Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas

This study reports the outcome of 70 patients who were treated by a consistent treatment plan of surgery and postoperative radiotherapy (RT) for pituitary macroadenomas in the modern era [computed tomographic scan or magnetic resonance imaging (MRI), dopamine agonist therapy (DA) added as indicated, and immunohistochemical staining]. Sixty-two patients underwent transsphenoidal surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions postoperatively (vs. other dose fractionation schemes). Twenty-four patients received DA for prolactin-secreting tumors. With a median follow-up of 8 years (range 2-15), 68 patients have experienced continuous control of their tumors. Most symptoms related to mass effect abated, while physiologic symptoms such as amenorrhea from markedly elevated prolactin levels tended to persist. Treatment-induced hypopituitarism occurred in 42% of the patients at risk. No patients in this series have died as a result of their pituitary tumor. No gross neuropsychologic dysfunction after treatment has been noted. While it is possible at this time with serial MRI to withhold postoperative RT and observe some patients who have had a "gross total" resection of a macroadenoma, the therapeutic ratio for surgery and adjuvant radiotherapy for patients with nonfunctional tumors as well as select patients with secretory macroadenomas is favorable.     

Transsphenoidal microsurgery of pituitary macroadenomas with long-term follow-up results

The authors have reported on 108 patients with pituitary macroadenomas (measuring 2 cm in at least one diameter) who underwent 117 transsphenoidal operations and five craniotomies, and were followed for periods ranging from 6 months to 14 years. Vision improved in 90% of the patients. Gross total tumor removal with no evidence of residual tumor tissue demonstrable on the postoperative computerized tomography scan was accomplished in 41% of cases. However, gross total tumor removal is not synonymous with complete tumor removal. Endocrine cure was possible in 25% of prolactin-secreting and 20% of growth hormone-secreting adenomas. The incidence of recurrence was 12%, with the majority occurring from 4 to 8 years postoperatively. Both the tumors with suprasellar extension of more than 2 cm and the hard fibrotic tumors had a higher recurrence rate. Postoperative administration of radiation therapy has been associated with a significantly lower recurrence rate than when this therapy was withheld. Transsphenoidal surgery of pituitary macroadenomas confined to the extra-arachnoid space is associated with a relatively small number of complications. The operative technique used in this series is described.     

External irradiation of macroinvasive pituitary adenomas with telecobalt: a retrospective study with long-term follow-up in patients irradiated with doses mostly of between 40-45 Gy

PURPOSE: Published dose recommendations for radiotherapy in patients with pituitary macroadenomas vary. Therefore, we retrospectively analyzed the results in our patients from the treatment period 1973-1992. METHODS AND MATERIALS: From a total of 89 patients with macroinvasive adenomas, 66 received radiation therapy immediately following subtotal surgical removal (combined treatment modality), and 22 were irradiated as primary treatment or after surgical recurrence. Only one patient was reirradiated. The surgical interventions have been performed by the same surgeon. For the majority of patients (79 out of 89) with a mean follow-up of 8.1 years (0.5-19 years) the total tumor dose ranged between 40-45 Gy at a dose per fraction of 1.8-2.25 Gy. All patients had bilateral opposed fields with telecobalt. Eleven patients had an additional arc rotation. RESULTS: The 10-year progression-free survival for all 89 patients independent of treatment modality was 88.1%. The 10-year progression-free survival for patients treated by surgery and adjuvant radiation therapy (40-45 Gy at 1.8-2.25 Gy, 60 out of 79) was 90.3%, and for radiation therapy alone (40-45 Gy at 1.8-2.25 Gy, 19 out of 79), 100% (p = 0.32). The prognostic factors for progression-free survival were the subtype of adenoma, the presence of visual symptoms at the time of diagnosis, the suprasellar extension, and the initial hormone levels. The presence of infiltration of adenoma cells in the basal dura or in the mucosa of the sinus sphenoidalis do not represent prognostic factors showing the special biological behavior of pituitary adenomas. Signs of x-ray-induced cerebral necrosis have not been observed in any patient. Long-term visual complications developed in four patients. This could be due to scar formation in the treated region, which can compress the optic nerve and provoke disturbance similar to an empty-sella syndrome. The latter occurred prevalently years after treatment, even though surgical methods of sellar plugging were used. The incidence of hypopituitarism after combined treatment modality at time of last follow-up (irradiated between 40-45 Gy at 1.8-2.25 Gy) was low (36%, 21 out of 60). CONCLUSION: In patients with pituitary macroadenomas, radiotherapy with a total dose of 40-45 Gy at 1.8-2.25 Gy per fraction resulted in a high local tumor control without serious morbidity.     

