Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population.

BACKGROUND: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. RESULTS: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). CONCLUSIONS: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.

Awareness and perceptions of nutrition support in upper gastrointestinal cancer surgery: A national survey of multidisciplinary clinicians.

BACKGROUND: Patients undergoing surgery for upper gastrointestinal (UGI) cancer are at high risk of malnutrition, and a multidisciplinary approach to management is recommended. This study aimed to determine practices, awareness and perceptions of multi-disciplinary clinicians with regards to malnutrition screening and provision of nutrition support. METHODS: A national survey of dietitians, surgeons, oncologists and nurses was conducted using a 30-item online REDCap survey, including questions regarding self-reported malnutrition screening/nutrition support practices, awareness and perceptions, and barriers and enablers. The survey was distributed via professional organisations/networks between 1st September and 30th November 2020. Results are presented as counts and percentages. RESULTS: There were 130 participants (56% dietitians, 25% surgeons, 11% nurses, 8% oncologists). The majority reported that dietitians and nurses performed malnutrition screening, and dietitians and surgeons prescribed nutrition support. Most participants reported that their health service had dietetics support available overall (98%), however only 41% reported having an outpatient service. Participants (>90%) demonstrated very high awareness of the significance of malnutrition and the importance of early nutrition support. Participants mostly perceived dietitians, nurses and surgeons to be responsible for malnutrition screening, whilst responsibility of prescription of nutrition support was mostly dietitians and surgeons. There were a higher number of barriers for the outpatient setting (48%) than the inpatient setting (38%). CONCLUSIONS: Participants identified a high awareness of the importance of identification and treatment of malnutrition in UGI cancer surgery. However reported practices varied and appear to be lacking in the outpatient setting, with significant barriers identified to providing optimal nutrition care.

Evaluation of palliative treatments in unresectable pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) presents as unresectable disease in 80% of patients. Limited Australian data exists regarding management and outcome of palliative management for PDAC. This study aims to: (i) identify patients with PDAC being managed with palliative intent; (ii) assess the type of palliative management being used. METHODS: A prospectively maintained pancreatic database at Western Health (2015-2017) was used to identify patient demographics; stage and multidisciplinary decision regarding resectability and operative interventions; palliative care; use of chemotherapy, radiotherapy and; management of exocrine and endocrine insufficiency. Data on chemotherapy use, number of hospital admissions, emergency department attendances and intensive care unit admissions 30 days prior to death were recorded. RESULTS: One-hundred and eleven patients had diagnosis of PDAC, 15% with locally advanced and 45% with metastatic PDAC. Among the locally advanced and metastatic PDAC, 48% received biliary stent insertions, 93% had palliative care referral, 45% received palliative chemotherapy and 10% received radiotherapy. Dietitian referral occurred in 79% and 36% were prescribed with a pancreatic enzyme replacement therapy. Diabetes mellitus was present in 52% of which 31% was new onset. Within 30 days prior to death, 11% patients received palliative chemotherapy, 32% were hospitalized and 11% visited an emergency department more than once. Sixty-five percent died in hospital. CONCLUSION: A high proportion of patients diagnosed with locally advanced and metastatic PDAC received palliative care referrals and appropriate level of end-of-life care. Further prospective studies are necessary, examining the management and impacts of pancreatic insufficiency in this group.

Splenic autotransplantation: a systematic review.

