Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

Background Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. Methods Observational retrospective multicenter study. Inclusion criteria: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. Results Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. Conclusion It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here (AU)

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

Retroperitoneal soft-tissue sarcomas: Radiotherapy experience from a tertiary cancer center and review of current evidence.

BACKGROUND: Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy. PATIENTS AND METHODS: We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months (2-114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2. CONCLUSIONS: Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.

Robotic versus laparoscopic surgery for rectal cancer: a comparative cost-effectiveness study.

BACKGROUND: The differences between the costs of robotic rectal resection and of the laparoscopic approach are still not well known. The aim of this study was to evaluate the cost-effectiveness of robotic versus laparoscopic surgery. METHODS: We conducted an observational, comparative, prospective, non-randomized study on patients having laparoscopic and robotic rectal resection between February 2014 and March 2018 at the Sanchinarro University Hospital, Madrid. Outcome parameters included surgical and post-operative costs, quality adjusted life years (QALY) and incremental cost per QALY gained or the incremental cost effectiveness ratio (ICER). The primary endpoint was to compare cost effectiveness in the robotic and laparoscopic surgery groups. A willingness-to-pay of 20,000€ and 30,000€ per QALY was used as a threshold to determine the most cost-effective treatment. RESULTS: A total of 81 RRR and 104 LRR were included. The mean operative costs were higher for RRR (4307.09€ versus 3834.58€; p = 0.04), although mean overall costs were similar (7272.03€ for RRR and 6968.63€ for the LLR; p = 0.44). Mean QALYs at 1 year for the RRR group (0.8482) was higher than that associated with LRR (0.6532) (p = 0.018). At a willingness-to-pay threshold of 20,000€ and 30,000€ there was a 95.54% and 97.18% probability, respectively, that RRR was more cost-effective than LRR. CONCLUSIONS: Our data regarding the cost-effectiveness of RRR versus LRR shows a benefit for RRR.

A prospective observational study of the clinical and pathological impact of stereotactic body radiotherapy (SBRT) as a neoadjuvant strategy of chemoradiation in pancreatic cancer.

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.

Robotic-assisted gastrectomy compared with open resection: a comparative study of clinical outcomes and cost-effectiveness analysis.

In the last decade, there have clearly been important changes in the surgical approach of gastric cancer treatment due to an increased interest in the minimally invasive surgical approach (MIS). The higher cost of robotic surgery procedures remains an important issue of debate. The objective of the study is to compare the main operative and clinical outcomes and to assess the incremental cost-effectiveness ratios (ICERs) of the two techniques. This is a prospective cost-effectiveness and clinical study when comparing the robotic gastrectomy (RG) technique with open gastrectomy (OG) in gastric cancer. Outcome parameters included surgical and post-operative costs, quality-adjusted life years (QALY) and incremental cost per QALY gained or the incremental cost-effectiveness ratio (ICER). The incremental utility was 0.038 QALYs and the estimated ICER for patients was dominated by robotic approach. The probability that the robotic approach was cost effective was 94.04% and 94.20%, respectively, at a WTP threshold of 20,000€ and 30,000€ per QALY gained. RG for gastric cancer represents a cost-effective procedure compared with the standard OG.

First case of complete full robotic surgical resection of leiomyosarcoma of the right renal vein.

BACKGROUND: Leiomyosarcomas present high postoperative morbidity and poor prognosis [1]. In the literature, only few cases of localized small leiomyosarcoma have been described [2, 3]. These cases might benefit from a minimally invasive approach. Robotic surgery has been claimed to have several advantages over laparoscopy such as enhanced vision and instruments movements which might make more feasible the execution of this type of surgery where partial renal resection is required. METHODS: A 53-year-old female with a medical history of myeloid leukemia and with chronic renal failure (creatinine: 2.6) was referred to our hospital for an incidental finding of right perirenal tumor of almost 3 cm compatible with leiomyosarcoma arising from the right renal vein. RESULTS: The operation was performed using a Da Vinci Robotic Surgical System model Si (Intuitive Surgical, Sunnyvale, CA, USA).Robotic ports were placed in a standard configuration for minimally invasive right nephrectomy. The dissection started with the partial mobilization of the right liver and Kocher maneuver. After the identification of the inferior vena cava the tumor was finally localized and dissected. Resection ended with a partial right vein resection and suture. Pathological final exam confirmed the diagnosis with margins free from tumor. CONCLUSIONS: In selected cases, robotic resection of leiomyosarcoma might be a safe and feasible procedure in experienced hands.

