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G J Poston

Publications and source records attributed to G J Poston.

At least 19 recordsLinked to original sources
PubMed2006

Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies.

No consensus on the indications for surgical resection of colorectal liver metastases exists. This systematic review has been undertaken to assess the published evidence for its efficacy and safety and to identify prognostic factors. Studies were identified by computerised and hand searches of the literature, scanning references and contacting investigators. The outcome measures were overall survival, disease-free survival, postoperative morbidity and mortality, quality of life and cost effectiveness, and a qualitative summary of the trends across all studies was produced. Only 30 of 529 independent studies met all the eligibility criteria for the review, and data on 30-day mortality and morbidity only were included from a further nine studies. The best available evidence came from prospective case series, but only two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for selected groups of patients: those undergoing hepatic resection or those undergoing curative resection. Postoperative mortality rates were generally low (median 2.8%). The majority of studies described only serious postoperative morbidity, the most common being bile leak and associated perihepatic abscess. Approximately 30% of patients remained alive 5 years after resection and around two-thirds of these are disease free. The quality of the majority of published papers was poor and ascertaining the benefits of surgical resection of colorectal hepatic metastases is difficult in the absence of randomised trials. However, it is clear that there is group of patients with liver metastases who may become long-term disease-free survivors following hepatic resection. Such survival is rare in apparently comparable patients who do not have surgical treatment. Further work is needed to more accurately define this group of patients and to determine whether the addition of adjuvant treatments results in improved survival.

Colorectal Neoplasms↗
PubMed2005

The use of irinotecan and oxaliplatin in the treatment of advanced colorectal cancer.

In 2002, the UK National Institute for Clinical Excellence (NICE) issued guidance on the use of irinotecan, oxaliplatin and raltitrexed in advanced colorectal cancer. This guidance recommended that UK patients with advanced colorectal cancer (CRC) receive 5-FU+folinic acid [leucovorin] as first line therapy, and were only eligible for irinotecan if their disease progressed. NICE guidance is adopted worldwide by more than 25 countries in addition to the British National Health Service. This guidance specifically recommended that, 'oxaliplatin could be used in first line treatment if in the opinion of an experienced liver surgeon, a patient might become potentially resectable'. Since 2002, the definition of hepatic resectability with curative intent for these patients has changed radically to encompass any patient in whom a 70% liver resection will achieve total macroscopic removal of all liver disease. Furthermore, compelling evidence has emerged over the last 2 years, which clearly demonstrates the therapeutic superiority of oxaliplatin and irinotecan based regimens over 5FU and leucovorin in the treatment of patients with advanced colorectal cancer. The original guidance was not due for review until 2007, presently NICE are reviewing this guidance prematurely, and new guidance will be issued by the summer of 2005, and clearly this review will have an impact in many countries. This paper summarises the present evidence for the use of these regimens. Most importantly, it is now a prerequisite for liver surgeons to work hand in hand with medical oncologists to obtain maximum survival benefit and increased chance of cure for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Cutaneous manifestations of the malignant carcinoid syndrome.

BACKGROUND: The incidence of carcinoid tumours is approximately 1.5 per 100 000 of the population. The malignant carcinoid syndrome, which is caused by circulating neuroendocrine mediators produced by the tumour, occurs in less than 10% of patients. Cutaneous involvement, although recognized in this rare syndrome, has rarely been reported. OBJECTIVES: To examine a series of patients with the malignant carcinoid syndrome, to establish the prevalence and types of cutaneous involvement and to assess whether these could be used as indicators of disease activity, progression and prognosis. METHODS: Patients with the malignant carcinoid syndrome who attended a multidisciplinary clinic for neuroendocrine tumours over a 23-month period between February 2001 and December 2002 were invited to participate in the study. This involved completion of a standard history proforma and a detailed cutaneous examination with findings recorded by clinical photography. RESULTS: Twenty-five patients were enrolled. All but one had experienced flushing, three had rosacea, five had clinical features of pellagra and two had scleroderma. Flushing was generally an early manifestation of the syndrome, whereas both the pellagra and scleroderma tended to occur in more advanced disease. CONCLUSIONS: This descriptive case series indicates that cutaneous features are not uncommon in the syndrome. They are readily diagnosed on clinical examination, and may be useful indicators of disease activity and prognosis.

Aged↗
PubMed2003

The management of retroperitoneal liposarcoma with synchronous intra-duodenal sarcoma.