Pharmacokinetics of tacrolimus (FK506) in primary orthotopic heart transplant patients

STUDY OBJECTIVES: Local recurrence is high when sublobar resection is chosen as primary management of stage I non-small cell lung carcinoma. Postoperative external-beam radiotherapy may reduce this local recurrence problem. A technique of intraoperative brachyradiotherapy following thoracoscopic wedge resection is described as an alternative to adjuvant external-beam radiotherapy for high-risk patients who are not candidates for pulmonary lobectomy. PATIENTS: Fourteen patients with significant impairment in cardiopulmonary function having small peripheral solitary pulmonary nodules underwent video-assisted thoracoscopic (VATS) wedge resection and were found to have non-small cell cancer. Surgical margins were pathologically clear and mediastinal nodes were benign-stage I (T1NO). INTERVENTIONS: A custom polyglyconate mesh (Vicryl) containing 125I seeds was applied to pulmonary resection margins following wedge resection of peripheral lung cancers. A total dose of 100 to 120 Gy at 1 cm was applied to the target area. RESULTS: All patients had histologically clear surgical margins. Postoperative dosimetry confirmed adequate resection margin coverage. There was neither operative mortality nor morbidity related to the VATS wedge resection or the brachytherapy implants. Implants did not migrate, and there were no cases of significant radiation pneumonitis or local recurrence at mean follow-up of 7 months (range, 2 to 12 months). CONCLUSIONS: Intraoperative brachytherapy appears to be a safe and efficient alternative to external-beam radiation therapy when adjuvant radiotherapy is considered following therapeutic wedge resection of stage I (T1NO) lung cancers. The impact on local recurrence, disease-free interval, and survival will require additional follow-up.     

Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience

OBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.     

Improvement in cumulative response rates following implementation of a financial incentive

We present our experience in the treatment of growth hormone (GH)-producing pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients suffering from GH-secreting pituitary adenomas were treated with radiotherapy alone. Two bilateral opposing coaxial fields were used in 10 patients and in the remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2 Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was given using a cobalt unit. Four patients treated with somatostatin prior to and 14 patients treated after the end of radiotherapy experienced symptom relief for 6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%) patients. Whereas RT alone is effective in the treatment of microadenomas, this is not true for large infiltrative macroadenomas.     

Radiation therapy in the management of desmoid tumors

PURPOSE: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery. METHODS AND MATERIALS: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods. RESULTS: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05). CONCLUSIONS: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.     

Surgical aspects in the multidisciplinary treatment of soft tissue sarcomas

Sarcomas are rare malignant tumors with a large variety of histologic subtypes. The surgical approach depends more on the histologic grade, the size and the site of the tumor. Radiologic diagnosis relies predominantly on MR-imaging. Discernible improvements have taken place in soft tissue sarcoma patient survivorship and quality of life over the past 20 years, with overall 5-year survival currently at approximately 50-80%. The place of surgery in the treatment of soft-tissue sarcoma is defined in the light of a review of the recent literature. Radical surgical resection is the mainstay of therapy. Local recurrence is the most common type of failure. Local recurrence is resectable and limb preservations possible in the majority of patients. Survival after treatment of local recurrence is determined mainly by the grade and secondarily by the size of the tumor. The essential risk factor for local recurrence is the quality of surgical resection, defined by the definitive resection margins. A lateral safety margin of 5 cm and of 2 cm to the depth should be respected. In sarcoma of the extremity the compartment is defined based on clinical, radiographic, histopathologic and operative findings. The use of muscle flaps to fill the surgical defects can improve the functional result and reduce the complication rate. Only about 5% of the patients need amputation. Evaluation of functional results must be based on objective criteria. In retroperitoneal sarcoma the significant factors for determining prognosis are grade and completeness of exzision. Multidisciplinary treatment according to common protocols is essential. Shifts in treatment have taken place over the past decade, from single-modality treatment involving radical surgery with compartment resection to sophisticated limb-salvage strategies combined with radiation therapy. In case of inadequate surgery e.g. in a large tumor with positive margins in high-grade soft tissue sarcomas the addition of radiotherapy can improve local control, but cannot ensure that obtained by adequate surgery. Patients with large (greater than 5 cm), high grade soft tissue sarcoma are at high risk for distant recurrence and disease-related mortality. Investigations of combined modality therapy with newer chemotherapy agents and dose intensification treatment strategies are warranted.     

