Y Quijano

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.

Chronic intestinal pseudo-obstruction due to lymphocytic leiomyositis: is there a place for immunomodulatory therapy?

There is a rare cause of chronic intestinal pseudo-obstruction (CIPO) characterised by a lymphocytic infiltrate in the muscle of the intestine, which is called idiopathic lymphocytic leiomyositis. Few cases have been reported and prognosis is very poor. We present a case with a comparatively benign evolution, showing good response to immunosuppressive therapy.nnThe patient was a healthy 16 year old female who presented with a crisis of postprandial bloating followed by diarrhoea and vomiting. During the following months she lost 10 kg in weight and any attempt at oral feeding resulted in severe abdominal distension and vomiting. Therefore, total parenteral nutrition was finally prescribed. Plain abdominal film and small bowel follow through indicated huge dilatation of the small intestine with air fluid levels. Gastroscopy and colonoscopy were normal, as were mucosal biopsies.nnHuman immunodeficiency virus, hepatitis …

Pediatric intestinal transplantation

AIMnAnalyze the results of a paediatric intestinal transplantation (IT) program in Spain.nnnPATIENTSnDuring an 5-year period, 18 children were included as candidates for IT. The causes for intestinal failure (IF) were short bowel syndrome (n=13), motility disorders (n=3), and congenital epithelial disorders (n=2). Nine children were admitted for a combined liver-small bowel transplant (LSBT), seven for an isolated intestinal transplantation (IIT) and two for a multivisceral transplantation (MVT). In three of the candidates for IIT the indication had to be changed to LSBT because of progression of the liver damage.nnnRESULTSnEight candidates are on the waiting list: four for LSBT, two for IIT, and two for MVT. Four children died before transplantation. All were children under 1 year and candidates for LSBT. One child died during an attempted MVT. Five children underwent transplantation. Grafts were IIT in two and LSBT in three. Of these children, two are on a normal diet (respective follow-up times: 40 and 18 months), two died, both with functioning liver and intestinal grafts (hemorrage after liver biopsy and lymphoproliferative disease), and one developed an untreatable rejection that lead to loss of the intestinal graft; currently, she is on the waiting list for LSBT.nnnCONCLUSIONSnThe morbidity and mortality of IT are high, but it is the only possible treatment for children in IF who cannot be adequately managed with parenteral nutrition. A severe problem is the the scarcity of suitable donors for the very low weight children who are candidates for LSBT.

A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer

SummaryA 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 5–15xa0days 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.

Beneficial effects of HLA class II incompatibility in living donor liver transplantation.

OBJECTIVEnTo analyze the impact of HLA matching in both patient and graft evolution after LDLT.nnnMATERIAL AND METHODSnTwenty recipients underwent LDLT with follow-up of 3 to 30 months. HLA typing was performed on all donor-recipient pairs; class I antigens were typed using serological methods and class II loci (DRB1 and DQB1) using low-resolution molecular typing. Recipient sera were cross-matched with donor lymphocytes. Antigen mismatches were analyzed for each locus individually, for each class as a whole and for HLA class I immunogenic triplets according to HLA Matchmaker software.nnnRESULTSnEighteen of 20 donor-recipient pairs were HLA haploidentical. All but one of the recipients had a negative cross-match before transplantation. While there was not a statistically significant correlation between HLA class I mismatches and the incidence of acute rejection episodes, HLA class II matching in DRB1 and DQB1 loci appeared to be associated with a higher incidence of acute rejection episodes after LDLT. Both host-versus-graft (HvG) and graft-versus-host (GvH) HLA class II compatibilities correlated with rejection episodes, especially for the GvH direction.nnnCONCLUSIONSnHLA class II matching for DRB1 and DQB1 loci appears to be associated with a higher incidence of acute rejection episodes after LDLT. In this study, mismatches in class I HLA antigens are not related to an higher incidence of acute rejection episodes nor other complications after LDLT. Further studies are needed to unveil the role of HLA matching in LDLT.

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 15.1xa0days. Mean future liver remnant hypertrophy was 93.2xa0%. Severe complications occurred in 44.4xa0% of patients and mortality occurred in two cases (22.2xa0%). Small for size syndrome occurred in two cases (22.2xa0%). 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.

