Surgical ampullectomy: an underestimated operation in the era of endoscopy

AbstractIntroductionBenign neoplastic, inflammatory or functional pathologies of the ampulla of Vater are mainly treated by primary endoscopic interventions. Consequently, transduodenal surgical ampullectomy (TSA) has been abandoned in many centres, although it represents an important tool not only after unsuccessful endoscopic treatment. The aim of the study was to analyse TSA for benign lesions of the ampulla of Vater.Patients and methodsAll patients who underwent TSA between 2001 and 2014 were included. Patients were analysed in terms of indications, postoperative morbidity and mortality as well as long-term success.ResultsEighty-three patients underwent TSA. Indications included adenomas in 44 and inflammatory stenosis in 39 patients. 96% of the patients had undergone endoscopic therapeutic approaches prior to TSA (median no. of interventions n = 3). Postoperative morbidity occurred in 20 patients (24%). There was one procedure-associated death (mortality 1.2%). The mean follow-up was 54 months. Long-term overall success rate for TSA was 83.6%. After TSA for ampullary adenoma, the recurrence rate was 4.5%.ConclusionTSA is an underestimated surgical procedure, which can be performed safely with high long-term efficacy. It can be implemented in clinical algorithms for patients with benign pathologies of the ampulla of Vater, particularly after unsuccessful endoscopic treatment

Surgical ampullectomy: an underestimated operation in the era of endoscopy

AbstractIntroductionBenign neoplastic, inflammatory or functional pathologies of the ampulla of Vater are mainly treated by primary endoscopic interventions. Consequently, transduodenal surgical ampullectomy (TSA) has been abandoned in many centres, although it represents an important tool not only after unsuccessful endoscopic treatment. The aim of the study was to analyse TSA for benign lesions of the ampulla of Vater.Patients and methodsAll patients who underwent TSA between 2001 and 2014 were included. Patients were analysed in terms of indications, postoperative morbidity and mortality as well as long-term success.ResultsEighty-three patients underwent TSA. Indications included adenomas in 44 and inflammatory stenosis in 39 patients. 96% of the patients had undergone endoscopic therapeutic approaches prior to TSA (median no. of interventions n = 3). Postoperative morbidity occurred in 20 patients (24%). There was one procedure-associated death (mortality 1.2%). The mean follow-up was 54 months. Long-term overall success rate for TSA was 83.6%. After TSA for ampullary adenoma, the recurrence rate was 4.5%.ConclusionTSA is an underestimated surgical procedure, which can be performed safely with high long-term efficacy. It can be implemented in clinical algorithms for patients with benign pathologies of the ampulla of Vater, particularly after unsuccessful endoscopic treatment

Intrapulmonal dislocation of a totally implantable venous access device

BACKGROUND: Totally implantable venous access devices are widely used for infusion of chemotherapy or parenteral nutrition. Device associated complications include technical operative problems, infections, paravasal infusions and catheter or punction chamber dislocation. CASE PRESENTATION: We present the case of a 49-year-old patient with the rare complication of a intrapulmonal catheter dislocation of a totally implantable venous access system. Treosulfane for chemotherapy of metastatic breast cancer was infused via the catheter causing instant coughing and dyspnoea which lead to the diagnosis of catheter dislocation. The intrapulmonal part of the catheter was removed under thoracoscopic control without further complications. CONCLUSION: Intrapulmonal catheter dislocation is a rare complication of a totally implantable venous access device which can not be avoided by any prophylactic measures. Therefore, the infusion system should be tested before each use and each new symptom, even when not obviously related to the catheter should be carefully documented and evaluated by expert physicians to avoid severe catheter-associated complications

Epithelial to Stromal Re-Distribution of Primary Cilia during Pancreatic Carcinogenesis

Background The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. Methods PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated alpha-tubuline and gamma-tubuline. Co-staining for the HH receptors PTCH1, PTCH2 and SMO was also performed. Results PC are gradually lost during pancreatic carcinogenesis in the epithelium: the fraction of cells with PC gradually and significantly decreased from 32% in ducts of normal pancreas, to 21% in ducts of chronic pancreatitis, to 18% in PanIN1a, 6% in PanIN2, 3% in PanIN3 and to 1.2% in invasive PDAC. However, this loss of PC in the neoplastic epithelium is accompanied by a gain of PC in the surrounding stroma. The fraction of stromal cells with PC significantly increased from 13% around normal ducts to about 30% around PanIN and PDAC. HH-receptors were detected in tumor stroma but not in epithelial cells. PC are also present in PSC and pancreatic cancer cell lines. Conclusion PC are not lost during pancreatic carcinogenesis but re-distributed from the epithelium to the stroma. This redistribution may explain the re-direction of HH signaling towards the stroma during pancreatic carcinogenesis

Tspan8 and Tspan8/CD151 knockout mice unravel the contribution of tumor and host exosomes to tumor progression