Intra-abdominal (as opposed to extremity or limb and limb-girdle) soft tissue sarcomas (STS) are rare and account for less than 1% of all diagnosed neoplasms. These tumours are usually associated with a poor prognosis and are often locally invasive and metastatic at the time of presentation. Retroperitoneal sarcomas with synchronous or metachronous different histological types are rare and intra-duodenal sarcomas extremely unusual. A case of a giant retroperitoneal STS weighing approximately 15 kg consisting of two histologically different types is presented. Intra-duodenal involvement with sarcoma was found intra-operatively. We discuss the management of this condition in the context of an illustrative case in our recent experience.

Adult↗
PubMed2003

Surgery for midgut carcinoid.

Many clinicians prefer to avoid surgery in patients with carcinoid neoplasia, because of its slow growth and relatively favourable prognosis. Nevertheless, the commonest cause of death in patients with carcinoid is advanced metastatic disease, and both clinical and epidemiological data indicate that the more effectively the disease is ablated, the more long-lasting the benefit. Multidisciplinary management of patients with carcinoid must consider inherited risk, possible multiple carcinoids and/or synchronous non-carcinoid cancer, and the use of a range of investigations that also evaluate the 10% of patients with carcinoid syndrome with or without valvular heart disease. Although primary size is correlated with the presence of nodal with or without liver metastases, carcinoid tumours <1 cm in diameter may be metastatic at presentation, particularly those arising within the small intestine. In the jejunum and ileum, resection of all sizes of carcinoid with local and regional nodes is preferred, to prevent nodal dissemination causing mesenteric ischaemia with or without infarction. Resection of nodal metastases should be undertaken in those with persistent or recurrent nodal disease if possible. Appendiceal and right colonic carcinoids are most effectively treated by right hemicolectomy with local and regional nodal clearance, as for adenocarcinoma. However, for most appendiceal carcinoids which are <1 cm in diameter and non-invasive, appendicectomy alone is sufficient. For appendiceal carcinoids 1-2 cm in diameter, histopathological assessment helps to determine the need for hemicolectomy. Liver resection has been followed by prolonged 5 year survival in several series and is recommended in appropriate patients to attempt cure or to debulk metastatic disease. Liver transplantation has had only qualified success in highly selected patients without extra-hepatic disease in whom other therapies have failed.

Carcinoid Tumor↗
PubMed2002

Cryotherapeutic ablation of liver tumours.

BACKGROUND: This paper reports a 7-year experience of cryoablation for colorectal and non-colorectal liver metastases. METHODS: A retrospective review was undertaken of patients treated in two adjacent UK centres in the north-west of England. RESULTS: Over a 7-year period (1993-2000), 57 patients underwent cryotherapy for malignant hepatic tumours (41 colorectal, 16 non-colorectal). In the patients with colorectal metastases, preoperative carcinoembryonic antigen (CEA) levels fell significantly, from a mean of 444.1 to 6.22 micro g/l (P = 0.002). One patient died, two developed cryoshock and six had cardiorespiratory complications. All patients with colorectal metastases subsequently received 5-fluorouracil-based chemotherapy. The remaining 16 patients with non-colorectal tumours (seven neuroendocrine metastases, five hepatocellular carcinomas, three sarcomas, one cholangiocarcinoma) all received cryotherapy alone, with no major complications. The median survival for patients with non-colorectal metastases was 37 months, compared with 22 months for those with colorectal metastases (P = 0.005). CONCLUSION: Hepatic cryotherapy is effective and safe, as demonstrated by the significant reduction in postoperative CEA concentration and the low risk of complications. However, this initial short-term success was not reflected in 5-year survival rates. Cryotherapy for non-colorectal metastases had a greater long-term survival benefit and is a useful means of controlling symptoms.

Adolescent↗
PubMed2001

Lessons from Japan--endoscopic management of early gastric and oesophageal cancer.

A significant proportion of gastric and oesophageal cancers are diagnosed at an early stage in Japan. Early cancer is not obvious to the untrained eye as the mucosal changes are subtle. Better awareness by endoscopists of the different appearances of early cancer probably contributes significantly to this high incidence in Japan. Routine use of chromoendoscopy in high risk patients is also helpful. Survival figures after open surgery for these early cancers are excellent. Although the mortality of open surgery for carcinoma of the stomach and oesophagus is low, the morbidity is still considerable. A stage of early cancer, when the lesion is limited to the mucosa has been demonstrated to have minimal risk of metastatic spread (even to the local lymph nodes). These lesions can be reliably diagnosed with the help of endoscopic ultrasound. Once diagnosed, endoscopic mucosal resection can be performed with low morbidity. This provides tissue for histological evaluation, which is a definite advantage over other ablative methods used to treat early gastric and oesophageal cancer. Gastric cancers which are difficult to resect endoscopically, can be dealt with laparoscopically with equally satisfactory results

Endoscopy↗
PubMed2001

(131)I-MIBG radionuclide therapy is safe and cost-effective in the control of symptoms of the carcinoid syndrome.

