Stereotactic Radiotherapy for Cushing's Disease and Prolactinoma

Stereotactic radiotherapy (SRT) for secretory pituitary adenoma offers precise localization of dose with potential sparing of optic and hypothalamic functions. We collated the indications, treatment parameters, and both the clinical and biochemical results of Stereotactic radiotherapy for ACTH- 1 and prolactin-secreting pituitary adenoma. Between May 1990 and February 1996, nine patients (4 males and 5 females) with a mean age of 31.9 years had fractionated SRT for ACTH- or prolactin-secreting pituitary adenomas (Cushing's disease: n = 5; prolactinoma: n = 3; Nelson's syndrome: n = 1). These 9 patients had subtotal transphenoidal resections before SRT. An additional patient with Cushing's disease had aborted transphenoidal surgery and single-fraction Stereotactic radiosurgery (SRS). Prior to SRT, 4 patients received planned conventional fractionated external beam radiotherapy (XRT) (median dose 33.3 Gy). The median SRT dose was 34.5 Gy (range 14.4–50.4 Gy). The median total radiation dose (XRT plus SRT) for patients receiving fractionated treatment was 47.7 Gy. The median follow-up was 62 months (range 22–91 months). One patient with Nelson's syndrome was lost to follow-up. Of the 9 evaluable patients, none required reoperation for growth of pituitary tumor and all had radiographic control as shown by serial MRI scans. In 4 of the 6 patients with Cushing's disease, treatment resulted in normalization of hormone levels and resolution of symptoms. All 4 patients were able to discontinue medications. In 2 patients, normalization occurred within 4 months of treatment. Two patients with Cushing's disease failed, requiring adrenalectomy. For patients with prolactinoma, treatments resulted in a significant decrease of plasma prolactin levels. All patients treated for prolactinoma became asymptomatic; 2 were able to discontinue bromocriptine and 1 patient had a successful pregnancy. After radiation therapy, 1 patient developed new hypopituitarism. None of the patients developed worsened visual acuity, visual fields, or new neurological deficits. SRT with or without XRT may yield meaningful reductions in hormone levels with concomitant clinical improvement in selected patients with prolactinomas or Cushing's disease. In certain situations, combining conventional XRT with SRT is appropriate. Modifications of the Stereotactic radiation delivery may maximally reduce the hypothalamic dose, thereby possibly reducing the risk of clinical hypopituitarism. This treatment is safe and is without visual or other neurological toxicity.     

Stereotactic Radiosurgery for Patients with Single Brain Metastasis

The efficacy of stereotactic radiosurgery (SRS) was evaluated for patients with single brain metastasis from extracranial primary cancer and the outcome was compared with that of external whole brain irradiation (WBI) alone or with surgical resection. Between January 1976 and December 1996, 225 patients with single brain metastases were treated in the Department of Therapeutic Radiology—Radiation Oncology at the University of Minnesota Hospital. One hundred six patients (47%) were treated with WBI alone (Group 1), 71 patients (32%) underwent surgical resection prior to WBI (Group 2), and 48 patients (21%) underwent SRS ± WBI (Group 3). The most common site of primary cancer was the lung (40%), followed by breast (14%), unknown primary (11%), skin (malignant melanoma, 9%), gastrointestinal tract (8%), kidney (renal cell carcinoma, 8%), gynecological organs (3%), and other (6%). Median dose to the whole brain was 3750 cGy in 15 fractions (range, 2000–5000 cGy). Median radiosurgical dose of 1750 cGy (range, 1200–4000 cGy) was delivered to the 40 to 90% isodose line encompassing the target. Actuarial survival was calculated from the date of treatment using the Kaplan–Meier method and statistical significance was assessed with the log-rank test. Actuarial median survival was 3.8 months for Group 1 (range, 1–84 months), 10.5 months for Group 2 (range, 1–125 months), and 9.8 months for Group 3 (range, 1–51 months). Survival at 1 and 2 years was 20% and 8% for Group 1, 47% and 18% for Group 2, and 37% and 27% for Group 3, respectively. Group 2 (surgery + WBI) and Group 3 (SRS ± WBI) had a statistically significant survival advantage over Group 1 (WBI alone) (p < 0.0001, log-rank test). No survival advantage was found between Groups 2 and 3 (p = 0.69, log-rank test). Our retrospective data suggest that SRS (± WBI) improves survival when compared to WBI alone and is comparable to surgical resection and WBI. Given that SRS is minimally invasive, is able to treat lesions in surgically inaccessible locations, and is potentially more cost-effective than surgery, it is a reasonable and potentially more attractive alternative to surgery in the management of single brain metastasis.     

