Multifocal osteosarcoma as second tumor after childhood retinoblastoma.

We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases.

[Non-invasive lymphatic staging of lung neoplasms: comparative study with computerized tomography and endoscopic ultrasonography]. / La stadiazione linfonodale non invasiva delle neoplasie polmonari: studio comparato tomografia computerizzata-ecoendoscopia.

INTRODUCTION: A prospective comparative study with pathology was performed at the National Cancer Institute, Milan, to assess the clinical value of Computed Tomography (CT) and endoscopic ultrasound (EUS) for nodal staging in lung cancer. MATERIAL AND METHODS: In three years, 71 patients with histological diagnosis of non-small-cell lung cancer were operated on. They underwent CT and EUS examinations to identify mediastinal lymphadenopathies after major nodal involvement had been excluded by chest X-ray. Diagnostic staging was completed in two weeks prior to treatment. Patients received complete tumor removal and radical lymphadenectomy (55 patients), invasive staging with node resection and sampling (11 patients), or mediastinoscopy (5 patients). Blinded interpretation of CT alone, EUS alone, and CT and EUS together were performed, with systematic correlation of imaging findings and pathological results. RESULTS: The frequency of mediastinal involvement was 42.2%. A total of 329 nodal stations were dissected or sampled and 755 lymph nodes were examined at histology. On a per-station basis, CT had greater sensitivity (74%) than EUS (56%), but EUS was more specific (83.4% vs 92.7%). The accuracy rates of the two techniques were similar (CT 81%, EUS 83%). A site by site analysis showed highest sensitivity (100%) in the lower right paratracheal nodes for CT, and in the superior left paratracheal and subcarinal nodes for EUS. When the EUS and CT images were studied together by specialists on a per-station basis, sensitivity, specificity, and accuracy increased to 85%. CONCLUSIONS: Endoscopic ultrasound should be part of the routine preoperative diagnostic approach to non-small-cell lung cancer, because of its high specificity. Results can be improved when EUS and CT are combined, which suggests that these imaging modalities should be used together in selected patients for the noninvasive staging of non-small-cell lung cancer to identify local lymphatic spread.

Oral doxifluridine plus levoleucovorin in elderly patients with advanced breast cancer.

BACKGROUND: There currently is no agreement regarding the appropriate treatment of elderly patients with advanced breast carcinoma (ABC). Doxifluridine (5-dFUR), a prodrug of 5-fluorouracil, has been found to be effective in this entity, but its use is limited by neurotoxicity and cardiotoxicity that are not observed when the oral formulation is used. The objective of this Phase II trial was to evaluate the effectiveness and tolerability of oral 5-dFUR, biomodulated with levoleucovorin (1-leucovorin), in elderly patients (age > 70 years) with ABC. METHODS: 5-dFUR was administered orally at 600 mg/m2 twice daily for 4 consecutive days every 12 days, and oral 1-leucovorin was administered as 25 mg 2 hours before each 5-dFUR administration. Response was assessed every five cycles according to the World Health Organization criteria. In the presence of response or stable disease, the patients were treated for a maximum of 15 cycles. RESULTS: Seventy-three eligible patients were enrolled, 27 of whom had been pretreated with chemotherapy and/or hormonotherapy; all were assessable for response and toxicity after a median follow-up of 15 months. The objective response rate was 26% (95% confidence interval, 17.4-45.4). Regression predominantly occurred in the presence of soft tissue involvement (skin, lymph nodes, and breast). The median time to response was 2 months (range, 1-2 months) and the median response duration was 7 months (range, 2-17+ months). The median survival was 24 months (range, 2-42+ months). The treatment was very well tolerated, and the side effects were manageable and always reversible. CONCLUSIONS: The results of the current study show that 5-dFUR plus 1-leucovorin, both given orally, are associated with excellent patient compliance. Although the results are suboptimal in terms of an objective response, this characteristic could allow 5-dFUR to be used in elderly patients considered unsuitable for "aggressive" chemotherapy.

The minimal effective exemestane dose for endocrine activity in advanced breast cancer.