BACKGROUND: The standard treatment used to control the symptoms of carcinoid syndrome (CS) involves subcutaneous injections of the somatostatin analogue octreotide. This is expensive (US $8000--16,000 per year), and treatment may be for many years. The aim of this study was to evaluate the efficacy and cost-effectiveness of our experience over the last 5 years with 1-131-labelled metaiodobenzylguanidine (MIBG) radionuclide therapy in the palliation of patients with CS. METHODS: A consecutive series of 20 symptomatic patients (referred between 1994 and 1999) with CS were evaluated. Fifteen of them underwent(123)I-MIBG scanning. Of the 13 patients with significant tracer uptake in metastatic deposits compared to background, 12 underwent a course of therapeutic(131)I-MIBG (one patient refused). Symptoms, biochemical markers, CT scans, follow-up(123)I-MIBG scans, and the requirement for octreotide were used to assess outcome of treatment. Costs of(131)I-MIBG and octreotide treatments were compared. RESULTS: MIBG treatment was well tolerated in all with only transient side-effects. Ten patients showed a measurable clinical improvement. Seven had a complete clinical response. The mean duration of response was 15.4 months. Octreotide was not required or was reduced in eight patients. Treatment with(131)I-MIBG resulted in a saving of US $1000 per patient, with effective symptom control, when compared to octreotide. CONCLUSION: 1-131 MIBG therapy is a safe and cost-effective therapeutic option to successfully control symptoms in patients with carcinoid syndrome.

3-Iodobenzylguanidine↗
PubMed2001

The management of retroperitoneal soft tissue sarcoma: a single institution experience with a review of the literature.

AIM: Ten percent of soft tissue sarcomas (STS) arise in the retroperitoneal tissues. The prognosis for patients with retroperitoneal sarcoma is poor with a 5-year survival rate between 12% and 70%. Stage at presentation, high histological grade, unresectable primary tumour and incomplete resection are associated with a less favourable outcome. METHODS: Complete follow-up data were available on 22 patients who underwent surgery for retroperitoneal STS in our institution between 1990 and 2000. Patient, tumour and treatment variables were analysed including use of adjuvant therapy and survival status. RESULTS: Eighteen patients underwent surgery for primary disease, four patients were treated for recurrent disease or metastases. Ten patients presented with pain, seven with an abdominal mass, other presentation included weight loss and haematuria. Thirteen patients presented with tumours larger than 10 cm. The tumours were seven liposarcomas, six leiomyosarcomas, three malignant fibrous histiocytomas, two rhabdomyosarcomas, two malignant schwannomas and two undifferentiated sarcomas. Six primary tumours were completely excised, five patients received radiotherapy and five received chemotherapy. Local recurrence rate was 45% and recurrence-free interval for 10 patients with recurrence was 11 months. Five patients received radiotherapy and five received chemotherapy. The median survival for patients with primary tumours was 36 months, and 5-year survival was 44%. Adjuvant therapy was not associated with higher survival rates. CONCLUSION: This study re-emphasizes the poor outcome of patients with retroperitoneal STS. Adjuvant radiotherapy and chemotherapy do not appear to be any proven benefit and the single most important prognostic factor is aggressive successful en bloc resection of the primary tumour. Our resection rate and 5-year survival rates are comparable with previous reported UK series although lower than large reports from North American centres. This might partly be explained by difficulty in data collection in a retrospective analysis, but may reflect inadequate subspecialization in UK centres.

Adult↗
PubMed1999

beta-catenin expression in primary and metastatic colorectal carcinoma.

beta-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin-catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or beta-catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of beta-catenin. In this study, we examined beta-catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous beta-catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of beta-catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of beta-catenin expression and either tumor stage or tumor grade. Cellular distribution of beta-catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced beta-catenin in the cytoskeletal fraction and increased beta-catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated beta-catenin protein of approximately M(r) 80,000. Immunoprecipitation studies showed that the truncated beta-catenin proteins only bound weakly to E-cadherin and beta-catenin compared with non-truncated beta-catenin. These results demonstrate gross alterations in the cellular distribution of beta-catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or beta-catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex.