Stereotactic Radiosurgery for Human Glioma: Treatment Parameters and Outcome for Low vs. High Grade

Stereotactic radiosurgery (SRS) offers the precise, local delivery of radiation for the treatment of recurrent gliomas. We examined the comparative characteristics, treatments, and outcome in a population having with low– and high–grade gliomas. Between September 1991 and December 1995, 20 patients (13 males, 7 females) had SRS for low-grade [9 patients: World Health Organization (WHO) grade II] vs. high-grade (11 patients: 9 WHO grade IV and 2 WHO grade III) gliomas. The patients with low-grade gliomas were younger (mean age ± SE, 39.6 ± 5.4 years; range, 11.4–61.0 years) than those with high-grade gliomas (51.3 ± 13.9 years; range, 32.9–78.5 years) (P = 0.09). Tumor locations were similar in the two groups: lobar for 7 of 9 low-grade vs. 9 of 11 high-grade gliomas (P = NS) and diencephalic or cerebellar for the remainder. The initial surgical treatments were biopsy, subtotal resection, and total resection for three, three, and three patients with low-grade gliomas, vs. three, seven, and one patients with high-grade gliomas, respectively (P = NS). Except for three patients with low-grade gliomas, all patients had conventional postoperative fractionated external-beam radiotherapy. The doses were 5583 ± 342 vs. 5345 ± 261 cGy (P = NS) for low- vs. high-grade gliomas, respectively. Intervals from surgery and conventional radiation (if given) to progression and SRS tended to be longer for low-grade gliomas: 37.5 ± 9.5 vs. 30.6 ± 11.1 months (P = NS) for low- vs. high-grade gliomas, respectively. High-grade gliomas were larger. The diameters of the collimators that allowed enclosure of the enhancing tumor volume within the specified treatment isodoses were 22.4 ± 2.0 mm for low-grade vs. 29.8 ± 2.8 mm for high-grade gliomas (P = 0.02, ANOVA). SRS doses and isodose percentiles were similar, however, for the two groups: 1650 ± 191 cGy and 79 ± 4.0% vs. 1932 ± 182 cGy and75 ± 3.5% for low- vs. high-grade gliomas, respectively (P = NS, dose and isodose). All patients with high-grade gliomas were followed until death. The mean survival after SRS was 11.6 ± 1.5 months (42 ± 12 months after surgery). Five of nine patients with low-grade gliomas expired 31.6 ± 6.0 months after SRS (P < 0.001, Kaplan–Meier log rank) (74.0 ± 16.0 months after surgery). The four survivors have been followed for 8, 13, 35, and 38 months after SRS, respectively. Multivariate analysis shows that the category of histologic grade correlates significantly with survival after radiosurgery (P = 0.01). SRS may be an important therapeutic option for patients with recurrent gliomas, regardless of their grade.     

Gamma Knife Radiosurgery of Skull Base Meningiomas

Summary  Background. The standart surgical treatment of meningiomas is total resection of the tumour. The complete removal of skull base meningiomas can be difficult because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an effective therapy, either for adjuvant treatment in case of subtotal or partial tumour resection, or as solitary treatment in asymptomatic meningiomas.  Method. Between September 1992 and October 1995, SRS using the Leksell Gamma Knife was performed on 46 patients (f:m=35:15), ranging in age from 35 to 81 years, with skull base meningiomas at the Neurosurgical Department of the University of Vienna. According to the indication of gamma knife radiosurgery (GKRS) the patients (n=46) were devided into two subgroups. Group I (combined procedure: subtotal resection followed by GKRS as a planned procedure or because of a recurrent meningioma), group II (GKRS as the primary treatment). Histological examination of tumour tissue was available for 31 patients (67%) after surgery covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes.  Findings. The overall tumour control rate after a mean follow-up period of 48 months (ranging from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas). Group I displayed a 96.7% tumour control rate, followed by group II with 93.3% respectively. Neurological follow-up showed an improvement in 33%, stable clinical course in 58% and a persistant deterioration of clinical symtoms in 9%. Remarkable neurological improvement after GKRS was observed in group II (47%), whereas in group I (26%) the amelioration of symptoms was less pronounced.  Interpretation. GKRS in meningiomas is a safe and effective treatment. A good tumour control and low morbidity rate was achieved in both groups (I, II) of our series, either as a primary or adjunctive therapeutic approach. The planned combination of microsurgery and GKRS extends the therapeutic spectrum in the treatment of meningiomas. Reduction of tumour volume, increasing the distance to the optical pathways and the knowledge of the actual growing tendency by histological evaluation of the tumour minimises the risk of morbidity and local regrowth. Small and sharply demarcated tumours are in general ideal candidates for single high dose-GKRS, even after failed surgery and radiation therapy, and in special cases also in larger tumour sizes with an adapted/reduced margine dose.     

