The Prognostic Impact of PD-L2 in Papillary Renal-Cell Carcinoma.

INTRODUCTION: Programmed death-1 ligand (PD-L1) has been often studied in different types of renal-cell carcinoma (RCC). For example, in clear-cell renal carcinoma it is well established that programmed death-1 receptor and PD-L1 are important prognostic markers. In contrast, the role of programmed death-2 ligand (PD-L2) as prognostic marker remains unclear. The aim of this study was to evaluate if PD-L2 expression could play a role as a prognostic marker for papillary RCC (pRCC). METHODS: The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of PD-L2 was determined by immunohistochemistry. In total, PD-L2 staining was evaluable in 185 of 240 type 1 and 99 of 128 type 2 pRCC cases. RESULTS: PD-L2 staining was positive in 67 (36.2%) of type 1 and in 31 (31.3%) of type 2 pRCC specimens. The prevalence of PD-L2+ cells was significantly higher in high-grade type 1 tumors (p = 0.019) and in type 2 patients with metastasis (p = 0.002). Kaplan-Meier analysis disclosed significant differences in 5-year overall survival (OS) for patients with PD-L2- compared to PD-L2+ in pRCC type 1 of 88.4% compared to 73.6% (p = 0.039) and type 2 of 78.8% compared to 39.1% % (p < 0.001). However, multivariate analysis did not identify the presence of PD-L2+ cells neither in type 1 nor type 2 pRCC as an independent predictor of poor OS. DISCUSSION/CONCLUSION: PD-L2 expression did not qualify as an independent prognostic marker in pRCC. Future studies will have to determine whether anti-PD-L2-targeted treatment may play a role in pRCC and expression can potentially serve as a predictive marker for these therapeutic approaches.

cMET: a prognostic marker in papillary renal cell carcinoma?

The tyrosine-protein kinase c-Met plays a decisive role in numerous cellular processes, as a proto-oncogene that supports aggressive tumor behavior. It is still unknown whether c-Met could be relevant for prognosis of papillary RCC (pRCC). Specimen collection was a collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from 197 and 110 patients with type 1 and 2 pRCC, respectively. Expression of cMET was determined by immunohistochemistry. In total, cMET staining was evaluable in of 97 of 197 type 1 and 63 of 110 type 2 pRCC cases. Five-year overall survival revealed no significant difference in dependence of cMET positivity (cMET- vs. cMET+: pRCC type 1: 84.8% vs. 80.3%, respectively [p = 0.303, log-rank]; type 2: 71.4% vs. 64.4%, respectively [p = 0.239, log-rank]). Interestingly, the subgroup analyses showed a significant difference for cMET expression in T stage and metastases of the pRCC type 2 (p = 0.014, p = 0.022, chi-square). The cMET-positive type 2 collective developed more metastases than the cMET-negative cohort (pRCC type 2 M+: cMET-: 2 [4.3%] vs. cMET+: 12 [19%]). cMET expression did not qualify as a prognostic marker in pRCC for overall survival.

Expression of Prostate-specific Membrane Antigen (PSMA) in Papillary Renal Cell Carcinoma - Overview and Report on a Large Multicenter Cohort.

Prostate specific membrane antigen (PSMA) is an emerging diagnostic and therapeutic target in prostate cancer. 68Ga-PSMA-labeled hybrid imaging is used for the detection of prostate primary tumors and metastases. Therapeutic applications such as Lutetium-177 PSMA radionuclide therapy or bispecific antibodies that target PSMA are currently under investigation within clinical trials. The expression of PSMA, however, is not specific to prostate-tissue. It has been described in the neovascular endothelium of different types of cancer such as breast cancer, and clear cell renal cell carcinoma (ccRCC). The aim of this study was to analyze PSMA expression in papillary RCC (pRCC) type 1 and type 2, the most common non-ccRCC subtypes, and to evaluate the potential of PSMA-targeted imaging and treatment in pRCC. Formalin-fixed, paraffin-embedded tissue samples of primary tumors were analyzed for PSMA expression by immunohistochemistry. Out of n=374 pRCC specimens from the multicenter PANZAR consortium, n=197 pRCC type 1 and n=110 type 2 specimens were eligible for analysis and correlated with clinical data. In pRCC type 1 PSMA staining was positive in 4 of 197 (2.0%) samples whereas none (0/110) of the pRCC type 2 samples were positive for PSMA in this large cohort of pRCC patients. No significant PSMA expression was detected in pRCC. Reflecting current clinical evaluation of PMSA expression in RCC do not encourage further analysis in papillary subtypes.