Treatment of pituitary adenoma]

RECOMMENDED TREATMENTS: The different therapeutic strategies proposed for pituitary adenomas are relatively well-known thanks to numerous studies evaluating their effect on outcome. Unfortunately, large comparative clinical trials are difficult to construct due to the small number of cases of this rare condition. Therapeutic recommendations are thus generally based on the opinion of recognized experts. MICROADENOMA: Small (< 10 mm) prolactin-secreting adenomas should be treated surgically, generally by transsphenoidal adenomectomy, or medically by dopaminergic agonists: bromocriptin, quinagolide or cabergolin (the two latter drugs are more effective and better tolerated than their parent compound bromocriptin). MACROADENOMA: The expected success rate for surgical treatment of macroadenomas is low and dopaminergic agonists is generally recommended (including cases with visual impairment since the effect can be very rapid). Prolactin levels can be lowered and tumor volume reduced (in > 70% of cases). ACROMEGALY: Surgery is the firs intention treatment for acromegaly. In case of unsuccessful surgery (the criteria for "cure" are much more strict in 1998 than previously), somatostatin analog and/or hypothalamo-hypophyseal radiotherapy are recommended. Slow release formulations of somatostatin analogs can now be given by monthly (octreotide LP) or biweekly (lanreotide LP) injections. CUSHING'S DISEASE: Cure can be achieved in > 80% of cases with surgery, the first intention treatment of choice. If surgery is unsuccessful, radiotherapy can be proposed associated with anticortisol drugs (mitotane), if needed, while waiting for the late effect of radiotherapy. CLINICALLY SILENT ADENOMAS: Non-functional adenomas should be operated. Some propose adjuvant radiotherapy in all cases and others only if residual tissue persists post-operatively.     

Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae

PURPOSE: To assess the local control and survival in patients who received pelvic irradiation for locally recurrent rectal carcinoma. METHODS AND MATERIALS: The records of 519 patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1975 to 1985 at a single institute were retrospectively reviewed. These included 326 patients who relapsed locally following previous abdominoperineal resection, 151 after previous low anterior resection, and 42 after previous local excision or electrocoagulation for the primary. No patients had received adjuvant radiation therapy or chemotherapy for the primary disease. Concurrent extrapelvic distant metastases were found in 164 (32%) patients at local recurrence and, in the remaining 355, the relapse was confined to the pelvis. There were 290 men and 229 women whose age ranged from 23 to 91 years (median = 65). Median time from initial surgery to radiation therapy for local recurrence was 18 months (3-138 months). Radiation therapy was given with varying dose-fractionation schedules, total doses ranging from 4.4 to 65.0 Gy (median = 30 Gy) over 1 to 92 days (median = 22 days). For 214 patients who received a total dose > or = 35 Gy, radiation therapy was given in 1.8 to 2.5 Gy daily fractions. RESULTS: The median survival was 14 months and the median time to local disease progression was 5 months from date of pelvic irradiation. The 5-year survival was 5%, and the pelvic disease progression-free rate was 7%. Twelve patients remained alive and free of disease at 5 years after pelvic irradiation. Upon multivariate analysis, overall survival was positively correlated with ECOG performance status (p = 0.0001), absence of extrapelvic metastases (p = 0.0001), long intervals from initial surgery to radiation therapy for local recurrence (p = 0.0001), total radiation dose (p = 0.0001), and absence of obstructive uropathy (p = 0.0013). Pelvic disease progression-free rates were positively correlated with ECOG performance status (p = 0.0001), total radiation dose (p = 0.0001), and previous conservative surgery for the primary (p = 0.02). CONCLUSIONS: Survival is poor for patients who develop local recurrence following previous surgery for rectal carcinoma. Pelvic radiation therapy provides only short-term palliation, and future efforts should be directed to the use of effective adjuvant therapy for patients with rectal carcinoma who are at high risk of local recurrence.     

Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma

BACKGROUND: The results of a Phase II study of concurrent chemotherapy and accelerated fractionation radiation therapy followed by surgical resection for patients with both adenocarcinoma and squamous cell carcinoma of the esophagus are presented. Pretreatment and postinduction staging were correlated with pathologic findings at surgery to assess the role of surgical resection and the predictive value of noninvasive staging techniques. METHODS: Patients received 2 induction courses with 4-day continuous intravenous infusions of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day) beginning on Day 1 and Day 21, concurrent with a split course of accelerated fractionation radiation (1.5 grays [Gy] twice daily, to a total dose of 45 Gy). All patients were subsequently referred for surgical resection. A single, identical postoperative course of chemotherapy and 24 Gy accelerated fractionation radiation was planned for patients with residual tumor at surgery. RESULTS: Seventy-four patients were entered on this study; 72 patients were considered eligible and evaluable. Induction toxicity included nausea (85%), increased dysphagia (90%), neutropenia (<1000/mm3) (43%), thrombocytopenia (<20,000/mm3) (10%), and reversible nephrotoxicity (8%). Sixty-seven patients (93%) underwent surgery, and 65 (90%) were found to have resectable tumors. Twelve of these patients (18%) died perioperatively, and 18 (27%) had no residual pathologic evidence of disease. Resolution of symptoms and normalization of radiographic studies, endoscopy, or esophageal ultrasound did not identify pathologic complete responders accurately. No patient completing induction therapy and surgery experienced a locoregional recurrence. The Kaplan-Meier 4-year projected recurrence free and overall survival rates were 49% and 44%, respectively. CONCLUSIONS: Although this regimen is feasible, there was significant preoperative toxicity and perioperative mortality. Nonetheless, the recurrence free and overall survival rates were encouraging. However, no staging tool can predict a pathologic complete response after induction therapy accurately, suggesting a continued need for surgical resection.     

Influence of radiotherapy on long-term relapse in clinically non-secreting pituitary adenomas. A retrospective study (1970-1988)

OBJECTIVE: We wished to evaluate the influence of postoperative radiotherapy on the incidence of tumour regrowth in non-secreting pituitary adenomas. METHODS: The cases of 57 patients with clinically non-secreting pituitary adenomas were retained for a retrospective study of long-term disease-free survival out of a series of 66 patients treated between 1970 and 1988. Thirty-three patients were treated by surgery only (Group A), and twenty-four by surgery followed by external radiotherapy (Group B). Disease-free survival curves were calculated according to the Kaplan-Meyer method and compared by the Logrank test. The impact of some supposed prognostic parameters--such as tumoural volume, macroscopic features of invasiveness and quality of surgical resection--on the disease-free survival was analyzed according to the Logrank adjusted test. RESULTS: The mean follow-up duration was 7.1 +/- 6.2 years, and eleven patients relapsed: nine in group A (27.0%) and two in group B (8.3%), with respective free intervals of 6.1 +/- 5.0 years and 9.6 +/- 2.4 years. Statistical analysis of the disease-free survival curves confirmed that this difference was significant (p < 0.01). Further analysis of putative risk factors (the importance of extrasellar extension and the estimated quality of surgical resection) was attempted, but it did not reach statistical significance. CONCLUSIONS: Radiotherapy is effective in preventing post-operative regrowth of non-secreting pituitary adenomas. Whether it should be systematically proposed or reserved to selected cases remains to be evaluated.     

Diagnostic imaging 100 years ago

The aim of the present study was the evaluation of the role of adjuvant radiation therapy in the prevention of recurrence after excision. Between July 1, 1985, and April 1, 1993, 64 patients (43 men, 21 women) were referred for radiation therapy after excision of a nasal pterygium. All patients were followed for 1-9 years (median 5.5 years). Radiation therapy was done with a strontium 90 eye applicator at a total dose of 30 Gy fractionated into six fractions of 5 Gy each. In all, 49 patients were treated after their first excision and 15 patients had undergone multiple prior excisions. In 8 of 64 irradiated patients, recurrent pterygium was detected (12.5%); 4 recurrences developed after first excision and adjuvant radiation therapy (8.16%) and the other 4, following multiple former reexcisions and radiotherapy (26.7%). Pterygium did not recur in any of the primarily treated patients who were irradiated within 3 days of surgery. In contrast, 3 of 7 accordingly treated patients (42.9%) who started radiation therapy at between 7 and 10 days after surgery developed recurrent pterygium. Adjuvant radiation therapy after excision of pterygium lowers the overall rate of recurrence to 12.5%. In an adjuvant situation after first excision, radiation therapy should be initiated within 3 days of surgery, the result being freedom from recurrence.     