Robotic versus laparoscopic surgery for rectal cancer: a comparative study of clinical outcomes and costs.

PURPOSE: The costs involved in performing robotic surgery present a critical issue which has not been well addressed yet. The aims of this study are to compare the clinical outcomes and cost differences of robotic versus laparoscopic surgery in the treatment of rectal cancer and to conduct a literature review of the cost analysis. METHODS: This is an observational, comparative study whereby data were abstracted from a retrospective database of patients who underwent laparoscopic and robotic rectal resection from October 2010 to March 2017, at Sanchinarro University Hospital, Madrid. An independent company performed the financial analysis, and fixed costs were excluded. RESULTS: A total of 86 robotic and 112 laparoscopic rectal resections were included. The mean operative time was significantly lower in the laparoscopic approach (336 versus 283 min; p = 0.001). The main pre-operative data, overall morbidity, hospital stay and oncological outcomes were similar in both groups, except for the readmission rate (robotic: 5.8%, laparoscopic: 11.6%; p = 0.001). The mean operative costs were higher for robotic surgery (4285.16 versus 3506.11€; p = 0.04); however, the mean overall costs were similar (7279.31€ for robotic and 6879.8€ for the laparoscopic approach; p = 0.44). We found four studies reporting costs, three comparing robotic versus laparoscopy costs, with all of them reporting a higher overall cost for the robotic rectal resection. CONCLUSION: Robotic rectal resection has similar clinical outcomes to that of the conventional laparoscopic approach. Despite the higher operative costs of robotic rectal resection, overall mean costs were similar in our series.

Total pancreatoduodenectomy en bloc with superior mesenteric artery and vein resection after gemcitabine and nab-paclitaxel neoadjuvancy.

BACKGROUND: Pancreatectomy for locally advanced adenocarcinoma affecting the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) is still under discussion [1]. However, in selected cases, in light of the advancement of recent neoadjuvant treatments, it must be taken into account [2,3]. This video demonstrates some of the technical aspects of SMA and SMV resection as well as some tips of vascular reconstruction. METHODS: A 48-year-old man with a large adenocarcinoma of the uncinated process affecting the SMA and SMV underwent 3 cycles of gemcitabine and nab-paclitaxel neoadjuvancy. Post chemotherapy studies showed no disease progression with a normalization of CA 19.9 and SUV of FDG PET CT scan and a downsizing of the tumor, as well. Therefore, an en bloc total spleno-pancreato-duodenectomy with resection of SMA and SMV was planned. RESULTS: Through a bilateral subcostal incision, an "arterial first approach" [3] was performed. Considering the large length of the vascular resection, the replacement of the resected SMA and SMV was performed using two PTFE grafts, as showed in the video. Postoperative pathology showed margins free from disease with an important pathological response (grade 2 of Ryan classification adapted from rectal cancer) [4]. The post-operative course was uneventful and the patient is still free from disease at 31 months from surgery. CONCLUSIONS: This case is part of a large experience our group have acquired since we started neoadjuvancy in 2010. In our experience, we gathered 25 cases of locally advanced pancreatic tumors, of which 12 underwent to pancreatic resection after good response to the neoadjuvant treatment. In 5 of them concomitant SMA and SMV resection was required and post-operative mortality occurred in 1 of them. Morbidities and mortalities are higher compared with standard pancreatectomies, specially related to the vascular reconstruction (bleeding, graft thrombosis) [5]. However, in some circumstances like young age, great radiological and biological response to neoadjuvancy (such as the case herein presented), surgery might be considered the best option of care providing the only possibility to increase survival for these types of locally advanced tumors. However, further studies are needed to know which patients might benefit from this approach. En bloc total spleno-pancreato-duodenectomy with resection of SMA and SMV might be considered as an effective procedure in selected cases of pancreatic adenocarcinoma with good response to preoperative treatment.