Endoscopic diagnosis and treatment of far distal obstructive hydrocephalus.

PURPOSE: Obstruction of the CSF circulation distal to the fourth ventricle is a rare cause of noncommunicating hydrocephalus. Endoscopic third ventriculostomy (ETV) represents one of the treatment options, but reports of results are rare. METHODS: Between March 1997 and June 2008, 20 ETVs in 20 patients (mean 32.4 years, range 1 month-79 years) for noncommunicating hydrocephalus distal to the fourth ventricle were undertaken. All patients suffered from severe internal hydrocephalus and typical clinical symptoms. In addition to the standard ETV, a transaqueductal inspection of the posterior fossa with a flexible scope was performed. All patients were prospectively followed. RESULTS: An ETV was achieved in all patients. It was clinically successful in 15 of 20 patients (75%) with an improvement of 50% (three out of six) of the pediatric and of 83% (12 out of 14) of the adult population. A reduction of ventricle size was found in ten (50%). Five patients (25%) received ventriculoperitoneal shunting. A transaqueductal inspection of the posterior fossa cerebrospinal fluid (CSF) pathways was performed in 16. In the remaining four patients, no inspection with the flexible scope was done. One clinically silent fornix contusion and one CSF fistula which was treated conservatively occurred. There was no permanent morbidity. CONCLUSIONS: ETV is a successful treatment option in CSF pathway obstructions distal to the fourth ventricle. Although the success rate particularly of the pediatric population appears to be lower than with other indications of obstructive hydrocephalus, a relevant part of the patient population improves after ventriculostomy and shunting can be avoided.

Endoscopic third ventriculostomy in obstructive hydrocephalus due to giant basilar artery aneurysm.

OBSTRUCTIVE: hydrocephalus due to giant basilar artery (BA) aneurysm is a rare finding, and endoscopic treatment has not been reported. Here the authors present their experience with endoscopic third ventriculostomy (ETV) in obstructive hydrocephalus due to giant BA aneurysm. Between December 2000 and March 2007, 3 patients (2 men and 1 woman; age range 32-80 years) underwent an ETV for the treatment of obstructive hydrocephalus caused by a giant BA aneurysm. All 3 patients presented with cephalgia, nausea, vomiting, and a variable decrease in consciousness. An obstructive hydrocephalus caused by a giant BA aneurysm was found in each case as the underlying pathological entity. Intraoperatively, a narrowing of the third ventricle by upward displacement of the tegmentum was found in all 3 patients. A standard ETV was performed and included an inspection of the prepontine cisterns. The endoscopic treatment was successful in all patients with respect to clinical signs and radiological ventricular enlargement. No complications were observed. In all, the endoscopic ventriculostomy was proven to be a successful treatment option in obstructive hydrocephalus even if it is caused by untreated giant BA aneurysm.

PEEK cage cervical ventral fusion in spondylodiscitis.

