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1.
Pancreatology ; 20(3): 537-544, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31996296

ABSTRACT

BACKGROUND: Surgical resection remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). The prognostic value of resection margin status following pancreatoduodenectomy (PD) remains controversial. Standardised pathological assessment increases positive margins but limited data is available on the significance of involved margins. We investigated the impact of resection margin status in PDAC on patient outcome. METHOD: We identified all patients with PD for PDAC at one pancreatic cancer centre between August 2008 and December 2014. Demographic, operative, adjuvant therapeutic and survival data was obtained. Pathology data including resection margin status of specific anatomic margins was collected and analysed. RESULTS: 107 patients were included, all pathologically staged as T3 with 102 N1. 87.9% of patients were R1 of which 53.3% showed direct extension to the resection margin. Median survival for R0 patients versus R1<1 mm and R1 = 0 mm was 28.4 versus 15.4 and 25.1 versus 13.4 months. R1 = 0 mm status remained a predictor of poor outcome on multivariate analysis. Evaluation of individual margins (R1<1 mm) showed the SMV and SMA margins were associated with poorer overall survival. Multiple involved margins impacted negatively on outcome. SMA margin patient outcome with R1 = 1-1.9 mm was similar to R1=>2 mm. CONCLUSION: Using an R1 definition of <1 mm and standardised pathology we demonstrate that R1 rates in PDAC can approach 90%. R1 = 0 mm remained an independent prognostic factor for overall survival. Using R1<1 mm we have shown that involvement of medial margins and multiple margins has significant negative impact on overall survival. We conclude that not all margin positivity has the same prognostic significance.


Subject(s)
Carcinoma, Pancreatic Ductal/surgery , Margins of Excision , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/mortality , Female , Humans , Incidence , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/mortality , Prognosis , Prospective Studies , Survival Analysis , Terminology as Topic , Treatment Outcome
2.
Br J Surg ; 106(13): 1837-1846, 2019 12.
Article in English | MEDLINE | ID: mdl-31424576

ABSTRACT

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.


ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.


Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/pathology , Hepatectomy/methods , Liver Neoplasms/therapy , Colorectal Neoplasms/therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Metastasis , Radiotherapy, Adjuvant , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
3.
Am J Transplant ; 15(12): 3239-46, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26227015

ABSTRACT

Outcomes after islet transplantation continue to improve but etiology of graft failure remains unclear. De novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) posttransplant are increasingly recognized as a negative prognostic marker. Specific temporal associations between DSA and graft function remain undefined particularly in programs undertaking multiple sequential transplants. Impact of de novo DSA on graft function over 12 months following first islet transplant was determined prospectively in consecutive recipients taking tacrolimus/mycophenolate immunosuppression at a single center. Mixed-meal tolerance test was undertaken in parallel with HLA antibody assessment pretransplant and 1-3 months posttransplant. Sixteen participants received a total of 26 islet transplants. Five (19%) grafts were associated with de novo DSA. Five (31%) recipients were affected: three post-first transplant; two post-second transplant. DSA developed within 4 weeks of all sensitizing grafts and were associated with decreased stimulated C-peptide (median [interquartile range]) at 3 months posttransplant (DSA negative: 613(300-1090); DSA positive 106(34-235) pmol/L [p = 0.004]). De novo DSA directed against most recent islet transplant were absolutely associated with loss of graft function despite maintained immunosuppression at 12 months in the absence of a rescue nonsensitizing transplant. Alemtuzumab induction immunosuppression was associated with reduced incidence of de novo DSA formation (p = 0.03).


