Neoadjuvant tyrosine kinase inhibitors in rectal gastrointestinal stromal tumours: a provision for enhanced oncological and functional outcomes.

BACKGROUND: The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs. METHODS: A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared. RESULTS: Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1-3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group. CONCLUSIONS: Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.

P.R.O.P.S. - A novel Pre-Operative Predictive Score for unresectability in patients with colorectal peritoneal metastases being considered for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Twenty to thirty percent of planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) procedures are abandoned intra-operatively. Pre-operative factors associated with unresectability identified previously were used to develop a Pre-Operative Predictive Score (PROPS), which was compared with current selection criteria-Peritoneal Surface Disease Severity Score (PSDSS), Verwaal's Prognostic Score (PS) and Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), to determine which score provides the best prediction for unresectability. METHODS: Fifty-six patients with peritoneal metastases of colorectal origin were included. Beta-coefficient values of significant variables (p < 0.05) were determined from multivariate analysis to develop PROPS. PROPS, PSDSS, PS and COMPASS were compared using a receiver operating characteristic curve to calculate its accuracy, sensitivity and specificity. RESULTS: PROPS consisted of nine patient and tumour factors which were categorised into three groups: (i) poor tumour biology: previous inadequate resection, underwent multiple lines of chemotherapy and poorly differentiated or signet cell histology; (ii) heavy tumour burden: abdominal distension, palpable abdominal mass and computed tomography findings of ascites, small bowel disease and/or omental thickening; and (iii) active tumour proliferation: elevated tumour markers. Overall, PROPS achieved 86% accuracy with 100% sensitivity and 68% specificity, PSDSS achieved 85% accuracy with 100% sensitivity and 63% specificity, PS achieved 73% accuracy with 100% sensitivity and 68% specificity and COMPASS achieved 61% accuracy with 27% sensitivity and 100% specificity. CONCLUSIONS: PROPS is more effective in predicting unresectability as compared to PSDSS, PS and COMPASS, and has the added advantage of using solely pre-operative factors.

Unresectability during open surgical exploration in planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are the treatment of choice for selected patients with peritoneal metastasis. Despite a stringent selection process, some patients were found to be unresectable only at surgery, which leads to disappointment and poor utilisation of limited infrastructural resources. This study aims to determine the pre-operative factors associated with unresectability in planned CRS and HIPEC. METHODS: Retrospective analysis of 172 consecutive patients eligible for CRS and HIPEC at the National Cancer Centre Singapore from April 2004 to May 2014 was performed. Pre-operative factors (clinical presentation, disease factors, and investigation findings) between the unresectable (13%) and the successful groups (87%) were compared. RESULTS: Patient demographics between the two cohorts were comparable. In terms of clinical presentation, the unresectable group was more likely to present with bloating (p = .00), altered bowel habits (p = .04), abdominal distension (p = .00), palpable abdominal masses (p = .00) and palpable pouch of Douglas nodules (p = .00). Differences were also noted in disease factors with the unresectable group having more high-grade tumours (p = .01), inadequate initial resections (p = .01), progression through chemotherapy (p = .00) and shorter median disease-free intervals (p = .03). In addition, investigations in the unresectable group revealed more patients with elevated tumour markers (p = .01), thrombocytosis (p = .00) and computed tomography findings of ascites (p = .00), omental thickening (p = .00), lymphadenopathy (p = .02) and small bowel disease (p = .00). CONCLUSIONS: Significant factors associated with unresectability that were identified in our study could potentially create a new treatment algorithm and refine current selection process to exclude patients at risk of unresectability in planned CRS and HIPEC.

Type A aortic dissection into brachial artery causing upper limb ischaemia: A case report.

INTRODUCTION: Acute type A aortic dissection (AAAD) is a surgical emergency with high operative mortality. Distal propogration of the dissecting flap can lead to malperfusion of territory supplied by the aorta including axillary and brachial arteries causing ischaemia of the upper limb. CASE PRESENTATION: We present a case of a 67 year old gentleman who had AAAD and developed upper limb malperfusion after repair. Despite adequate repair, the residual dissecting flap propagated distally in the upper arm vasculature causing thombosis of the brachial artery. The patient subsequently underwent brachial artery cut-down and embolectomy but revascularization was not achieved. He ultimately required an above-elbow amputation. CONCLUSION: Upper limb ischaemia from AAAD is a rare phenomenon that is mainly due to malperfusion. Majority of malperfusion resolve after aortic dissection repair. This is an unusual case of persistent upper limb ischaemia despite adequate repair due to the direct extension of the residual dissection flap from the aortic root into the brachial artery.