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Article ; Online: Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience.

Das, Bibek / Fehervari, Matyas / Hamrang-Yousefi, Sahar / Jiao, Long R / Pai, Madhava / Jenkins, John T / Spalding, Duncan R C

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2022 Volume 25, Issue 1, Page(s) 16–23

Abstract: Aim: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure ... ...

Abstract	Aim: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK. Method: A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed. Results: Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05). Conclusion: En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.
MeSH term(s)	Male ; Humans ; Pancreaticoduodenectomy/methods ; Retrospective Studies ; Colonic Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Colectomy/methods
Language	English
Publishing date	2022-09-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.16303
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Article ; Online: Pancreatobiliary and pancreatoduodenal fistulae in intraductal papillary mucinous neoplasm of the pancreas: report of a case.

Bong, Jan Jin / Wang, Jayson / Spalding, Duncan R

Surgery today

2011 Volume 41, Issue 2, Page(s) 281–284

Abstract: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas present more commonly in the elderly. This report describes a case of IPMN in a 36-year-old man who presented with obstructive jaundice and weight loss. The initial investigation by ... ...

Abstract	Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas present more commonly in the elderly. This report describes a case of IPMN in a 36-year-old man who presented with obstructive jaundice and weight loss. The initial investigation by computed tomography scan revealed a cystic lesion in the head of pancreas fistulating into the duodenum and the common bile duct (CBD). Subsequent endoscopic retrograde cholangiopancreatography revealed a low CBD stricture with proximal filling defects. Mucin was observed extruding from the biliary orifice following an endoscopic sphincterotomy. A classic Whipple's pancreatoduodenectomy was performed to excise the lesion. A histological examination of the lesion confirmed the presence of a malignant IPMN of the pancreas complicated by pancreatobiliary and pancreatoduodenal fistulae.
MeSH term(s)	Adenocarcinoma, Mucinous/complications ; Adenocarcinoma, Papillary/complications ; Adult ; Biliary Fistula/etiology ; Duodenal Diseases/etiology ; Humans ; Intestinal Fistula/etiology ; Male ; Pancreatic Fistula/etiology ; Pancreatic Neoplasms/complications
Language	English
Publishing date	2011-01-26
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1115435-4
ISSN	1436-2813 ; 0941-1291
ISSN (online)	1436-2813
ISSN	0941-1291
DOI	10.1007/s00595-009-4217-0
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Article ; Online: Does neostigmine improve time to resolution of symptoms in acute colonic pseudo-obstruction?

Kayani, Babar / Spalding, Duncan R / Jiao, Long R / Habib, Nagy A / Zacharakis, Emmanouil

International journal of surgery (London, England)

2012 Volume 10, Issue 9, Page(s) 453–457

Abstract: A best evidence topic was written according to a structured protocol. In [patients with acute colonic pseudo-obstruction] is [neostigmine] superior to [conservative treatment] with respect to [duration of symptoms and complications]. In total 51 papers ... ...

Abstract	A best evidence topic was written according to a structured protocol. In [patients with acute colonic pseudo-obstruction] is [neostigmine] superior to [conservative treatment] with respect to [duration of symptoms and complications]. In total 51 papers were found using the reported search, and ten of these represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. We conclude that intravenous neostigmine is associated with significantly reduced duration of acute colonic pseudo-obstruction (ACPO) compared to conservative treatment alone. Neostigmine infusion should be administered with continuous cardiac monitoring for possible bradycardia, which may require treatment with atropine. Seven prospective analyses and one retrospective study showed that intravenous neostigmine reduces time to resolution of clinical and radiological features of ACPO. One prospective study showed that neostigmine is only effective in improving duration of ACPO when it is combined with proponalol. One prospective study showed no difference in time to resolution of ACPO between neostigmine and conservative treatment but this study was limited by small sample size, lack of radiological examinations and poor reporting of adverse effects. In four separate studies patients experienced bradycardia with intravenous neostigmine and this required treatment with atropine. No other significant adverse effects were reported. Overall, intravenous neostigmine is associated with a significant reduction in duration of ACPO. In addition to regularly reviewing patients for antic-cholinergic side effects, patients should undergo continuous cardiac monitoring for bradycardia. The wide variety in methodology and measurement of outcomes reinforce the need for higher power studies to improve patient selection and monitoring of outcomes.
MeSH term(s)	Acute Disease ; Cholinesterase Inhibitors/therapeutic use ; Colonic Pseudo-Obstruction/drug therapy ; Humans ; Neostigmine/therapeutic use ; Time Factors ; Treatment Outcome
Chemical Substances	Cholinesterase Inhibitors ; Neostigmine (3982TWQ96G)
Language	English
Publishing date	2012
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2212038-5
ISSN	1743-9159 ; 1743-9191
ISSN (online)	1743-9159
ISSN	1743-9191
DOI	10.1016/j.ijsu.2012.08.008
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Article ; Online: The "malignant truth" about the recurrence of pancreatic intraductal papillary mucinous neoplasms.