Subject(s)
Diabetes Mellitus, Type 1/surgery , Graft Rejection/epidemiology , HLA Antigens/immunology , Islets of Langerhans Transplantation/adverse effects , Isoantibodies/blood , Tissue Donors , Adult , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Histocompatibility Testing , Humans , Incidence , Isoantibodies/immunology , Male , Middle Aged , Postoperative Complications , Prognosis , Prospective Studies , Risk Factors
4.
Br J Surg ; 102(12): 1533-40, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26364826

ABSTRACT

BACKGROUND: Selective internal radiation therapy (SIRT) is a non-ablative technique for the treatment of liver primaries and metastases, with the intention of reducing tumour bulk. This study aimed to determine optimal patient selection, and elucidate its role as a downsizing modality. METHODS: Data were collected retrospectively on patients who underwent SIRT between 2011 and 2014. The procedure was performed percutaneously by an expert radiologist. Response was analysed in two categories, based on radiological (CT/MRI according to Response Evaluation Criteria In Solid Tumours (RECIST)) and biological (α-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9, chromogranin A) parameters. RESULTS: Forty-four patients were included. Liver metastases from colorectal cancer (22 patients) and hepatocellular carcinoma (HCC) (9) were the most common pathologies. Radiological response data were collected from 31 patients. A reduction in sum of diameters (SOD) was observed in patients with HCC (median -24.1 (95 per cent c.i. -43.4 to -3.8) per cent) and neuroendocrine tumours (-30.0 (-45.6 to -7.7) per cent), whereas a slight increase in SOD was seen in patients with colorectal cancer (4.9 (-10.6 to 55.3) per cent). Biological response was assessed in 17 patients, with a reduction in 12, a mixed response in two and no improvement in three. Six- and 12-month overall survival rates were 71 and 41 per cent respectively. There was no difference in overall survival between the RECIST response groups (median survival 375, 290 and 214 days for patients with a partial response, stable disease and progressive disease respectively; P = 0.130), or according to primary pathology (P = 0.063). Seven patients underwent liver resection with variable responses after SIRT. CONCLUSION: SIRT may be used to downsize tumours and may be used as a bridge to surgery in patients with tumours deemed borderline for resection.


Subject(s)
Liver Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular , Female , Follow-Up Studies , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Staging , Radiation Dosage , Retrospective Studies , Survival Rate , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
5.
World J Surg ; 38(2): 476-83, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24081543

ABSTRACT

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is performed increasingly for pancreatic pathology in the body and tail of the pancreas. However, only few reports have compared its oncological efficacy with open distal pancreatectomy (ODP). We compared these two techniques in patients with pancreatic ductal adenocarcinoma. METHODS: From a prospectively maintained database, all patients who underwent either LDP or ODP for adenocarcinoma in the body and tail of the pancreas between January 2008 and December 2011 were compared. Data were analysed using SPSS(®) v19 utilising standard tests. A p value <0.05 was considered significant. RESULTS: Of 101 patients who underwent distal pancreatectomy, 22 had histologically confirmed adenocarcinoma (LDP n = 8, ODP n = 14). Both groups were well matched for age and the size of tumour (22 vs. 32 mm, p = 0.22). Intraoperative blood loss was 306 ml compared with 650 ml for ODP (p = 0.152). A longer operative time was noted for LDP (376 vs. 274 min, p < 0.05). Total length of stay was shorter for LDP compared with ODP (8 vs. 12 days, p = 0.05). The number of postoperative pancreatic fistulas were similar (LDP n = 2 vs. ODP n = 3, p = 0.5). Complete resection (R0) was achieved in 88 % of LDP (n = 7) compared with 86 % of ODP (n = 12). The median number of lymph nodes harvested was 16 for LDP versus 14 for ODP. Overall 3-year survival also was similar: LDP = 82 %, ODP = 74 % (p = 0.89). CONCLUSIONS: From an oncological perspective, LDP is a viable procedure and its results are comparable to ODP for ductal adenocarcinomas arising in the body and tail of the pancreas.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Pancreatic Ductal/surgery , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Feasibility Studies , Female , Humans , Laparoscopy , Length of Stay , Lymphatic Metastasis , Male , Middle Aged , Pancreatic Fistula/epidemiology , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Postoperative Complications/epidemiology , Young Adult
6.
Br J Cancer ; 109(9): 2396-403, 2013 Oct 29.
Article in English | MEDLINE | ID: mdl-24113143