Use of adjuvant ICE chemotherapy in the treatment of anaplastic ependymomas

Despite the improved outcome for patients with ependymoma treated by surgery and radiotherapy, their prognosis remains relatively poor. To assess the impact of adjuvant chemotherapy, we reviewed the overall survival of consecutive patients with anaplastic ependymoma treated over a 10-year period with surgery and ICE (ifosfamide+ VP 16+carboplatin) chemotherapy with or without radiation at our institution. There were 11 patients (6 male, 5 female), with a median age of 3.4 years (range 1.2-1 1.1): 4 under 2 years and 7 were over 2 years old. Overall, 5 had gross total resections: 4 are alive, 2 in continuous complete remission and 2 in second complete remission. One patient who was less than 2 years old died. Among the 6 with subtotal resection, 2 achieved a complete remission after chemotherapy. However, 5 of the 6 patients have since died of progressive disease, with a median overall survival of 75 months. Overall survival was 24% and progression-free survival was 39%. In 2 of 6 patients with residual postoperative disease a temporary objective response was noted with adjuvant ICE chemotherapy. This regimen did not confer an overall survival advantage.     

Surgical treatment of adenocarcinoma of the rectum

OBJECTIVE: The authors' aim was to determine survival and recurrence rates in patients undergoing resection of rectal cancer achieved by abdominoperineal resection (APR), coloanal anastomosis (CAA), and anterior resection (AR) without adjuvant therapy. SUMMARY BACKGROUND DATA: The surgery of rectal cancer is controversial; so, too, is its adjuvant management. Questions such as preoperative versus postoperative radiation versus no radiation are key. An approach in which the entire mesorectum is excised has been proposed as yielding low recurrence rates. METHODS: Of 1423 patients with resected rectal cancers, 491 patients were excluded, leaving 932 with a primary adenocarcinoma of the rectum treated at Mayo. Eighty-six percent were resected for cure. Surgery plus adjuvant treatment was performed in 418, surgery alone in 514. These 514 patients are the subject of this review. Among the 514 patients who underwent surgery alone, APR was performed in 169, CAA in 19, AR in 272, and other procedures in 54. Eighty-seven percent of patients were operated on with curative intent. The mean follow-up was 5.6 years; follow-up was complete in 92%. APR and CAA were performed excising the envelope of rectal mesentery posteriorly and the supporting tissues laterally from the sacral promontory to the pelvic floor. AR was performed using an appropriately wide rectal mesentery resection technique if the tumor was high; if the tumor was in the middle or low rectum, all mesentery was resected. The mean distal margin achieved by AR was 3 +/- 2 cm. RESULTS: Mortality was 2% (12 of 514). Anastomotic leaks after AR occurred in 5% (16 of 291) and overall transient urinary retention in 15%. Eleven percent of patients had a wound infection (abdominal and perineal wound, 30-day, purulence, or cellulitis). The local recurrence and 5-year disease-free survival rates were 7% and 78%, respectively, after AR; 6% and 83%, respectively, after CAA; and 4% and 80%, respectively, after APR. Patients with stage III disease, had a 60% disease-free survival rate. CONCLUSIONS: Complete resection of the envelope of supporting tissues about the rectum during APR, CAA, and AR when tumors were low in the rectum is associated with low mortality, low morbidity, low local recurrence, and good 5-year survival rates. Appropriate "tumor-specific" mesorectal excision during AR when the tumor is high in the rectum is likewise consistent with a low rate of local recurrence and good long-term survival. However, the overall failure rate of 40% in stage III disease (which is independent of surgical technique) means that surgical approaches alone are not sufficient to achieve better long-term survival rates.     

Long-term preoperative management of thyrotropin-secreting pituitary adenoma with octreotide

Thyrotropin (TSH)-secreting pituitary adenomas are the less frequent form of presentation of pituitary tumors. Selective transsphenoidal surgical resection of the tumor is the treatment of choice. Given that native somatostatin inhibits TSH secretion, treatment with somatostatin analogues has been recently employed in patients with unresectable tumors or after surgery. We report on the case of a 58 year-old man with a TSH-secreting pituitary adenoma who was treated with octreotide for long-term before neurosurgery. The patient was referred to us because of a pituitary mass on CT scanning. Hormonal evaluation resulted in hyperthyroidism with high serum TSH concentrations. Serum alpha subunit concentration was elevated and TSH response to exogenous TRH stimulation was absent. Magnetic resonance imaging of the hypothalamic-pituitary area confirmed the presence of a pituitary mass (2.0 by 1.8 by 1.7 cm). Acutely administered subcutaneous octreotide (100 microg) was followed by a reduction of the serum TSH concentrations. Therefore, the patient received octreotide, 100 microg three times daily for 12 months. At first month after beginning therapy serum TSH, free thyroxine, total triiodothyronine, and alpha subunit concentrations were normalized and persisted into the normal range for the next 11 months. On the other hand, a shrinkage of the tumor mass (1.6 by 1.7 by 1.4 cm) was noted after 6 months of octreotide therapy, however, its volume did not modify in the following next months. Then, the tumor was removed by transsphenoidal surgery and the diagnosis was confirmed by immunohistochemical staining. This case demonstrates that long-term treatment with octreotide gave rise to a normalization of the thyroid function and a reduction of the tumor volume before surgery. This clinical observation suggests that octreotide therapy might be useful in preparation for pituitary surgery in patients with TSH-secreting pituitary adenomas.     

