Undifferentiated carcinoma of nasopharyngeal type (UCNT): a Swiss single-institutional experience during 1990-2005.

BACKGROUND: Nasopharyngeal carcinoma is a rare tumor entity in Switzerland. In contrast, it is endemic in Asian and African countries. Retrospective studies have been conducted in order to identify risk factors and prognostic determinants of nasopharyngeal carcinoma. Nonetheless, these trials were mostly conducted in regions with high prevalence for the disease and little is known about the risk factors and prognosis of nasopharyngeal carcinoma for a non-endemic population in Western Europe. METHODS: This retrospective trial was conducted to identify risk factors and prognostic determinants of nasopharyngeal carcinoma for a non-endemic population in Switzerland. RESULTS: Overall survival was 91%, 77% and 58% for one, three and five years, respectively. Factors with favourable prognostic value were concomitant radiochemotherapy regimens, photon radiotherapy, and a delay between diagnosis and first therapy session of less than ten weeks, respectively. Factors with unfavourable prognostic values were age over 65 years at time of diagnosis and nasopharyngeal carcinoma of WHO type I. CONCLUSION: Risk factors, biological behaviour and survival are well comparable between endemic and non-endemic populations for nasopharyngeal carcinoma. Nonetheless, an aggressive diagnostic procedure and sophisticated interdisciplinary therapy are indispensable in order to achieve favourable outcome. Therefore, diagnosis and therapy of nasopharyngeal carcinoma in non-endemic populations should be limited to highly specialized tertiary centres.

Successful brachytherapy of coronary vasospasm.

Brachytherapy is a proposed treatment for in-stent restenosis and is the subject of several clinical trials and debates. The standard treatment of patients with variant angina is to eliminate vasoconstrictive factors and to administer vasodilating drugs. This is the first description of successful brachytherapy for coronary spasm.

Needle acupuncture in tension-type headache: a randomized, placebo-controlled study.

UNLABELLED: A study with needle acupuncture was performed in tension-type headache employing a new placebo acupuncture METHOD: Sixty-nine patients (mean age 48.1 years, SD = 14.1) fulfilling the International Headache Society criteria for tension-type headache were randomly assigned to verum or placebo condition. No significant differences between placebo and verum with respect to visual analogue scale and frequency of headache attacks could be observed immediately, 6 weeks and 5 months after the end of treatment. There was a significant but weak improvement in quality of life parameters (clinical global impressions, Nottingham Health Profile) after verum treatment. In decision tree analyses, the changes in clinical global impressions and headache frequency depended significantly on primary headache frequency with a limit value of 24.5 days headache per month. High values in the von Zerssen Depression Score resulted in high mean visual analogue scale values.

Postoperative altered plasma growth hormone levels--a predictor for postoperative complications? A case report.

We compared the onset of predictors for postoperative complications (lactate, total T2 (tT2), total T4 (tT4) and cortisone) retrospectively with the onset of altered growth hormone (GH) concentration in a patient who had had a lethal postoperative outcome and in 13 patients who were without postoperative complications for a period of 24 hours postoperatively. Compared with the values of the patients without postoperative complications, GH values were elevated (68-fold) 1 h after surgery to 103 ng/ml and lactate was increased (12-fold) to 12.7 mmol/l at 6 h postoperatively in the patient with the lethal outcome. The other parameters measured (tT3, tT4 and cortisone) showed no rapid alteration during the first hours postoperatively. This case report suggests that the rapid postoperative onset of raised GH concentration in plasma may be an earlier marker for postoperative complications than the 'established' predictors.

[Multimodal therapy concepts in esophageal carcinoma: importance of radio- and chemotherapy]. / Multimodale Behandlungskonzepte beim Osophaguskarzinom: Stellenwert der Radio- und Chemotherapie.

Five-year survival of surgically treated patients with operable oesophageal carcinoma does not exceed 20%. The results with curative radiotherapy are even worse, with < or = 10% alive after 5 years. New treatment strategies are needed. Pre- or postoperative radiotherapy and perioperative chemotherapy alone do not improve survival. A simultaneous radiochemotherapy with cisplatin is significantly more effective than radiotherapy alone. A subgroup of patients with pathological complete remission after preoperative treatment (radio- and/or chemotherapy) survives significantly longer. It seems likely that survival in oesophageal cancer is improved by multimodal therapy encompassing radiotherapy, chemotherapy and surgery. Further randomised trials are needed, possibly in combination with other potentially active drugs.

Postoperative pattern of various hormonal and metabolic variables. A pilot study in patients without complications following cardiac surgery.

The use of single predictors for threatening postoperative complications are widely accepted. However, a typical pattern of multiple parameters could be more helpful than a single predictor. To study this hypothesis, various variables of normal postoperative changes in patients without postoperative complications were investigated. Secondly, this pattern needs to be compared in the future with those findings in patients with postoperative complications. Blood parameters of 13 patients undergoing cardiovascular surgery without postoperative complications for 24 hours were evaluated. Samples were obtained on the afternoon before the operation and 1, 3, 6, 12 and 24 hours after the end of surgery. At one hour postoperation increased levels of the following parameters were noted: growth hormone (p < 0.0001), glucose (p < 0.0001), insulin (p < 0.001), c-peptide (p < 0.001), lactate (p < 0.002), glutamate (p < 0.0001), aspartate (p < 0.001) and total amino acids (p < 0.05), although the concentration of some amino acids decreased. Three hours postoperatively free fatty acids (p < 0.05) were increased. Total-T3 concentrations were reduced postoperatively. Other parameters were not altered. Most of the parameters returned to normal values during the period of observation.

Different effects of dopamine and dopexamine on the isolated perfused rat kidney.

We have investigated the effect of dopamine and dopexamine on the isolated perfused rat kidney. After an equilibration period of 20 min and two control periods of 10 min, dopexamine 1.0, 2.5 or 4.0 micrograms kg-1 min-1 or dopamine 2.0 micrograms kg-1 min-1 were perfused for a further 40 min in random order. Renal blood flow, urine volume, glomerular filtration rate, absolute sodium excretion and fractional sodium reabsorption of the isolated perfused kidney were measured every 10 min during the experiment. Dopamine increased significantly urine production from mean 61.54 (SEM 4.7) to 117.2 (9.7) microliters min-1 g-1 and absolute sodium excretion from 0.4 (0.1) to 1.2 (0.1) mumol min-1 g-1, and decreased significantly fractional sodium reabsorption from 97.3 (0.5) to 90.7 (0.7)%. Renal blood flow and glomerular filtration rate were not altered. In contrast, dopexamine had no effect on the isolated kidney. These data suggest that the diuretic and natriuretic effects of dopexamine in humans may not result from a direct action on the kidney.

Pediatric medulloblastoma: radiation treatment technique and patterns of failure.

PURPOSE: In this study factors are analyzed that may potentially influence the site of failure in pediatric medulloblastoma. Patient-related, disease-related, and treatment-related variables are analyzed with a special focus on radiotherapy time-dose and technical factors. METHODS AND MATERIALS: Eighty-six children and adolescents with a diagnosis of medulloblastoma were treated in Switzerland during the period 1972-1991. Postoperative megavoltage radiotherapy was delivered to all patients. Simulation and portal films of the whole-brain irradiation (WBI) fields were retrospectively reviewed in 77 patients. The distance from the field margin to the cribiform plate and to the floor of the temporal fossa was carefully assessed and correlated with supratentorial failure-free survival. In 19 children the spine was treated with high-energy electron beams, the remainder with megavoltage photons. Simulation and port films of the posterior fossa fields were also reviewed in 72 patients. The field size and the field limits were evaluated and correlated with posterior fossa failure-free survival. RESULTS: In 36 patients (47%) the WBI margins were judged to miss the inferior portion of the frontal and temporal lobes. Twelve patients failed in the supratentorial region and 9 of these patients belonged to the group of 36 children in whom the inferior portion of the brain had been underdosed. On multivariate analysis only field correctness was retained as being significantly correlated with supratentorial failure-free survival (p = 0.049). Neither the total dose to the spinal theca nor the treatment technique (electron vs. photon beams) were significantly correlated with outcome. Posterior fossa failure-free survival was not influenced by total dose, overall treatment time, field size, or field margin correctness. Overall survival was not influenced by any of the radiotherapy-related technical factors. CONCLUSION: A correlation between WBI field correctness and supratentorial failure-free survival was observed. Treatment protocols should be considered that limit supratentorial irradiation mainly to subsites at highest risk of relapse. Optimized conformal therapy or proton beam therapy may help to reach this goal. Treating the spine with electron beams was not deletereous. A significant correlation between local control and other technical factors was not observed, including those relating to posterior fossa treatment. The use of small conformal tumor bed boost fields may be prefered to the larger posterior fossa fields usually considered as the standard treatment approach.