BACKGROUND: Splenectomy is a surgical procedure indicated in a variety of medical conditions including trauma. Post-operatively, there is a lifelong risk of developing overwhelming sepsis from encapsulated bacteria, most commonly due to Streptococcus pneumoniae. Splenic autotransplantation has been proposed as a method to recover splenic function in patients requiring splenectomy with otherwise normal spleens. This study aims to systematically review the literature to determine the efficacy of spleen autotransplantation. METHODS: MEDLINE, PubMed and the Cochrane Library were searched for all studies assessing splenic autotransplantation (January 1947 to July 2018). Data were extracted on study characteristics, outcomes assessed, including spleen scintigraphy results, blood film counts and serum immunoglobulin (Ig) levels. RESULTS: Data were obtained from 18 primary studies. All studies demonstrated return of regenerated spleen tissue in the majority of their patients (95.3%) on spleen scintigraphy. In 12 studies, 90.2% of patients had blood films return to normal following transplantation. Ig levels were shown to return to normal in all 12 studies where it was assessed. In 11 studies, 3.7% of patients had post-operative complications. In five studies, 1.3% of patients had post-operative infections in the follow-up period. CONCLUSION: Splenic autotransplantation is a safe procedure with minimal complications that can return splenic filtration function and Ig levels to normal ranges. It has not been confirmed whether autotransplantation provides meaningful protection against overwhelming post-splenectomy infections.

Surgical outcomes for duodenal adenoma and adenocarcinoma: a multicentre study in Australia and the United Kingdom.

BACKGROUND: Pancreaticoduodenectomy is often required in patients with duodenal adenoma and adenocarcinoma and these patients generally have soft pancreatic texture and small pancreatic ducts, the two most significant factors associated with post-operative pancreatic fistula (POPF). The aims of the study were to evaluate the rate of POPF and long-term outcomes for patients with duodenal adenoma and adenocarcinoma who underwent curative resection. METHODS: This retrospective study (2004-2014) examined patients treated surgically with non-ampullary duodenal tumours (NADTs) in two hepatopancreaticobiliary units in Victoria, Australia, and Swansea, UK. RESULTS: There were 49 resections performed including 33 pancreaticoduodenectomies, five pancreas-preserving total duodenectomies and 11 segmental duodenal resections. Median length of follow-up was 23.5 months. Final histopathology revealed 18 duodenal adenomas and 31 adenocarcinomas. POPF rate for NADTs was 28.9% (of which 54.5% were grade C) compared to 14.5% for all other pathologies. Grade C POPF was associated with poorer survival outcomes (hazard ratio = 6.73; P = 0.005). The 5-year overall survival for patients with duodenal adenocarcinoma was 66.5%. CONCLUSION: Due to the soft pancreatic texture and small pancreatic duct, pancreatic resection for NADTs is associated with a high rate of POPF which contributes to reduced survival. Nevertheless, surgery is associated with favourable 5-year survival compared to pancreatic resection for pancreatic adenocarcinoma.

Are we getting the critical view? A prospective study of photographic documentation during laparoscopic cholecystectomy.

BACKGROUND: At laparoscopic cholecystectomy, most surgeons have adopted the operative approach where the 'critical view of safety' (CVS) is achieved prior to dividing the cystic duct and artery. This prospective study evaluated whether an adequate critical view was achieved by scoring standardized intra-operative photographic views and whether there were other factors that might impact on the ability to obtain an adequate critical view. METHODS: One hundred consecutive patients undergoing a laparoscopic cholecystectomy were studied. At each operation, two photographs were taken. Two independent experienced hepatobiliary surgeons scored the photographs on whether a critical view of safety was achieved. Inter-observer agreement was calculated using the weighted kappa coefficient. The Cochran-Mantel-Haenszel test was used to analyse the scores with potential confounding clinical factors. RESULTS: The kappa coefficient for adequate display of the cystic duct and artery was 0.49; 95% confidence interval (CI) 0.33 to 0.64; P = 0.001. No bias was detected in the overall scorings between the two observers (χ(2) 1.33; P = 0.312). Other clinical factors including surgeon seniority did not alter the outcome [odds ratio (OR) 0.902; 95% confidence interval 0.622 to 1.264]. CONCLUSION: Heightened awareness of the CVS through mandatory documentation may improve both trainee and surgeon technique.

The Role of CT cholangiography in the Detection and Localisation of Suspected Bile Leakage Following Cholecystectomy.