ABSTRACT

BACKGROUND: Chemotherapy-associated liver injury (CALI) has been linked to increased morbidity and poorer disease-specific outcomes in patients undergoing resection of colorectal liver metastases (CRLM). The aim of this study was to assess the contribution of tumour-related factors to the development of FOLFOX-induced liver injury. METHODS: We assessed the effect of FOLFOX treatment on the murine liver either in the presence or absence of CRLM to evaluate the contribution of both chemotherapy and tumour death to the development of CALI. RESULTS: In the presence of liver metastases, there was increased hepatic expression of plasminogen activator inhibitor-1 (146-fold; P<0.01) and vWF (2.4-fold; P<0.01) transcript as compared with sham-operated controls. In addition, we detected large clusters of megakaryocytes in the spleen of FOLFOX-treated tumour-bearing animals. The livers of FOLFOX-treated animals also showed changes in matrix remodelling genes such as TGFß (P<0.01), MMP2 (P<0.001), TIMP1 (P<0.001) and Pro-Collagen I (P<0.05) which was exacerbated in the presence of tumour. These genes have previously been demonstrated to have a key role in FOLFOX-induced liver injury. CONCLUSION: It appears that the toxicity of FOLFOX chemotherapy is enhanced by tumour-related factors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Chemical and Drug Induced Liver Injury/genetics , Hepatic Veno-Occlusive Disease/chemically induced , Hepatic Veno-Occlusive Disease/genetics , Animals , Cell Line, Tumor , Collagen Type I/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Fluorouracil/adverse effects , Fluorouracil/pharmacology , Inflammation/genetics , Leucovorin/adverse effects , Leucovorin/pharmacology , Liver/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Matrix Metalloproteinase 2/genetics , Megakaryocytes/drug effects , Mice , Mice, Inbred C57BL , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/pharmacology , Plasminogen Activator Inhibitor 1/genetics , Spleen/drug effects , Tissue Inhibitor of Metalloproteinase-1/genetics , Transforming Growth Factor beta/genetics
7.
Br J Surg ; 100(3): 381-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23280607

ABSTRACT

BACKGROUND: During the past decade the number of livers recovered and transplanted from donation after circulatory death (DCD) donors has increased significantly. As reported previously, injuries are more frequent during kidney procurement from DCD than from donation after brain death (DBD) donors. This aim of this study was to compare outcomes between DCD and DBD with respect to liver injuries. METHODS: Data on liver injuries in organs procured between 2000 and 2010 were obtained from the UK Transplant Registry. RESULTS: A total of 7146 livers were recovered from deceased donors during the study, 628 (8·8 per cent) from DCD donors. Injuries occurred in 1001 procedures (14·0 per cent). There were more arterial (1·6 versus 1·0 per cent), portal (0·5 versus 0·3 per cent) and caval (0·3 versus 0·2 per cent) injuries in the DBD group than in the DCD group, although none of these findings was statistically significant. Capsular injuries occurred more frequently in DCD than DBD (15·6 versus 11·4 per cent; P = 0·002). There was no significant difference between DCD and DBD groups in liver discard rates related to damage. CONCLUSION: There were no differences in terms of vascular injuries between DCD and DBD livers, although capsular injuries occurred more frequently in DCD organs. Continuing the trend for increased frequency of DCD liver recovery, and ensuring that there is an adequately skilled surgical team available for procurement, is vital to improving the utilization of DCD livers.


Subject(s)
Brain Death , Heart Arrest , Liver Transplantation/adverse effects , Liver/injuries , Tissue and Organ Harvesting/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Liver Transplantation/methods , Male , Middle Aged , Tissue and Organ Procurement/methods , Young Adult
8.
Dig Surg ; 30(4-6): 293-301, 2013.
Article in English | MEDLINE | ID: mdl-23969407

