Ventral Tumor Research Articles

Current Knowledge on Spinal Meningiomas-Surgical Treatment, Complications, and Outcomes: A Systematic Review and Meta-Analysis (Part 2).

Most of the knowledge on spinal meningiomas is extrapolated from their intracranial counterparts, even though they are considered separate entities. This review aimed to systematically summarize studies covering different aspects of spinal meningiomas and their management. Databases were searched for all studies concerning spinal meningiomas dating from 2000 and onwards. When possible, a meta-analysis was performed. Neurological outcomes of surgery were consistently favorable across studies, with a complication rate of 7.9% and 78.9% of the patients demonstrating good postoperative neurological function (McCormick score 1-2). The most relevant predictors of unfavorable outcomes were poor preoperative status, longer time from diagnosis to surgery, and surgery of recurrent tumors. The recurrence rate after surgery was estimated at 6%. Meta-analysis and/or survival analysis revealed that higher WHO grade (p < 0.001), higher Simpson grade (p < 0.001), ventral tumor location (p = 0.02), and male sex (p = 0.014) were all associated with higher odds of recurrence. However, the meta-analysis did not show any difference between Simpson grade 1 and grade 2 with respect to the odds of recurrence (p = 0.94). Surgery provided immediate and durable health-related quality-of-life improvement, as well as a high frequency of return to work. Spinal meningioma surgery is a relatively safe procedure with a low risk of tumor recurrence and high likelihood of favorable postoperative outcomes.

ODP538 A Case of Multiple Endocrine Neoplasia Type 2A with Malignant Paraganglioma

Abstract Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), pheochromocytoma/paraganglioma and primary hyperparathyroidism. Case presentation At the age of 54, the patient became aware of a thyroid mass and went to the hospital. She was diagnosed as MTC by cytology. She was referred to our hospital for treatment. No thyroid cancer patients were found in her relatives. Her thyroid gland was elastic and soft, and a hard nodule about 1.5 cm in the lower pole of her left thyroid lobe was found. An Ultrasonography found the multiple nodules in both lobes of the thyroid gland, suggesting multiple or metastases of MTC. Although there was no family history, MEN2 was suspected, and screening of the abdominal organs by a CT scan revealed a 35 mm nodular lesion with calcification on the ventral side of the inferior vena cava (IVC). Multiple neoplastic lesions were found in her liver S2, S6 and S8 region. A CT scan also found the overall thickened right adrenal gland. An MIBG scintigraphy showed abnormal accumulations in these lesions. Laboratory data showed the increased the catecholamine metabolites both in blood and urine, and slightly increased CEA and calcitonin levels in the serum. After the genetic counselling, an informed consent was obtained and genetic test of RET oncogene was performed. A germline mutation was found in codon 634. Based on these findings, we diagnosed her as MEN2A with MTC, malignant paraganglioma and multiple liver metastases. First, IVC ventral lesions, multiple hepatic lesions, and right adrenal gland resection were performed. One month after the operation, total thyroidectomy and cervical lymph node dissection were performed. Pathologically, the IVC ventral tumor was a ganglion tumor covered with a pseudocapsule, with fibrous vitrification and coarse calcification inside. The histology of the liver regions were almost the same, and there was no finding suggesting the metastasis of MTC, and the histological image was consistent with the liver metastasis of paraganglioma. The right adrenal gland was diagnosed with adrenal medulla hyperplasia. Since then, she has been receiving continuous Cyclophosphamide Hydrate/ Vincristine Sulfate/Dacarbazine chemotherapy, and at the end of the 24th course, she has progressed without recurrence or the appearance of new metastases. It was reported that most Paragangliomas and pheochromocytomas in MEN2 with RET germline mutation are characterized by nonaggressive behavior, and paraganglioma was thought to be rare in onset than pheochromocytoma in MEN2A. In particular, cases of malignant paraganglioma in MEN2 with the RET634 germline mutation are extremely rare. Presentation: No date and time listed