Robotic versus laparoscopic distal pancreatectomy: A comparative study of clinical outcomes and costs analysis

BACKGROUNDnThe robotic surgery cost presents a critical issue which has not been well addressed yet. This study aims to compare the clinical outcomes and cost differences of robotic distal pancreatectomy (RDP) versus laparoscopic distal pancreatectomy (LDP).nnnMETHODSnData were abstracted prospectively from 2011 to 2017. An independent company performed the financial analysis.nnnRESULTSnA total of 28 RDP and 26 LDP were included. The mean operative time was significantly lower in the LDP (294 vs 241xa0min; pxa0=xa00.02). The main intra and post-operative data were similar, except for the conversion rate (RDP: 3.6% vs LDP: 19.2%; pxa0=xa00.04) and hospital stay (RDP: 8.9 vs LDP 13.1 days; pxa0=xa00.04). The mean total costs were similar in both groups (RDP: 9198.64 € vs LDP: 9399.74 €; pxa0>xa00.5).nnnCONCLUSIONSnRDP showed lower conversion rate and shorter hospital stay than LDP at the price of longer operative time. RDP is financially comparable to LDP.

A prospective randomized study comparing laparoscopic transabdominal preperitoneal (TAPP) versus Lichtenstein repair for bilateral inguinal hernias

BACKGROUNDnIn literature, only a few studies have prospectively compared the results of laparoscopic with open inguinal hernia repair yet none have compared bilateral inguinal hernia repair. The aim of this study is to compare the open Lichtenstein repair (OLR) with laparoscopic trans-abdominal preperitoneal (TAPP) repair in patients undergoing surgery for bilateral inguinal hernia.nnnMETHODSnPatients were prospectively randomized between March 2013 and March 2015. Outcome parameters included hospital stay, operation time, postoperative complications, immediate postoperative pain and chronic pain, recurrence and quality of life.nnnRESULTSnSixty-one patients underwent TAPP repair and 73 underwent OLR. TAPP procedure had less early post-operative pain up to 7 days from surgery (pxa0=xa00.003), a shorter length of hospital stay (pxa0=xa00.001), less postoperative complications (pxa0=xa00.012) and less chronic pain (0.04) when compared with the OLR approach.nnnCONCLUSIONSnTAPP procedure for bilateral inguinal hernia effectively reduces early postoperative pain, hospital stay and postoperative complications.

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.

BACKGROUNDnF-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.nnnAIMnWe study the prognostic impact of FDG-PET scan in neuroendocrine pancreatic tumors.nnnMETHODOLOGYnBetween 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.nnnRESULTSnFDG-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 (pxa0=xa00.032), mitotic index (pxa0=xa00.002), tumor grade (pxa0=xa00.017) and tumor size (pxa0=xa00.01).nnnCONCLUSIONSnFDG-PET provides a good prognostic value for PNETs. Present results must be further validated with larger sample studies.

Cavoatrial Thrombectomy without the Use of Cardiopulmonary Bypass for Abdominal Tumors. Our Experience and State of the Art

BACKGROUNDnSurgical resection of a tumor with thrombus formation extending from the inferior vena cava (IVC) to the right atrium can be performed without the use of a cardiopulmonary bypass. However, this technique is not widely known or used by general surgeons. Our aim was to present our experience in a general surgical unit setting and to present a literature review.nnnMETHODSnRetrospective analysis of 3 cases with successful cavoatrial thrombectomy without the use of cardiopulmonary bypass by a transabdominal, transdiaphragmatic, and transpericardic approach. We also performed a review of the English literature of this procedure.nnnRESULTSnThree cases are presented: right-sided hepatocellular carcinoma, a right renal carcinoma, and a recurrent hepatic hydatid cyst all which required surgery. An approach from the right atrium to the IVC was used, and then, after cavoatrial occlusion, a cavotomy was performed to carry out the thrombectomy. In all cases, a transesophageal echocardiography was performed during surgery. We only found 6 other similar cases that were performed successfully in current medical literature.nnnCONCLUSIONSnOur own experiences and cases identified through a literature review demonstrate that a thrombectomy for IVC thrombus in the setting of abdominal pathology can be performed successfully in selected cases without the support of cardiopulmonary bypass.