Frampton, Adam E / Pai, Madhava / Krell, Jonathan / Vlavianos, Panagiotis / Jiao, Long R / Spalding, Duncan R C

Archives of surgery (Chicago, Ill. : 1960)

2012 Volume 147, Issue 10, Page(s) 977–79; author reply 979–80

MeSH term(s)	Carcinoma, Pancreatic Ductal/surgery ; Female ; Humans ; Male ; Pancreas/pathology ; Pancreatic Neoplasms/surgery
Language	English
Publishing date	2012-10-08
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80055-7
ISSN	1538-3644 ; 0004-0010 ; 0096-6908 ; 0272-5533
ISSN (online)	1538-3644
ISSN	0004-0010 ; 0096-6908 ; 0272-5533
DOI	10.1001/archsurg.2012.2287
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Article: Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma.

Wadsworth, Christopher A / Dixon, Peter H / Taylor-Robinson, Simon / Kim, Jin U / Zabron, Abigail A / Wong, Jason H / Chapman, Michael H / McKay, Siobhan C / Spalding, Duncan R / Wasan, Harpreet S / Pereira, Steve P / Thomas, Howard C / Whittaker, John C / Williamson, Catherine / Khan, Shahid A

Journal of clinical and experimental hepatology

2018 Volume 9, Issue 2, Page(s) 171–175

Abstract: Background and aims: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients ... ...

Abstract	Background and aims: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. Methods: Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. Results: The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls ( Conclusion: The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required.
Language	English
Publishing date	2018-07-20
Publishing country	India
Document type	Journal Article
ISSN	0973-6883
ISSN	0973-6883
DOI	10.1016/j.jceh.2018.06.521
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Article ; Online: Radio-frequency-assisted Liver Partition with Portal vein ligation (RALPP) for liver regeneration.

Gall, Tamara M H / Sodergren, Mikael H / Frampton, Adam E / Fan, Ruifang / Spalding, Duncan R / Habib, Nagy A / Pai, Madhava / Jackson, James E / Tait, Paul / Jiao, Long R

Annals of surgery

2015 Volume 261, Issue 2, Page(s) e45–6

MeSH term(s)	Aged ; Catheter Ablation/methods ; Colorectal Neoplasms/pathology ; Female ; Hepatectomy ; Humans ; Ligation ; Liver/physiology ; Liver/surgery ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Liver Regeneration ; Male ; Middle Aged ; Portal Vein/surgery ; Treatment Outcome
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Evaluation Studies ; Letter
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000000607
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Article: Liver resection with bipolar radiofrequency device: Habib 4X.

Pai, Madhava / Jiao, Long R / Khorsandi, Shirin / Canelo, Ruben / Spalding, Duncan R C / Habib, Nagy A

HPB : the official journal of the International Hepato Pancreato Biliary Association

2008 Volume 10, Issue 4, Page(s) 256–260

Abstract: Background: Intraoperative blood loss has been shown to be an important factor correlating with morbidity and mortality in liver surgery. In spite of the technological advances in hepatic parenchymal transection devices, bleeding remains the single most ...

Abstract	Background: Intraoperative blood loss has been shown to be an important factor correlating with morbidity and mortality in liver surgery. In spite of the technological advances in hepatic parenchymal transection devices, bleeding remains the single most important complication of liver surgery. The role of radiofrequency (RF) in liver surgery has been expanded from tumour ablation to major hepatic resections in the last decade. Habib 4X, a new bipolar RF device designed specifically for liver resection is described here. Methods: Habib 4X is a bipolar, handheld, disposable RF device and consists of two pairs of opposing electrodes which is introduced perpendicularly into the liver, along the intended transection line. It produces controlled RF energy between the electrodes and the heat produced seals even major biliary and blood vessels and enables resection of the liver parenchyma with a scalpel without blood loss or biliary leak. Results: Three hundred and eleven patients underwent 384 liver resections from January 2002 to October 2007 with this device. There were 109 major resections and none of the patients had vascular inflow occlusion (Pringle's manoeuvre). Mean intraoperative blood loss was 305 ml (range 0-4300) ml, with less than 5% (n=18) rate of transfusion. Conclusion: Habib 4X is an additional device for hepatobiliary surgeons to perform liver resections with minimal blood loss and low morbidity and mortality rates.
Language	English
Publishing date	2008-09-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2131251-5
ISSN	1365-182X
ISSN	1365-182X
DOI	10.1080/13651820802167136
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Article ; Online: MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial.

Sarker, Debashis / Plummer, Ruth / Meyer, Tim / Sodergren, Mikael H / Basu, Bristi / Chee, Cheng Ean / Huang, Kai-Wen / Palmer, Daniel H / Ma, Yuk Ting / Evans, T R Jeff / Spalding, Duncan R C / Pai, Madhava / Sharma, Rohini / Pinato, David J / Spicer, James / Hunter, Sarah / Kwatra, Vineet / Nicholls, Joanna P / Collin, David /

Nutbrown, Robert / Glenny, Helen / Fairbairn, Sonia / Reebye, Vikash / Voutila, Jon / Dorman, Stephanie / Andrikakou, Pinelopi / Lloyd, Peter / Felstead, Steve / Vasara, Jenni / Habib, Robert / Wood, Chris / Saetrom, Pal / Huber, Hans E / Blakey, David C / Rossi, John J / Habib, Nagy

Clinical cancer research : an official journal of the American Association for Cancer Research

2020 Volume 26, Issue 15, Page(s) 3936–3946

Abstract: Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that ... ...

