Background and AimChemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers.Patients and MethodsWe retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed.ResultsThe median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities.ConclusionsSTZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response.

PurposeGenome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas.Materials and methodsTumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1).ResultsHierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score >1 for CK5 and >6 for CK20 were defined as positive. In multivariate Cox’s regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes.ConclusionsImmunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis.

The severity of structural nerve injury after needle-nerve contact was directly related to force exposure via needle advancement.

The severity of nerve injury after needle nerve perforation was related to the diameter of the applied cannula. However, no such difference exists for regional inflammation. Functional consequences of these findings need to be determined. Currently, small-diameter cannulae may be advisable for peripheral nerve blocks to minimize the risk of nerve injury in the case of nerve perforation.

Background. Nerve stimulation can facilitate correct needle placement in peripheral regional anesthesia. The aim of this study was to determine whether the high threshold current is associated with reduced nerve injury due to fewer needle-nerve contacts compared with low current. Methods. In anaesthetized pigs, thirty-two nerves of the brachial plexus underwent needle placement at low (0.2 mA) or high current (1.0 mA). The occurrence of needle-nerve contact was recorded. After 48 hours, the nerves were analyzed for occurrence of histological changes. Nerve injury was scored ranging from 0 (no injury) to 4 (severe injury). Results. The frequency of needle-nerve contact was 94% at low compared to 6% at high current. The score was significantly higher at low (median [interquartile range] 2.0 [1.0-2.0]) compared to high current (0.0 [0.0-1.0] P = .001). Conclusions. Inflammatory responses were directly related to needle-nerve contacts. Hence, posttraumatic inflammation may be diminished using higher current for nerve localization.