[Bronchus carcinoid tumor in the Tessin canton, retrospective analysis of 13 years and literature review]. / Das Bronchuskarzinoid im Kanton Tessin, Retrospektive Analyse über 13 Jahre und Literaturübersicht.

Between 1981 and 1993, 27 bronchial carcinoids were diagnosed in patients living in the Swiss Canton of Ticino, with a mean age of 55 (24-78) years. The incidence was 0.79/100,000 inhabitants. Main symptoms were cough (41%), hemoptysis (30%) and bronchial obstruction such as pneumonia or atelectasis (26%). There were no cases with carcinoid crisis. Preoperative evaluation included chest X-ray (100%), bronchoscopic biopsy (84%), computed tomography (44%) and mediastinoscopy (15%). Some 69% of the patients underwent lobectomy and 15% segmental resection. Pneumonectomy was required for curative surgery in 2 patients. One patient underwent bronchoscopic resection. Surgery is generally indicated. The 5-year survival rate for typical carcinoid was 94% and was significantly reduced to 42% in atypical carcinoid cases (p = 0.02). Prognosis after radical surgery is favorable and depends mainly on lymph node involvement and the histological type of carcinoid.

[Fournier's gangrene. Experiences and changes in the disease picture since its initial description]. / Die Fournier'sche Gangrän. Erfahrungen und Veränderung des Krankheitsbildes seit der Erstbeschreibung.

Fournier's disease mostly occurs in immunosuppressed men in the 5th to 7th decade of life. Bacteria from the urogenital or colorectal tract lead to a rapid spreading soft tissue infection. Painful scrotal or perineal swelling and a black spot as a sign of beginning necrosis are guiding symptoms. Involved bacteria are grampositive cocci, enterobacteriaceae and anaerobes. Main principles of therapy are immediate radical debridement and broad spectrum antibiotics. Sepsis renders the prognosis more infaust.

[Ulcerated breast cancer of the young patient: a case report]. / Das exulzerierte Mammakarzinom der jungen Patientin: ein Fallbericht.

A 29-year-old woman presented with an exulcerating cancer of the right breast. She underwent a total mastectomy and axillary clearance which revealed a pathological stage of T4 N+ (21/23) M0. She received chemotherapy followed by radiation therapy and by chemotherapy again. 30 months later, a contralateral breast cancer was diagnosed. A close team-work of gynaecologist, plastic surgeon, medical and radiation oncologists allowed to combine the operation with the reconstruction of both breasts together with chemotherapy and irradiation of the left chest wall (the tumor was focally infiltrating the pectoralis muscle). We would like to show that a reconstruction of the breast in a young woman presenting with a bad prognosis can be carried out provided a well-organized team-work.

Conformal radiotherapy for unresectable retroperitoneal soft tissue sarcoma.

Local tumor control remains a continuing challenge in the treatment of retroperitoneal soft tissue sarcoma. Though complete resection by means of wide excision or excisional biopsy can be performed in a minority of patients only, aggressive surgical approach remains the treatment of choice. Unresectable sarcoma can rarely be controlled by conventionally applied radiotherapy--only a few percent of patients survive. A superior dose distribution of external radiation is demanded in order to spare healthy tissue. The presumably greatest advantage will occur when radiotherapy is used preoperatively. The possible clinical gain of superior dose distribution is demonstrated by results of the dynamic, 3-D conformal pion radiotherapy at PSI. Between April 1983 and June 1988 a total of 21 patients were treated with high doses (greater than or equal to 30 Gy) for unresectable retroperitoneal soft tissue sarcoma. The follow-up time is 13-74 months, median 24. Fifteen patients were treated with 20 fx, and 19 patients were treated with fraction sizes of 150 or 165 cGy. Except for one patient with thrombocytopenia after chemotherapy, no treatment interruption was necessary. Five patients developed late reactions, caused also by surgery and chemotherapy: two intestinal obstructions, one liver abscess, one leg edema, and one superficial skin necrosis. Nine patients had laparotomy after pion irradiation, five for resection of the previous unresectable tumor; 3/5 sarcoma were completely resected. Morbidity rate after post-pion laparotomy did not increase. Three patients had local tumor progression, 1/3 inside the treatment volume. The actuarial five-year local tumor control rate of these unresectable retroperitoneal sarcoma is 60%, the actuarial five-year survival rate is 33%. Out of the 21 patients, 15 are alive, two have died from local progression, one from peritoneal progression, and three from metastases.

