Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Two-Week Wait Gastrointestinal (GI) Cancer Pathway: A Single Tertiary Centre Experience During the COVID-19 Pandemic.

BACKGROUND: This article investigated the impact of COVID-19 on the two-week wait referral pathway at the University Hospitals of Leicester NHS Trust. The conversion rate of these referrals was also explored as an indicator of the appropriateness of referrals from primary care. METHODS: Two-week wait referrals to the Cancer Centre of the University Hospitals of Leicester NHS Trust from 2018 to 2020 were collected for upper gastrointestinal (UGI), lower gastrointestinal (LGI), and hepato-pancreato-biliary (HPB) surgery. The confirmed cancer cases out of these referrals were also recorded. Additionally, the outcomes of the multidisciplinary team (MDT) meetings for all patients discussed in June 2018, 2019, and 2020 were collected, and their staging and treatment data were examined. RESULTS: The number of two-week referrals decreased in 2020 compared to the previous two years across the three specialities. This was more pronounced in April, with a reduction of over 50%. The conversion rate of these referrals increased in 2020 compared to 2018 and 2019 among all three specialities. The increase in conversion rate was statistically significant for LGI referrals (2018 vs 2020 p = 0.0056; 2019 vs 2020 p = 0.0005). There was no significant difference in the MDT outcome across the three specialities. CONCLUSION: Two-week wait remains a cornerstone pathway in the management of patients with suspected cancer in the National Health Service. The COVID-19 pandemic appeared to have reduced inappropriate referrals, as evidenced by the increased conversion rate. This did not appear to negatively impact tumour staging and outcomes for those patients who were referred on the pathway.

Sarcopenia: An Assessment into the Prevalence and Disease Burden in Chronic Pancreatitis Patients.

Objectives: To evaluate the prevalence of sarcopenia in patients referred to a Multidisciplinary Chronic Pancreatitis (CP) Clinic at the University Hospitals of Leicester. Methods: All patients who had undergone CT scans were identified. Controls were identified from CT colonograms with no features of malignancy or pancreatic pathology. The psoas muscle index (PMI) was calculated using the formula: total psoas muscle cross-sectional area at the third lumbar vertebral level (cm2)/ the patient's height squared (m2). PMI cut-offs were <6.31cm2/m2 and <3.91cm2/m2 for males and females, respectively. Results: 58 CP CT scans were available for analysis along with 62 control scans. 71.9% of CP patients had a PMI below the cut-off for their gender, compared to 45.2% of the controls. The mean PMI (±SD) for male CP patients and male controls were 5.54cm2/m2 (±1.60) and 6.73 cm2/m2 (±1.54), (P=0.0023). The mean PMI (±SD) for female CP patients and female controls were 3.82 cm2/m2 (+/-1.46) and 4.98 cm2/m2 (+/-1.43), (P=0.0021). Conclusions: CP patients had a mean PMI below the cut-off value, suggesting that CP patients are largely sarcopenic. As malnutrition is a significant feature of CP, optimisation of nutrition may help to ameliorate sarcopenia in CP patients.

Induction Implications: Shaping the Competence and Confidence of Junior Doctors Within Complex Medical Specialties.

Introduction The newly qualified junior doctors in the United Kingdom face challenges due to their limited experience and unfamiliarity with their rotations. We aim to share the experience of establishing a hepato-pancreato-biliary (HPB) surgery-specific induction program at the University Hospitals of Leicester NHS Trust and assess its impact on doctors' knowledge and experience. Methods A booklet was distributed to new junior doctors, and a two-hour structured teaching session was also conducted, with pre- and post-session assessments using multiple-choice questions and a feedback survey. The survey measured understanding of HPB anatomy, interventions, and satisfaction with the teaching methodology. Results The pre-session questionnaire included 22 participants, while the post-session had 20 participants. Regarding HPB anatomy understanding, in the pre-session, six (28.6%) and 11 (52.4%) participants reported levels 2 and 3, respectively, while levels 4 and 5 were reported by three (13.3%) and one (4.8%) participants. In the post-session, levels 4 and 5 were reported by six (30%) and 13 (65%), with only one (5%) reporting level 3 and none at levels 1 or 2. Similar trends were observed in understanding HPB investigation. In the pre-session, levels 2 and 3 were reported by eight (36.4%) and 11 (50%), while levels 4 and 5 were reported by two (9.1%) and one (4%). In the post-session, eight (40%) and 11 (55%) reported levels 4 and 5, with only one (5%) at level 3 and none at levels 1 or 2. For HPB management methods before teaching, levels 2 and 3 were equally reported by eight (36.4%), level 4 by four (22.7%), and none at level 5. After teaching, nine (45%) and 10 (50%) reported levels 4 and 5, with only one (5%) at level 3 and none at levels 1 or 2. Factual knowledge showed a 38% increase, rising from 49% pre-session to 87% post-session. In post-session feedback, 12 (60%) strongly agreed that the session helped augment their medical practice, and six (30%) agreed, with two (10%) neutral. Feedback on the teaching session's organization was positive, with 13 (65%) strongly agreeing that it was structured coherently, and six (30%) agreeing, with only one (5%) neutral regarding the clarity of the structure and delivery method. Conclusion Specialty-specific induction programs are crucial for providing support and ensuring the development of competent doctors. Efforts should be made to create supportive working environments for junior doctors to alleviate stress and improve their well-being.