ABSTRACT

INTRODUCTION: A variety of factors have been identified in the literature which influence survival following resection of colorectal liver metastases (CRLM). Much of this literature is historical, and its relevance to contemporary practice is not known. The aim of this study was to identify those factors which influence survival during the era of preoperative chemotherapy in patients undergoing resection of CRLM in a UK centre. METHODS: All patients having liver resection for CRLM during an 11-year period up to 2011 were identified from a prospectively maintained database. Prognostic factors analysed included tumour size (≥5 or <5 cm), lymph node status of the primary tumour, margin positivity (R1; <1 mm), neo-adjuvant chemotherapy (for liver), tumour differentiation, number of liver metastases (≥4), preoperative carcinoembryonic antigen (CEA; ≥200 ng/ml) and whether metastases were synchronous (i.e. diagnosed within 12 months of colorectal resection) or metachronous to the primary tumour. Overall survival (OS) was compared using Kaplan-Meier plots and a log rank test for significance. Multivariate analysis was performed using a Cox regression model. Statistical analysis was performed in SPSS v19, and p < 0.05 was considered to be significant. RESULTS: 432 patients underwent resection of CRLM during this period (67% male; mean age 64.5 years), and of these, 54 (13.5%) had re-resections. The overall 5-year survival in this series was 43% with an actuarial 10-year survival of 40%. A preoperative CEA ≥200 ng/ml was present in 10% of patients and was associated with a poorer 5-year OS (24 vs. 45%; p < 0.001). A positive resection margin <1 mm was present in 16% of patients, and this had a negative impact on 5-year OS (15 vs. 47%; p < 0.001). Tumour differentiation, number, biliary or vascular invasion, size, relationship to primary disease, nodal status of the primary disease or the use of neo-adjuvant chemotherapy had no impact on OS. Multivariate analysis identified only the presence of a positive resection margin (OR 1.75; p < 0.05) and a preoperative CEA ≥200 ng/ml (OR 1.88; p < 0.01) as independent predictors of poor OS. CONCLUSION: Despite the wide variety of prognostic factors reported in the literature, this study was only able to identify a preoperative CEA ≥200 ng/ml and the presence of tumour within 1 mm of the resection margin as being of value in predicting survival. These variables are likely to identify patients who may benefit from intensive follow-up to enable early aggressive treatment of recurrent disease.


Subject(s)
Colorectal Neoplasms/mortality , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Colorectal Neoplasms/etiology , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/etiology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Invasiveness , Preoperative Care , Prognosis , Reoperation , Retrospective Studies , Survival Rate
9.
Ann R Coll Surg Engl ; 105(2): 166-172, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35446720

ABSTRACT

INTRODUCTION: Enhanced recovery after surgery (ERAS) is well established in many specialties but has not been widely adopted in renal transplantation. The aim of this survey was to understand current national practices and sentiment concerning ERAS for renal transplant recipients in the UK. METHODOLOGY: A national web-based survey was sent to consultant surgeons at all 23 UK adult renal transplant units. Completed questionnaires were collected between May and July 2020. Data were analysed according to individual responses and grouped according to the existence of formal ERAS pathways within units. RESULTS: All transplant units were represented in this survey. Three units had a formal ERAS pathway for all recipients. Of the remaining units, 65.9% considered implementing an ERAS pathway in the near future. The most commonly perceived barrier to ERAS implementation was 'embedded culture within transplant units' (54.8% of respondents). A fifth of respondents insert surgical drains selectively and 11.7% routinely discontinue patient-controlled analgesia on postoperative day 1. Most respondents routinely remove urinary catheters on day 5 (70%) and ureteric stents 4-6 weeks post-transplantation (81.7%). Median length of stay for deceased donor kidney transplant recipients was lower in units with ERAS programmes (5-7 days versus 8-10 days, respectively). The main cited barriers for discharge were 'suboptimal fluid balance' and 'requirement of treatment for rejection'. CONCLUSIONS: Despite slow uptake of ERAS in kidney transplantation, appetite appears to be increasing, particularly in the post-COVID-19 era. The current practice and opinions of transplant specialists highlighted in this survey may help to establish nationally agreed ERAS guidelines in this field.