Synovial sarcoma in children and adolescents. A report from the Kiel Pediatric Tumor Registry.

Of 49 cases of synovial sarcoma, which represent 5.8% of all soft tissue sarcomas with confirmed diagnosis in the files of the Kiel Pediatric Tumor Registry (Kiel, Germany), 35 occurred in patients up to the age of 18 years. The lower extremities were the most common. The 35 cases included 21 biphasic and 14 monophasic fibrous synovial sarcomas. The different cell types constituting synovial sarcoma could be demonstrated by conventional light microscopic study, but more readily so by immunohistochemical study, particularly when antibodies against cytoskeletal components were applied. Aberrant antigen expression was noticed for the neural markers, protein S-100, and neuron-specific enolase. Moreover, four tumors were positive for Ki M7. Collagen type IV was found in all tumors tested. For the 20 patients enrolled in the Cooperative Soft Tissue Sarcoma Study of the German Society of Pediatric Oncology (GPO) the survival rate at 7 years is 63%. When five patients with initial recurrence are excluded, the survival rate is 72%. It is concluded that immunohistochemical study is useful in the diagnosis and differential diagnosis of synovial sarcomas despite certain limitations. Multimodality treatment approach has improved the overall prognosis. There is no relationship between histologic subtype and prognosis according to the classification scheme employed in this study.

[Hyperfractionated irradiation with simultaneous cisplatin chemotherapy in patients with far-advanced carcinoma of the head and neck]. / Hyperfraktionierte Bestrahlung und simultane Chemotherapie mit Cisplatin bei Patienten mit fortgeschrittenen Karzinomen der Kopf-Hals-Region.

From January 1988 to April 1989, 22 of 28 patients with advanced carcinomata of the head and neck have been treated by hyperfractionated radiotherapy (2 x 1.2 Gy/day, five days/week, total dose 74.4 to 79.2 Gy) and simultaneous application of Cisplatinum (20 mg/m2 day, i.v., five days in the first and fifth week of the radiotherapy). In 68% of the patients the treatment could be applied in full dose. All eight patients with primary application of a gastrostomy could be irradiated without split, whereas five of 14 patients without a gastrostomy had a split of greater than or equal to 2 weeks. The mucositis healed in all patients after the end of the irradiation. Up to now, no serious complications have been seen. One year cumulative locoregional control rate is 65%. This study serves as a pilot study for a randomized trial. According to the acute and subacute toxicity the applied treatment is feasible.

Pion irradiation at Paul Scherrer Institute. Results of dynamic treatment of unresectable soft tissue sarcoma.

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN; now Paul Scherrer Institute, PSI) a dynamic, three-dimensional spot scan application technique has been in use. To exploit this technique a special planning system for optimisation of the dose distribution has been designed. From November 1981 to December 1988 a total of 406 patients have been treated with pions. From April 1983 to October 1987 a total of 35 patients were prospectively treated for unresectable soft tissue sarcomas in a phase I/II-study. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. 27 patients received a high, curative total dose of 30 to 36 Gy. After a median follow-up time of 19 months (13 to 68) the actuarial five-year rate of local tumor control for these 27 patients was 64%; the actuarial five-year survival rate of the 20 patients treated without metastases was 58%. Late reactions appeared in 5/27 patients: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer given). Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

Anaplastic astrocytoma and glioblastoma: pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN).

Clinical phase I/II studies have been performed at the Swiss Institute for Nuclear Research (SIN) since February 1982. Fifty-two out of 249 patients accepted for pion treatment by the end of 1986 were treated for malignant glioma with high dose pion irradiation. A substantial influence of their radioresistance was expected from increased radiation quality due to the contribution of high LET particles from pion capture, and by the possibility of target volume shaping and dose distribution related to the dynamic spot-scan conformation technique. The patients' treatment followed a dose escalation program with total doses from 2720-3420 cGy, fraction sizes from 170 to 205 cGy (90% isodose, minimum target dose), and treatment times from 4 to 5 weeks. 12/52 patients received an accelerated treatment with 3280 cGy in 14-22 days. 49/52 patients are eligible: 3 with astrocytoma of clinical aggressive behaviour, 14 with anaplastic astrocytoma (median age 42 years), and 32 patients with glioblastoma (median age 52 years). 8/49 patients had total/subtotal tumour resection, 19 patients a stereotactic biopsy. The patients were divided into three groups according to total dose, and a fourth group which received the accelerated treatment. There was no statistically significant difference in the median survival rate between the four groups, which was 13 months for the non-glioblastoma patients and 9 months for the glioblastoma patients. No radiation necrosis and no demyelination was found in 17 patients (6 recraniotomies, 11 autopsies). In 10/17 patients, clearly identifiable tumour cells were not demonstrated. NMR findings showed the tumour-surrounding oedema mostly stimulated by tumour necrosis and tumour progression. From these findings, further dose escalation programs, together with a shaping of the target volume close to the tumour, are not contraindicated.