Pilot study examining the impact of a specialist multidisciplinary team clinic for patients with chronic pancreatitis.

OBJECTIVE: -To assess the efficacy of a pilot Chronic Pancreatitis (CP) Multidisciplinary (MDT) clinic. METHODS: - 60 patients referred to a pilot MDT CP clinic were analysed. Anthropometric data, nutrition status, malabsorption evidence, glycaemic control, opiate use, bone mineral density (BMD) assessment and quality of life (QoL) were examined. RESULTS: -The average age was 51.27 (±12.75). The commonest aetiology was alcohol (55%). Ninety one point five percent had evidence of ongoing pancreatic exocrine insufficiency, with 88.1% requiring initiation or up-titration of pancreatic enzyme replacement (PERT). Up to half of the patients exhibited micronutrient deficiency. Twenty eight percent were diagnosed with type IIIc diabetes. There was an average daily reduction of 6 mg of morphine usage per patient with a concurrent decline in median pain scores from 83.3 to 63.3, which was non-significant. The median QoL score was 33.3 compared to a score of 75 from the reference population. QoL scores increased from 31.0 to 37.3 at follow up appointments. Seventy two point five percent of patients had undiagnosed low BMD. CONCLUSION: The data suggest that CP patients have significant nutritional deficiencies as well as undiagnosed diabetes, poor pain and glycaemic control which negatively impacts QoL. Assessment in a multi-disciplinary clinic ensures appropriate management.

Indeterminate liver lesions - a virtual epidemic: a cohort study over 8 years.

BACKGROUND: Within the last decade, advances and availability in radiological imaging have led to an increase in the detection of incidental liver lesions (ILLs) in the asymptomatic patient population. This poses a diagnostic conundrum. This study was undertaken to review the outcome of liver lesions labelled as 'indeterminate' in asymptomatic patients without a biopsy-proven concomitant primary tumour. The secondary aim was to assess the impact on healthcare resources and cost-effectiveness with regards to the frequency and modality of radiological scans, multidisciplinary team discussions and clinic reviews. METHODS: The study consisted of a retrospective analysis of prospectively collected data from the University Hospitals of Leicester multidisciplinary team database. The study period ranged from 2010 to 2015. All patients were followed-up for 3 years to ensure no late re-occurrences with malignancy. RESULTS: A total of 92 patients with ILL were identified. The median age was 72 years. The median size of these ILLs was 10 mm. Eighty-seven patients required supplementary imaging and 42 required a third imaging. Ninety-one patients had benign lesions. Only one case was biopsy proven to be malignant. CONCLUSION: Small (<15 mm) hepatic lesions discovered incidentally in patients with no known primary malignancy and risk factors are virtually always benign, with a 1% risk of malignancy. There is a need for a classification system, which stratifies ILLs by malignant potential based on a standardized and evidence-based approach. This is important to prevent unnecessary investigations. A multidisciplinary approach in an experienced hepatobiliary and pancreatic centre is recommended until such a classification exists.

Isolated submandibular lymph node metastasis in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is a highly aggressive malignancy that usually presents at a late stage. Common sites of metastasis include the liver, lung and adjacent lymph nodes. Cervical lymph node involvement has been reported previously but there are no documented cases of submandibular lymph node metastasis in the available literature. We describe a case of pancreatic adenocarcinoma metastasis to the left submandibular lymph node with no confirmed concurrent sites of metastasis.

Management implications of resection margin histology in patients undergoing resection for IPMN: A meta-analysis.

