Patients Underwent Tumor Resection Research Articles

Treatment-related changes in functional connectivity in brain tumor patients: A magnetoencephalography study

Widespread disturbances in resting state functional connectivity between remote brain areas have been demonstrated in patients with brain tumors. Functional connectivity has been associated with neurocognitive deficits in these patients. Thus far, it is unknown how (surgical) treatment affects functional connectivity. Functional connectivity before and after tumor resection was compared in primary brain tumor patients. Data from 15 newly diagnosed brain tumor patients were analyzed. Patients underwent tumor resection, and both preoperative (up to five months prior to surgery) and postoperative (up to ten months following surgery) resting state magnetoencephalography (MEG) recordings. Seven of the patients (47%) underwent radiotherapy after neurosurgery. Functional connectivity was assessed by the phase lag index (PLI), a measure of the correlation between MEG sensors that is not sensitive to volume conduction. PLIs were averaged to one short-distance and two long-distance (interhemispheric and intrahemispheric) scores in seven frequency bands. We found that functional connectivity changed in a complex manner after tumor resection, depending on frequency band and functional connectivity type. Post-hoc analyses yielded a significant decrease of interhemispheric PLI in the theta band after tumor resection. This result proved to be robust and was not influenced by radiotherapy or a variety of tumor- and patient-related factors.

Cachexia Worsens Prognosis in Patients with Resectable Pancreatic Cancer

IntroductionPancreatic cancer is the fourth leading cause of cancer-related death in Western countries with a poor prognosis (5-year survival rates, 25% in patients after tumor resection with adjuvant treatment; overall, the 5-year survival rate is about 4%; Jemal et al., CA Cancer J Clin, 55:10–30, 2005). Many patients develop a cachectic status during the progression of the disease, and this syndrome accounts for up to 80% of deaths in patients with advanced pancreatic cancer. Remarkably, there are only a few data available on the impact of cachexia in patients with pancreatic cancer scheduled for tumor resection. Material and MethodsTherefore, in this study, 227 consecutive patients with ductal adenocarcinoma of the pancreas were documented over an 18-month period regarding the prevalence of cachexia and its influence on perioperative morbidity and mortality with a special interest to postoperative weight gain and survival in a prospectively designed database and followed up. ResultsIn 40.5% of the patients, cachexia was already present at the time of operation. The cachectic patients did present in a worse nutritional status, represented by lower protein, albumins, and hemoglobin levels. Despite no significant differences in tumor size, lymph node status, and CA19-9 levels, the resection rate in patients with cachexia was reduced (77.8% vs. 48.9%) due to a higher rate of metastatic disease in patients with cachexia. The morbidity and in-hospital mortality revealed no significant difference. However, patients with and without cachexia lost weight after operation, and the weight gain started not until 6 months after operation. The survival in patients with cachexia was significantly reduced in patients undergoing tumor resection as well as in palliative treated patients. ConclusionCachexia has a significant impact on survival and performance status in palliative patients as well as in patients operated for pancreatic cancer. But tumor-related cachexia is not necessarily dependent on tumor size or load and that metastatic dedifferentiation of the tumor might be a critical step in the development of tumor-associated cachexia.

Intraarterial infusion chemotherapy and conformal radiotherapy for cancer of the mouth: prediction of the histological response to therapy with magnetic resonance imaging

Although intraarterial chemotherapy has been used to treat head and neck cancers, some cases have shown poor response. If we can predict the response to this therapy on MRI, individual treatment plans may be altered to the most appropriate form of treatment. To evaluate whether MRI can predict the histological response to preoperative chemoirradiation in patients with cancer of the mouth. This study comprised of 29 consecutive patients with 30 oral cancers. All patients underwent tumor resection after intraarterial infusion chemotherapy and conformal radiotherapy. We compared the margin of the tumor, the presence of bone invasion, tumor area, and volume on pre- and post-treatment MRI with histological responses. Eighteen lesions showed an excellent response, nine exhibited a good response, and three a poor response. Only the tumor area on pretreatment T1-weighted images and the tumor area and volume on pretreatment enhanced T1-weighted images were significantly correlated with the histological response (P = 0.039, 0.008, and 0.016, respectively); smaller cancers showed better responses. The other factors were not significantly correlated with the histological responses. MRI parameters, excluding initial tumor area and volume, were not predictive of the histological response of oral tumors to preoperative treatment.

Direct Intracerebral Delivery of Cintredekin Besudotox (IL13-PE38QQR) in Recurrent Malignant Glioma: A Report by the Cintredekin Besudotox Intraparenchymal Study Group

Glioblastoma multiforme (GBM) is a devastating brain tumor with a median survival of 6 months after recurrence. Cintredekin besudotox (CB) is a recombinant protein consisting of interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin (PE38QQR). Convection-enhanced delivery (CED) is a locoregional-administration method leading to high-tissue concentrations with large volume of distributions. We assessed the use of intracerebral CED to deliver CB in patients with recurrent malignant glioma (MG). Three phase I clinical studies evaluated intracerebral CED of CB along with tumor resection. The main objectives were to assess the tolerability of various concentrations and infusion durations; tissue distribution; and methods for optimizing delivery. All patients underwent tumor resection followed by a single intraparenchymal infusion (in addition to the intraparenchymal one following resection), with a portion of patients who had a preresection intratumoral infusion. A total of 51 patients with MG were treated including 46 patients with GBM. The maximum tolerated intraparenchymal concentration was 0.5 microg/mL and tumor necrosis was observed at this concentration. Infusion durations of up to 6 days were well tolerated. Postoperative catheter placement appears to be important for optimal drug distribution. CB- and procedure-related adverse events were primarily limited to the CNS. Overall median survival for GBM patients is 42.7 weeks and 55.6 weeks for patients with optimally positioned catheters with patient follow-up extending beyond 5 years. CB appears to have a favorable risk-benefit profile. CED is a complex delivery method requiring catheter placement via a second procedure to achieve accurate catheter positioning, better drug distribution, and better outcome.

Management of Hydrocephalus in Children with Posterior Fossa Tumors: Role of Tumor Surgery

Objective: The majority of children with posterior fossa tumors have hydrocephalus (HC) at the time of presentation. There is no consensus regarding the management of HC in these children. Here, we report the rate of cure of HC with tumor surgery alone. Patients and Methods: This is a retrospective study of 87 children with posterior fossa tumors in which 35 patients had medulloblastoma, 38 had astrocytoma and 14 had ependymoma. The mean age at presentation was 7.3 years (range: 0.2–19.7 years). All patients underwent tumor resection and were followed with close clinical and image surveillance to detect persistent HC. HC was treated with endoscopic third ventriculostomy (ETV) or shunt. We have focused on patients who needed permanent cerebrospinal fluid diversion (ETV or shunt) within 30 days of tumor resection. HC presenting after this time period is, in the majority of cases, due to tumor recurrence or progression. In this series, 24/87 (28%) patients had a suboccipital craniectomy and 63/87 (72%) had a craniotomy. Results: At the time of presentation, 69/87 (79%) patients had symptomatic HC. In 41/69 (59%) patients presenting with HC, the HC was cured by tumor resection alone. The HC cure rate for patients with astrocytoma was 83%, whereas it was 47% for patients with medulloblastoma and 54% for patients with ependymoma. The cure rate was equal in the craniectomy and craniotomy groups. Conclusions: An 87% cure rate of HC by tumor resection alone in children with posterior fossa astrocytoma warrants no change in treatment strategy. However, the low cure rate of HC by tumor resection alone in patients with medulloblastoma and ependymoma raises the issue of whether these patients would benefit from preresection ETV.

The Effect of Stress-Reducing, Low-Dose Ethanol Infusion on Frequency of Bleeding Complications in Long-Term Alcoholic Patients Undergoing Major Surgery

Perioperative low-dose ethanol infusion is a feasible option for stress reduction and prophylaxis of alcoholism-associated complications. Because alcohol has inhibitory effects on hemostasis, our study focused on the effect of perioperative low-dose ethanol infusion on bleeding complications, defined as transfused blood units and reoperations, in alcoholic patients undergoing major surgery. We included 44 long-term alcoholic patients scheduled for tumor resection of the aerodigestive and gastrointestinal tract. Patients were randomly assigned to the ethanol or control group. Ethanol infusion (0.5 g ethanol/kg body weight/24 hours) started before surgery and was continued until the postoperative Day 3. Regarding all patients, there was no statistically significant difference in the amount of transfused blood between the ethanol and control groups. However, the effect of ethanol infusion on bleeding complications depended on the site of surgery. Ethanol infusion resulted in an increased number of transfused blood units in gastrointestinal patients and a decreased number of transfused units in patients undergoing tumor resection of the aerodigestive tract. In conclusion, perioperative ethanol infusion in long-term alcoholic patients with tumor resections of the aerodigestive tract is an option for stress reduction without increased risk for blood transfusion. In contrast, ethanol infusion in patients with tumor resections in the gastrointestinal tract could increase the risk for bleeding complications.

Intraoperative Risk of Seizures Associated With Transient Direct Cortical Stimulation in Patients With Symptomatic Epilepsy

Direct cortical stimulation--either with the 60-Hz stimulation or the train-of-five technique--is commonly agreed on being the gold standard for intraoperative mapping of the motor cortex and the motor pathways but may result in an intraoperative seizure. The occurrence of intraoperative stimulation associated seizures with respect to symptomatic epilepsy was evaluated in a group of 129 patients undergoing tumor resection within the central region. Data were reviewed with respect to the frequency of seizures with both stimulation techniques and symptomatic epilepsy. Direct stimulation of the motor cortex was performed with a train of five consecutive pulses, an interstimulus interval of 4 ms, an individual pulse width of 0.5 ms, and 40 mA stimulation intensity at maximum. In 1 of 63 patients (1.6%) presenting with symptomatic epilepsy, a stimulation-associated seizure occurred, and 1 of the other 66 patients (1.5%) had a seizure (n.s., not significant). In the literature, stimulation associated seizures are reported in 1.2% with the train-of-five technique and significantly more frequently in 9.5% with the 60-Hz technique (P < 0.001). In summary, there is no increased risk of the occurrence of stimulation-associated seizures during surgery for patients with symptomatic epilepsy compared with those patients without.

Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features.

The p53 gene mutation is closely related to carcinogenesis in most malignant diseases. The main function of wild p53 protein is to maintain the integrity of genes by detecting mutations and preventing the division of cells with damaged DNA. The mutated form of p53 protein is overexpressed due to an extended half-life and can be easily detected by immunohistochemistry. To estimate the frequency of p53 protein overexpression in colorectal carcinoma and its correlation with some clinicopathologic variables. One hundred paraffin-preserved colorectal carcinoma samples were collected randomly from patients undergoing tumor resection from April 1995 through April 2001 in Omid Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The overexpression of p53 protein was studied using a monoclonal antibody (clone DO-7; Dako). The number of cells stained were classified semiquantitatively as (-): <5% positive cells, (+): 5 - 25% positive cells, (++): 25 - 75% positive cells, and (+++): >75% positive cells. Clinicopathologic data including gender, age, tumor location, histologic type, and stage (Astler-Coller) were collected from the files maintained at the Department of Pathology. The correlation between p53 protein overexpression and each variable was evaluated using Chi-square analysis. p53 staining was positive in 59 of 100 specimens. Out of these 100 specimens, 16 were weekly (+), 16 moderately (++), and 27 intensely (+++) positive for p53 protein over-expression. There was no significant correlation between p53 staining and gender (P = 0.34), age (< 40 vs. > or = 40 yr; P = 0.74), site of tumor (right vs. left colon and rectum; P = 0.26), pathologic type (mucinous vs. nonmucinous; P = 0.63), and stage of the disease (P = 0.12). Considering the p53 protein overexpression in a relatively high percentage of patients, it seems that p53 mutation plays an important role in development of colorectal carcinoma. There was no significant association between p53 protein expression and some common clinicopathologic variables such as age, gender, site of tumor, pathologic type, and stage of the disease.

Incidence of De Novo Nonmelanoma Skin Tumors After Liver Transplantation for Alcoholic and Nonalcoholic Liver Diseases

Introduction Skin tumors are the most common malignancies after orthotopic liver transplantation (OLT). They have been related to sunlight exposure, tobacco consumption, and immunosuppression. The aim of this study was to compare the incidence of de novo skin tumors (nonmelanoma) in patients who underwent liver transplantation for alcoholic cirrhosis versus nonalcoholic diseases. Patients and Methods Between April 1986 and July 2004, we performed 1000 OLT in a population of 888 recipients. This study was performed in a sample of 701 adult recipients who survived >2 months after transplantation: 276 patients (39.4%) underwent OLT for alcoholic cirrhosis (AC-group), and 425 (60.6%) for nonalcoholic disease (N-AC). The overall incidence of de novo skin tumors was 3.5% (25 tumors): 5.4% (15 tumors) in the AC-group and 2.4% (10 tumors) in the N-AC group ( P = .027). Two patients developed two tumors. There were 19 men and 4 women, mean age at OLT of 54.4 ± 6.8 years (range, 40 to 66 years). The mean time from OLT to tumor diagnosis was 66.1 ± 51.4 months (range, 3 to 165 months): 56.4 ± 44.4 months in the AC-group versus 80.6 ± 59.8 months in the N-AC group ( P = NS). Histologically, 17 tumors (68%) were basal cell carcinomas and eight tumors (32%) were squamous cell carcinomas ( P = .128). Fourteen patients (60.8%) were smokers: 11 patients (84.6%) in the AC-group versus 3 patients (30%) in the N-AC group ( P = .012). All the patients underwent tumor resection, with only one patient dying, because of lymph node invasion of the neck. Conclusion There was a higher incidence of de novo skin tumors among patients who smoked who underwent OLT for alcoholic cirrhosis.

Gradual Formation of an Operative Corridor by Balloon Dilation for Resection of Subependymal Giant Cell Astrocytomas in Children with Tuberous Sclerosis: Specialized Minimal Access Technique of Balloon Dilation

Major sources of morbidity and mortality in patients with tuberous sclerosis who develop subependymal giant cell astrocytomas (SEGAs) relate to tumor growth and resultant hydrocephalus. We describe a modification of a specialized minimal access resection technique in which an operative corridor is formed with balloon dilation over the course of a week prior to tumor resection. Three patients with tuberous sclerosis who had an enlarging SEGA and concomitant hydrocephalus underwent surgical resection with this modified technique. A frontal craniotomy was performed and the optimal trajectory for tumor resection was confirmed by image guidance. After initial insertion of the deflated balloon into the ventricle and removal of the peel-away sheath, inflation of the balloon with a 1-mL saline injection sealed the tract. Additional 1-mL saline injections were continued during the next week until the balloon reached a 15-mm diameter, thus creating the operative corridor. One week after the first operation, the balloon was deflated and removed, and the patient underwent tumor resection via the newly formed operative corridor. Three patients with tuberous sclerosis underwent gross total resections of SEGAs and experienced subsequent resolution of ventricular dilation. Postoperative imaging confirmed minimal cortical disruption. Use of balloon dilation for the gradual formation of an operative corridor eliminated the need for additional retraction during SEGA resection, potentially decreasing injury to the surrounding neural tissue. In our three patients, the dilation tract retained its integrity during the operation and had sealed completely on postoperative imaging.

Glioblastoma multiforme with diffusion-weighted magnetic resonance imaging characteristics mimicking primary brain lymphoma

The authors report on the first case of corpus callosum glioblastoma multiforme (GBM) with diffusion-weighted (DW) magnetic resonance (MR) imaging findings that mimicked those for lymphoma but with MR spectroscopy results absent of lymphoma characteristics. This 68-year-old man presented with rapid, progressive impairment in short-term memory as well as slow responses and a change in his personality within 3 weeks of admission. Results of cranial computed tomography revealed a slightly hyperdense corpus callosum tumor with bihemispheric involvement. Magnetic resonance images showed a homogeneous mass with strong enhancement. The mass showed water restriction on DW MR images and apparent diffusion coefficient (ADC) maps but no markedly elevated lipid resonance on MR spectroscopy. The patient underwent tumor resection. Results of pathological studies with immunohistochemical analysis confirmed that the lesion was GBM. Diffusion-weighted MR imaging together with ADC mapping and MR spectroscopy was reported to be useful in differentiating GBM and primary brain lymphoma. The lymphomas were hyperintense to gray matter on DW MR images and isointense to hypointense on ADC maps because of water restriction. In contrast, the GBMs were hyperintense to gray matter on both DW MR images and ADC maps because of the T2 shine-through effect. On MR spectroscopy, lipid resonance was markedly elevated in lymphoma but only slightly elevated in GBM.

Use of Diffusion Weighted Mriin Predicting Early Post-Operative Outcome of a New Neurological Deficit Afterbrain Tumor Resection

To study risk factors for the development of postoperative neurological deficits after brain tumor resection and to define prognostic factors for recovery. We prospectively studied 82 brain tumor patients undergoing tumor resection. Pre- and postoperative neurological examination, functional and performance status, cancer treatment, cardiovascular risk factors, seizure history, and blood pressure and oxygen saturation were recorded perioperatively. Postoperative magnetic resonance imaging scans were obtained within 72 hours of surgery, and the radiologist was blinded to the patient's status. Abnormalities on magnetic resonance diffusion weighted images were classified as new if they extended beyond the tumor cavity margins and were absent before surgery. Of the 80 assessable patients, 24 had a new or increased postoperative deficit by at least one point on the National Institutes of Health Stroke Scale. Presence of preoperative neurological deficits predicted development of postoperative deficits, whereas a new diffusion weighted imaging lesion after craniotomy predicted incomplete recovery of a new postoperative deficit. Postoperative diffusion magnetic resonance imaging is useful in predicting early functional recovery from new deficits after brain tumor surgery.

Thymidylate synthase expression in resectable and unresectable pancreatic cancer: role as predictive or prognostic marker?

Thymidylate synthase (TS) is an important enzyme for DNA synthesis and the target for 5-fluorouracil (5-FU). Its expression may determine the outcome of patients with gastrointestinal cancers. We examined the prognostic and predictive value of TS-protein expression in patients with ductal adenocarcinoma of the pancreas. TS expression from 131 patients with ductal adenocarcinoma of the pancreas was analyzed by immunohistochemistry in paraffin-embedded primary tumour specimens or biopsies. The median disease-specific survival among all patients (n=131) was 13 months. The invasion depth, the presence of metastases, grading and Union Internationale Contre le Cancer [International Union Against Cancer] (UICC) stage were associated with survival. Among resected patients (n=98), a difference in median survival was seen in the group receiving postoperative adjuvant treatment (21.1 months) compared with the group treated by surgery alone (12.4 months) (p=0.025). Low- and high-TS immunoreactivity was present in 74 (56%) and 56 (43%) of the cancers, respectively. One sample was not evaluable. No difference in median survival was observed among low- and high-TS-expressing tumours. Among patients undergoing resection and receiving postoperative intra-arterial chemotherapy (n=23), a marked trend to a longer median survival was seen for the group with low-TS-expressing tumours compared with the corresponding high-TS group (25.0 vs 16.0 months) (p=0.3834). There was no difference in survival among all palliative treated patients with low- and high-TS-expressing tumours. Especially patients undergoing tumour resection with low-TS values seemed to have taken advantage from an intensified postoperative chemotherapeutic protocol. However due to the heterogeneous group of patients in the present report, larger trials of more homogenous patient populations will be necessary to confirm this hypothesis.

Rapid Growth of Mucinous Cystic Adenoma of the Pancreas Following Pregnancy

A 25-yr-old woman delivered a healthy child by cesarean section. At 8 mo postpartum, she became aware of an upper abdominal tumor. Abdominal computed tomography and upper abdominal ultrasonography revealed a large cystic mass in the body of the pancreas. Endoscopic retrograde pancreatography showed no connection between the main pancreatic duct and the cystic lesion. The patient underwent tumor resection at 11 mo postpartum. Pathological examination of the tumor revealed mucin-producing columnar epithelial cells lining the cystic wall with ovarian-type stromal tissue and no findings indicative of malignancy, giving a diagnosis of mucinous cystic adenoma of the pancreas. Immunohistochemical studies revealed positive staining for progesterone receptor but not for estrogen receptor in the stromal cell nuclei. Postpartum rapid growth of a benign mucinous cystic neoplasm might be linked to the production of female sex hormones during lactation.

Primary Fibrosarcoma of the Liver Infiltrating the Right Atrium of the Heart

A rare case of a primary fibrosarcoma of the liver infiltrating the right heart is described in a 72-year-old woman. The patient presented with a history of progressive dyspnea and ascites and her general condition was poor. Preoperative cardiac magnetic resonance (CMR) imaging revealed a large mass, which originated from the liver and had infiltrated the right atrium via the inferior vena cava. The patient underwent tumor resection yet died shortly afterwards. Histologically the mass was classified as a fibrosarcoma with positive immunostaining for vimentin. We report the CMR imaging characteristics in this uncommon case. Preoperative CMR proved to be useful for clinical decision making and the planning of surgery.

Tumors of the endolymphatic sac in patients with von Hippel–Lindau disease: implications for their natural history, diagnosis, and treatment

Object Endolymphatic sac tumors (ELSTs), which often are associated with von Hippel–Lindau (VHL) disease, cause irreversible hearing loss and vestibulopathy. Clinical and imaging surveillance protocols provide new insights into the natural history, mechanisms of symptom formation, and indications for the treatment of ELSTs. To clarify the uncertainties associated with the pathophysiology and treatment of ELSTs, the authors describe a series of patients with VHL disease in whom serial examinations recorded the development of ELSTs. Methods Patients with VHL disease were included if serial clinical and imaging studies captured the development of ELSTs, and the patients underwent tumor resection. The patients' clinical, audiological, and imaging characteristics as well as their operative results were analyzed. Five consecutive patients (three men and two women) with a mean age at surgery of 34.8 years and a follow-up period of 6 to 18 months were included in this study. Audiovestibular symptoms were present in three patients before a tumor was evident on neuroimaging. Imaging evidence of an intralabyrinthine hemorrhage coincided with a loss of hearing in three patients. Successful resection of the ELSTs was accomplished by performing a retrolabyrinthine posterior petrosectomy (RLPP). Hearing stabilized and vestibular symptoms resolved after surgery in all patients. No patient has experienced a recurrence. Conclusions Audiovestibular symptoms, including hearing loss, in patients with VHL disease can be the result of microscopic ELSTs. Once an ELST has been detected, it can be completely resected via an RLPP with preservation of hearing and amelioration of vestibular symptoms. Early detection and surgical treatment of small ELSTs, when hearing is still present, should reduce the incidence and severity of hearing loss, tinnitus, vertigo, and cranial nerve dysfunction, which are associated with these tumors.

Ergebnisse der chirurgischen Therapie beim Papillen- und Pankreaskarzinom sowie Prognoseparameter nach R0-Resektion

Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates.Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model.Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic factor was R0-resection. In addition, prognosis after successful R0-resection is determined significantly by tumor site, stage of the tumor (according to UICC), T- and N-category.Resection of pancreatic and ampullary carcinoma according to oncological criteria with tumor-free margins can be considered a treatment option with curative intention and potential. Despite relative high postoperative morbidity, only a low mortality rate was observed. The 5-year survival-rate of 16.2 % in ductal pancreatic carcinoma underlines the demand for the development of effective multimodal therapeutic concepts. Interventions with primary palliative intention or resections with microscopically or macroscopically detectable tumor residual in situ lead to no significant or only marginal prolongation of survival time. Such interventions in patients with pancreatic carcinoma are no reasonable treatment alternative. They are of value only for treatment of tumor-associated complications and problems.

Final results of phase I/II studies of IL13-PE38QQR administered intratumorally (IT) and/or peritumorally (PT) via convection-enhanced delivery (CED) in patients undergoing tumor resection for recurrent malignant glioma

1506 Background: IL13-PE38QQR (IL13PE) is a recombinant cytotoxin which binds selectively to the IL13 receptor that is over-expressed on malignant glioma cells. CED utilizes positive pressure infusion to achieve loco-regional delivery of therapeutic agents via intracerebral catheters. Given the infiltrative nature of malignant glioma, two approaches were examined in three Phase I/II studies. Methods: IL13PE was infused IT before resection, and/or PT after resection. Safety and tolerability of IL13PE, different dosing regimens, catheter positioning, and efficacy as measured by overall survival (OS) were evaluated. The distribution of an imaging tracer co-infused with IL13PE was also assessed by SPECT. Results: Enrollment is complete; 74 adult patients received IL13PE. Dose-limiting toxicity consisted of non-specific necrosis of tumor-infiltrated and normal brain parenchyma which occurred at 1.0 μg/mL with PT administration. The maximum tolerated dose for PT infusions was 0.5 μg/mL. Higher concentrations (up to 3 μg/mL) were tolerated in the IT setting. The most common drug related adverse events were headache (31%), hemiparesis (16%), and fatigue (11%). SPECT imaging showed that distribution was confined to the solid tumor with IT infusion, but distribution to parenchyma at risk for tumor infiltration could be achieved with PT infusion. Improved OS was observed in patients with glioblastoma multiforme (GBM) receiving PT infusions (45.9 wks, n=45) as compared to patients given IT infusion (37.1 wks, n=22). In the PT setting, OS was 70.3 weeks (n=26) for patients with ≥2 optimally placed catheters compared to 41.4 weeks (n=19) for those with <2 optimally placed catheters. Deferred catheter placement led to a greater percentage of optimally placed catheters. Conclusions: CED of IL13PE has a favorable risk/benefit profile for treatment of patients with GBM undergoing tumor resection. Based on these results, the design of the ongoing Phase III study incorporates deferred catheter placement and PT infusion of 0.5 μg/mL of IL13PE. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm

Primitive Neuroectodermal Tumor of the Uterus: A Case Report

Primitive neuroectodermal tumors (PNETs) are a group of unusual malignancies arising in the bone and soft tissue. Pure uterine neuroectodermal tumors are rare. We report the first case of PNET arising from the uterus in our hospital. A 52-year-old perimenopausal woman had multiple myoma and was regularly followed-up in our hospital. She suddenly developed lower abdominal pain without vaginal bleeding. Sonography revealed a pelvic mass measuring 10.7 × 6.8 cm with multiple myoma. The patient underwent tumor resection. There were multiple necrotic tumors on the uterus, bladder, broad ligaments, cardinal ligaments, and cul-de-sac. Final pathology revealed PNET because tumor cells were CD99 positive. PNETs belong to the Ewing's sarcoma family. They are closely related to malignant, small round-cell tumors of soft tissue and bones. They strongly express the glycoprotein p30/32 (CD99) on the cell membrane, which is encoded by the MIC2 gene. A translocation at t(11;22)(q24;q12) has been identified. PNETs are mostly recognized by the histologic characteristics of neural differentiation and immunohistochemical expression of at least two different neural markers. Uterine PNETs have a poor prognosis and, to date, there is no standard treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy plus adjuvant chemotherapy or radiotherapy are recommended.

Selected Papers: Neuroimaging

Abstract *Taketoshi Maehara, *Tadashi Nariai, †Nobutaka Arai, ‡Kensuke Kawai, ‡Hiroyuki Shimizu, §Kenji Ishii, §Kiich Ishiwata, and *Kikuo Ohno *Neurosurgery, Department of Brain Medical Science, Tokyo Medical and Dental University; Bunkyo-ku ; †Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu ; ‡Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital; Fuchu ; §Tokyo Metropolitan Institute of Gerontology; Itabashi, Tokyo, Japan . Purpose: We assessed the diagnostic value of 11C-methionine (MET)-PET in the differential diagnosis of benign tumors presenting with temporal lobe epilepsy. Methods: This series consisted of seven patients who had a type of complex partial seizure (CPS) associated with temporal lobe epilepsy, and were found to have benign tumors in the temporal lobe. They included three males and four females, ranging in age from 13 to 48 years. The age at seizure onset ranged from 6 to 26 years old, and the time to operation ranged from 2 to 28 years. High-resolution magnetic resonance imaging (MRI) with a 1.5 T magnet revealed organic lesions in the temporal lobes. MET-PET was performed in all seven patients, and 18F-fluoro-2-deoxy-glucose (FDG)-PET was performed in four patients. After presurgical examinations including repeated EEGs, video-EEG monitoring, and neuropsychological testing, three patients underwent invasive monitoring for focus detection and functional mapping. All seven patients underwent tumor resection together with focus excision under intraoperative ECoG guidance. Using the image analysis software Dr. View (Asahi Kasei Joho, Tokyo, Japan) on a personal computer, the region of interests (ROIs) were placed on the tumor and contralateral brain over the MRI, and then transferred to the PET images co-registered with MRI. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV), a value calculated by dividing the brain activity of tracer per volume of brain by the injected activity of tracer per body weight. Surgical specimens were examined to investigate the tumor histology and Ki-67 labeling index. Microdygenesis of the resected foci was also examined. Statistical significance of differences in MET uptake between patients with dysembryoplastic neuroepithelial tumor (DNT) and those with ganglioglioma and gliomas was analyzed using the SUV and L/C ratio by the Student's t test. Results: After surgery, six patients remained seizure-free and one achieved a rare-seizure outcome for at least 6 months. The tumor was identified as high MET uptake lesion in three cases and was not depicted on MET-PET in four patients. Among the four patients who underwent FDG-PET, two patients showed high MET uptake in the tumor. However, all four patients showed low glucose uptake in the tumor and surrounding cerebral cortex. Pathological examination demonstrated DNTs in four cases, ganglioglioma in one case, low grade astrocytoma in one case, and pleomorphic xanthoastrocytoma (PXA) in one case. One patient with DNT showed a number of ectopic neurons in the white matter, a finding compatible with microdysgenesis. Ki-67 labeling index was 4% in one patient with DNT and 5% in one patient with PXA. The labeling index of the remaining five patients was 1% or lower. While four patients with DNT did not show visually high MET uptake, ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake-lesions. MET uptake was significantly higher in patients with gliomas than in patients with DNT (SUV: P = 0.045, L/C ratio: P = 0.0079). The Ki-67 labeling index was not related to MET uptake expressed in SVU (P = 0.91) and L/C ratio (P = 0.38). Conclusion: In the seven patients with temporal lobe epilepsy and benign tumors in this study, we observed a high MET uptake in brain gliomas but not in DNTs. This high MET uptake was not related to the proliferation capacity measured by Ki-67 labeling index. MET-PET was useful for the differential diagnosis of DNT.