Robot-assisted pancreaticoduodenectomy. Safety and feasibility

Background: The availability of robotic assistance could make laparoscopic pancreaticoduo- denectomy safely feasible. We herein provide a systematic review on laparoscopic robot-assisted pancreaticoduodenectomy (RAPD). Methods: Literature search was conducted on multiple databases considering articles published in English up to October 31, 2014, reporting on ten or more patients. Results: A total of 262 articles were identified. Excluding duplicates (n=172), studies not matching inclusion criteria (n=77), and studies not suitable for other reasons (n=6), a total of seven studies reporting on 312 RAPDs were eventually reviewed. These studies were either retrospective cohort studies (n=4) or case-matched studies (n=3). No randomized controlled trial was identified. Most patients undergoing RAPD were diagnosed with malignant tumors (224/312; 71.8%). RAPD was feasible in most patients. Conversion to open surgery was reported in 9.2% of the patients. A hybrid RAPD technique, employing standard laparoscopy or open surgery through a mini-incision, was adopted in most patients (178/312; 57.0%). Overall, there were six postoperative deaths at 30 days (6/312; 1.9%), including one intraoperative death caused by portal vein injury, while 137 out of 260 patients with complete information developed postoperative complications (52.7%). The mean length of hospital stay ranged from 10–29 days. Postoperative pancreatic fistula (POPF) occurred in 66 patients (66/312; 21.1%). Grade C POPF was reported in eight patients (8/312; 2.5%). The costs of RAPD were assessed in two studies, demonstrating additional costs ranging from 4,000–5,000 US dollars to 6,193 Euro. The mean number of examined lymph nodes and the rate of positive surgical margins indicate that RAPD could be an appropriate oncologic operation. Conclusion: RAPD is safely feasible. These results were obtained in selected patients and in specialized centers. RAPD should not be implemented in the occasional patient by surgeons without advanced laparoscopic skills and formal training in robotic surgery

Systematic review and metanalysis of clinical outcomes after enucleation of pancreatic metastases from renal cell carcinoma

Introduction: A systematic review of the literature was carried out to determine the clinical and oncological outcome of patients who had enucleation of solitary pancreatic metastases from renal cell carcinoma. Methods: Operative mortality, postoperative complications, observed survival and disease free survival were analyzed. The clinical outcomes of patients who had enucleation were compared to those of 857 patients collected from the literature who had standard or atypical pancreatic resection for the same disease using propensity score matching Results: There was no postoperative mortality in the 56 patients who had enucleation of pancreatic metastases from renal cell carcinoma . In 51 patients postoperative complications could be analyzed. Ten patients (10/51=19.6%) had postoperative complications. Three patients (3/51 = 5.9%) had major complications (Clavien-Dindo III or more). Five year observed survival rates and disease free survival for patients with enucleation were 92% and 79% respectively. These results compared favourably with those obtained in patients who had standard resection and other forms of atypical resection (also using propensity score matching). Patients who had partial pancreatic resection (atypical or not) with pancreatic-jejunal anastomosis had increased rates of postoperative complications and local recurrences. Conclusions: Enucleation of pancreatic metastases offers a valid solution in selected patients

Surgical-only treatment of pancreatic and extra-pancreatic metastases from renal cell carcinoma. Quality of life and survival analysis

Background: Treatment of pancreatic metastases (PM) from renal cell carcinoma (RCC) is still an issue between surgeons and oncologists, in the era of target-therapy. Methods: Data from 26 patients undergoing resection of PM and extra-PM from RCC, with R0 intention were retrospectively analysed. No one received adjuvant chemotherapy. Patients were divided into two groups; Group A comprehends 14 patients who developed synchronous (5) or methacronous (9) extra-PM. Group B comprehends 12 patients that developed PM only. Results: No intraoperative mortality was recorded. Complications occurred in 14 patients (53.8%), all but 2 (7.26%) were graded I and II according to Clavien-Dindo classification. Recurrences occurred in 8 patients (30.8%), of whom, 5 (62.5%) were submitted for further resections in other sites. Three-, five- and ten-year observed overall survival were respectively 88,5% [95%CI: 0,56 – 1,33], 76,9% [95%CI: 0,47 – 1,19] and 50% [95%CI: 0,20 – 1,03]. Disease-free survival was 65,4% [95%CI: 0,38 – 1,05], at 3 years, 57,7% [95%CI 0, 323 – 0,952] at 5 years and 42,9% [95%CI 0,157 – 0,933], at 10 years. QoL analysis, through WHOQOL-BREF questionnaire, assessed at last available follow up revealed a mean score of 75,9 ± 11,6 on 100 points. Conclusion: Despite no significant differences in survival between patients affected by Pancreatic or Extra- Pancreatic metastases, PM patients seems to show better outcome when managed surgically. mRCC patients, eligible for radical metastasectomy, tend to have long survival rates, reduced recurrence rates and good QoL. Study registration: This paper was registered retrospectively in ClinicalTrials.gov with Identification number: NCT03670992

HCC in Elderly Patients. Curative Intraoperative Strategies and Management in Recurrences