BACKGROUND: Most bile duct injuries are not recognized at the time of initial surgery. Optimal treatment requires early recognition. CT IVC has become increasingly important in identifying bile leaks and their source after cholecystectomy. Our study aims to report the outcomes of using CT IVC post operatively and how accurately it can detect or localise bile leaks. METHODS: From 2000 - 2009, twenty patients were managed for suspected bile leak post cholecystectomy within the Alfred Hospital. The study included a retrospective evaluation of the initial procedure, presenting symptoms, site of ductal injury, diagnostic procedures and therapeutic interventions. Results were analysed to determine success of the imaging procedure, and to correlate imaging diagnosis with results both diagnostically and clinically. RESULTS: Twenty patients had a suspected bile leak, of which 3 were detected at the time of surgery. Seven patients had a CTIVC as their primary investigation. It identified bile leak in 6 and the anatomical site in 5. One had a leak excluded and was managed conservatively. CONCLUSIONS: CT Cholangiography is a feasible and low-risk tool for imaging of the biliary tract in suspected bile leaks post cholecystectomy. It is a valuable non-invasive investigation that may help avoid endoscopic retrograde Cholangiography or surgery.

Correlations between histopathological diagnosis of chemotherapy-induced hepatic injury, clinical features, and perioperative morbidity.

BACKGROUND: Chemotherapy has in some series been linked with increased morbidity after a hepatectomy. Hepatic injuries may result from the treatment with chemotherapy, but can also be secondary to co-morbid diseases. The aim of the present study was to draw correlations between clinical features, treatment with chemotherapy and injury phenotypes and assess the impact of each upon perioperative morbidity. PATIENTS AND METHODS: Retrospective samples (n= 232) were scored grading steatosis, steatohepatitis and sinusoidal injury (SI). Clinical data were retrieved from medical records. Correlations were drawn between injury, clinical features and perioperative morbidity. RESULTS: Injury rates were 18%, 4% and 19% for steatosis, steatohepatitis and SI, respectively. High-grade steatosis was more common in patients with diabetes [odds ratio (OR) = 3.33, P= 0.01] and patients with a higher weight (OR/kg = 1.04, P= 0.02). Steatohepatitis was increased with metabolic syndrome (OR = 5.88, P= 0.02). Chemotherapy overall demonstrated a trend towards an approximately doubled risk of high-grade steatosis and steatohepatitis although not affecting SI. However, pre-operative chemotherapy was associated with an increased SI (OR = 2.18, P= 0.05). Operative morbidity was not increased with chemotherapy, but was increased with steatosis (OR = 2.38, P= 0.02). CONCLUSIONS: Diabetes and higher weight significantly increased the risk of steatosis, whereas metabolic syndrome significantly increased risk of steatohepatitis. The presence of high-grade steatosis increases perioperative morbidity, not administration of chemotherapy per se.

mRNA gene expression correlates with histologically diagnosed chemotherapy-induced hepatic injury.

INTRODUCTION: Chemotherapy-induced hepatic injuries (CIHI) are an increasing problem facing hepatic surgeons. It may be possible to predict the risk of developing CIHI by analysis of genes involved in the metabolism of chemotherapeutics, previously established as associated with other forms of toxicity. METHODS: Quantitative reverse transcriptase-polymerase chain reaction methodology (q-RT-PCR) was employed to quantify mRNA expression of nucleotide excision repair genes ERCC1 and ERCC2, relevant in the neutralization of damage induced by oxaliplatin, and genes encoding enzymes relevant to 5-flurouracil metabolism, [thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)] in 233 hepatic resection samples. mRNA expression was correlated with a histopathological injury scored via previously validated methods in relation to steatosis, steatohepatitis and sinusoidal obstruction syndrome. RESULTS: Low-level DPD mRNA expression was associated with steatosis [odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.53-10.19, P < 0.003], especially when stratified by just those patients exposed to chemotherapy (OR = 4.48, 95% CI = 1.31-15.30 P < 0.02). Low expression of ERCC2 was associated with sinusoidal injury (P < 0.001). There were no further associations between injury patterns and target genes investigated. CONCLUSIONS: Predisposition to the development of CIHI may be predictable based upon individual patient expression of genes encoding enzymes related to the metabolism of chemotherapeutics.

Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS).

BACKGROUND: A standardized definition of post-hepatectomy haemorrhage (PHH) has not yet been established. METHODS: An international study group of hepatobiliary surgeons from high-volume centres was convened and a definition of PHH was developed together with a grading of severity considering the impact on patients' clinical management. RESULTS: The definition of PHH varies strongly within the hepatic surgery literature. PHH is defined as a drop in haemoglobin level > 3 g/dl post-operatively compared with the post-operative baseline level and/or any post-operative transfusion of packed red blood cells (PRBC) for a falling haemoglobin and/or the need for radiological intervention (such as embolization) and/or re-laparotomy to stop bleeding. Evidence of intra-abdominal bleeding should be obtained by imaging or blood loss via the abdominal drains if present. Transfusion of up to two units of PRBC is considered as being Grade A PHH. Grade B PHH requires transfusion of more than two units of PRBC, whereas the need for invasive re-intervention such as embolization and/ or re-laparotomy defines Grade C PHH. CONCLUSION: The proposed definition and grading of severity of PHH enables valid comparisons of results from different studies. It is easily applicable in clinical routine and should be applied in future trials to standardize reporting of complications.

Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery.

BACKGROUND: Despite the potentially severe impact of bile leakage on patients' perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. METHODS: An international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients' serum and drain fluid. RESULTS: After evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients' clinical management. Grade A bile leakage causes no change in patients' clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required. CONCLUSION: We propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy.

Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS).

BACKGROUND: Posthepatectomy liver failure is a feared complication after hepatic resection and a major cause of perioperative mortality. There is currently no standardized definition of posthepatectomy liver failure that allows valid comparison of results from different studies and institutions. The aim of the current article was to propose a definition and grading of severity of posthepatectomy liver failure. METHODS: A literature search on posthepatectomy liver failure after hepatic resection was conducted. Based on the normal course of biochemical liver function tests after hepatic resection, a simple and easily applicable definition of posthepatectomy liver failure was developed by the International Study Group of Liver Surgery. Furthermore, a grading of severity is proposed based on the impact on patients' clinical management. RESULTS: No uniform definition of posthepatectomy liver failure has been established in the literature addressing hepatic surgery. Considering the normal postoperative course of serum bilirubin concentration and International Normalized Ratio, we propose defining posthepatectomy liver failure as the impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased international normalized ratio and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5. The severity of posthepatectomy liver failure should be graded based on its impact on clinical management. Grade A posthepatectomy liver failure requires no change of the patient's clinical management. The clinical management of patients with grade B posthepatectomy liver failure deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C posthepatectomy liver failure. CONCLUSION: The current definition of posthepatectomy liver failure is simple and easily applicable in clinical routine. This definition can be used in future studies to allow objective and accurate comparisons of operative interventions in the field of hepatic surgery.

Staged liver resection for colorectal metastases: a valuable strategy or a waste of time?

BACKGROUND: The use of staged liver resections for colorectal metastases has been increasing in recent times. The aim of this study was to determine the practices and outcomes of those surgeons attending the Australia and New Zealand Hepatic, Pancreatic and Biliary Association (ANZHPBA) meeting in 2008 who perform staged resections. METHODS: A questionnaire was sent to all members of the ANZHPBA and the international faculty who were invited to attend the annual meeting held in Coolum, Queensland, Australia in October 2008. RESULTS: There were 30 responses from 7 centres across the UK, Germany and Australia. Twenty-eight patients completed treatment. The study population was predominantly male (n = 20, 67%), with an average age of 59.4 years. All patients had bilobar disease. A right-sided first resection was planned in 39% of cases. Seventeen percent of patients underwent portal vein embolization prior to first resection. A second operation was performed at an average of 2.8 months from the first resection. Overall, 50% (n = 14) of patients eventually achieved a complete (R0) staged procedure. Twelve complications after the first resection were seen in 32% patients (n = 9). Twenty-three patients underwent a second liver resection. Twenty-five complications after the second resection were present in 57% (n = 13). CONCLUSIONS: Two-stage liver resections are beneficial if both stages are completed and an R0 resection is achieved. While there is increased morbidity and mortality, we believe that staged liver resection for colorectal metastases is a valuable strategy in selected cases.