Subject(s)
COVID-19 , Enhanced Recovery After Surgery , Kidney Transplantation , Surgeons , Adult , Humans , COVID-19/epidemiology , COVID-19/prevention & control , United Kingdom , Length of Stay , Postoperative Complications
10.
Am J Transplant ; 12(4): 932-6, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22225959

ABSTRACT

During the last 10 years, kidneys recovered/transplanted from donors after circulatory death (DCD) have significantly increased. To optimize their use, there has been an urgent need to minimize both warm and cold ischemia, which often necessitates more rapid removal. To compare the rates of kidney injury during procurement from DCD and donors after brain death (DBD) organ donors. A total of 13 260 kidney procurements were performed in the United Kingdom over a 10-year period (2000-2010). Injuries occurred in 903 procedures (7.1%). Twelve thousand three hundred seventy-two (93.3%) kidneys were recovered from DBD donors and 888 (6.7%) from DCD donors. The rates of kidney injury were significantly higher when recovered from DCD donors (11.4% vs. 6.8%, p < 0.001). Capsular, ureteric and vascular injuries were all significantly more frequent (p = 0.002, p < 0.001 and p = 0.017, respectively). Discard because of injury was more common after DCD donation (p = 0.002). Multivariate analysis demonstrated procurement injuries were significantly associated with DCD donors (p = 0.035) and increased donor age (<0.001) and donor body mass index (BMI; 0.001), donor male gender (p = 0.001) and no liver donation (0.009). We conclude that procurement from DCD donors leads to higher rates of injury to the kidney and are more likely to be discarded.


Subject(s)
Death, Sudden, Cardiac , Kidney/injuries , Organ Preservation , Tissue Donors/supply & distribution , Tissue and Organ Procurement , Adolescent , Adult , Brain Death , Cadaver , Child , Child, Preschool , Delayed Graft Function , Female , Graft Survival , Humans , Infant , Infant, Newborn , Kidney Transplantation , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment Outcome , United Kingdom , Young Adult
11.
Br J Surg ; 99(9): 1290-4, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22828960

ABSTRACT

BACKGROUND: Postoperative complications are increased in patients with reduced cardiopulmonary reserve undergoing major surgery. Pancreatic leak is an important contributor to postoperative complications and death following pancreaticoduodenectomy. The aim of this study was to determine whether reduced cardiopulmonary reserve was a risk factor for pancreatic leak. METHODS: All patients who underwent pancreaticoduodenectomy between January 2006 and July 2010 were identified from a prospectively held database. Data analysis was restricted to those who underwent cardiopulmonary exercise testing during preoperative assessment. Pancreatic leak was defined as grade A, B or C according to the International Study Group on Pancreatic Fistula definition. An anaerobic threshold (AT) cut-off value of 10·1 ml per kg per min was used to identify patients with reduced cardiopulmonary reserve. Univariable and multivariable analyses were performed to identify other risk factors for pancreatic leak. RESULTS: Some 67 men and 57 women with a median age of 66 (range 37-82) years were identified. Low AT was significantly associated with pancreatic leak (45 versus 19·2 per cent in patients with greater cardiopulmonary reserve; P = 0·020), postoperative complications (70 versus 38·5 per cent; P = 0·013) and prolonged hospital stay (29·4 versus 17·5 days; P = 0·001). On multivariable analysis, an AT of 10·1 ml per kg per min or less was the only independent factor associated with pancreatic leak. CONCLUSION: Low cardiopulmonary reserve was associated with pancreatic leak following pancreaticoduodenectomy. AT seems a useful tool for stratifying the risk of postoperative complications.


Subject(s)
Anaerobic Threshold/physiology , Anastomotic Leak/etiology , Heart Diseases/physiopathology , Pancreaticoduodenectomy , Respiration Disorders/physiopathology , Adult , Aged , Aged, 80 and over , Exercise Test , Female , Heart Diseases/complications , Humans , Male , Middle Aged , Preoperative Care , Prospective Studies , Respiration Disorders/complications , Risk Factors
13.
BJS Open ; 5(2)2021 03 05.
Article in English | MEDLINE | ID: mdl-33855363

