27 research outputs found

    Staged celiac artery resection with pancreatosplenectomy (SCARPS) - a novel approach to pancreatic cancer encasing celiac axis trunk robotically

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    To avoid hepatobiliary and gastric ischaemia related directly to Appleby and Kondo’s procedures, a novel SCARPS procedure (Staged Celiac Artery Resection with PancreatoSplenectomy) for resection of pancreatic cancer involving celiac axis trunk is described here. A 67-year-old female with biopsy proven Pancreatic Ductal Adenocarcinoma (PDAC) encasing celiac and common hepatic artery underwent two stage robotic operation with Da Vinci Xi following 12 cycles of neoadjuvant FOLFIRINOX and 45 Gy chemoradiation. Stage 1 consisted of diagnostic laparoscopy and ligation of Common Hepatic Artery (CHA) after a trial of vascular clamping with real time assessment of hepatic artery flow using laparoscopic / robotic intraoperative doppler ultrasound and stage 2 resection of celiac axis trunk and CHA with pancreatosplenectomy 2 weeks after stage 1 following a repeat CT abdomen/pancreas. Both procedures were performed robotically. Hepatic Artery Resistive Index (HARI) increased to 0.8 after ligation of CHA with preserved forward flows. The operative time was 80 min and 240 min for stage 1 and 2 respectively with minimal blood loss without perioperative blood transfusion. SCARPS offers a safe ligation of CHA following an intraoperative assessment of disease status and a real-time hepatic haemodynamic study prior to major pancreatosplenectomy with celiac axis trunk resection. Furthermore, it is described fervently as a minimally invasive approach to resection of pancreatic cancer with vascular involvement to benefit patients directly for quick recovery

    Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision

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    Background Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1–2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84–99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. Methods Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. Findings Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67–80] vs 65 years [61–71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6–12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. Interpretation The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. Funding Cancer Research UK

    The diagnostic accuracy of (18) F-FGD-PET/CT for cancer of the gallbladder: a retrospective study

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    Background Gallbladder cancer has a poor prognosis and imaging can have variable diagnostic accuracy. We assessed the ability of preoperative 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) imaging to predict a postoperative histological diagnosis of gallbladder cancer. Method A retrospective analysis was undertaken in a cohort of patients, who had suspected gallbladder cancer on cross-sectional imaging and that underwent preoperative FDG-PET/CT scan. The discriminatory power of FDG-PET/CT was determined in receiver operator characteristic (ROC) analysis and diagnostic accuracy parameters were estimated at different thresholds of maximum standard unit value (SUVmax). Results Twenty-two patients were included in the study; 7 had malignant and 15 benign diagnoses. There was no statistically significant difference between the measured SUVmax between the two groups (p = 0.71). With an area under the curve of 0.486, the ROC curve did not indicate any discriminatory power of FDG-PET/CT at any potential threshold of SUVmax. Conclusion This study indicates that the diagnosis of primary gallbladder cancer cannot be accurately confirmed with FDG PET/CT scanning

    Interobserver variation in the classification of tumor deposits in rectal cancer – is the use of histopathological characteristics the way to go?

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    The focus on lymph node metastases (LNM) as the most important prognostic marker in colorectal cancer (CRC) has been challenged by the finding that other types of locoregional spread, including tumor deposits (TDs), extramural venous invasion (EMVI), and perineural invasion (PNI), also have significant impact. However, there are concerns about interobserver variation when differentiating between these features. Therefore, this study analyzed interobserver agreement between pathologists when assessing routine tumor nodules based on TNM 8. Electronic slides of 50 tumor nodules that were not treated with neoadjuvant therapy were reviewed by 8 gastrointestinal pathologists. They were asked to classify each nodule as TD, LNM, EMVI, or PNI, and to list which histological discriminatory features were present. There was overall agreement of 73.5% (κ 0.38, 95%-CI 0.33–0.43) if a nodal versus non-nodal classification was used, and 52.2% (κ 0.27, 95%-CI 0.23–0.31) if EMVI and PNI were classified separately. The interobserver agreement varied significantly between discriminatory features from κ 0.64 (95%-CI 0.58–0.70) for roundness to κ 0.26 (95%-CI 0.12–0.41) for a lone arteriole sign, and the presence of discriminatory features did not always correlate with the final classification. Since extranodal pathways of spread are prognostically relevant, classification of tumor nodules is important. There is currently no evidence for the prognostic relevance of the origin of TD, and although some histopathological characteristics showed good interobserver agreement, these are often non-specific. To optimize interobserver agreement, we recommend a binary classification of nodal versus extranodal tumor nodules which is based on prognostic evidence and yields good overall agreement

    The Mutational Concordance of Fixed Formalin Paraffin Embedded and Fresh Frozen Gastro-Oesophageal Tumours Using Whole Exome Sequencing.

