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1.
HPB (Oxford) ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38755085

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

2.
Eur J Surg Oncol ; 50(6): 108353, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701690

ABSTRACT

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Neoplasm Recurrence, Local , Pancreaticoduodenectomy , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/pathology , Female , Male , Retrospective Studies , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Neoplasm Recurrence, Local/epidemiology , Aged , Middle Aged , Risk Factors , Time Factors , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/pathology
3.
Ann Hepatobiliary Pancreat Surg ; 28(1): 70-79, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38092429

ABSTRACT

Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

4.
BJS Open ; 7(6)2023 11 01.
Article in English | MEDLINE | ID: mdl-38036696

ABSTRACT

BACKGROUND: Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. METHOD: Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012-2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien-Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. RESULTS: Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P < 0.0001) and a classic Whipple approach (P = 0.005) were all associated with increased overall morbidity. In addition, ASA grade > II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). CONCLUSION: In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens.


Subject(s)
Pancreatic Neoplasms , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/methods , Retrospective Studies , Pancreas/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Pancreatic Neoplasms/surgery
5.
Ann Hepatobiliary Pancreat Surg ; 27(4): 403-414, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37661767

ABSTRACT

Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6-21), group B (49 days, 39-64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p < 0.001) were associated with a delay to PD, but magnetic resonance imaging (32 vs. 32 days, p = 0.5), positron emission tomography (40 vs. 31 days, p > 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence.

6.
Eur J Surg Oncol ; 49(9): 106919, 2023 09.
Article in English | MEDLINE | ID: mdl-37330348

ABSTRACT

INTRODUCTION: Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. MATERIALS AND METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. RESULTS: Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). CONCLUSION: In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreaticoduodenectomy/adverse effects , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/pathology , Chemotherapy, Adjuvant , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Pancreatic Neoplasms
7.
HPB (Oxford) ; 25(7): 788-797, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37149485

ABSTRACT

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.


Subject(s)
Adenocarcinoma , Ampulla of Vater , Common Bile Duct Neoplasms , Duodenal Neoplasms , Humans , Pancreaticoduodenectomy/adverse effects , Retrospective Studies , Ampulla of Vater/surgery , Ampulla of Vater/pathology , Duodenal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Pancreatic Neoplasms
8.
Eur J Surg Oncol ; 49(1): 142-149, 2023 01.
Article in English | MEDLINE | ID: mdl-36075841

ABSTRACT

INTRODUCTION: Patients who suffer a serious complication of pancreatoduodenectomy (PD) may have their adjuvant chemotherapy (AC) delayed or omitted as a result. We aimed to investigate whether PD complications affected AC rates. MATERIALS AND METHODS: A retrospective analysis of all PD patients with histologically-confirmed pancreatic ductal adenocarcinoma (2006-2015) was performed; 90-day mortality patients were excluded. Patients who commenced AC were compared to those who did not (morbidity rates and survival) and patients who developed selected postoperative complications were compared to those who did not (AC rates and survival). RESULTS: 157 patients were included and 90-day mortality was 3.8%. Of the remaining patients, 102 (68.5%) received AC (AC data unavailable for two patients). Survival was longer in the AC group (p = 0.004). AC patients had less frequently experienced a postoperative chest infection (8.82% vs 34.0%, p = 0.0003) or a postoperative complication which was Clavien-Dindo (CD) grade ≥ II (29.4% vs 57.4%, p = 0.0019) or ≥ III (6.86% vs 21.3%, p = 0.023). Patients who experienced a postoperative chest infection (36.0% vs 75.0%, p = 0.0003) or a postoperative complication which was CD grade ≥ II (48.9% vs 73.1%, p = 0.0099) or ≥ III (29.4% vs 70.3%, p = 0.0018) less frequently commenced AC. CONCLUSION: Patients who received AC had less frequently experienced a serious postoperative complication. Efforts should be made to preoperatively identify those who are high-risk for a serious complication as this cohort may benefit from neoadjuvant therapy.