PURPOSE: Cervical spondylodiscitis is a quite rare finding regarding the number and the common location of spinal abscesses in the lumbar region. While in thoracic and lumbar discitis, single-step surgery with neural decompression, disc space evacuation, and subsequent fusion is well known, there is no such report in cervical discitis. Here the authors present their experience with ventral polyetherketone (PEEK) cage fusion in cervical spondylodiscitis in a single-step procedure. METHODS: Between January 2006 and November 2008, five patients (three men, two woman; ages 71, 77, 58, 66 and 66 years) suffering from cervical spondylodiscitis and epidural abscess underwent disc evacuation, myelon decompression and subsequent ventral fusion using an empty PEEK cage disc replacement in one single setting. All five patients presented with significant neurological symptoms like cervicobrachialgia, tetraparesis and disturbance of the urinary incontinence. In all five patients, disc evacuation, myelon decompression and cervical fusion using a PEEK cage disc replacement in a single-stage surgery were performed. All wounds were closed primarily. Postoperatively, all patients received a specific antibiotic therapy for at least 6 weeks. RESULTS: This treatment strategy was successful in all patients with respect to clinical signs, laboratory parameters and radiological findings. All patients improved neurologically. Follow-up revealed a stable osteosynthesis without signs of instability. One cage was explanted despite neurological improvement and normal infectious parameters at another surgical department. No complications were observed. CONCLUSIONS: In all, abscess drainage and ventral fusion with PEEK-cage disc replacement in one single setting was proven to be a successful treatment option in cervical discitis and spinal epidural abscess.

A new endoscopic spine system: the first results with "Easy GO".

PURPOSE: Endoscopy meets increasing interest by spine surgeons. However, endoscopic results are diverging and many spinal endoscopic systems are difficult to apply and handle. METHODS: A system for endoscopic spinal surgery was developed where the main goals were: (1) easy intraoperative handling with standard microsurgical techniques, and (2) avoidance of a prolonged learning curve. The system consists of various dilators, two different work sheaths, two different 30 degrees endoscopes, and an endoscope holder. RESULTS: Between August 2006 and April 2008, 80 spinal surgeries were performed in degenerative lumbar spine cases (mean age 52 years, range 22-85 years). Intraoperatively, the system was easy to handle. Standard microsurgical techniques were used. Mean surgical time scored 75 min (range 28-168 min). There was no intraoperative complication, no new postoperative deficit and no infection. In four cases, the endoscope was abandoned and the procedure microsurgically continued (5%). At the last follow-up (mean FU 10 months, range 2 weeks up to 21 months), 89% of the patient were pain free (71/80). Four patients suffered from recurrent disc prolapses (5%). Another five patients (6%) were not satisfied without evidence of re-prolaps. Of those who answered the questionnaire of patient satisfaction, 83% (45/54) considered their postoperative status as excellent, 13% as good (7/54), 4% were not satisfied (2/54). CONCLUSIONS: The Easy GO system was easy and safe to handle with the standard bimanual microsurgical technique and good postoperative results. Further studies are needed to show a significant advantage of the technique in comparison to the microsurgical standard procedure.

Chronic subdural hematoma--craniotomy versus burr hole trepanation.

The authors present a series of more than 200 surgical procedures for chronic subdural hematoma in a 5-year-period. Clinical presentation and neurosurgical treatment were regarded with a special focus on the surgical technique. Between March 2003 and July 2008, 193 patients (113 male and 80 female, mean age 72.5 yrs [range 26-97 yrs]) suffering from chronic subdural hematoma were retrospectively analyzed. One-hundred-fifty-one craniotomies and 42 burr holes were performed. Forty-two craniotomy patients (27.8%) in contrast to 6 burr hole patients (14.3%) required surgical revision. A craniectomy was performed as an ultima ratio after at least 2 prior evacuations in 3 cases. Chronic subdural hematoma is a disease of the elderly. A craniotomy seems to possess a higher rate of recurrence of the chronic subdural hematoma so that a burr hole evacuation should be preferred. Craniectomy might be a good therapeutic option in complicated recurrent chronic subdural hematomas.

Endoscopic treatment of arachnoid cysts: a detailed account of surgical techniques and results.