ABSTRACT

BACKGROUND: Biliary leaks and anastomotic strictures are common early anastomotic biliary complications (EABCs) following liver transplantation. However, there are no large multicentre studies investigating their clinical impact or risk factors. This study aimed to define the incidence, risk factors and impact of EABC. METHODS: The NHS registry on adult liver transplantation between 2006 and 2017 was reviewed retrospectively. Adjusted regression models were used to assess predictors of EABC, and their impact on outcomes. RESULTS: Analyses included 8304 liver transplant recipients. Patients with EABC (9·6 per cent) had prolonged hospitalization (23 versus 15 days; P < 0·001) and increased chance for readmission within the first year (56 versus 32 per cent; P < 0·001). Patients with EABC had decreased estimated 5-year graft survival of 75·1 versus 84·5 per cent in those without EABC, and decreased 5-year patient survival of 76·9 versus 83·3 per cent; both P < 0.001. Adjusted Cox regression revealed that EABCs have a significant and independent impact on graft survival (leak hazard ratio (HR) 1·344, P = 0·015; stricture HR 1·513, P = 0·002; leak plus stricture HR 1·526, P = 0·036) and patient survival (leak HR 1·215, P = 0·136, stricture HR 1·526, P = 0·001; leak plus stricture HR 1·509; P = 0·043). On adjusted logistic regression, risk factors for EABC included donation after circulatory death grafts, graft aberrant arterial anatomy, biliary anastomosis type, vascular anastomosis time and recipient model of end-stage liver disease. CONCLUSION: EABCs prolong hospital stay, increase readmission rates and are independent risk factors for graft loss and increased mortality. This study has identified factors that increase the likelihood of EABC occurrence; research into interventions to prevent EABCs in these at-risk groups is vital to improve liver transplantation outcomes.


Subject(s)
Bile Ducts/surgery , Biliary Tract Diseases/etiology , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Adolescent , Adult , Aged , Anastomosis, Surgical/methods , Biliary Tract Diseases/epidemiology , Biliary Tract Diseases/surgery , Female , Graft Survival , Humans , Incidence , Logistic Models , Male , Middle Aged , Postoperative Complications/epidemiology , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Survival Analysis , United Kingdom/epidemiology , Young Adult
14.
Eur J Surg Oncol ; 45(12): 2268-2278, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31387755

ABSTRACT

Indications for liver transplantation have expanded over the past few decades owing to improved outcomes and better understanding of underlying pathologies. In particular, there has been a growing interest in the field of transplant oncology in recent years that has led to considerable developments which have pushed the boundaries of malignant indications for liver transplantation beyond hepatocellular carcinoma (HCC). In this article, we review and summarise the published evidence for liver transplantation in non-HCC primary and metastatic liver malignancies and highlight ongoing clinical trials that address unresolved questions therein. We also examine the current technical, immunological and oncological challenges that face liver transplantation in this growing field and explore potential approaches to overcome these barriers.


Subject(s)
Liver Neoplasms/surgery , Liver Transplantation , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma/surgery , Colorectal Neoplasms/pathology , Hemangioendothelioma, Epithelioid/surgery , Hepatoblastoma/surgery , Humans , Liver Neoplasms/secondary , Neuroendocrine Tumors/pathology
15.
Clin Oncol (R Coll Radiol) ; 31(1): 58-66, 2019 01.
Article in English | MEDLINE | ID: mdl-30297164

ABSTRACT

AIMS: Patients with chemotherapy-refractory colorectal cancer liver metastases have limited therapeutic options. Selective internal radiation therapy (SIRT) delivers yttrium 90 microspheres as a minimally invasive procedure. This prospective, single-arm, observational, service-evaluation study was part of National Health Service England Commissioning through Evaluation. METHODS: Patients eligible for treatment had histologically confirmed carcinoma with liver-only/liver-dominant metastases with clinical progression during or following oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT plus standard of care. The primary outcome was overall survival; secondary outcomes included safety, progression-free survival (PFS) and liver-specific PFS (LPFS). RESULTS: Between December 2013 and March 2017, 399 patients were treated in 10 centres with a median follow-up of 14.3 months (95% confidence interval 9.2-19.4). The median overall survival was 7.6 months (95% confidence interval 6.9-8.3). The median PFS and LPFS were 3.0 months (95% confidence interval 2.8-3.1) and 3.7 months (95% confidence interval 3.2-4.3), respectively. During the follow-up period, 143 patients experienced an adverse event and 8% of the events were grade 3. CONCLUSION: Survival estimates from this pragmatic study show clinical outcomes attainable in the National Health Service comparable with previously published data. This study shows the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treatments.