Predictive prognostic value of local and distant recurrence of F-fluorodeoxyglucose positron emission tomography for pancreatic neuroendocrine tumors with reference to World Health Organization classifications (2004, 2010). Case series study.

BACKGROUND: F-flurodeoxyglucose positron emission tomography (FDG-PET) have been claimed to be an important prognostic tool in different malignancies. However, its predictive prognostic value on pancreatic neuroendocrine tumors (PNETs) is still under investigation. AIM: We study the prognostic impact of FDG-PET scan in neuroendocrine pancreatic tumors. METHODOLOGY: Between 2007 and 2012, 26 patients with no metastastatic histologically confirmed PNETs (mean age: 57 years) were examined with FDG-PET. We studied its captation in relation with the well established hystopathological prognostic markers assessed in the tumoral resected specimen according to the WHO 2004 and ENETS/WHO 2010 classification. RESULTS: FDG-PET captation was positive in 17 cases (65.4%). The median follow-up period was 34.4 months and recurrences occurred in 4 cases (15.4%). We found a significant correlation between this captation and Ki 67 index (p = 0.032), mitotic index (p = 0.002), tumor grade (p = 0.017) and tumor size (p = 0.01). CONCLUSIONS: FDG-PET provides a good prognostic value for PNETs. Present results must be further validated with larger sample studies.

First ALPPS procedure using a total robotic approach.

BACKGROUND: ALPPS procedure is gaining interest. Indications and technical aspects of this technique are still under debate [1]. Only 4 totally laparoscopic ALPPS procedures have been described in the literature and none by robotic approach [2-4]. This video demonstrates the technical aspects of totally robotic ALPPS. METHODS: A 58 year old man with sigmoid adenocarcinoma with multiple right liver metastases extended to segment IV and I underwent Xelox and 5 Fluoro-uracil neoadjuvancy. Preoperative CT volumetric scan showed a FLR/TLV (Future Liver Remnant/Total Liver Volume) of 28%. ALPPS totally robotic procedure was planned using the DaVinci Si. RESULTS: Tumor resection from the FLR (including segment I) is followed by parenchymal transection between the FLR and the diseased part of the liver with concomitant right portal vein ligation. Small branches to segment IV from left portal vein have been resected along the round ligament, at this step. The right biliary tract was resected as it was partially debilitated after its dissection as partially encircled by a metastasis at segment IV. Second stage was performed totally robotic on 13th postoperative days with a FLR/TLV of 40%. No strong adherences are found, making this stage much easer than open approach. During this step, right hepatic artery and right supra hepatic vein are resected. Finally, the specimen was retrieved inside a plastic bag through a Pfannenstiel incision. Postoperative pathology showed margins free from disease. CONCLUSIONS: ALPPS procedure performed by robotic approach could be a safe and feasible technique in experienced centers with advanced robotic skills.

Preoperative treatment with gemcitabine plus nab-paclitaxel is a safe and effective chemotherapy for pancreatic adenocarcinoma.

INTRODUCTION: Recently, novel chemotherapeutic agents like nab-paclitaxel and gemcitabine demonstrated a survival benefit over gemcitabine alone in metastatic pancreatic cancer. However, there are limited clinical results using this chemotherapy in potentially resectable pancreatic adenocarcinoma. Our aim is to report the oncological results of patients affected by potentially resectable pancreatic adenocarcinoma that underwent surgery after a combination of gemcitabine and nab-paclitaxel. METHODS: A total of 25 patients have been included. We evaluated: (1) Drug toxicity; (2) tumoral response (tumoral size at CT scan, SUV of FDG PET-CT scan and CA 19.9; (3) resection rate; (4) R0 resection rate and histopathological response and (5) survival and disease free survival. RESULTS: Overall treatment was well tolerated. Treatment resulted in a statistical decrease of CA19-9 (p = 0.019) tumoral size (p = 0.04) and SUV (p = 0.004). The resection rate was 68% (17/25 patients). All specimens were R0 and 13 of 17 specimens had major pathological regressions (complete and important response). Median survival and medial disease free survival of patients that underwent surgery was 21 months and 19 months, respectively at a mean follow up of 38.5 months. CONCLUSIONS: This data suggests that nab-paclitaxel and gemcitabine is a safe and effective neoadjuvant treatment for potentially resectable pancreatic adenocarcinoma. This promising data should be confirmed in larger, randomized studies.