Permanent I Interstitial Radiation Therapy in the Treatment of Non-GBM High-Grade Gliomas

This study evaluates prognostic factors influencing survival outcomes for 50 patients with permanent¹²⁵ iodine-125 implants in the primary treatment of non-GBM high-grade gliomas. Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/hour with ¹²⁵I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan–Meier method for unvariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 31 patients received external radiation therapy (5000 to 6000 cGy) before the implant; 10 patients were implanted without additional external beam radiation, and 9 patients underwent external radiation therapy before implant placement. With a mean follow-up of 40.76 months (range 3.47–87 months); 1–, 3–, and 5-year survival were 78.5% (± .05%), 58.7% (± .07%), and 56.2% (± .07%) respectively. Since 56.2% of the patients were alive at 5 years, median survival has not been reached yet. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%), and brain abcess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky, and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location, and preoperative Karnofsky greater than 70. Surgical treatment of patients with non-GBM high grade gliomas combined with external beam radiation and permanent ¹²⁵I implants represent a valuable alternative for the treatment of patients with malignant gliomas, allowing patients good quality of life and long survival.     

Surgical treatment of cerebellopontine angle meningiomas in elderly patients

Summary Background. The aim of this study is to assess the morbidity and mortality of meningioma surgery in patients over 70 years of age harbouring a tumour at the cerebellopontine angle as one representative location of the posterior fossa in comparison with a matched group of young patients.Method. A retrospective analysis based on clinical charts, surgical records, histological records, imaging studies and follow up records was conducted to select patients over 70 years who underwent surgery for cerebellopontine angle meningiomas. Tumours with comparable size and location were matched with the younger group.Findings. There were 421 meningiomas located in the cerebellopontine angle, 21 patients were older than 70 years (range 70–84). Median Karnofsky-Index at presentation was 80 (50–90), 16 patients had a physical status grading ASA 2 and 5 patients ASA 3. The average length of hospital stay was 22 days (7–99 days). The postoperative median Karnofsky score at time of discharge was 80 (50–90). The most common medical complication was postoperative pneumonia in 4 patients, among them 3 patients had lower cranial nerve disturbances postoperatively. There were 56 younger patients (mean age 52.4 years; range 24.5–69.75 years) with corresponding tumour size and location. Pre-op Karnofsky score was 80 (70–90), 53 patients were graded as ASA 2 and 3 patients as ASA 3. Length of hospital stay was 13.6 days (8–32 days). Post-op Karnofsky score was 80 (50–90). Among 5 patients with postoperative lower cranial nerve disturbances no patient had pneumonia postoperatively. There was no peri-operative mortality in either group.Conclusions. With modern neurosurgical techniques and neuro-anesthesia elderly patients with CPA meningiomas can be operated on with acceptable low morbidity and good neurological outcome but recovery from surgery lasts longer compared to younger patients. However, postoperative lower cranial nerve deficits in elderly patients may not be well tolerated compared with younger patients.     

Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

Clinical and pathological impact of an optimal assessment of brain invasion for grade 2 meningioma diagnosis: lessons from a series of 291 cases

Brain invasion has not been recognized as a standalone criterion for atypical meningioma by the WHO classification until 2016. Since the 2007 edition suggested that meningiomas harboring brain invasion could be classified as grade 2, brain invasion study was progressively strengthened in our center, based on a strong collaboration between neurosurgeons and neuropathologists regarding sample orientation and examination. Practice changes were considered homogeneous enough in 2011. The aim of the present study was to evaluate the impact of gross practice change on the clinical and pathological characteristics of intracranial meningiomas classified as grade 2.

The characteristics of consecutive patients with a grade 2 meningioma surgically managed before (1998–2005, n?=?125, group A) and after (2011–2014, n?=?166, group B) practices changed were retrospectively reviewed.