Evaluation of optimal measuring site and index by QDR4500A for postmenopausal bone loss]

Adjuvant therapy and microsurgery have allowed advances in surgical extirpation of lower extremity neoplasms. This retrospective study was designed to evaluate the microvascular transfer for lower extremity reconstruction in patients receiving pre- or post-operative irradiation and chemotherapy alone and in combination. Over a 5-year period, 24 free tissue transfers were performed in 22 patients undergoing surgical resection with adjuvant therapy for lower extremity neoplasms. There were 13 male and 9 female patients with an average age of 51 years. The latissimus dorsi muscle was most commonly transferred (N = 15). Eighteen tumors received pre- and three received postoperative radiotherapy. Two tumors received a combination of radiotherapy and brachytherapy. Pre- and/or postoperative chemotherapy was used in 14 patients. Twelve of these patients had both chemo- and radiation therapy. A total of six complications occurred, with no flap loss. Complications were evenly distributed among adjuvant regimens. All patients who underwent attempted limb salvage were able to ambulate postoperatively, except for 1 patients who had local recurrence. In conclusion, adjuvant therapy did not increase the complication rate for free tissue transfer in the lower extremity. Adjuvant therapy did not require alterations in the free tissue transfer and, similarly, free tissue transfer did not alter adjuvant therapy. We believe that free tissue transfer in complicated wounds allows for better wound healing with adjuvant therapy rather than local or primary wound closure alone.     

Sensitization of olfactory guanylyl cyclase to a specific imprinted odorant in coho salmon

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.     

A critical study of the influence of negative symptoms on the therapeutic response in schizophrenia]

The treatment modalities for gliomas are still questioning and searching. We reviewed the effect of the extent of surgical resection and reoperation on the length and quality of survival in 152 consecutive patients who underwent operation for supratentorial gliomas at GATA Neurosurgery clinic between 1985 to 1995. Seventy-two patients (50%) had glioblastoma multiforme (GBM), and 48 patients (33%) had anaplastic astrocytoma (AA). Gross total resection was achieved in 70 cases (49%), subtotal resection was performed in 60 cases (42%), and biopsy was carried out in 14 cases (9%). Thirty-two patients were reoperated for recurrency and the median interval between the first operation and reoperation was 9.5 months in glioblastoma multiforme, and 11.7 months in anaplastic astrocytoma. The resection groups were compared for age, sex, preoperative and postoperative Karnofsky rating, tumor location, postoperative radiation therapy, and chemotherapy, and survival according to multivariate analysis. Preoperative Karnofsky rating and surgical resection type were the most important factors related to survival after operation or reoperation. The gross total resection group lived longer than the subtotal resection group by life table analysis. Median survival of GBM was 76 weeks in gross total resection group, and 33 months in AA group with total resection (p < 0.001). Preoperative Karnofsky scores had a statistically significant effect on the quality of life and survival after operation and reoperation in all cases (p = 0.005). Radical surgery and reoperation also improve quality and length of life in selective malignant supratentorial gliomas.     

Detection of hibernated myocardium using intracoronary technetium-99m-sestamibi

Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's Hospital between 1975 and 1988 presented with local recurrence after definitive surgery. No patient received radiation therapy after surgery as part of initial treatment and none had evidence of distant metastases at the time of local recurrence. The median time to first recurrence was 14 months. At recurrence, patients presented with disease in the bronchial stump (eight patients), ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five), or some combination thereof (23). Sixty-five percent of patients had histologic evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15 patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR) response--tumor response to radiation therapy. Among these patients, local control was achieved in 70% of patients with marginal recurrences (i.e., stump, parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival after radiation therapy for all patients was 8.5 months. The best indicators for long-term survival were the interval from initial surgery to first recurrence and tumor response to radiation therapy.