Is "small for size syndrome" a relatively new complication after the ALPPS procedure?

Aim of this study is to assess the incidence and outcome of small for size syndrome after ALPPS procedure. This novel procedure is claimed to induce accelerated and increased growth of future liver remnant after major hepatectomies. We prospectively collected data on nine consecutive patients undergoing ALPPS procedure at our center. Main patients' characteristics, outcome and postoperative complications, including small for size syndrome were analyzed. Main interval between two stages of ALPPS was 15.1 days. Mean future liver remnant hypertrophy was 93.2%. Severe complications occurred in 44.4% of patients and mortality occurred in two cases (22.2%). Small for size syndrome occurred in two cases (22.2%). The first one was detected intraoperatively during first stage. It was successfully managed by spleno-renal venous shunt. Second case was not promptly detected and died on postoperative day 64. This case series provides evidence that SFFS can be an important complication after ALPPS procedure. If it is not promptly detected and properly managed it can be a cause of death as occurred in our case.

An organizational model to improve the robotic system among general surgeons.

INTRODUCTION: Robotic surgery has gained wide acceptance in recent years. However its development is slower and the lack of high level experience with this technique is an important limitation. This manuscript discusses some of the reasons of it and aims to describe the organizational system we have progressively established in our center in order to improve the development of Robotic program in our surgical area. METHODS: Some points may be required to improve the robotic program development in a general surgical department, including: a broad availability of robotic system in a surgical area; an ideal setting area with mainly oncological and hepato-biliary-pancreatic disease; the need of a mainly young team; a broad application of the robotic system in more general surgical fields; a high motivation on robotic use; a departmental and institutional economical effort. We have tried to achieve these goals before starting the robotic program in our department at October 2010. RESULTS: From October 2010 until November 2013 a total of 170 procedures have been performed, 92% of them for malignant diseases. Conversion rate and overall morbidity was 5% and 19%, respectively. CONCLUSIONS: The organizational model defined in our center is facilitating the constant and progressive development of the robotic program. A broad and flexible availability of the robotic system, a progressive increase of young surgeons joining this technology as well as the institutional and departmental economical effort are the points with which the robotic system may increase its development in a surgical department.

Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.

A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer.

A high throughput screening for anticancer activity of FDA approved drugs identified mycophenolic acid (MPA), an inhibitor of inositol monophosphate dehydrogenase (IMPDH) as an active agent with an antiangiogenesis mode of action. Exposure of pancreatic cancer cell lines to MPA resulted in growth inhibition and reduced the expression of VEGF that was reversed by supplementing the media with guanosine supporting and IMPDH-dependant mechanism. In preclinical in vivo study, MPA showed a moderate inhibition of tumor growth in a panel of 6 human derived pancreatic cancer xenografts but reduced the expression of VEGF. To investigate the effects of MPA in human pancreatic cancer, a total of 12 patients with resectable pancreatic cancer (PDA) received increasing doses of mycophenolate mofetil (MMF) in cohorts of 6 patients each from 5-15 days prior to surgical resection. Treatment was well tolerated with one episode of grade 1 muscle pain, one episode of grade 2 lymphopenia (2 gr/day dose) and one episode of grade 2 elevantion in LFT (all in the 2 gr./day dose). Patients recovered from surgery uneventfully with no increased post-operative complications. Assessment of CD31, VEGF, and TUNEL in resected specimens compared to a non treated control of 6 patients showed no significant variations in any of the study endpoints. In conclusion, this study shows the feasibility of translating a preclinical observation to the clinical setting and to explore a drug mechanism of action in patients. MPA, however, did not show any hints of antiangiogenesis of anticancer clinical activity questioning if this agent should be further developed in PDA.