Sociodemographical and clinical parameters were comparable in groups A and B, and the median age was 62 years in both groups (p?=?0.18). The 5-year recurrence rates (23.2% vs 29.5%, p?=?0.23) were similar. In group A, brain invasion was present in 48/125 (38.4%) cases and was more frequent than in group B (14/166, 8.4%, p?<?0.001). In group A, 33 (26.4%) meningiomas were classified as grade 2 solely based on brain invasion (group A_SBI), and 92 harbored other grade 2 criteria (group A_OCA). Group A_SBI meningiomas had a similar median progression-free survival compared to groups A_OCA (68 vs 80 months, p?=?0.24) and to A_OCA and B pooled together (n?=?258, 68 vs 90 months, p?=?0.42).

An accurate assessment of brain invasion is mandatory as brain invasion is a strong predictor of meningioma progression.

     

Gamma knife radiosurgery in skull base meningiomas: a possible relationship between somatostatin receptor decrease and early neurological improvement without tumour shrinkage at short-term imaging follow-up

Summary Background. This study investigates a possible relationship between the effects of gamma knife (GK) on meningioma somatostatin receptors (SRs) and the high rate of early neurological improvement without tumour reduction at short-term imaging follow-up.Methods. From December 1997 to December 2002, somatostatin receptor scintigraphy (SRS) using an ¹¹¹Indium-labelled somatostatin analogue, Octreotide, was performed both before and 7–12 months after radiosurgery in 20 patients with intracranial meningiomas. Semiquantitative data were calculated as an SRS index.Findings. The pre-GK SRS index was always >1, averaging 4.44±3.20. There were no statistically significant differences between the pre-GK average values of primary (4.80±3.65) and residual (3.75±1.93) meningiomas. At the first clinical/MRI follow-up, the neurological examination had improved in 15/20 (75%) and had not changed in 5/20 patients. A corresponding slight tumour shrinkage on high-resolution MRI was documented in 3/20 cases only. The post-GK average SRS index was lower than pre-GK values both in primary (3.87±3.19) and in adjuvant (2.52±1.14) treatments, but the differences were not significant. However, the subgroup of patients with early neurological improvement showed a higher pre-GK average SRS index (5.21±3.33) and a more substantial post-GK average SRS index decrease (3.86±3.00) than the patients whose clinical condition remained stable (2.10±0.59 and 1.99±0.55, respectively). The difference between the two subgroups of patients proved to be statistically significant (P<0.05).Conclusions. Our preliminary findings suggest a possible relationship between a decrease in the concentration of SRs on meningioma cells at short-term functional imaging follow-up after radiosurgery and early neurological improvement.     

Potential doubling time and tumour doubling time in meningiomas and neurinomas

Summary Cell kinetic study plays an important role in treatment planning of brain tumour patients. MIB-1 antibody has recently become available, which detects Ki-67 antigen even in the formalin-fixed paraffin-embedded specimens. We performed MIB-1 immunostaining in 50 meningiomas and 50 neurinomas, and estimated the cell cycle time (tc) and potential doubling time (Tpot) from MIB-1 staining index (MIB-1 SI) and mitotic index (MI). MIB-1 SI logarithmically correlated with MI in both meningiomas and neurinomas. The tc and the Tpot were expressed as a function of the mitosis time (tm), while the tm is known to be around one hour and not exceeding two hours. When the tm was assumed to be one hour, the average tcs of meningiomas and neurinomas were 6.53±3.56 days and 7.67±3.27 days, respectively. The Tpots were447 × (MIB-1 SI)^–1.29 × tm in meningiomas, and490 × (MIB-1 SI) ^–0.98 × tm in neurinomas.The tumour doubling times (Tds) were calculated from serial imaging studies in 22 neurinomas and 15 meningiomas. The Tds were formulated as794 × (MIB-1 SI) ^–0.83 in meningiomas and1380 × (MIB-1 SI) ^–0.97 in neurinomas. Most of the Tds correlated well with the Tpots in meningiomas and neurinomas, and exceeded values of the Tpot when the tm is assumed to be one hour, although a few tumours showed unexpectedly longer Tds. The Tpot and the tc estimated from MIB-1 SI and MI are clinically useful parameters for predicting the growth potential of meningiomas and neurinomas where no other simple methods are available.     