Subject(s)
Pancreatic Neoplasms , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Neoadjuvant Therapy/adverse effects , Retrospective Studies , Survival Rate , Pancreatic Neoplasms/pathology , Chemotherapy, Adjuvant , Postoperative Complications/epidemiology , Postoperative Complications/etiology
9.
Ann Hepatobiliary Pancreat Surg ; 27(1): 76-86, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36168824

ABSTRACT

Backgrounds/Aims: The aim of this study was to describe short- and long-term outcomes of patients who underwent pancreatoduodenectomy (PD) at a typical United Kingdom hepatopancreatobiliary unit. Methods: A retrospective analysis of all PD patients with histologically-confirmed pancreatic ductal adenocarcinoma (PDAC), ampullary adenocarcinoma (AA), or distal cholangiocarcinoma (CC) from September 1st, 2006 to May 31st, 2015 was carried out. The following information was obtained: demographics, comorbidities, preoperative investigations, neoadjuvant treatment, operative details, postoperative management, complications, adjuvant treatment, five-year recurrence, and five-year survival. Effects of selected preoperative variables on short- and long-term outcomes were investigated. Results: Of 271 included patients, 57.9% had PDAC, 25.8% had AA, and 16.2% had CC. In total, 67.9% experienced morbidity and 17.3% developed a Clavien-Dindo grade ≥ III complication. The 90-day mortality was 3.3%. Clinically-relevant postoperative pancreatic fistula, bile leak, gastrojejunal leak, postpancreatectomy haemorrhage and delayed gastric emptying affected 8.1%, 4.1%, 0.0%, 9.2%, and 19.9% of patients, respectively. American Society of Anesthesiologists grade III-VI correlated with overall morbidity (p = 0.002) and major morbidity (p = 0.009), but not 90-day mortality or five-year survival. The same pattern was observed in patients with a preoperative serum bilirubin > 29 µmol/L and/or a neutrophil/lymphocyte ratio > 3.1. Five-year cancer recurrence and five-year survival were 68.3% and 22.5%, respectively. PDAC patients had higher five-year recurrence but lower five-year survival rates (both p = 0.001). Conclusions: In our series, the majority of patients experienced a complication. However, few patients experienced major morbidity. Surgical risk factors did not affect five-year survival.

10.
Cells ; 11(22)2022 11 17.
Article in English | MEDLINE | ID: mdl-36429078

ABSTRACT

Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Cell Line, Tumor , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/metabolism , Pancreas/pathology , Extracellular Matrix/metabolism , Adenocarcinoma/metabolism , Pancreatic Neoplasms
11.
Colorectal Dis ; 24(9): 1063-1072, 2022 09.
Article in English | MEDLINE | ID: mdl-35437885

ABSTRACT

AIM: Young colorectal cancer (CRC) patients are reported to have more aggressive disease, an advanced stage at diagnosis and conflicting survival outcomes. The aim of this study was to analyse the demographics, clinicopathological features and prognosis of young CRC at a population-based level in England. METHOD: This is a retrospective review of all CRC patients using data from Public Health England collated from regional cancer registries in England between 2010 and 2014. Those aged 40 years and below were classified as young and those over 40 were classified as older. RESULTS: Overall, 167,501 patients had CRC. Of these, 3757 patients (2.2%) were young. Right-sided cancers were more common in younger patients (48.2% vs. 32.9%, p < 0.001). Favourable histological grade (well or moderately differentiated) was present in 83.1% and 73.5% of young and older patients, respectively. The percentage of young and older patients being diagnosed at an early stage (Stages 1 and 2) was similar at 40.6% vs. 42.9%. The 5-year age- and gender-adjusted relative survival (cancer specific) was significantly better for young patients when compared with older patients diagnosed with CRC. Additionally, overall 5-year survival was better for younger patients (71.6% and 47.2%, p < 0.001 in young and older CRC patients respectively). CONCLUSION: The increased right-sided colon cancer in young CRC patients in England warrants attention. Contrary to previous reports, they do not present at later stage. Young CRC patients have better overall and relative survival than older patients with CRC.