Subject(s)
Colorectal Neoplasms/complications , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
16.
Br J Surg ; 95(12): 1512-20, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18942059

ABSTRACT

BACKGROUND: This study compared multislice computed tomography (MSCT) with endoscopic ultrasonography (EUS) in the diagnosis and staging of pancreatic and periampullary malignancy. METHODS: Data were collected prospectively on patients having MSCT and EUS for suspected pancreatic and periampullary malignancy. RESULTS: Eighty-four patients had MSCT and EUS, of whom 35 underwent operative assessment (29 resections). In assessing malignancy, there was no significant difference between MSCT and EUS, and agreement was good (82 per cent, kappa = 0.49); the sensitivity and specificity of MSCT were 97 and 87 per cent, compared with 95 and 52 per cent respectively for EUS (P = 0.264). For portal vein/superior mesenteric vein invasion, MSCT was superior (P = 0.017) and agreement was moderate (72 per cent, kappa = 0.42); the sensitivity and specificity were 88 and 92 per cent for MSCT, and 50 and 83 per cent for EUS. For resectability, there was no significant difference and agreement was good (78 per cent, kappa = 0.51). EUS had an impact on the management of 14 patients in whom MSCT suggested benign disease or equivocal resectability. CONCLUSION: MSCT is the imaging method of choice for pancreatic and periampullary tumours. Routine EUS should be reserved for those with borderline resectability on MSCT.


Subject(s)
Ampulla of Vater/pathology , Endosonography/methods , Pancreatic Neoplasms/pathology , Tomography, X-Ray Computed/methods , Aged , Female , Humans , Male
17.
Surg Oncol ; 16(1): 33-45, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17544654

ABSTRACT

At some point in the natural course of colorectal cancer up to 50% of patients will develop metastasis to the liver. Historically only 20% of these patients would have to be deemed resectable, with an intent to cure, at the time of presentation. But with recent improvements in cross-sectional imaging, chemotherapeutic agents and advances in the techniques of surgical resection the emphasis of resection has now changed to 'who is not resectable' as opposed to 'who is resectable'. There are few contraindications to liver resection on the proviso that the patient is fit enough. As a result of this paradigm shift, 5 year survival rates are approaching 60%. Historically liver resection was perceived as a formidable operation but now liver resection for CRLM is safe and specialist centres are reporting mortality rates of less than 1%. This review briefly covers the standard techniques currently employed and some of the recent innovations being developed to improve resectability.


Subject(s)
Colorectal Neoplasms/surgery , Hepatectomy , Liver Neoplasms/surgery , Colorectal Neoplasms/pathology , Embolization, Therapeutic , Humans , Liver Neoplasms/secondary
18.
Transplant Proc ; 39(5): 1474-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17580165

ABSTRACT

BACKGROUND: Liver transplantation is the treatment of choice for patients with end-stage liver disease (ESLD) and early hepatocellular carcinoma (HCC), Routine laparoscopy with intraoperative ultrasound was employed in an attempt to improve patient selection for transplantation. Our aim was to assess whether laparoscopy improved the patient selection with ESLD and HCC being considered for transplantation. METHODS: We retrospectively reviewed the clinical notes and transplant database of all patients with ESLD complicated by HCC, being assessed for liver transplantation, from January 2000 to April 2005. RESULTS: Twenty-five patients with ESLD and HCC underwent assessment for liver transplantation. Eight were deemed untransplantable on cross-sectional imaging alone. Sixteen patients underwent laparoscopy and intraoperative ultrasound. One patient had undergone a previous segmental hepatectomy and laparoscopy was not technically feasible. At laparoscopy, all 16 patients were found to be free from extrahepatic disease and major vascular involvement. All 16 patients were listed for transplantation. At transplantation, one patient was found to have extrahepatic disease; the procedure was abandoned. One patient was found to have lesser curvature lymphadenopathy, Two patients had major vascular involvement noted in the explanted liver. All these findings were missed on pretransplant imaging and at laparoscopy. CONCLUSIONS: As an additional investigation, laparoscopy did not improve staging or alter the management of patients with HCC being assessed for liver transplantation. Since July 2005, we have ceased routine laparoscopic assessment of patients prior to listing. The decision use laparoscopy on patients is now being taken on a more selective basis.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Failure/surgery , Liver Neoplasms/surgery , Ultrasonography , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Humans , Laparoscopy , Liver Failure/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Monitoring, Intraoperative , Neoplasm Staging , Retrospective Studies
19.
Transplant Proc ; 39(2): 351-2, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362727