Hepatocellular carcinoma (HCC) incidence is growing among general population and especially in elderly patients. Recent development in surgical technique, surgical equipment, interventional radiology, and radiotherapy (hadrontherapy) allows us to use different techniques and approaches in order to treat this cancer. Patients are conventionally considered disease-free after a 10-year recurrence-free period. Commonly, patients remain into a lifelong follow-up and recurrences are treated as they show. In this chapter, we will give description and indications of different curative techniques, especially hepatic resections and Radio-frequency thermal ablation (RFTA). We will also describe and give indications to palliative care techniques such as transarterial chemoembolization (TACE), Selective Internal Radio-Therapy (SIRT), hadrontherapy, and supportive care. The aim of this chapter is to give information to clinicians and specialists dealing with the disease about the most effective approach to treat HCC, taking into account not only biological age, but also “physiological age,” performance status, comorbidities, and number of liver operative treatments. This chapter highlights that patients advanced in age are in particular need of a tailored medicine, where benefits are well weighted against invasivity of treatment and its side effects, in spite of assuring the best QoL and survival

HCC in Cirrhotic and Non-cirrhotic Liver: Timing to Surgery and Outcome - State of the Art

In this chapter we aim at presenting the state of the art in liver surgery. After a brief introduction about natural evolution of hepatocellular carcinoma (HCC) either in cirrhotic or non-cirrhotic patients, this manuscript will focus on planning and timing surgery: CT evaluation of the remnant liver; biopsy and ultrasonography (US) evaluation of liver disease; intraoperative US; surgical techniques, such as major and limited hepatectomies and two-stage hepatectomies, each of them in open or mini-invasive approach; and their possible complications. Follow-up and further interventions during expected recurrences will be highlighted. Our chapter will also treat topics such as patient’s quality of life, importance of multidisciplinary evaluation and the role of surgeon in it

Il carcinoma colo-rettale nel giovane. Fattori prognostici

Colorectal carcinoma is the third most frequently diagnosed malignant neoplasm. Usually patients affected by this neoplasia belong to VI decade of life. However approximately 2-8% of tumors arise in patients with age under 40 years. Aim of the study was to analyse the results of surgical treatment of colorectal cancer in patiets aged under forty. From January 1987 to December 2002, 46 patients under forty years with colorectal cancer underwent surgical procedure. No perioperative mortality was registered, and complicantions were evidenced in nine patients (20%). Actuarial five years survival was 33%, and overall mean survival was 53 months. Univariate and multivariate analyses identified as prognostic factors the tumor grade, Dukes' stage, nodal status, and length of symptom

Follicle-Stimulating Hormone influences biliary epithelium growth in Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development of renal cysts and various extrarenal manifestations, such as hepatic cysts that bud from biliary epithelium (Alvaro et al., 2008; Onori et al., 2010). We previously showed that Follicle-Stimulating Hormone (FSH) is a trophic factor for the biliary cells in normal rat and in experimental model of bile duct ligation. (Mancinelli et al, 2009). From these data, we aimed to investigate the role of FSH on biliary epithelium in ADPKD. In vivo evaluation of FSH receptor, FSH, p-ERK and c-myc expression in liver fragments from normal and ADPKD patients and in vitro PCNA and cAMP levels in normal human cholangiocytes (H69) and in a cell line obtained from the epithelium lining the hepatic cysts (LCDE) was performed. We found that FSH induces the proliferation of the cystic epithelium and co-localize with p-ERK and c-myc, proteins activated in cAMP signalling mechanism. In vitro FSH sustains cellular growth by the activation of cAMP/ERK signalling pathway with or without the transient silencing of the FSH gene in LCDE by siRNA. These results indicate that FSH has an important role in cystic growth via the cAMP pathway. FSH candidates as a possible target for medical therapy of hepatic cysts during ADPKD

Total Versus Completion Thyroidectomy: A Multidimensional Evaluation of Long-Term Vocal Alterations.

Background: Total thyroidectomy (TT) and completion thyroidectomy (CT) are two common surgical operations that are frequently followed by vocal symptoms despite preservation of the recurrent laryngeal nerve (RLN) and of the external branch of superior laryngeal nerve (EBSLN). The aim of this study was to analyze vocal alterations through endoscopic findings, videolaryngostroboscopy (VLS), acoustic vocal parameters and impact on patients' quality of life after surgery in the absence of laryngeal nerve injury. Methods: We enrolled 198 patients who underwent thyroidectomy by the same surgeon. One hundred twenty-six patients underwent TT (group TT) while 72 underwent CT (group CT). All patients underwent preoperative VLS and Voice Handicap Index (VHI) assessment and postoperative VHI, VLS and Acoustic Voice Analysis with Multidimensional Voice Program Analysis 12 to 18 months after surgery. Results: We observed a statistically significant higher rate of EBSLN injury in CT compared to TT. Even in the absence of RLN and EBSLN injury, patients who underwent TT and CT presented slightly worse acoustic vocal parameters and VHI scores compared to healthy controls. Interestingly, some acoustic vocal parameters and VHI scores were significantly worse in group CT compared to group TT. Conclusions: The higher rate of EBSLN injury in CT rather than in TT suggests a higher surgical risk in CT. The vocal parameters of loudness and self-perception of voice were significantly worse after CT, suggesting a larger trauma in patients' vocal outcome in CT if compared to TT, although these alterations were not reported as psychologically limiting daily life of patients. Nevertheless, the existence of multiple factors contributing to vocal alterations after thyroidectomy highlight the importance of a routine comprehensive functional voice analysis before and after surgery

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1-tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis ( 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1-ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1- tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis (< 3 years survival after partial liver resection, HCCP), levels of YAP1, CTGF, 14–3–3, and TEAD proteins, and YAP1-14-3-3 and YAP1-TEAD complexes were higher than in HCCs with better outcome (> 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1-ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells