Intraoperative pancreas stump perfusion assessment during pancreaticoduodenectomy:A systematic scoping review

BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.

Resection of isolated liver oligometastatic disease in pancreatic ductal adenocarcinoma:Is there a survival benefit?A systematic review

BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma(PDAC),either synchronous or metachronous after pancreatic resection,is a terminal diagnosis that warrants management with palliative intent as per all international practice guidelines.However,there is an increasing interest on any potential value of surgical treatment of isolated oligometastatic disease in selected cases.AIM To present the published evidence on surgical management of PDAC liver metastases,synchronous and metachronous,and compare the outcomes of these treatments to the current standard of care.METHODS A systematic review was performed in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to compare the outcomes of both synchronous and metachronous liver metastases resection to standard care.RESULTS 356 studies were identified,31 studies underwent full-text review and of these 10 were suitable for inclusion.When synchronous resection of liver metastases was compared to standard care,most studies did not demonstrate a survival benefit with the exception of one study that utilised neoadjuvant treatment.However,resection of metachronous disease appeared to confer a survival advantage when compared to treatment with chemotherapy alone.CONCLUSION A survival benefit may exist in resection of selected cases of metachronous liver oligometastatic PDAC disease,after disease biology has been tested with time and systemic treatment.Any survival benefit is less clear in synchronous cases;however an approach with neoadjuvant treatment and consideration of resection in some selected cases may confer some benefit.Future studies should focus on pathways for selection of cases that may benefit from an aggressive approach.

Increased hepcidin expression in colorectal carcinogenesis

AIM:To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anae- mia and whether it might have a role in colorectal car- cinogenesis. METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using im- munohistochemistry. RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was posi- tively associated with increasing T-stage of colorectal cancer (P < 0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repres- sion. This was supported by hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.

Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma

BACKGROUND Para-aortic lymph nodes(PALN)are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma(PDAC).The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis,while others not sharing the same results.PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases.AIM To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC.METHODS This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020.Statistical comparison of the data between PALN+and PALN-subgroups,survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed,specifically assessing oncological outcomes such as median overall survival(OS)and disease-free survival(DFS).RESULTS 81 cases had PALN sampling and 17(21%)were positive.Pathological N stage was significantly different between PALN+and PALN-patients(P=0.005),while no difference was observed in any of the other characteristics.Preoperative imaging diagnosed PALN positivity in one case.OS and DFS were comparable between PALN+and PALN-patients with lymph node positive disease(OS:13.2 mo vs 18.8 mo,P=0.161;DFS:13 mo vs 16.4 mo,P=0.179).No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting(OS:23.4 mo vs 20.6 mo,P=0.192;DFS:23.9 mo vs 20.5 mo,P=0.718).On the contrary,when patients did not receive chemotherapy,PALN disease had substantially shorter OS(5.5 mo vs 14.2 mo;P=0.015)and DFS(4.4 mo vs 9.8 mo;P<0.001).PALN involvement was not identified as an independent predictor for OS after multivariable analysis,while it was for DFS doubling the risk of recurrence.CONCLUSION PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC,surgery and chemotherapy,and should not be considered as a contraindication to resection.

Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics

BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer cases.Data are conflicting on the role of IGBC diagnosis in oncological outcomes.Some studies suggest that IGBC diagnosis does not affect outcomes,while others that overall survival(OS)is longer in these cases compared to non-incidental diagnosis(NIGBC).Furthermore,some studies reported early tumour stages and histopathologic characteristics as possible confounders,while others not.AIM To investigate the role of IGBC diagnosis on patients’overall survival,especially after surgical treatment with curative intent.METHODS Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre.Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed.Survival analysis for the whole cohort,surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test.Risk analysis was performed with univariable and multivariable Cox regression analysis.RESULTS The cohort included 261 patients with gallbladder cancer.65%of cases had NIGBC and 35%had IGBC.A total of 90 patients received surgical treatment(66%of IGBC cases and 19%of NIGBC cases).NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones.OS was longer in patients with IGBC in the whole cohort(29 vs 4 mo,P<0.001),as well as in the non-surgical(14 vs 2 mo,P<0.001)and surgical subgroups(29 vs 16.5 mo,P=0.001).Disease free survival(DFS)after surgery was longer in patients with IGBC(21.5 mo vs 8.5 mo,P=0.007).N stage and resection margin status were identified as independent predictors of OS and DFS.NIGBC diagnosis was identified as an independent predictor of OS.CONCLUSION IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics.Prospective studies are required to further investigate this,including detailed pathological analysis and molecular gene expression.