Progesterone-receptor index in meningiomas: correlation with clinico-pathological parameters and review of the literature

For recurrent and untreatable meningiomas alternative therapies, such as anti-progesterone treatment, have been sought. However, the few clinical studies have not determined progesterone receptor (PgR) expression in most cases, and studies correlating quantitative PgR expression (PgR index) with clinico-pathological variables are scarce. The aim of our study was to assess the PgR indices in a consecutive series of meningiomas and correlate these values with clinico-pathological parameters. We analyzed immunohistochemically 82 consecutive meningioma specimens (73 primary and nine recurrent tumors) for PgR and Ki-67 antigen (MIB-1). The male/female ratio was 1:1.7, and median age at the time of surgery was 57 years (range 29–77 years). The series comprised 55 grade I (subtyped as 36 meningothelial, seven fibrous, nine transitional, two psammomatous, and one angiomatous), 23 grade II, and one grade III meningiomas. Nuclear immunostaining for PgR was positive in 56 meningioma specimens (71%). PgR index was 21.4±2.8% (mean ± SE; range 0–79%). Significantly higher expression was found in male patients in the age group <50 years than in those 60 years and in grade I meningothelial meningiomas than in fibrous and transitional subtypes. There was a trend to lower PgR indices in non-benign meningiomas. Cell proliferation rate (MIB-1 index) was 4.4±0.4% (mean ± SE; range 0.3–15.4%). Significantly higher MIB-1 indices were found in male than female patients,in recurrent than primary and in grade II than grade I meningiomas. We observed a trend to higher PgR indices in meningiomas with MIB-1 index <5%. In sum, the highest PgR index in our series was observed in patients under the age of 50 years with WHO grade I meningiomas of the meningothelial subtype and low cell proliferation indices. If hormonal therapy has a direct action on the PgR, these patients should respond best to anti-progesterone treatment. We conclude that PgR index is variable in meningioma, depending on clinical parameters and histopathological features. Stratification of anti-progesterone therapy trials on the basis of PgR index should be considered.     

An initial evaluation of post-cardiopulmonary bypass acute kidney injury in swine

Objective: Acute kidney injury (AKI) post-cardiac surgery is associated with mortality rates approaching 20%. The development of effective treatments is hindered by the poor homology between rodent models, the mainstay of research into AKI, and that which occurs in humans. This pilot study aims to characterise post-cardiopulmonary bypass (CPB) AKI in an animal model with potentially greater homology to cardiac surgery patients. Methods and results: Adult pigs, weighing 50–75 kg, underwent 2.5 h of CPB. Pigs undergoing saphenous vein grafting procedures served as controls. Pre-CPB measures of porcine renal function were within normal ranges for adult humans. The effect of CPB on renal function; a 25% reduction in ⁵¹Cr-EDTA clearance (p = 0.068), and a 33% reduction in creatinine clearance (p = 0.043), was similar to those reported in clinical studies. CPB resulted in tubular epithelial injury (median NAG/creatinine ratio 2.6 u mmol⁻¹ (interquartile range (IQR): 0.81–5.43) post-CPB vs 0.48 u mmol⁻¹ (IQR: 0.37–0.97) pre-CPB, p = 0.043) as well as glomerular and/or proximal tubular injury (median albumin/creatinine ratio 6.8 mg mmol⁻¹ (IQR: 5.45–13.06) post-CPB vs 1.10 mg mmol⁻¹ (IQR: 0.05–2.00) pre-CPB, p = 0.080). Tubular injury scores were significantly higher in kidneys post-CPB (median score 2.0 (IQR: 1.0–2.0) relative to vein graft controls (median score 1.0 (IQR 1.0–1.0), p = 0.019). AKI was associated with endothelial injury and activation, as demonstrated by reduced DBA (dolichos biflorus agglutinin) lectin and increased endothelin-1 and vascular cell adhesion molecule (VCAM) staining. Conclusions: The porcine model of post-CPB AKI shows significant homology to AKI in cardiac surgical patients. It links functional, urinary and histological measures of kidney injury and may offer novel insights into the mechanisms underlying post-CPB AKI.     