Abstract	Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. Patients and methods: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). Results: Thirty-eight participants have been treated across six dose levels (28-160 mg/m Conclusions: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacokinetics ; CCAAT-Enhancer-Binding Proteins/agonists ; CCAAT-Enhancer-Binding Proteins/genetics ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Dose-Response Relationship, Drug ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Infusions, Intravenous ; Liposomes ; Liver Neoplasms/diagnosis ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Male ; Middle Aged ; Nanoparticles/administration & dosage ; Neoplasm Staging ; Oligoribonucleotides/administration & dosage ; Oligoribonucleotides/adverse effects ; Oligoribonucleotides/pharmacokinetics ; Treatment Outcome ; Tumor Microenvironment/drug effects ; Up-Regulation/drug effects
Chemical Substances	Antineoplastic Agents ; CCAAT-Enhancer-Binding Proteins ; CEBPA protein, human ; Liposomes ; Oligoribonucleotides
Language	English
Publishing date	2020-05-01
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-20-0414
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Article ; Online: Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma.

McKay, Siobhan C / Unger, Kristian / Pericleous, Stephanos / Stamp, Gordon / Thomas, Gerry / Hutchins, Robert R / Spalding, Duncan R C

HPB : the official journal of the International Hepato Pancreato Biliary Association

2011 Volume 13, Issue 5, Page(s) 309–319

Abstract: Background: Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC ... ...

Abstract	Background: Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets. Methods: DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment. Results: DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained. Conclusions: We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.
MeSH term(s)	Adult ; Aged ; Bile Duct Neoplasms/chemistry ; Bile Duct Neoplasms/diagnosis ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/therapy ; Bile Ducts, Intrahepatic/chemistry ; Bile Ducts, Intrahepatic/pathology ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Cholangiocarcinoma/chemistry ; Cholangiocarcinoma/diagnosis ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; Cholangiocarcinoma/therapy ; Chromosomes, Artificial, Bacterial ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Genetic Testing ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Targeted Therapy ; Oligonucleotide Array Sequence Analysis ; Patient Selection ; Precision Medicine ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/analysis ; Receptor, ErbB-2/genetics
Chemical Substances	Biomarkers, Tumor ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2011-03-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1111/j.1477-2574.2010.00286.x
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Article ; Online: Tumor infiltration in the medial resection margin predicts survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

Zhang, Yaojun / Frampton, Adam E / Cohen, Patrizia / Kyriakides, Charis / Bong, Jan J / Habib, Nagy A / Spalding, Duncan R C / Ahmad, Raida / Jiao, Long R

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

2012 Volume 16, Issue 10, Page(s) 1875–1882

Abstract: Background: Microscopic tumor involvement (R1) in different surgical resection margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been debated.: Methods: Clinico-pathological data for 258 patients who underwent ...

Abstract	Background: Microscopic tumor involvement (R1) in different surgical resection margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been debated. Methods: Clinico-pathological data for 258 patients who underwent PD between 2001 and 2010 were retrieved from a prospective database. The rates of R1 resection in the circumferential resection margin (pancreatic transection, medial, posterior, and anterior surfaces) and their prognostic influence on survival were assessed. Results: For PDAC, the R1 rate was 57.1% (48/84) for any margin, 31.0% (26/84) for anterior surface, 42.9% (36/84) for posterior surface, 29.8% (25/84) for medial margin, and 7.1% (3/84) for pancreatic transection margin. Overall and disease-free survival for R1 resections were significantly worse than those for R0 resection (17.2 vs. 28.7 months, P = 0.007 and 12.3 vs. 21.0 months, P = 0.019, respectively). For individual margins, only medial positivity had a significant impact on survival (13.8 vs. 28.0 months, P < 0.001), as opposed to involvement in the anterior (19.7 vs. 23.3 months, P = 0.187) or posterior margin (17.5 vs. 24.2 months, P = 0.104). Multivariate analysis demonstrated R0 medial margin was an independent prognostic factor (P = 0.002, HR = 0.381; 95% CI 0.207-0.701). Conclusion: The medial surgical resection margin is the most important after PD for PDAC, and an R1 resection here predicts poor survival.
MeSH term(s)	Adult ; Aged ; Carcinoma, Pancreatic Ductal/mortality ; Carcinoma, Pancreatic Ductal/pathology ; Carcinoma, Pancreatic Ductal/surgery ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Pancreaticoduodenectomy/methods ; Pancreaticoduodenectomy/mortality ; Retrospective Studies ; Survival Analysis ; Treatment Outcome
Language	English
Publishing date	2012-08-10
Publishing country	United States
Document type	Evaluation Study ; Journal Article
ZDB-ID	2012365-6
ISSN	1873-4626 ; 1934-3213 ; 1091-255X
ISSN (online)	1873-4626 ; 1934-3213
ISSN	1091-255X
DOI	10.1007/s11605-012-1985-4
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