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    1.Background The application of massively parallel sequencing has led to the identification of aberrant druggable pathways and somatic mutations within therapeutically relevant genes in gastro-oesophageal cancer. Given the widespread use of formalin-fixed paraffin-embedded (FFPE) samples in the study of this disease, it would be beneficial, especially for the purposes of biomarker evaluation, to assess the concordance between comprehensive exome-wide sequencing data from archival FFPE samples originating from a prospective clinical study and those derived from fresh-frozen material. 2.Methods We analysed whole-exome sequencing data to define the mutational concordance of 16 matched fresh-frozen and FFPE gastro-oesophageal tumours (N = 32) from a prospective clinical study. We assessed DNA integrity prior to sequencing and then identified coding mutations in genes that have previously been implicated in other cancers. In addition, we calculated the mutant-allele heterogeneity (MATH) for these samples. 3.Results Although there was increased degradation of DNA in FFPE samples compared with frozen samples, sequencing data from only two FFPE samples failed to reach an adequate mapping quality threshold. Using a filtering threshold of mutant read counts of at least ten and a minimum of 5% variant allele frequency (VAF) we found that there was a high median mutational concordance of 97% (range 80.1-98.68%) between fresh-frozen and FFPE gastro-oesophageal tumour-derived exomes. However, the majority of FFPE tumours had higher mutant-allele heterogeneity (MATH) scores when compared with corresponding frozen tumours (p < 0.001), suggesting that FFPE-based exome sequencing is likely to over-represent tumour heterogeneity in FFPE samples compared to fresh-frozen samples. Furthermore, we identified coding mutations in 120 cancer-related genes, including those associated with chromatin remodelling and Wnt/β-catenin and Receptor Tyrosine Kinase signalling. 4.Conclusions These data suggest that comprehensive genomic data can be generated from exome sequencing of selected DNA samples extracted from archival FFPE gastro-oesophageal tumour tissues within the context of prospective clinical trials

    Interobserver variation in the classification of tumor deposits in rectal cancer-is the use of histopathological characteristics the way to go?

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    The focus on lymph node metastases (LNM) as the most important prognostic marker in colorectal cancer (CRC) has been challenged by the finding that other types of locoregional spread, including tumor deposits (TDs), extramural venous invasion (EMVI), and perineural invasion (PNI), also have significant impact. However, there are concerns about interobserver variation when differentiating between these features. Therefore, this study analyzed interobserver agreement between pathologists when assessing routine tumor nodules based on TNM 8. Electronic slides of 50 tumor nodules that were not treated with neoadjuvant therapy were reviewed by 8 gastrointestinal pathologists. They were asked to classify each nodule as TD, LNM, EMVI, or PNI, and to list which histological discriminatory features were present. There was overall agreement of 73.5% (κ 0.38, 95%-CI 0.33–0.43) if a nodal versus non-nodal classification was used, and 52.2% (κ 0.27, 95%-CI 0.23–0.31) if EMVI and PNI were classified separately. The interobserver agreement varied significantly between discriminatory features from κ 0.64 (95%-CI 0.58–0.70) for roundness to κ 0.26 (95%-CI 0.12–0.41) for a lone arteriole sign, and the presence of discriminatory features did not always correlate with the final classification. Since extranodal pathways of spread are prognostically relevant, classification of tumor nodules is important. There is currently no evidence for the prognostic relevance of the origin of TD, and although some histopathological characteristics showed good interobserver agreement, these are often non-specific. To optimize interobserver agreement, we recommend a binary classification of nodal versus extranodal tumor nodules which is based on prognostic evidence and yields good overall agreement

    Can extranodal tumour deposits be diagnosed on MRI? Protocol for a multicentre clinical trial (The COMET Trial)

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    Introduction: Tumour deposits (TDs) are a poor prognostic marker when seen on pathology, and are worse than lymph node metastases (LNM). They are now being reported on Magnetic resonance imaging (MRI) as discontinuous nodules of extramural venous invasion but this diagnosis has not been validated and it is unclear how it correlates with the diagnosis of TDs on pathology. Methods and analysis: This is a prospective interventional clinical trial which aims to directly map the location of TDs on MRI and correlate what is seen on MRI with the pathology findings at each location. All patients with rectal cancer undergoing resectional surgery are eligible (including those undergoing pre-operative therapy) The primary outcome is the prevalence of TDs seen on pathology. Secondary outcomes are to assess radiological and pathological interobserver agreement, assess the effect of TDs on prognosis and carry out exploratory work looking at differences between TDs and LNMs. The estimated sample size is 100 to detect a 2 fold increase in the pathological diagnosis of TD when MRI mapping is used. Ethics and dissemination: Ethical approval has been granted from the South Central – Hampshire B Research and Ethics Committee (IRAS 217627). The study will be carried out under standard operative procedures within the Royal Marsden Hospital Registration details: Registered on Clinicaltrials.gov NCT0330354

    Ex-vivo specimen MRI and pathology confirm a recto-sigmoid mesenteric waist at the junction of the mesorectum and mesocolon

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    Introduction: Continuity of the mesentery has recently been established and may provide an anatomical basis for optimal colorectal resectional surgery. Preliminary data from operative specimen measurements suggests there is a tapering in the mesentery of the distal sigmoid. A mesenteric waist in this area may be a risk factor for local recurrence of colorectal cancer. This study aimed to investigate the anatomical characteristics of the mesentery at the colorectal junction. Methods: In this cross‐sectional study, 20 patients were recruited. After planned colorectal resection, the surgical specimens were scanned in a magnetic resonance imaging (MRI) system, and subsequently dissected and photographed as per national pathology guidelines. Mesenteric surface area and linear measurements were compared on MRI and pathology to establish the presence and location of a mesenteric waist. Results: Specimen analysis confirmed that a narrowing in mesenteric surface area was consistently apparent at the rectosigmoid junction. Above the anterior peritoneal reflection, the surface area and posterior distance of the mesentery of the upper rectum initially decreased before increasing as the mesentery of the sigmoid colon. These anatomical properties created the appearance of a mesenteric “waist” at the rectosigmoid junction. Using the anterior reflection as a reference landmark, the rectosigmoid waist occurred at a mean height of 23.6mm and 21.7mm on MRI and pathology respectively. Conclusion: A rectosigmoid waist occurs at the junction of the mesorectum and mesocolon, and is a mesenteric landmark for the rectum that is present on both radiology and pathology
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