Score Index for Stereotactic Radiosurgery of Brain Metastases

A reliable prognostic score for cancer patients with brain metastases submitting to stereotactic radiosurgery (SR) was established. Between July 1993 and December 1995, 34 cancer patients (36 treatments and 69 lesions) with brain metastases were treated with SR at the Hospital Israelita Albert Einstein of São Paulo, Brazil. The exclusion criteria were: more than 5 lesions, any lesion larger than 30 cm³, Karnofsky performance status (KS) less than 50, clinical evidence urging neurosurgical intervention or very poor overall prognosis due to fast progressive systemic disease (SD). The score index for stereotactic radiosurgery of brain metastases (SIR) was obtained by summing up the points of the five variables: age, KS, SD, size (LS), and number of lesions (NL). The Kaplan–Meier method together with log rank was used to estimate and test correlation between survival and all prognostic factors. Applying the SIR definition to our patients' survival data through the Kaplan–Meier method we found out that the expected median survival for patients with 6 points or less was 3.67 months and for those with more than 6 points it was 16.16 months (p = 0.0005). Age, SD, KS, and NL were also significantly correlated with the prognosis (p-values at log-rank test of 0.0020, 0.0071, 0.0181, and 0.0454, respectively). Analyzing our data we concluded that the SIR is a reliable prognostic score for cancer patients with brain metastases submitting to SR. This index should be tested for larger series.     

Comparison between the right side and subxiphoid bilateral approaches in performing video-assisted thoracoscopic extended thymectomy for myasthenia gravis

Background This study aimed to compare the efficacy of the right thoracoscopic (RtT) approach and the subxiphoid bilateral thoracoscopic (SxBiT) approach in performing thymectomy for myasthenia gravis.Methods Between March 2001 and April 2003, 27 myasthenic patients were enrolled in this prospective study. The operations were conducted by two surgical teams in a single institute. The surgical procedures included RtT for 12 patients and SxBiT for 15 patients. The operation time, resected thymus weights, and thoracic drainage periods were compared.Results Subxiphoid video-assisted thoracoscopic extended thymectomy (SxVATET) and right-side thoracoscopic extended thymectomy (RtVATET) were performed for 27 consecutive myasthenic patients. The mean operation time, weights of resected specimens, and duration of hospital stay for the SxVATET and RtVATET groups were, respectively, 151.3 min (range, 120–200 min) versus 191.5 min (range, 120–225 min) (p = 0.0012), 73.3 g (range, 40–90 g) versus 50.8 g (range, 5–90 g) (p = 0.0029), and 3.1 days (range, 2–4 days) versus 3.8 days (range, 2–4 days) (p = 0.914). Ten patients (37%) had complete remission, observed during a mean follow-up period of 18.5 months (range, 6–30 months).Conclusions During this consecutive experience, both the RtT and SxBiT approaches showed satisfactory results for nonthymomatous myasthenic patients. However, a better view of the bilateral pleural cavities and more radical thymectomy could be achieved only by the SxBiT approach.     

Prevention of chronic radiation enteropathy by dietary glutamine

Background: Nearly 50% of all cancer patients receive therapeutic radiation during the course of their disease. The risk of late complications is the main dose-limiting factor in the delivery of radiation therapy. The small intestine, the major site of chronic radiation enteropathy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. Methods: This study evaluated the effects of supplemental oral glutamine on the development of chronic radiation (XRT) enteropathy. After scrotalization of a loop of small intestine, rats were randomized to receive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 days of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n=10), GLY + XRT (n=10), GLN only (n=10), GLY only (n=10). Twenty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirradiation. Chronic radiation injury was assessed microscopically. Results: Injury scores in GLN + XRT were similar to those of unirradiated bowel and significantly different from GLY + XRT (1.89 ± 0.48 in XRT + GLN vs. 6.42 ± 1.55 in the XRT + GLY,p<0.01). Elevated Injury Scores in the XRT + GLY group correlated with gross thickening and fibrosis, a 10-fold decrease in gut GLN extraction (1.40 ± 4.3% in GLY + XRT vs. 16.0 ± 5.1% in GLN + XRT,p<0.05), and a 30% decrease in glutathione content (2.46 ± 0.19 and GLY + XRT vs. 3.17 ± 0.17 GLN + XRT,p<0.05). Conclusions: Provision of GLN during abdominal/pelvic XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy. Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993. Dr. Jensen is a recipient of the Armand Hammer Travel Award from the Society of Surgical Oncology.     