ABSTRACT

Intraarterial cooling (IAC) of non-heart-beating donors (NHBD) for renal donation requires a cheap, low-viscosity solution. HTK contains a high hydrogen ion buffer level that theoretically should reduce the observable acidosis associated with ongoing anaerobic metabolism. A retrospective comparison of all retrieved NHBD kidneys as well as of viability on the Organ Recovery Systems Lifeporter machine perfusion circuit was performed with respect to the preservation solution HTK or Marshall's HOC. Forty-two NHBD kidneys (19 HTK and 23 HOC) were machine perfused between February 2004 and May 2005. Most of the HTK kidneys were obtained from uncontrolled donors (12 vs 5; Fisher exact test, P = .01). As a consequence, the glutathione-s-transferase viability assay (411 vs 292 IU/L, P = .12) and the lactate concentrations (2.33 vs 1.94 mmol/L, P = .13) were higher among the HTK cohort. There was evidence of greater buffering capacity in HTK, since the lactate:hydrogen ion ratios were consistently lower during the first 2 perfusion hours (1 hour P = .03, 2 hour P = .02). A linear regression analysis confirmed that this was related to the IAC solution (ANCOVA, P < .001). All controlled donor kidneys passed viability testing and were transplanted. In contrast, 83% (10/12) of the uncontrolled donor kidneys preserved with HTK passed the viability test and were transplanted, compared with only 20% (1/5) of the HOC-treated comparators (Fisher exact test, P = .03). It may be concluded that the postulated advantages of improved pH buffering with HTK appear to have clinical relevance.


Subject(s)
Heart Arrest , Hypertonic Solutions , Kidney , Organ Preservation Solutions , Tissue Donors , Adolescent , Adult , Child , Cohort Studies , Female , Glucose , Humans , Male , Mannitol , Middle Aged , Patient Selection , Perfusion , Potassium Chloride , Procaine , Tissue and Organ Harvesting/methods
20.
Eur J Surg Oncol ; 42(10): 1597-607, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27329369

ABSTRACT

BACKGROUND: Reduction of perioperative blood loss and intraoperative transfusion are two major factors associated with improving outcomes in liver surgery. There is currently no consensus as to the best technique to achieve this. METHODS: An international Panel of Experts (EP), made up of hepatobiliary surgeons from well-known high-volume centres was assembled to share their experience with regard to the management of blood loss during liver resection surgery. The process included: a review of the current literature by the panel, a face-to-face meeting and an on-line survey completed by the EP prior to and following the face-to-face meeting, based on predetermined case scenarios. During the meeting the most frequently researched surgical techniques were appraised by the EP in terms of intraoperative blood loss. RESULTS: All EP members agreed that high quality research on the subject was lacking. Following an agreed risk stratification algorithm, the EP concurred with the existing research that a haemostatic device should always be used along with any user preferred surgical instrumentation in both open and laparoscopic liver resection procedures, independently from stratification of bleeding risk. The combined use of Ultrasonic Dissector (UD) and saline-coupled bipolar sealing device (Aquamantys(®)) was the EP preferred technique for both open and laparoscopic surgery. CONCLUSIONS: This EP propose the use of a bipolar sealer and UD for the best resection technique and essential equipment to minimise blood loss during liver surgery, stratified according to transfusion risk, in both open and laparoscopic liver resection.


Subject(s)
Hemostasis, Surgical/methods , Hepatectomy/methods , Hemostasis, Surgical/instrumentation , Humans , Laparoscopy/methods
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