INTRODUCTION: IPMN is a relatively new clinical entity and surgeons are continuing to develop their understanding of this complex pathology. Little is known of the natural disease process post-resection of an IPMN, particularly the impact of gland histology and margin status on the chance of recurrence and survival in benign and invasive IPMN. METHODS: An online search was conducted to evaluate and include those studies which reported on gland histology, margin status and disease recurrence in resected benign and malignant IPMN. A Meta analysis was then performed using a random effects model. RESULTS: The chance of recurrence in non-invasive margin positive IPMN is similar to margin negative IPMN. The chance of recurrence is higher in invasive gland IPMN compared to non-invasive gland. The vast majority of recurrences occurred in patients with positive margins demonstrating invasion. CONCLUSION: All patients with intra- or post-operative evidence of invasive carcinoma at the resection margin should undergo further resection to achieve a negative margin. Patients with evidence of IPMN at the transaction margin (even with changes of high grade dysplasia/CIS) may not achieve any benefit from further resection. Patients with recurrence in benign/non-invasive IPMN should undergo re-resection, whereas patients with recurrence in invasive IPMN should not.

The Surgical Management of Klatskin Tumours: Has Anything Changed in the Last Decade?

Surgical treatment of hilar cholangiocarcinomas requires complex pre-, intra- and post-operative decision-making. Despite the significant progress in liver surgery over the years, several issues such as the role of pre-operative biliary drainage, portal vein embolisation, staging laparoscopy and neo-adjuvant chemotherapy remain unresolved. Operative strategies such as vascular resection, caudate lobe resection and liver transplant have also been practiced in order to improve R0 resectability and improved survival. The review aims to consolidate evidence from major studies in the last 11 years. Survival data were only included from studies that reported the results in at least 30 patients with 1-year follow-up. A significant number of patients may be prevented an unnecessary laparotomy if they underwent a staging laparoscopy. There remain no guidelines as to when portal vein embolisation or pre-operative biliary drainage should be employed but most studies agree with pre-operative biliary drainage being an absolute indication if portal vein embolisation is performed. Concomitant hepatectomy and caudate lobectomy increases R0 resection but vascular resection cannot be routinely recommended. Liver transplant at specialised centres in selective patients has had impressive results. Guidelines are required for pre-operative biliary drainage and portal vein embolisation and randomised trials are required in order to define the role of vascular resection in achieving a R0 resection and increasing survival.

Prospective randomized assessment of acquisition and retention of SILS skills after simulation training.

BACKGROUND: Skills in single-incision laparoscopic surgery (SILS) are difficult to acquire. Simulation training leads to skill acquisition but circumstances about skill deterioration are unclear. The aim of this study was to evaluate skill acquisition and retention after single-incision laparoscopic simulation training. METHODS: From October 2013 to January 2014, 30 surgically naive participants underwent a SILS training curriculum and completed two validated tasks (peg transfer, precision cutting) with subsequent testing to assess acquisition of skills (baseline testing, BT). The participants were randomized into two groups and skill retention testing (RT) was measured after 4 weeks (group A) or 12 weeks (group B). Task completion was measured in time with penalties for inaccurate performance. RESULTS: A SILS training curriculum was established. 90 % of the participants completed the training successfully and reached the required levels of proficiency. Comparison of BT and RT revealed significantly better RT performances for peg transfer and precision cutting in group A (P < 0.05). These effects were not seen for RT in group B. Evaluating the RT performance of both groups, group A showed a non-significant trend for improved peg transfer and precision cutting compared to group B. CONCLUSION: A proficiency-based training curriculum for acquisition of basic SILS skills was successfully established in our department. The results of this study indicate that acquired SILS skills are well retained for a short period without training (4 weeks) but a longer non-training period (12 weeks) resulted in a significant loss of acquired skills. For enhancement of surgical skills, specialised SILS training curricula could be developed for novices and inexperienced surgeons; however, continuous training is essential to maintain these acquired skills.

Bronchopleural fistula following laparoscopic liver resection.

A rare case is presented of a 58-year-old woman who developed a bronchopleural fistula following a laparoscopic liver resection for a colorectal metastasis. The bronchopleural fistula was finally diagnosed when after repeated admissions for chest infections, the patient coughed up surgical clips. We propose a management plan based on our experience and hope this case report will add to the scarce reports of postoperative bronchopleural fistula cases in the literature.

Spontaneous regression of a biopsy confirmed hepatocellular carcinoma.

A 74-year-old woman was diagnosed with histologically proven multiple bilobar hepatocellular carcinomas (HCC) in 2012. The lesions were inoperable and a repeat CT scan prior to starting chemotherapy revealed spontaneous regression of these lesions. Subsequent repeat scans have revealed continued regression of these lesions despite no active treatment. The case is presented with a literature review and discussion summarising the possible aetiologies of this phenomenon.