Laparoscopic hepatectomy is a safe procedure for cancer patients.

BACKGROUND: Utilizing laparoscopy for major surgeries such as hepatectomy is a relatively new concept. Initially, benign pathologies dominated indications for resection. Our experience in an Australian setting with primarily malignant diagnoses is described. METHODS: A review of patients' profiles, pathology, surgery and outcome was performed on 35 patients between December 2005 and August 2008. Data were collected and analysed retrospectively from medical records on a pre-designed datasheet. RESULTS: Commonest indication for resection was colorectal metastasis (54%), 71% of all resections were for malignancy. Average operating time was 2 h 31 min (range 30 min-7 h, 15 min). Major morbidity consisted of one bile leak, two subphrenic abscesses and one pulmonary embolus. There were no deaths. Conversion to open was required in 20% and two patients required intra-operative blood transfusions. Average length of stay overall was 6.1 days (range 1-27), but as low as 2 days for some left lateral sectionectomies. Cessation of parenteral analgesia, return to normal diet and full mobility were achieved on average at 2.4, 2.3 and 2.8 days. Significant post-operative liver dysfunction was seen in two patients, which returned to normal by discharge. One patient died of disease progression 4 months after surgery. There were two involved margins in 35 patients (6%). CONCLUSIONS: Laparoscopic hepatectomy is a developing and safe technique in a select group of patients including those with malignancies, resulting in short hospital stays, rapid return to normal diet, full mobility and minimal morbidity with acceptable oncological parameters. This study is not comparative in nature, but provides evidence to support further investigation and establishment of this new technique for liver resection.

Consideration of anatomical structures relevant to the surgical strategy for managing gallbladder carcinoma.

AIMS: Gallbladder carcinoma usually presents late with advanced disease. It develops in an anatomically complex area. Consideration is given to resection of relevant local structures with respect to outcome. METHODS: A comprehensive literature review was performed, searching Medline for articles published since 2000, using the MeSH heading of 'gallbladder cancer' and 'surgery'. Abstracts were reviewed and articles retrieved if the main focus of the article centred on the surgical management of gallbladder carcinoma. OBSERVATIONS: Hepatic resection is advocated and tailored to pathological T stage. Lymph node dissection and bile duct resection, as well as en bloc resection of other viscera, remain areas of controversy. CONCLUSIONS: Eastern and Western practice standards of care differ, but hepatic resection with some lymph node dissection is present in both approaches. Philosophy regarding aggression with respect to en bloc resection of adjacent organs and actual extent of lymphatic resection remains disparate.

A review of the surgical strategies for the management of gallbladder carcinoma based on T stage and growth type of the tumour.

AIMS: Surgery for gallbladder carcinoma is a technically challenging exercise. The extent of resection varies based on a number of factors, and controversy exists regarding what constitutes an acceptable resection. A review of current recommendations and practice was undertaken. METHODS: A comprehensive literature review was performed, searching Medline for articles published since 2000, using the MeSH heading of 'gallbladder cancer' and 'surgery'. Abstracts were reviewed and articles retrieved if the main focus of the article centred on the surgical management of gallbladder carcinoma. OBSERVATIONS: The extent of hepatic resection and lymph node dissection required varies in particular with T stage. Growth pattern and anatomical location of the tumour within the gallbladder also influence surgical management. CONCLUSIONS: Discrepancy exists between the Eastern and Western literature in terms of what constitutes an acceptable limit of resection, and these issues are discussed.