Subject(s)
Colorectal Neoplasms , Age Factors , Colorectal Neoplasms/diagnosis , Humans , Neoplasm Staging , Prognosis , Registries , Retrospective Studies
12.
BMJ Case Rep ; 14(4)2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33853816

ABSTRACT

A 49-year-old man presented with a 1-week history of abdominal pain, distension, diarrhoea and fatigue. CT of the abdomen and pelvis revealed peritonitis with no identifiable cause. Diagnostic laparoscopy was performed, which excluded gastrointestinal perforation. Peritoneal fluid tested positive for Chlamydia trachomatis and rectal swabs were positive for C. trachomatis serovars consistent with lymphogranuloma venereum (LGV). Additional blood tests also revealed a diagnosis of syphilis. This is a rare documented case of LGV peritonitis in a male without associated immunodeficiency. The patient recovered well following laparoscopic washout and a course of appropriate antibiotics.


Subject(s)
Lymphogranuloma Venereum , Peritonitis , Anti-Bacterial Agents/therapeutic use , Chlamydia trachomatis , Homosexuality, Male , Humans , Lymphogranuloma Venereum/complications , Lymphogranuloma Venereum/diagnosis , Lymphogranuloma Venereum/drug therapy , Male , Middle Aged , Peritonitis/diagnosis , Peritonitis/drug therapy
16.
Surg Endosc ; 34(1): 170-176, 2020 01.
Article in English | MEDLINE | ID: mdl-30863928

ABSTRACT

BACKGROUND: The aim of this study was to investigate the short- and long-term outcomes after elective laparoscopic surgery (LPS) for colorectal cancer patients over 80 years of age. METHODS: This was a retrospective study of all patients of 80 and above, who underwent elective colorectal resection, between January 2007 and January 2016. Data were analysed from a prospectively collected cancer database and cross checked with patient records. Determinants of survival were analysed using log-rank test and Kaplan-Meier curves. RESULTS: We identified 293 patients; 110 underwent LPS. LPS had significantly better overall survival (p = 0.0065) and disease-free survival (DFS) (p = 0.006). The LPS group also had a shorter length of stay (LOS)-9 vs 11 days (p < 0.00001), 90-day mortality-5.5 vs 13.7% (p = 0.03) and required fewer blood transfusions 22.7 vs 40.4% (p = 0.002), when compared to open surgery (OPS). There was no difference in 30-day mortality 1.8 vs 4.9% (p = 0.22), anastomotic leakage 2.3 vs 6% (p = 0.20) or post-operative complication rates 44.5 vs 50.8% (p = 0.30). CONCLUSIONS: LPS for patients in their 80s is characterised by better overall and DFS compared to open procedures and is associated with shorter post-operative LOS, and significantly lower 90-day mortality. Patients operated on laparoscopically also required fewer post-operative blood transfusions.


Subject(s)
Colorectal Neoplasms , Elective Surgical Procedures , Laparoscopy , Long Term Adverse Effects , Postoperative Complications , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Disease-Free Survival , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/methods , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Laparoscopy/statistics & numerical data , Long Term Adverse Effects/epidemiology , Long Term Adverse Effects/etiology , Male , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Survival Analysis , Treatment Outcome
17.
BMJ Open Gastroenterol ; 6(1): e000336, 2019.
Article in English | MEDLINE | ID: mdl-31645990