The application of internal traction technique in retroperitoneal robot-assisted partial nephrectomy for renal ventral tumors

BackgroundFor patients with prior intra-abdominal surgery or multiple arteries, the retroperitoneal robot-assisted partial nephrectomy (rRAPN) is a better choice. The renal ventral tumor poses an additional challenge due to poor tumor exposure. This study is determined to assess the feasibility of an internal traction technique (ITT) in rRAPN for the management of renal ventral tumors.MethodsFrom November 2019 to March 2021, a total of 28 patients with renal ventral tumor underwent rRAPN. All patients had prior abdominal surgery or multiple arteries. The ITT group (20 patients), which improved the tumor exposure by traction of the kidney with suture, was compared with the traditional technique group (8 patients) in terms of warm ischemia time, estimated blood loss and postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine. Differences were considered significant when P < 0.05.ResultsAll rRAPN surgeries were successful without conversion to radical nephrectomy or open partial nephrectomy. The warm ischemia time was lower in the ITT group (17.10 min vs. 24.63 min; P < 0.05). Estimated blood loss in the traditional technique group was 324.88 ± 79.42 mL, and in the ITT group, it was 117.45±35.25 mL (P < 0.05). No significant differences with regard to postoperative hospital stay, retroperitoneal drainage, R.E.N.A.L. score, and serum creatinine were observed between both groups. Surgical margins were negative and no intraoperative complications occurred in all the patients. After 10 months of follow-up, no recurrence or metastasis occurred in all cases.ConclusionITT is a feasible, safe, and valid procedure in rRAPN for renal ventral tumors. Application of ITT improved the exposure and reduces warm ischemic time in comparison with the conventional procedure.

Analysis of Trifecta Results in a Single-Center Experience with Retroperitoneoscopic Partial Nephrectomy: An Observational Study.

To analyze the trifecta results in patients with T1a and T1b renal tumors treated with retroperitoneoscopic partial nephrectomy (RPN). A cross-sectional prospective observational study was conducted on 106 patients with cT1 renal tumor submitted to RPN. Trifecta was reported as no ≥ 2 Clavien-Dindo complications, warm ischemia time (WIT) ≤ 25 minutes, ≤ 15% postoperative ΔGFR, and nonpositive margins. The mean age was 58 years (SD ± 12). The median (Q1; Q3) tumor size was 3.5 (2.2; 4.5) cm. Of the treated patients, 33% had a ventral tumor. R.E.N.A.L nephrometry score was low complexity in 54% of cases and high complexity in 4%. WIT median (Q1; Q3) was 20 (14; 23) minutes. Estimated blood loss median (Q1; Q3) was 50 (0; 100) ml. There were no conversions to open surgery. ΔGFR was >15% in 17.5% of patients. There were no postoperative complications in 84% of cases. Nonpositive margins were observed. Sixty-eight percent were pT1a and 32% were pT1b. Seventy-two percent of patients presented trifecta. A statistically significant difference was found between trifecta and tumor size (3 cm vs. 4.4 cm; p<0.001), complexity (low complexity 90% vs. intermediate complexity 56%; p<0.0001), and pT (T1a 81% vs. T1b 53%; p<0.003). RPN is a safe and effective treatment modality for T1a and T1b renal tumors. Trifecta rate was 72%. Tumor size, tumor complexity, and pT were found to be an associated factor for trifecta.

Clinical characteristics and long-term outcomes for patients who undergo cytoreductive surgery for thoracic meningiomas: a retrospective analysis.

Primary spinal meningiomas represent a rare indolent neoplasm usually situated in the intradural-extramedullary compartment. They have a predilection for afflicting the thoracic spine and most frequently present with sensory and/or motor symptoms. Resection is the first-line treatment for symptomatic tumors, whereas other clinical factors will determine the need for adjuvant therapy. In this study, the authors aimed to elucidate clinical presentation, functional outcomes, and long-term outcomes in this population in order to better equip clinicians with the tools to counsel their patients. This is a retrospective analysis of patients treated at the authors' institution between 1998 and 2018. All patients with thoracic meningiomas who underwent resection and completed at least one follow-up appointment were included. Multiple preoperative clinical variables, hospitalization details, and long-term outcomes were collected for the cohort. Forty-six patients who underwent resection for thoracic meningiomas were included. The average age of the cohort was 59 years, and the median follow-up was 53 months. Persistent sensory and motor symptoms were present in 29 patients (63%). Fifteen lesions were ventrally positioned. There were 43 WHO grade I tumors, 2 WHO grade II tumors, and 1 WHO grade III tumor; the grade III tumor was the only case of recurrence. The median length of hospitalization was 4 days. Seventeen patients (37%) were discharged to rehabilitation facilities. Thirty patients (65.2%) experienced resolution or improvement of symptoms, and there were no deaths within 30 days of surgery. Only 1 patient developed painful kyphosis and was managed medically. Ventral tumor position, new postoperative deficits, and length of stay did not correlate with disposition to a facility. Age, ventral position, blood loss, and increasing WHO grade did not correlate with length of stay. Outcomes are overall favorable for patients who undergo resection of thoracic meningiomas. Symptomatic patients often experience improvement, and patients generally do not require significant future operations. Tumors located ventrally, while anatomically challenging, do not necessarily herald a significantly worse prognosis or limit the extent of resection.

Minimally Invasive Tubular Separation Surgery for Metastatic Spinal Cord Compression: 2-Dimensional Operative Video.

Symptomatic cord compression affects approximately 20% of patients with spinal metastatic disease. Direct decompressive surgery followed by conventional radiation was shown to be superior to radiation alone in a landmark trial published in 2005.1 For radioresistant tumors causing high-grade compression, however, "separation surgery" followed by stereotactic body radiation therapy was developed. The main goal of this newer technique is to decompress and create a distance between the spinal cord and tumor to allow for safe delivery of radiation.2 This technique has shown to provide durable local tumor control, pain relief, and preservation of neurological function.3,4 In this study, we describe a minimally invasive tubular separation surgery technique used to treat symptomatic cord compression in a 59-yr-old man with metastatic prostate adenocarcinoma to T9. The patient presented with acute motor weakness and sensory level. A tubular retraction system was used to dock over the pedicle at T9 bilaterally and a posterior decompression with ligamentectomy was first performed. This was followed by transpedicular decompression and ventral removal of the posterior longitudinal ligament. Space was created between the ventral tumor and spinal cord to allow for postoperative stereotactic body radiation. The patient had a significant improvement in his strength and gait postoperatively. Patient consent was obtained for videotaping prior to surgical intervention.

Microsurgical Resection of a C1-C2 Dumbbell and Ventral Cervical Schwannoma: 2-Dimensional Operative Video.

Dumbbell schwannoma of the cervical spine is a known entity,1-5 and should be radically resected with the preservation or improvement of neurological function. However, to our knowledge, an operative video of a C1-C2 cervical dumbbell schwannoma with ventral extension and dorsal spinal cord compression has not been reported previously. This tumor resection video performed by the senior author (KIA) includes details of dural opening, and techniques for microsurgical resection and for postoperative closure to avoid cerebrospinal fluid (CSF) leak and pseudomeningocele formation.Fat grafting was performed through a small paraumbilical incision. The patient was prone in MAYFIELD 3-point pin fixation (Integra LifeSciences, Plainsboro Township, New Jersey). Intraoperative neurophysiological electrodes were placed for somatosensory evoked potential (SSEP) and motor evoked potential (MEP) monitoring. Stealth neuronavigation was used to aid in tumor localization. A small suboccipital craniectomy and C1 laminectomy were performed before opening the dura. Using a microsurgical technique, the dura was opened in the form of the letter “Y.” The right-sided dentate ligament was cut to aid in the mobilization of the tumor away from the spinal cord. After dividing the tumor at the dumbbell isthmus, the ventral tumor component was removed, with attention paid to the division of a perforator coming from the vertebral artery. Intraforaminal tumor debulking was performed with a cavitron ultrasonic surgical aspirator (CUSA) and resected.High cervical dumbbell schwannoma should be radically resected while preserving and improving preoperative neurological function. Avoidance of CSF leak and formation of pseudomeningocele should be planned at the beginning, utilizing fascia and fat graft to avoid this feared complication.The patient provided written consent and permission to publish her image.

A Case of Ipsilateral Multifocal Renal Cell Carcinoma Treated with Robot-Assisted Partial Nephrectomy

A 55-year-old male was referred to our hospital for left lower back pain. Computer tomography suggested a left ureteral stone and two left renal tumors at ventral and lateral sites. The ventral tumor measured 7 mm, and it showed intense early enhancement. On the other hand, the lateral tumor measured 22 mm, and it was enhanced weakly. We performed a single-stage robot-assisted partial nephrectomy, because he had chronic renal insufficiency and the two tumors appeared to be different types of renal cell carcinoma. Pathological examination revealed the ventral tumor was clear cell renal cell carcinoma, while the lateral tumor was papillary renal cell carcinoma. He is free of recurrence 1 year and 2 months after operation.

Application of posterior approach for atlantoaxial subdural extramedullary nerve sheath tumors

To investigate the procedure and effectiveness of posterior approach for operation of atlantoaxial subdural extramedullary nerve sheath tumors. Between January 2012 and March 2017, 9 patients with atlantoaxial subdural extramedullary nerve sheath tumors were treated, including 7 males and 2 females, aged 25-62 years (mean, 45.4 years). There were 8 cases of neurinoma and 1 case of neurofibroma. The tumors were located at C1 in 1 case and C1, 2 in 8 cases. The disease duration ranged from 5 to 120 months, with an average of 45.9 months. The neural function was rated as grade D in 8 cases and grade E in 1 case according to the American Spinal Injury Association (ASIA) grading system. The Japanese Orthopaedic Association (JOA) score was 12.8±2.5. All patients underwent posterior cervical surgery. The laminae were replanted and fixed in 2 cases. The atlantoaxial or occipitocervical axis was not fixed in all patients. The operation time was 90-343 minutes, with an average of 179.2 minutes. The intraoperative blood loss was 50-1 000 mL, with an average of 335.6 mL. No relevant complication occurred after operation. All patients were followed up 6-21 months (mean, 11.1 months). The postoperative X-ray films showed the good stability of the cervical spine. All patients had complete tumor resection and no recurrence. The replanted laminae achieved fusion and the internal fixation was firm. According to ASIA grading system, 3 patients of preoperative ASIA grade D had upgraded to grade E at 3 months after operation, while the remaining patients had no change in grading. The JOA score was 15.1±1.4 at 6 months after operation, which was significantly improved when compared with that before operation (t=4.221, P=0.003). The atlantoaxial subdural extramedullary nerve sheath tumor (including the ventral tumor) can be removed completely via posterior approach. The axis lamina can be replanted and fixed with the small titanium plate or lamina screw when necessary, and the atlantoaxial or occipitocervical fixation was not needed.

Hybrid Therapy for Metastatic Epidural Spinal Cord Compression: Technique for Separation Surgery and Spine Radiosurgery.

Despite major advances in radiation and systemic treatments, surgery remains a critical step in the multidisciplinary treatment of metastatic spinal cord tumors. To describe the indications, rationale, and technique of "hybrid therapy" (separation surgery and concomitant spine stereotactic radiosurgery [SRS]) along with practical nuances. Separation surgery describes a posterolateral approach for circumferential epidural decompression and stabilization. The goal is to decompress the spinal cord, stabilize the spine, and create adequate separation between the neural elements and the tumor for SRS to achieve durable tumor control. A transpedicular route to achieve ventrolateral access and limited resection of the tumorous vertebral body is carried out. In the setting of high-grade cord compression, caution must be taken when performing the tumor decompression. "Separation" of the ventral epidural tumor component anteriorly creates space for concomitant SRS while a simple laminectomy would not adequately achieve this goal. Dissection of the posterior longitudinal ligament allows maximal ventral decompression. Gross total tumor resection is not crucial for durable tumor control using the "hybrid therapy" model. Thus, attempts at ventral tumor resection may unnecessarily increase operative morbidity. Cement augmentation of the construct or vertebral body may improve construct stability. CT myelogram is the preferred exam for postoperative SRS planning. Radiosurgical planning constitutes a multidisciplinary effort and guidelines for contouring in the postoperative setting have recently become available. Separation surgery is an effective, well-tolerated, and reproducible surgery. It provides safe margins for concomitant SRS. Combined, this "Hybrid Therapy" allows durable local control, maintenance of spinal stability, and palliation of symptoms, while minimizing operative morbidity.

Clinical study of transperitoneal and retroperitoneal robot-assisted partial nephrectomy for renal hilar tumors

Objective To investigate the clinical value and experience of transperitoneal and retroperitoneal robot-assisted partial nephrectomy for renal hi1ar tumors. Methods We evaluated 48 patients who had partial nephrectomy for renal hilar tumor by robotic surgical syestem from January 2013 to March 2017. In those cases, 35 were male and 13 were female, with an average age of 57.3 (range from 41 to 75 ), 27 cases were ventral tumor and 21 cases were dorsal tumor. 3 cases were totally confined to the renal parenchyma, the other 45 cases were partially confined to the renal parenchyma.18 cases were performed surgery by retroperitoneal route, the rest 30 cases were performed by peritoneal route. Results A total of 48 patients underwent successful robotic partial nephrectomy for renal hilar tumors. The mean warm ischemia time was 22 minutes (range from 16 to 33 minutes) and the mean estimated blood loss was 88 ml (range from 50 to 350 ml). No bleeding-related complications were found. Histopathology confirmed 39 cases of ccRCC, 7 cases of angioleiomyolipoma, 2 cases of renal oncocytoma. There was one case in this review was positive surgical margin (2.1%) and found no sign of recurrence during the short term post-operation follow-up. All cases in this review are following up after surgery to date from 2 months to 4 years, no cases of tumor recurrence or metastasis were found. Conclusions The application of transperitoneal and retroperitoneal RAPN is the effective and safe way for renal hilar tumor resection, and it has a clear advantage of renal surgical incision stitching and tumor complete resection.The choice of surgical approaches depends on the size and location of tumor and the clinical experience of the surgeon. Key words: Kidney cancer; Renal hilar tumor; Robotic surgery; Laparoscopy; Partial nephrectomy

Hearing preservation in acoustic neuroma resection: Analysis of petrous bone measurement and intraoperative application.

Background:There is an increased risk for labyrinthine injury for the resection of acoustic neuromas (AN) on the suboccipital, retrosigmoid approach. Prognostic factors should be analyzed for the postoperative hearing function.Methods:We examined 51 patients with ANs using preoperative intact hearing function. Audiological data were obtained by pure tone audiogram (PTA) and speech audiogram. The preoperative and postoperative anatomical localization of the labyrinth was measured with specific distances regarding the tumor and corresponding anatomy of the posterior fossa by high-resolution magnetic resonance imaging (MRI).Results:Postoperative MRI controls confirmed no injuries to the labyrinth (0%). The postoperative hearing results showed 100% hearing preservation for T1-tumors (<1 ml/<1.1 cm), 50% for T2-tumors (1–4 ml/1.1–1.8 cm), 40% for T3-tumors (4–8 ml/1.8–2.3 cm) and 18% for T4-tumors (>8 ml/>2.3 cm). Postoperative deafness was seen in all cases with ventral tumor extension higher than 5.5 mm. Postoperative loss of hearing was seen in all cases with hearing preservation with 6–8% of speech discrimination and an increase in the hearing threshold of 12 dB in the PTA compared to the preoperative hearing status.Conclusion:Petrous bone measurement by high-resolution MRI data enables safe surgical exposure of the internal acoustic canal with avoidance of injury to the labyrinth and a better postoperative prognosis, especially for intrameatal ANs and for the resection of intrameatal portions of larger neuromas. The prognostic factors enable the patients and the surgeon a better estimation of postoperative results regarding deafness and postoperative hypacusis and support a consolidated treatment planning.

Abstract 804: Combination simvastatin and metformin induces cell death by autophagy and secondary necrosis in osseous metastatic castration-resistant prostate cancer cells

Abstract Limited chemotherapeutic options exist for metastatic castration-resistant prostate cancer (CRPC). We have previously demonstrated that 1:500 combination simvastatin (SIM) and metformin (MET) synergistically inhibits cell viability, invasion, migration, and adhesion-independent cell growth of the C4-2B3 and C4-2B4 in vitro model of osseous metastatic CRPC, and inhibits primary ventral prostate tumor growth, incidence of cachexia and metastasis to femurs and spinal column, and prevents biochemical failure in an orthotopic C4-2B4 mouse model of osseous metastatic CRPC, more effectively than docetaxel, the standard-of-care chemotherapy for metastatic CRPC. Autophagy, apoptosis, and necrosis have all been reported as mechanisms by which SIM or MET induce cell death in prostate cancer cells; however, the mechanism of cell death remains unclear in combination. Therefore, the purpose of this study was to determine the mechanism of cell death associated with the synergistic effect of SIM/MET combination chemotherapy in CRPC cells. Treatment of C4-2B3 and C4-2B4 cells, in vitro models of osseous metastatic CRPC, with 4µM SIM and 2mM MET combination treatment led to an earlier (24h treatment) and more pronounced (&amp;gt;90%) G1-phase cell cycle arrest, which was sustained through 96h treatment. 4µM SIM and 2mM MET treatment, individually or in combination, for up to 96h, does not induce cell death by apoptosis in C4-2B3 and C4-2B4 cells, as determined by &amp;lt;3% of cells staining PI(-)/AV(+), &amp;lt;2% of cells staining Apo-BrdU(+), and no presence of activated cleaved caspase-3 protein expression, in comparison to 2µM camptothecin positive control. Treatment of C4-2B3 and C4-2B4 cells with 1:500 SIM and MET combination led to autophagy by 48h, sustained through 96h, ascertained by significantly increased LC3B-II/LC3B-I ratio, quantity of acidic vesicular organelles, and number of autophagic structures, both in the presence and absence of lysosomal inhibitor chloroquine, compared to untreated CRPC cells. SIM/MET-induced autophagy led to secondary necrosis by 96h which was determined by PI-Annexin V flow cytometry; 67% of C4-2B3 and 64% of C4-2B4 osseous metastatic CRPC cells were PI(+)/AV(-) or PI(+)/AV(+) necrotic following 96h of SIM and MET combination treatment. The caspase-independent necrotic cell death was confirmed by receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) protein expression following 96h SIM/MET combination treatment, in the presence or absence of necrostatin-1 inhibitor. Taken together, combination SIM and MET causes pronounced G1-phase cell cycle arrest in osseous metastatic CRPC cells by 24h, which culminates in cell death by autophagy and secondary necrosis by 48-96h of treatment. Citation Format: Melissa A. Babcook, R. Michael Sramkoski, Christine Z. Oak, Sanjay Gupta. Combination simvastatin and metformin induces cell death by autophagy and secondary necrosis in osseous metastatic castration-resistant prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 804. doi:10.1158/1538-7445.AM2014-804

Direct Decompressive Surgery Followed by Radiotherapy Versus Radiotherapy Alone for Metastatic Epidural Spinal Cord Compression

A systemic review and meta-analysis. To compare the ambulatory status and survival for metastatic epidural spinal cord compression (MESCC) in patients treated with direct decompressive surgical resection (DDSR) followed by radiotherapy (RTx) with those in patients treated with RTx alone. Surgical techniques have remarkably evolved from decompressive laminectomy without ventral tumor excision to DDSR, which has displayed favorable outcomes since the 2000s. RTx alone has also evolved and is regarded to have accomplished outcome comparable with that of the surgery. The optimal treatment of MESCC has not been clearly defined yet. We searched MEDLINE, EMBASE, and the Cochrane library in July 2013. Comparative studies enrolled patients with similar performance, primary cancer, age, and sex at the baseline state were included. Outcome measures included ambulatory status and overall survival rate. We did a fixed-effects meta-analysis of the ambulatory status and survival in patients with MESCC compared with DDSR+RTx and RTx alone. Five studies were used to obtain data from 238 and 1137 patients treated with DDSR+RTx and RTx alone, respectively. The DDSR+RTx group displayed substantial improvement in ambulatory status after the treatment that was superior to the improvement in the RTx-alone group (relative risk [RR], 1.43; 95% confidence interval [CI], 1.14-1.78) in a fixed-effects model and significantly lower deterioration after treatment than the RTx group (RR, 0.35; 95% CI, 0.19-0.63). The DDSR+RTx group showed significant improvement in the survival rate at 6 months post-treatment (RR, 1.21; 95% CI, 1.09-1.33). Similar findings were observed at 12 months post-treatment (RR, 1.32; 95% CI, 1.12-1.56). The meta-analysis indicates that DDSR+RTx may produce better clinical improvement of ambulation status and survival than RTx alone in the treatment of MESCC. Additional prospective studies are warranted to better address this question. 1.

The treatment of spinal metastases.

The rising life expectancy of cancer patients has led to a greater need for treatment of spinal metastases. Interdisciplinary collaboration is important so that each patient's treatment can be properly tailored to the overall prognosis. The main factors to be considered are the histology of the primary tumor, potential spinal instability, and compression of neural structures. We discuss the treatment options for spinal metastases on the basis of a selective literature review and our own extensive experience in an interdisciplinary tumor center. For spinal canal compression or impending spinal instability, the treatment of choice is decompression and stabilization, by either a dorsal approach (lumbar and thoracic spine) or a ventral approach (cervical spine). Radical ventral tumor resection is indicated only for solitary metastases in patients with a favorable long-range prognosis. If the tumor is radiosensitive, radiotherapy is given either as adjuvant treatment after surgery or as the primary treatment for multiple spinal metastases in the absence of an acute neurological deficit. Various fractionation schemes with different total radiation doses are used. Bisphosphonate treatment is an integral component of the overall treatment strategy. The treatment of spinal metastases requires interdisciplinary collaboration and must be tailored to each patient's overall prognosis.

Surgical treatment of primary and secondary malignant tumors of the thoracic and lumbar spine

After considering conservative therapeutic measures, the authors opt for surgical treatment of primary or secondary spinal tumors if neurologic deficits occur or the structural stability of the spine is at risk. The majority of the tumors are located in the ventral section of the spine, i.e., in the vertebral body, and therefore the present authors mainly perform ventral tumor resection and spinal reconstruction (traction implant plus bone cement and ventral traction bracing with the DKS system). In cases with tumor spread over several segments and/or lumbosacral involvement the authors recommend combined ventral and dorsal procedures in order to achieve adequate stability of the vertebral body prosthesis.

