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.

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.

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.

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.

Superior mesenteric artery (SMA) resection during pancreatectomy for malignant disease of the pancreas: a systematic review.

BACKGROUND: Resection of the superior mesenteric artery (SMA) during pancreatectomy is performed infrequently and is undertaken with the aim of removing non-metastatic locally advanced pancreatic tumours. SMA resection reports also encompass resection of other visceral vessels. The consequences of resection of these different arteries are not necessarily equivalent. This is a focused systematic review of the outcome of SMA resection during pancreatectomy for cancer. METHODS: A computerized search of the English language literature was undertaken for the period 1st January 2000 through 30th April 2016. The keywords "Pancreatic surgery" and "Vascular resections" were used. Thirteen studies reported 70 patients undergoing pancreatectomy with SMA resection from 10,726 undergoing pancreatectomy. Individual patient-level outcome data were available for 25. RESULTS: Median (range) accrual period was 132 (48-372) months. Reported peri-operative morbidity ranged from 39% to 91%. There were 5 peri-operative deaths in the 25 patients with individual-outcome data. Median survival was 11 months (95% Confidence interval 9.5-12.5 months; standard error 0.8 months). CONCLUSIONS: SMA resection during pancreatectomy is undertaken infrequently incurring high peri-operative morbidity and mortality. Median survival is 11 (95% CI 9.5-12.5) months. In contemporary practice there is no evidence to support SMA resection during pancreatectomy.

Antibiotic use in acute pancreatitis: Global overview of compliance with international guidelines.

INTRODUCTION: Practice guidelines for the management of acute pancreatitis make recommendations in relation to antibiotic prophylaxis and treatment in acute pancreatitis. However, it is difficult to ascertain whether this information translates into clinical practice. The aim of this study is to obtain a global overview assessing reports from across the world of the use of antibiotic use in acute pancreatitis. METHODS: A computerised literature search was performed from January 1992 to September 2015. Studies were either national physician surveys or national database reports on antibiotic prophylaxis in acute pancreatitis. Using these criteria, 10 studies were identified which comprise the final study population. RESULTS: Eight studies report on the questionnaire responses of 2397 physicians. The range of response rate was 38-96%. A separate study reported on outcome of a national insurance database outcomes in 7193 patients. The lowest incidence of use of antibiotic prophylaxis was 41% and the highest 88%. CONCLUSION: This study provides a unique global perspective on antibiotic use in acute pancreatitis and indicates that the use of antibiotics, both as prophylaxis and as treatment in this disease is widespread.

Antibiotic use in acute pancreatitis: An audit of current practice in a tertiary centre.

INTRODUCTION: Intravenous antibiotic prophylaxis is not recommended in acute pancreatitis. According to current international guidelines antibiotics together with further intervention should be considered in the setting of infected necrosis. Appropriate antibiotic therapy particularly avoiding over-prescription is important. This study examines antibiotic use in acute pancreatitis in a tertiary centre using the current IAP/APA guidelines for reference. METHODS: Data were collected on a consecutive series of patients admitted with acute pancreatitis over a 12 month period. Data were dichotomized by patients admitted directly to the centre and tertiary transfers. Information was collected on clinical course with specific reference to antibiotic use, episode severity, intervention and outcome. RESULTS: 111 consecutive episodes of acute pancreatitis constitute the reported population. 31 (28%) were tertiary transfers. Overall 65 (58.5%) patients received antibiotics. Significantly more tertiary transfer patients received antibiotics. Mean person-days of antibiotic use was 23.9 (sd 29.7) days in the overall study group but there was significantly more use in the tertiary transfer group as compared to patients having their index admission to the centre (40.9 sd 37.1 vs 10.2 sd 8.9; P < 0.005). Thirty four (44%) of patients with clinically mild acute pancreatitis received antibiotics. CONCLUSIONS: There is substantial use of antibiotics in acute pancreatitis, in particular in patients with severe disease. Over-use is seen in mild acute pancreatitis. Better consideration must be given to identification of prophylaxis or therapy as indication. In relation to repeated courses of antibiotics in severe disease there must be clear indications for use.

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.

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.

Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery.

BACKGROUND: Hepatic ischaemia-reperfusion (I/R) injury occurs in both liver resectional surgery and in transplantation. The biochemistry of I/R injury involves short-lived oxygen free radicals. N-acetylcysteine (NAC) is a thiol-containing synthetic compound used in the treatment of acetaminophen toxicity. The present study is a detailed overview of the experimental and clinical evidence for the use of NAC as a pharmaco-protection agent in patients undergoing major liver surgery or transplantation. METHODS: A computerized search of the Medline, Embase and SCI databases for the period from 1st January 1988 to 31st December 2008 produced 40 reports. For clinical studies, the quality of reports was assessed according to the criteria reported by the Cochrane communication review group. RESULTS: Nineteen studies evaluated NAC in experimental liver I/R injury. NAC was administered before induction of ischaemia in 13. The most widely used concentration was 150 mg/kg by intravenous bolus. Fifteen studies report an improvement in outcome, predominantly a reduction in transaminase. Seven studies used an isolated perfused liver model with all showing improvement (predominantly an improvement in bile production after N-acetylcysteine). Two out of four transplantation models showed an improvement in hepatic function. Clinical studies in transplantation show a modest improvement in transaminase levels with no beneficial effect on either patient or graft survival. CONCLUSION: N-acetylcysteine, given before induction of a liver I/R injury in an experimental model can ameliorate liver injury. Clinical outcome data are limited and there is currently little evidence to justify use either in liver transplantation or in liver resectional surgery.

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.