was used. Overall, 144 papers met inclusion criteria and were utilized for data extraction. There were 33 reports of duodenum-preserving pancreatic head resection. Twenty-one (64%) were from Germany. There were 60 reports of TPIAT, 53 (88%) from the USA. There are only two reports of TPIAT from outwith the USA and UK. The 34 reports of the Frey pancreaticojejunostomy originate from 12 countries. There were 20 reports of thoracoscopic splanchnotomy originating from nine countries. All three reports of the Izbicki 'V' procedure are from Germany. There is geographical variation in reporting of surgery for CP. There is a need for greater standardization in the selection and reporting of surgery for patients with painful CP.