Surgical resection and permanent brachytherapy for recurrent atypical and malignant meningioma

OBJECTIVE: Recurrent atypical and malignant meningiomas are difficult to treat successfully. Chemotherapy to date has been unsuccessful, and radiosurgery is limited to smaller tumors. Reoperation alone provides limited tumor control and limited prolonged survival. The addition of brachytherapy at the time of operation is an option. Here, we report the results of our series of patients with recurrent malignant meningioma treated with resection and brachytherapy with permanent low-dose (125)I. METHODS: The charts of patients in our database with recurrent atypical and malignant meningiomas treated by surgical resection and permanent (125)I brachytherapy at the University of California, San Francisco, between 1988 and 2002 were selected for this study. Calculations of disease-free survival and overall survival curves were made by the Kaplan-Meier actuarial method. Univariate analysis between Kaplan-Meier curves was based on the log-rank statistic, with a significance level set at a value of P 相似文献   

140 consecutive cases of minimally invasive,radio-guided parathyroidectomy

Background: The advent of highly accurate parathyroid imaging and the ever-increasing trend towards minimally invasive procedures have changed considerably the surgical approach to the patient with primary hyperparathyroidism (PHPT) caused by a single parathyroid adenoma. This study analyzes the short- and longer-term results of 140 patients who underwent minimally invasive, radio-guided parathyroidectomy. Methods: Demographic, clinical, and pre-operative imaging data, operative findings, and short- and long-term results of 140 consecutive patients operated within a 20 months period (8/1999–4/2002), were prospectively entered into a database. Immediate pre-operative sestamibi scintigraphy with skin marking of focal adenoma uptake were followed by intraoperative hand-held gamma probe for the removal of the parathyroid adenoma by unilateral minimal access surgery. Preoperative and surgical data were analyzed and correlated to outcomes, measured by success or failure to cure PHPT, associated morbidity and mortality, predictive value of localizing studies, and postoperative laboratory results in the immediate as well as long-term period. Results: 140 patients, mean age: 55.1 ± 14.1 years (range 19–88 years), female to male ratio 94:46 with PHPT proven by concomitantly elevated serum calcium and parathormone (PTH) levels, with a single adenoma identified by sestamibi single photon emission tomography (SPECT) scintigraphy and high-resolution sonography, underwent minimally invasive, radio-guided parathyroidectomy. Mean serum levels of preoperative calcium, phosphorus, and PTH were 11.6 ± 0.8 mg/dL (range 9.1–14), 3.0 ± 0.3 mg/dL, and 147.1 ± 94.3 pg/mL (range 68–784), respectively. Overall, in 3 out of 140 patients (2.1%), focused, minimally invasive surgery failed to identify and remove the adenoma. Positive predictive value when both localizing modalities concurred was 99.2%. Positive predictive value of SPECT scan alone was 97.2%. Overall success rate was 97.8% (137/140). 24 hours postoperative mean serum calcium was 9.2 ± 0.8 mg/dL and at 6 months mean serum calcium, phosphorus, and PTH were 9.4 ± 1.06 mg/dL, 3.2 ± 0.8 mg/dL, and 32.1 ± 11.9 pg/mL, respectively (p = 0.0001). There was no mortality. In 2 patients (1.4%) there was transient vocal cord paresis and there were 8 instances of clinically significant hypocalcemia. In 3 cases (2.1%), a second adenoma manifested itself 9–14 months following surgery and was removed by minimal access procedure. Conclusions: Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma is safe and effective in curing hyperparathyroidism with a 97% success rate. A second adenoma occurring in less than 3% may be successfully treated with a second minimal access operation. The combined positive predictive value of concurring sestamibi SPECT scintigraphy and sonography of 99.2% may increase success rate, and thus implementing this technique in patients with concurring sonography and scintigraphy may be advocated. Presented in part at the 10^th E.A.E.S. Congress, Karl Storz Award Session. Lisbon, Portugal     

During treatment protocol for univentricular heart serum levels of natriuretic peptides decrease