Adult↗
PubMed1999

Cadherin-catenin expression in primary colorectal cancer: a survival analysis.

Both cell adhesion and cell signalling events are mediated by components of the cadherin-catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin-catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, alpha-catenin and beta-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of beta-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous alpha-catenin expression significantly correlated with tumour de-differentiation (P = 0.009). There was a trend towards an association between advanced tumour stage and loss of membranous expression of alpha-catenin or beta-catenin, although these associations were not statistically significant. Univariate analysis revealed that advanced Dukes' stage, tumour de-differentiation, loss of membranous beta-catenin expression, cytoplasmic beta-catenin expression and widespread nuclear expression of beta-catenin all correlated with short survival following apparently curative resection of the primary tumour. However, only Dukes' stage (P = 0.002), tumour grade (P = 0.02) and widespread nuclear expression of beta-catenin (P = 0.002) were independent predictors of short survival. Disturbed growth signalling events in colorectal tumours are thought to result in nuclear accumulation of beta-catenin. Consequently, tumours with widespread nuclear expression of beta-catenin are likely to have severely abnormal growth characteristics, and which therefore might be predictive of short survival in these patients.

Cadherins↗
PubMed1997

Invasion of human colorectal carcinoma cells is promoted by endogenous basic fibroblast growth factor.

The growth-stimulatory and invasion-promoting effects of basic fibroblast growth factor (bFGF) were examined in 2 series of related human colon carcinoma cell lines (HCT116A, HCT116B and 20-10-1 as well as and LS180, LS174T and ARK1A) that exhibit different invasive potentials. The invasive cell lines 20-10-1 and ARK1A grew more rapidly than their non-invasive counterparts; exogenously added bFGF stimulated the proliferation of all the cells. When extracts of the cells were fractionated on columns of heparin-Sepharose, bFGF-like activity was found in extracts from each cell line. The amount of bFGF-like growth-stimulatory activity was greater in the more invasive cells: the invasive cells 20-10-1 contained 35-fold more activity than the non-invasive HCT116A cells, and the ARK1A cells contained 15-fold more activity than LS180 cells. Relatively small amounts of bFGF-like activity were recovered from medium conditioned by the invasive cells. The bFGF-like growth-stimulatory activity from the cell extracts was neutralised by an antibody to bFGF, and immunoblotting revealed the presence of an 18 kDa immunoreactive polypeptide, consistent with the presence of bFGF in the cell extracts. Exogenously added bFGF caused the usually non-invasive HCT116A cells to invade collagen gels. The HCT116B and 20-10-1 cells that were naturally invasive in a collagen gel assay also showed increased levels of invasiveness in the presence of bFGF, but an antibody that neutralised the activity of bFGF reduced the constitutive invasiveness of these cells. Our results suggest a causal relationship between the endogenous production of bFGF and the invasive potential of human colon carcinoma cells.

Adenocarcinoma↗
PubMed1997

Management strategies for colorectal liver metastases--Part I.

Colorectal cancer is a common malignancy and the incidence of this disease is increasing. Approximately 50% of patients with colorectal cancer die from recurrent disease following an apparently curative resection of the primary tumour and the liver is the most frequent site of relapse. Although only a small proportion of patients will benefit from resection of liver metastases, this form of treatment offers the only possibility of cure. In selected patients, 5-year survival rates of 25-35% may be achieved following liver resection. A poor prognosis after resection of hepatic metastases is likely when there are more than three metastatic deposits, involved resection margins often as a result of ¿wedge' resections, when there is extrahepatic disease, or when there is nodal involvement at the primary tumour site. Regional hepatic artery infusion chemotherapy may provide palliation and possibly even prolongation of survival for some patients with unresectable metastases. Cytoreductive techniques may also provide palliation in selected patients with hepatic metastases unsuitable for resection; cryotherapy is the most promising of these methods.

Clinical Trials as Topic↗
PubMed1997

Management strategies for colorectal liver metastases--Part II.

Liver metastases are relatively common in colorectal cancer and a small proportion of patients may benefit from resection of these liver metastases. In a selected subgroup of patients, 5-year survival rates of 25-35% may be achieved following liver resection. These survival figures compare favourably with those of patients with untreated liver secondaries. In the second part of this review the surgical and non-surgical treatment options for treating colorectal liver metastases are examined in detail.

Adult↗