What are the true benefits of robotic pancreaticoduodenectomy for patients with pancreatic cancer?

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, and multimodal treatment including high-quality surgery can improve survival outcomes. Pancreaticoduodenectomy (PD) has evolved with minimally invasive approaches including the implementation of robotic PD (RPD). In this special report, we review the literature whilst evaluating the 'true benefits' of RPD compared to open approach for the treatment of PDAC. AREAS COVERED: We have performed a mini-review of studies assessing PD approaches and compared intraoperative characteristics, perioperative outcomes, post-operative complications and oncological outcomes. EXPERT OPINION: RPD was associated with similar or longer operative times, and reduced intra-operative blood loss. Perioperative pain scores were significantly lower with shorter lengths of stay with the robotic approach. With regards to post-operative complications, post-operative pancreatic fistula rates were similar, with lower rates of clinically relevant fistulas after RPD. Oncological outcomes were comparable or superior in terms of margin status, lymph node harvest, time to chemotherapy and survival between RPD and OPD. In conclusion, RPD allows safe implementation of minimally invasive PD. The current literature shows that RPD is either equivalent, or superior in certain aspects to OPD. Once more centers gain sufficient experience, RPD is likely to demonstrate clear superiority over alternative approaches.

Which patients benefit from preoperative biliary drainage in resectable pancreatic cancer?

Recent studies have indicated that preoperative biliary drainage (PBD) should not be routinely performed in all patients suffering from obstructive jaundice before pancreatic surgery. The severity of jaundice that mandates PBD has yet to be defined. The evaluated paper examines the impact of PBD on intra-operative, and post-operative outcomes in patients initially presenting with severe obstructive jaundice (bilirubin ≥250 µmol/L). In this key paper evaluation, the impact of PBD versus a direct surgery (DS) approach is discussed. The arguments for and against each approach are considered with regards to drainage associated morbidity and mortality, resection rates, survival and the impact of chemotherapy and malnutrition. Concentrating on resectable head of pancreas tumors, this mini-review aims to scrutinize the authors' recommendations, alongside those of prominent papers in the field.

Transition from open and laparoscopic to robotic pancreaticoduodenectomy in a UK tertiary referral hepatobiliary and pancreatic centre - Early experience of robotic pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy is performed using an open technique (OPD) as the gold standard. An increase in those performed laparoscopically (LPD) and robotically (RPD) are now reported. We compared the short-term outcomes of RPD cases with LPD and OPD. METHODS: A retrospective review of a prospectively collected database was undertaken of our first consecutive RPD, our first LPD and consecutive OPD cases. Those requiring venous and/or arterial resection were excluded. RESULTS: RPD (n = 25) had longer median operating times (461 (IQR 358-564) mins) than LPD (n = 41) (330 (IQR 262.5-397.5) mins) and OPD (n = 37) (330 (IQR 257-403) mins, p < 0.0001). Estimated blood loss and transfusion requirement was less after RPD and LPD compared to OPD (p = 0.012 and p < 0.0001 respectively). No RPD cases required conversion to open operation compared to 24.4% of LPD. Morbidity was comparable with a Clavien Dindo score ≥3 in 20.00%, 24.39% and 18.92% for RPD, LPD and OPD respectively (p = 0.83). Post-operative pancreatic fistula rates were seen in 16.00%, 29.27% and 21.62% of our RPD, LPD and OPD cohorts respectively (p = 0.81). 90-day mortality was seen in 0.97% of the total cohort. Length of hospital stay (LOS) was shorter for RPD compared to both LPD (p = 0.030) and OPD (p = 0.002). CONCLUSION: RPD is safe to perform with comparable outcomes to LPD and OPD. Further evidence is provided that a randomised controlled trial for PD techniques is required.

Oncolytic vaccinia virus combined with radiotherapy induces apoptotic cell death in sarcoma cells by down-regulating the inhibitors of apoptosis.

Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity. This effect was not due to increased viral replication, but mediated through induction of intrinsic apoptosis. GLV-1h68 therapy downregulated the anti-apoptotic BCL-2 proteins (MCL-1 and BCL-XL) and the downstream inhibitors of apoptosis, resulting in cleavage of effector caspases 3 and 7. In an in vivo ILP model, the combination of OV and radiotherapy significantly delayed tumour growth and prolonged survival compared to single agent therapy. These data suggest that the virally-mediated down-regulation of anti-apoptotic proteins may increase the sensitivity of tumour cells to the cytotoxic effects of ionizing radiation. Oncolytic virotherapy represents an exciting candidate for clinical development when delivered by ILP. Its ability to overcome anti-apoptotic signals within tumour cells points the way to further development in combination with conventional anti-cancer therapies.

A totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy assisted with radiofrequency (radiofrequency assisted liver partition with portal vein ligation) for staged liver resection.

In order to induce liver hypertrophy to enable liver resection in patients with a small future liver remnant (FLR), various methods have been proposed in addition to portal vein embolisation (PVE). Most recently, the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has gained significant international interest. This technique is limited by the high morbidity associated with an in situ liver splitting and the patient undergoing two open operations. We present the case of a variant ALPPS technique performed entirely laparoscopically with no major morbidity or mortality. An increased liver volume of 57.9% was seen after 14 days. This technique is feasible to perform and compares favourably to other ALPPS methods whilst gaining the advantages of laparoscopic surgery.

Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma.

Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells. An orthotopic model of advanced extremity sarcoma was used to evaluate survival of animals after ILP with combinations of TNF-α, melphalan and GLV-1h68. We investigated the efficiency of viral tumour delivery by ILP compared to intravenous therapy, the locoregional and systemic biodistribution of virus after ILP, and the effect of mode of administration on antibody response. The combination of melphalan and GLV-1h68 was synergistic in vitro. The addition of virus to standard ILP regimens was well tolerated and demonstrated superior tumour targeting compared to intravenous administration. Triple therapy (melphalan/TNF-α/GLV-1h68) resulted in increased tumour growth delay and enhanced survival compared to other treatment regimens. Live virus was recovered in large amounts from perfused regions, but in smaller amounts from systemic organs. The addition of oncolytic vaccinia virus to existing TNF-α/melphalan-based ILP strategies results in survival advantage in an immunocompetent rat model of advanced extremity sarcoma. Virus administered by ILP has superior tumour targeting compared to intravenous delivery. Further evaluation and clinical translation of this approach is warranted.

Does the two-week rule pathway improve the diagnosis of soft tissue sarcoma? A retrospective review of referral patterns and outcomes over five years in a regional sarcoma centre.

INTRODUCTION: The NHS Cancer Plan was introduced in 2000 and included guidelines for the rapid assessment and referral of cases of suspected malignancy. We wished to assess the efficiency and appropriateness of patients referred under the Department of Health's general practitioner referral guidelines implemented for sarcomas in December 2000. PATIENTS AND METHODS: A retrospective case-note review was performed of all patients referred to our regional soft tissue sarcoma unit between 1 January 2004 and 31 December 2008. Patients referred under the two-week guidelines and all patients referred routinely were analysed. The main outcome measures were the total number of patients referred on the basis of the two-week guidelines and the proportion they constitute of all referrals. The referring criteria were noted and compared to the observed criteria recorded. The final histological diagnosis of patients referred on the basis of the two-week guidelines are documented. RESULTS: A total of 2746 referrals for suspected sarcoma were made from January 2004 to December 2008. Of these, 154 referrals were made under the two-week rule of which 102 were referred purely on the clinical criteria for suspected soft tissue sarcoma. The remaining patients were referred after non-urgent special investigations indicated the possibility of sarcoma. Twelve patients referred under the two-week rule were proved to have sarcoma, nine after specific investigations including imaging or histological diagnosis. Of the 102 patients referred on clinical suspicion of a sarcoma, two patients had proven soft tissue sarcomas and one patient a cutaneous sarcoma. Between 2004 and 2008, the number of 2-week referrals rose 25-fold but accounted for an increase of less than 1% of the sarcomas treated in this unit. CONCLUSIONS: The numbers of all referrals for suspected sarcoma are increasing; however, the rate of increase of 2-week referrals is increasing faster than routine referrals and will exceed it in 2012 if current trends continue. There has not been a commensurate rise in the detection of sarcoma or, more specifically, diagnosis of the deep sarcomas associated with worse prognosis. Current clinical guidelines have essentially had no impact on the early diagnosis and treatment of soft tissue sarcoma, and may negatively impact on the treatment of patients with proven sarcoma by delaying treatment within a regional centre because of redirection of a large number of patients with benign abnormalities to such centres.