Background: The tetraspanins Tspan8 and CD151 promote metastasis, exosomes (Exo) being suggested to be important in the crosstalk between tumor and host. The contribution of Tspan8 and CD151 to host versus tumor-derived exosome (TEX) activities being not defined, we approached the questions using 3-methylcholanthrene-induced (MCA) tumors from wt, Tspan8ko, CD151ko and Tspan8/CD151 (db)ko mice, implanted into tetraspanin-competent and deficient hosts. Methods: Tumor growth and dissemination, hematopoiesis and angiogenesis were surveyed in wild type (wt), Tspan8ko, CD151ko and dbko mice bearing tetraspanin-competent and -deficient MCA tumors. In vitro studies using tumor cells, bone marrow cells (BMC) and endothelial cells (EC) elaborated the mechanism of serum (s)Exo- and TEX-induced target modulation. Results: Tumors grew in autochthonous and syngeneic hosts differing in Tspan8- and/or CD151-competence. However, Tspan8ko- and/or CD151ko-tumor cell dissemination and settlement in metastatic organs was significantly reduced in the autochthonous host, and less severely in the wt-host. Impaired wt-MCA tumor dissemination in the ko-host confirmed a contribution of host- and tumor-Tspan8/-CD151 to tumor cell dissemination, delivery of sExo and TEX being severely impaired by a Tspan8ko/CD151ko. Coculturing tumor cells, BMC and EC with sExo and TEX revealed minor defects in epithelial mesenchymal transition and apoptosis resistance of ko tumors. Strongly reduced migratory and invasive capacity of Tspan8ko/CD151ko-MCA relies on distorted associations with integrins and CAM and missing Tspan8/CD151-promoted recruitment of proteases. The defects, differing between Tspan8ko- and CD151ko-MCA, were rescued by wt-TEX and, less efficiently Tspan8ko- and CD151ko-TEX. Minor defects in hematopoietic progenitor maturation were based on the missing association of hematopoietic growth factors /− receptors with CD151 and, less pronounced, Tspan8. Rescue of impaired angiogenesis in ko mice by wt-sExo and promotion of angiogenesis by TEX depended on the association of Tspan8 and CD151 with GPCR and RTK in EC and tumor cells. Conclusions: Tspan8-/CD151-TEX play central roles in tumor progression. Tspan8-/CD151-sExo and TEX contribute by stimulating angiogenesis. Tspan8 and CD151 fulfill these tasks by associating with function-relevant proteins, the additive impact of Tspan8 and CD151 relying on differences in preferred associations. The distinct Tspan8 and CD151 contributions suggest a blockade of TEX-Tspan8 and -CD151 promising for therapeutic intervention

Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming

Background: Cancer-initiating cell (CIC) exosomes (CIC-TEX) are suggested reprogramming Non-CIC. Mode of message transfer and engagement of CIC-markers being disputed, we elaborated the impact of CD44v6 and Tspan8 on the response of Non-CIC. Methods: Non-metastasizing CD44v6- and Tspan8-knockdown (kd) pancreatic cancer cells served as Non-CIC. CIC-TEX coculture-induced changes were evaluated by deep-sequencing and functional assays. Tumor progression was surveyed during in vivo CIC-TEX treatment. Results: Deep-sequencing of CIC-TEX-cocultured CD44v6kd-Non-CIC revealed pronounced mRNA changes in signaling, transport, transcription and translation; altered miRNA affected metabolism, signaling and transcription. CIC-TEX coculture-induced changes in Tspan8kd-Non-CIC mostly relied on CIC-TEX-Tspan8 being required for targeting. CIC-TEX transfer supported apoptosis resistance and significantly promoted epithelial mesenchymal transition, migration, invasion and (lymph)angiogenesis of the kd Non-CIC in vitro and in vivo, deep-sequencing allowing individual mRNA and miRNA assignment to altered functions. Importantly, CIC-TEX act as a hub, initiated by CD44v6-dependent RTK, GPCR and integrin activation and involving CD44v6-assisted transcription and RNA processing. Accordingly, a kinase inhibitor hampered CIC-TEX-fostered tumor progression, which was backed by an anti-Tspan8 blockade of CIC-TEX binding. Conclusions: This in depth report on the in vitro and in vivo impact of CIC-TEX on CD44v6kd and Tspan8kd Non-CIC unravels hub CIC-TEX activity, highlighting a prominent contribution of the CIC-markers CD44v6 to signaling cascade activation, transcription, translation and miRNA processing in Non-CIC and of Tspan8 to CIC-TEX targeting. Blocking CIC-TEX binding/uptake and uptake-initiated target cell activation significantly mitigated the deleterious CIC-TEX impact on CD44v6kd and Tspan8kd Non-CIC

A narrative review on endopancreatic interventions: an innovative access to the pancreas

The natural connection between the duodenum and the pancreatic duct enables a minimally invasive access to the pancreas. Endoscopically this access is already regularly used, mainly for diagnostic and even for certain therapeutic purposes. With per-oral pancreatoscopy the endopancreatic approach allows the direct visualization of the pancreatic duct system potentially improving the diagnostic work-up of pancreatic cystic neoplasms, intrapancreatic strictures and removal of pancreatic duct stones. However, the endopancreatic access can equally be applied for surgical interventions. The objective of this review is to summarize endoscopic and surgical interventions using the endopancreatic access. Endopancreatic surgery stands for a further development of the endoscopic technique: a rigid endoscope is transabdominally introduced over the duodenum and the papilla to enable resections of strictures and inflamed tissue from inside the pancreas under visual control. While the orientation and localization of target structures using this minimally invasive approach is difficult, the development of an accurate image guidance system will play a key role for the clinical implementation and widespread use of endoscopic and surgical endopancreatic interventions