BACKGROUND: Surgical treatment of arachnoid cysts remains under debate. Although many authors favor endoscopic techniques, others attribute a higher recurrence rate to the endoscope. OBJECTIVE: The authors report their experience with endoscopic procedures for arachnoid cyst. METHODS: All pure endoscopic procedures for arachnoid cysts performed by the authors were analyzed. Particular reference was given to surgical complications and patient outcome in relation to cyst location and endoscopic technique. RESULTS: Sixty-six endoscopic procedures were performed in 61 patients (mean age, 28 years; range, 23 days to 74 years; 35 males, 26 females). The main presenting symptoms were cephalgia (61%), hemisymptoms (18%), and macrocephalus (18%). Cyst location was temporobasal (34%), suprasellar (21%), at the cisterna quadrigemina (18%), paraxial supratentorial (16%), and various (10%). Thirty cystocisternostomies, 14 ventriculocystostomies, 12 cystoventriculostomies, and 10 ventriculocystocisternostomies were performed. The overall clinical success rate was 90%. The endoscopic technique was abandoned in 4 cases (7%). Postoperative complications were found in 16%; there was only one permanent deficit (2%). Five recurrences (8%) occurred up to 7 years after the first procedure. Of the various locations, the temporobasal cysts were the most difficult to treat with lowest clinical success (81%), highest recurrence (19%), and highest complication rate (24%). Of the various endoscopic techniques, ventriculocystostomy and ventriculocystocisternostomy reached the highest success rates with 100%. CONCLUSIONS: Endoscopic techniques provide very good results in arachnoid cyst treatment. The most frequent cyst location is the most difficult to treat. A long-term follow-up is recommended since recurrences can occur many years after the procedure.

Endoscopic third ventriculostomy for obstructive hydrocephalus due to intracranial hemorrhage with intraventricular extension.

Object Endoscopic third ventriculostomy (ETV) is well accepted for obstructive hydrocephalus of various etiologies. Nevertheless, it is seldom considered in intracranial hemorrhage even in cases involving obstruction of the CSF circulation. Methods Between May 1993 and April 2008, 34 endoscopic procedures were performed for hemorrhage-related obstructive hydrocephalus with an intraventricular component. All patients were prospectively followed up. Special attention was paid to presurgical clinical status, type of hemorrhage, type of surgery, postsurgical clinical status, postsurgical ventricular size, and necessity of ventriculoperitoneal shunt implantation. Results An ETV was performed for treatment of obstructive hydrocephalus due to intracranial hemorrhage in 34 patients (15 male, 19 female; mean age 60.8 years [range 3 months-83 years]). Hydrocephalus was caused by 17 cerebellar, 6 thalamic, 5 intraventricular, 3 basal ganglia, 2 subarachnoid, and 1 pontine hemorrhage. Thirty-three patients (97.1%) presented with impaired consciousness. Intraventricular blood was present in all cases. In 16 cases (47.1%), blood clots had to be evacuated to achieve access to the third ventricle floor. The mean operation time was 58.2 minutes (range 25-120 minutes). Three complications occurred (rate of 8.8%) with 2 being asymptomatic (5.9%) and 1 being transient (2.9%). There was no procedure-related permanent morbidity, and no procedure-related mortality. After surgery, there was clinical improvement in 17 cases (50.0%) and radiological evidence of improvement in 22 cases (64.7%). Two patients required postoperative ventriculoperitoneal shunting (5.9%). Seven patients died of hemorrhage while in the hospital (20.6%), and another 4 died during follow-up (11.8%). Fifteen patients (44.1%) showed a persistent clinical improvement at the final follow-up (mean 12.2 months after surgery). Conclusions Endoscopic third ventriculostomy represents a safe treatment option in intraventricular hemorrhage-related obstructive hydrocephalus yielding similar results as an external drainage but with less risk of infection and a very low subsequent shunt placement rate. In cases with a predominant obstructive component, ETV should be considered in hydrocephalus due to intracerebral hemorrhage. However, performing an ETV with a blurred field of vision and distorted ventricular anatomy is a challenge for any endoscopic neurosurgeon and should be reserved for experienced neuroendoscopists.