Split facial nerve course in vestibular schwannomas

The facial nerve in vestibular schwannomas (VSs) is located on the ventral tumor surface in more than 90% of cases; other courses are rare. A split facial nerve course with two distinct bundles has thus far been described exclusively for medial extrameatal tumors. Between 1996 and 2005, 16 consecutive cases of 241 surgically treated VSs were observed to have distinct splitting of the facial nerve. The mean tumor size measured 27 mm. In one third of the cases, intrameatal tumor extension with obliteration of the fundus was documented. All patients underwent extensive intraoperative neurophysiological monitoring using multichannel electromyography recordings. Patients were reevaluated 12 months after surgery. In all 16 patients, distinct splitting of the facial nerve was demonstrated. The major portion of the facial nerve followed a typical course on the ventral tumor surface. The smaller nerve portion in all cases ran parallel to the brainstem up to the level of the trigeminal root exit zone and crossed on the cranial tumor pole to the internal auditory canal. The two nerve portions rejoined at the level of the porus acusticus. The smaller portion carried fibers exclusively to the orbicularis oris muscle, whereas the major portion supplied all three branches of the facial nerve. In VSs, an aberrant course with distinct splitting of the facial nerve adds considerably to the surgical challenge. Long-term facial nerve results are excellent with extensive neurophysiological monitoring, which allows the differentiation and identification of aberrant facial nerve fibers and avoids additional risks to facial nerve preservation.

Precentral glioma location determines the displacement of cortical hand representation.

Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.

Combined Adrenal Myelolipoma and Pheochromocytoma

A 39-year-old woman had a 2-year history of headache and hyperhidrosis. Magnetic resonance imaging showed 2 right adrenal tumors with different intensities (fig. 1). 131Metaiodobenzylguanidine scintigraphy revealed accumulation at the ventral tumor. Serum levels of norepinephrine were increased (579 pg.1 ml., normal 94 to 322). A %-hour urine sample revealed abnormally increased levels of dopamine (9,206 pg., normal 190 to 7401, norepinephrine (250 pg., normal 26 to 1211, epinephrine (312 pg., normal 3 to 15), normetanephrine (2.25 mglml., normal 0.04 to 0.18) and vanillylmandelic acid (11.2 mglml., normal 0.7 to 7.0). Adrenocorticotropic hormone, cortisol and aldosterone were normal (less than 60 pg./ml., 5.6 to 21.3 pg ld l . and 2 to 3 ng./dl., respectively). Based on these results right adrenal myelolipoma combined with pheochmmocytorna was suspected and surgical extirpation was performed. Pathological evaluation revealed that the ventral tumor was a 47 X 45 X 40 mm. 48 gm. pheochmmocytoma and the dorsal tumor was a 43 X 34 X 30 mm. 23 gm. myelolipoma (fig. 2). Quantitative analysis of

12-O-tetradecanoylphorbol-13-acetate-mediated systemic co-promotion in the murine skin multistage carcinogenesis protocol.

The systemic promoting and co-promoting activities of 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined in a murine skin multistage carcinogenesis protocol. The dorsal skins of female inbred SENCAR (SSIN) mice were initiated with 25 nmol of 7,12-dimethylbenz[a]anthracene (DMBA). Topical treatment of initiated dorsal skin with 20 mg of benzoyl peroxide (BzP) promoted the eventual development of 8-15 dorsal papillomas per mouse. Repeated application of 2 micrograms of TPA to the ventral skins of dorsally initiated mice did not promote the formation of dorsal tumors. However, the latency of dorsal papilloma development was significantly decreased in initiated mice treated with 0.4 or 2 micrograms TPA (ventral application) and promoted with BzP (dorsal application). The co-promoting effects of topically applied TPA could not be mimicked by administering the promoter i.v. Only 6/23 initiated, BzP-promoted SSIN mice developed squamous cell carcinomas (SCC) during a 61 week promotion period. In contrast, during the same time-frame 12/24 and 11/24 BzP-promoted mice cotreated with 2 or 0.4 microgram of TPA developed SCC respectively. Repeated application of 2 micrograms of TPA to the ventral skins of dorsally initiated mice resulted in the development of ventral tumors. Ventral tumor incidence and multiplicities could be dramatically reduced by housing the mice individually, as opposed to collectively, for a day following initiation. Collectively these findings suggest that TPA can function as a co-promoter in the murine skin multistage carcinogenesis model through a systemic mechanism. The systemic co-promoting activity may be mediated by a factor(s) produced by the skin in response to TPA exposure. Furthermore, inter-mouse transfer of topically applied initiator from one cutaneous site to another occurs as a consequence of the huddling habits of mice.