Objective: In children treated for univentricular heart (UVH), prospective evaluation of serum levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed. Methods: Serum samples were analysed in 19 children before the first operation, before the bi-directional Glenn (BDG) operation, at age 1 year and before total cavopulmonary connection (TCPC). In addition, we performed cross-sectional measurement of peptide levels in 32 children: 22 hypoplastic left ventricle (LV), 10 hypoplastic right ventricle (RV) before; and in 12 children: nine hypoplastic LV, three hypoplastic RV, 2 (range: 0.5–5.3) years after the TCPC operation. Controls comprised 12 children aged less than 6 months and 41 children aged from 6 months to 7 years. Results: Between the first and second operations, peptide levels decreased. Before TCPC, further decreases had occurred. Throughout follow-up, peptide levels were higher than in controls. In the cross-sectional study, before TCPC, median ANPN concentration measured 0.37 (range: 0.18–1.00) nmol l⁻¹ (P = 0.059, compared with controls) and NT-proBNP 155 (range: 13–718) ng l⁻¹ (P < 0.001). After TCPC, median ANPN concentration measured 0.39 (range: 0.09–0.98) nmol l⁻¹ (P = ns) and NT-proBNP 201 (range: 76–1406) ng l⁻¹ (P < 0.001). Before TCPC, levels of NT-proBNP were higher in patients with RV than with LV morphology. Conclusions: Natriuretic peptide levels decreased during treatment protocol for UVH, but NT-proBNP levels remained higher than in controls. These reflect reduction of volume overload of the single ventricle and can prove useful for haemodynamic monitoring.     

Association between laminin γ1 expression and meningioma grade, recurrence, and progression-free survival

Background

Laminins are central components of basement membranes and play important roles in cell adhesion, proliferation, and migration. However, the role of laminins in tumor progression has not been thoroughly investigated in meningiomas.

Objective

The aim of the present study is to evaluate the expression of laminin γ1 in various grades of meningiomas in Chinese patients.

Methods

In the current study, clinical and pathological data for 32 meningioma patients with various tumor grades were collected. The expression of laminin γ1 in each tumor was assessed by using quantitative real-time polymerase chain reaction (qPCR), Western blot and immunohistochemical analysis and was correlated with the meningioma grade, tumor recurrence and patient survival. Patient prognoses were attained and the progression-free survival was calculated based on the Kaplan-Meier method. A two-sided probability cutoff of 0.05 was chosen for statistical significance.

Results

A total of 32 meningioma patients with various pathological subtypes (WHO grade I: 13, grade II: 10 and grade III: 9) were enrolled in this study. The qPCR results showed that laminin γ1 mRNA expression was significantly higher in grade III meningiomas than in grade I meningiomas (p?<?0.05), although there was no significant difference in laminin γ1 expression between grade II and grade I meningiomas (p?>?0.05). Western blot and immunohistochemistry analysis confirmed that the expression of laminin γ1 protein was relatively higher in grade III meningiomas when compared with grade I meningiomas. Higher levels of laminin γ1 expression in meningiomas are associated with a significantly shorter tumor recurrence time (p?<?0.05) and a decreased patient survival time (p?<?0.05).

Conclusions

Our results suggest that laminin γ1 is associated with meningioma grades and could play a role in enhancing tumor invasion. Laminin γ1 could be used as a predictor for meningioma recurrence and patient survival. Furthermore, laminin γ1 may represent a druggable molecular target for future therapies for tumors that overexpress this marker.     

Meningiomas

Opinion statement Meningiomas are extra-axial brain tumors of middle-to-late adult life and show a predominance in women. Overall, 90% of meningiomas are benign, 6% atypical, and 2% are malignant [1,2]. Most patients diagnosed with a meningioma decide to have it removed surgically, and are advised to do so based on their neurologic symptoms [2,3•,4,5]. Complete surgical resection is usually curative. For incompletely resected or recurrent tumors not previously irradiated, radiotherapy is administered [2,6-9]. Radiotherapy may be administered as either conventional external beam irradiation or stereotactically. Stereotactic radiotherapy (SRT) either as LINAC or gamma knife radiosurgery is increasingly utilized. Advocates of SRT have suggested this therapy as an alternative to surgery particularly in poor surgical risk patients, patients with meningiomas in eloquent or surgically inaccessible locations, and in those patients of advanced age [7,9•]. When the meningioma is unresectable or all other treatments (surgery, radiotherapy) have failed, immunochemotherapy may be considered [10]. Hydroxyurea, alpha interferon, tamoxifen, and mifepristone (RU-486) have been modestly successful in pateints with recurrent meningiomas whereas cyclophosphamide, Adriamycin (Pharmacia and Upjohn, Bridgewater, NJ) and vincristine (CAV), ifosfamide/Mesna (Bristol-Meyers Squibb, Princeton, NJ) or Adriamycin/dacarbazine (DTIC) have been administered to patients with aggressive or malignant meningiomas [10,11•,12–16•].