Dynamic pion irradiation of unresectable soft tissue sarcomas.

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN, now Paul Scherrer Institute, PSI) a dynamic, 3-dimensional spot scan treatment technique has been in use. To exploit this technique a special optimization treatment planning system has been designed. Of a total of 331 patients treated with pions from November 1981-December 1987, 35 were irradiated for unresectable soft tissue sarcomas. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. Twenty-nine tumors had a maximum diameter of greater than 10 cm, 18 tumors of greater than 15 cm; 30 tumors had grade 2/3 and 32 Stage III B/IV A/IV B. Eight of 35 patients received a low pion total dose, 7-27 Gy. Twenty-seven patients received a total dose of 30-36 Gy, fraction size 150-170 cGy (90%-isodose), 20 fractions, 4 times per week. Of these 27 patients, severe late reactions appeared in five: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer used). Seven of 27 patients had metastases at the beginning of irradiation. Three of 27 were treated with excisional biopsy, 9 with incisional biopsy or partial resection and in 15 patients biopsies were performed for histology only. The median follow-up of these 27 patients was 17 months (5-66). There was no progression in eight extremity/groin tumors but in 4 of 19 retroperitoneal/pelvic tumors. Three of these were marginal progressions. The actuarial 5-year rate of local tumor control is 64%; the actuarial 5-year survival rate of patients without metastases at the beginning of treatment is 58%. Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

[Pion radiotherapy of unresectable soft tissue sarcomas at the Swiss Institute for Nuclear Research]. / Pionen-Strahlentherapie nichtresektabler Weichteilsarkome am schweizerischen Institut für Nuklearforschung (SIN).

The Swiss Institute for Nuclear Research SIN at Villigen is one of the three centres in the world (LAMPF, Los Alamos; TRIUMF, Vancouver) where pion therapy is possible. A dynamic, tumour conforming spot scan technique for the treatment of deep-seated tumours has been in use since November 1981. With this technique with a favorable integral dose distribution, curative irradiation also of advanced tumours in the retroperitoneum and pelvis is possible. Only at SIN, the treatment of non-resectable soft tissue sarcomas with pions is part of the clinical program. Between 1983 and 1985 totally nine patients were treated, 1/9 with three manifestations, 1/9 with palliative intent. In 20 fractions over five weeks (four fractions a week) total doses of 30 to 36 Gy (90% isodose) were applied. In a follow-up period of eleven to 43 months (median 18 months) only 1/10 tumour manifestations treated with greater than or equal to 30 Gy failed locally. The two-year survival rate (Kaplan-Meier) is 56%. Metastases were the cause of death in 3/5 patients, 1/5 heart disease, 1/5 local tumour progression. Even though 9/11 tumours were located in the retroperitoneum or pelvis, no radiogenic morbidity of the bowel was found. These preliminary results stimulate the intensification of this clinical program. 1986 the same number of patients with non-resectable soft tissue sarcomas was treated as in the whole period 1982 to 1985 before.

[Radiotherapy of soft tissue sarcomas of the extremities]. / Die Strahlentherapie der Weichteilsarkome der Extremitäten.

Radiotherapy is fully integrated in the treatment of soft tissue sarcomas. Nonamputative limb salvage is combined with large-volume, high-dose (65 Gy), pre- or postoperative radiotherapy. The survival rate for the conservative, combined approach to tumors of the extremities is no worse than that of radical or amputative surgery alone. It is better for large tumors to receive irradiation preoperatively, as there is then a higher probability that the limb can be spared at surgery. For tumors less than 10 cm, at doses of greater than 64 Gy radiotherapy alone can attain a local control rate of as much as 50%. With neutron irradiation, half of the patients with nonresectable tumors can be successfully treated locally. Conformal and dynamic treatment techniques will increase the probability that local tumors can be controlled by irradiation alone. The pion treatment technique at SIN is described in some detail.