ABSTRACT

OBJECTIVE: Current surveillance strategies for duodenal adenomatosis in familial adenomatous polyposis (FAP) miss malignancies and underestimate cancer risk in ampullary disease. This study aimed to evaluate the utility of endoscopic ultrasound (EUS) in the assessment of FAP patients with duodenal and/or ampullary polyposis referred for surgical intervention. DESIGN: A retrospective analysis of FAP patients undergoing index EUS between December 2006 and May 2015 was performed. Follow-up was completed in January 2018, including review of all EUS procedures and surgical interventions (median follow-up 6 years). RESULTS: Fifty-five patients underwent 188 EUS procedures. Six patients (11%) developed malignancy (three duodenal, three ampullary). Ampullary cancer risk was underestimated by Spigelman stage and overestimated by Kashiwagi classification. Ultrasound findings were poor predictors of malignancy, with common bile duct dilatation being the only finding present in one EUS prior to a diagnosis of ampullary cancer. The best predictors of ampullary malignancy were an ampullary polyp size >3 cm and an increase >1 cm in ampullary polyp size. Ampullary polyp size >3 cm provided the best predictive value, correctly identifying two of the three cases of ampullary cancer and both patients with high-grade dysplasia. EUS biopsy failed to detect malignancy later confirmed by surgical histology in two patients. CONCLUSION: EUS surveillance confers little additional benefit to standard endoscopic surveillance in FAP patients. The best predictor of ampullary malignancy is an ampullary polyp >3 cm; this could be regarded as a relative indication for surgery.

18.
BMC Cancer ; 19(1): 185, 2019 Feb 28.
Article in English | MEDLINE | ID: mdl-30819129

ABSTRACT

BACKGROUND: Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. RISK FACTORS FOR CHOLANGIOCARCINOGENESIS: Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. MOLECULAR PATHOGENESIS OF CHOLANGIOCARCINOMA: Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-ß, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. CONCLUSION: Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease.


Subject(s)
Bile Duct Neoplasms/etiology , Bile Duct Neoplasms/metabolism , Cholangiocarcinoma/etiology , Cholangiocarcinoma/metabolism , Animals , Bile Duct Neoplasms/pathology , Biomarkers , Cholangiocarcinoma/pathology , Disease Susceptibility , Gene Expression Regulation, Neoplastic , Humans , Risk Factors , Signal Transduction
19.
Dig Surg ; 34(1): 36-42, 2017.
Article in English | MEDLINE | ID: mdl-27384180

ABSTRACT

BACKGROUND: Differentiating hepatic mucinous cystic neoplasms (MCNs) from simple hepatic cysts (SCs) preoperatively is a challenging task. Our aim was to determine whether radiological features on ultrasound scan (USS), CT or MRI, cyst fluid tumour markers, or multidisciplinary team (MDT) outcomes could differentiate MCN from SC. METHODS: A retrospective review of radiological features, cyst fluid tumour marker levels and MDT outcomes in 52 patients was performed. RESULTS: There were 13 patients with MCN, 38 with SC and one ciliated foregut cyst. MCNs were more often solitary (p = 0.006). Although no other individual radiological characteristic on USS, CT or MRI was predictive of MCN, MDT outcomes stating that a cyst was complex in nature were highly predictive (p = 0.0007). Cyst fluid carbohydrate antigen 19-9, carcino-embryonic antigen and cancer antigen 125 were unable to differentiate MCN from SC (p = 0.45, p = 0.49, and p = 0.73, respectively). CONCLUSIONS: MDT outcomes are of greatest value when trying to differentiate MCN from SC, as well as having a solitary cyst on imaging. Conventional cyst fluid tumour markers are unhelpful. All suspicious cystic liver lesions should be discussed pre-operatively by a hepatobiliary MDT to determine the most appropriate surgical approach.


Subject(s)
Cysts/chemistry , Cysts/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Neoplasms, Cystic, Mucinous, and Serous/diagnostic imaging , Patient Care Team , Adult , Aged , Aged, 80 and over , CA-125 Antigen/analysis , CA-19-9 Antigen/analysis , Diagnosis, Differential , Female , Humans , Liver Neoplasms/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasms, Cystic, Mucinous, and Serous/surgery , Retrospective Studies , Tomography, X-Ray Computed , Ultrasonography , Young Adult
20.
Hepat Oncol ; 4(4): 99-109, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29367874

ABSTRACT

Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.

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