Phase I studies have demonstrated that exemestane, an irreversible oral aromatase inhibitor, is able to suppress circulating oestrogen levels. In our previous experience, doses ranging from 2.5 to 25 mg induced a similar suppression of oestrogens. The aim of this study was to identify the minimum effective exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5 mg, in double-blind conditions. Oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate serum levels were evaluated from the first day of treatment to the 7th, 14th, 28th and 56th day. Serum E1, E2 and E1S levels were suppressed by all doses starting from day 7; the degree of inhibition versus baseline was 25 up to 72% for E1, 30 up to 62% for E2 and 16 up to 52% for E1S, with higher doses achieving greater suppression; these changes were maintained over time. A significant increase in FSH and LH levels was observed for all doses. Treatment tolerability was satisfactory. The endocrine effects of exemestane appear to be dose related and 0.5 and 1 mg are ineffective for adequately suppressing circulating oestrogens.

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.

Langerhans cell histiocytosis mimicking malignancy: a radiological appraisal.

AIMS: To analyze the radiologic characteristics, clinical course and long-term follow-up of 7 radiologically uncommon pediatric cases of Langerhans cell histiocytosis and to identify prognostic factors related to imaging patterns. METHODS: The clinical records and complete imaging data of 75 patients with LCH diagnosed and treated at the National Cancer Institute of Milan between January 1975 and December 1993 were analyzed, and 43 cases presenting as unifocal bone lesions were identified. The plain film, computed tomography and magnetic resonance characteristics enabled the identification of 7 radiologically aggressive and rapidly progressive cases, which were analyzed at presentation and during follow-up. RESULTS: Although at disease presentation bone lesions appeared lytic destructive, rapidly progressive and often involved adjacent soft tissues, after adequate therapy the disease course was invariably benign and led to almost complete restoration of normal structure and function. Long-term follow-up confirmed the favorable outcome and lack of disease recurrence in all cases. CONCLUSIONS: There is no correlation between radiologically aggressive characteristics and final outcome in Langerhans cell histiocytosis. Radiologists and pediatric oncologists should be acquainted with less common radiologic forms which, at presentation, can mimic more ominous diseases. If recognized and adequately treated, monostotic forms almost invariably have a benign prognosis.

[Transrectal prostatic echography in the study of hemospermia. An assessment of an 85-patient case load]. / L'ecografia prostatica transrettale nello studio dell'emospermia. Valutazione di una casistica di 85 pazienti.

Eighty-five patients with hemospermia were examined with blood tests, sperm culture, transrectal US (TRUS) and cystourethroscopy. Blood tests and sperm culture demonstrated bacterial inflammation in 48 patients (56.47%). At cystourethroscopy, the urethra was normal or hyperemic in all patients. TRUS demonstrated 40 cases (47.05%) of periurethral calcifications and also with calcifications in the two glandular lobes. TRUS also demonstrated prostatic inflammation in progress or its outcome in 21 patients (24.70%), ectasia and seminal vesicle inflammation in 10 patients (11.76%), a prostatic tumor in 3 patients (3.52%). No patient had cysts, stones or cancers in the seminal vesicles. In 11 patients (12.94%), no specific cause of hemospermia was detected, even though 4 of these patients (4.70%) had received anticoagulants for former heart ischemia. Benign prostatic hypertrophy was found in 44 patients (51.76%) but we did not consider it a possible cause of hemospermia because of the high frequency of this condition in the male population. To conclude, TRUS could demonstrate the cause of hemospermia in most of our patients, which makes us suggest it as the diagnostic technique of choice in the patients with ejaculatory conditions, after clinical exams and laboratory tests, because it allows to study the prostate, the seminal vesicles and the urethra.

The role of somatostatin analogues in the treatment of gastro-enteropancreatic endocrine tumours.

Neuroendocrine (NE) cells are involved in gastro-enteropancreatic (GEP) neoplasms. Biological markers, such as peptides hypersecreted by biologically active NE tumours, aid in the evaluation of response to treatment. For surgically untreatable NE neoplasms, the therapeutic approach remains undefined. Somatostatin analogues, particularly octreotide, can control the clinical effects of hormone overproduction in NE neoplasms and they have revolutionised individualised treatment, particularly for biologically active tumours. So far, like interferon, octreotide used at standard dosages has failed to control neoplastic growth per se. We gave the somatostatin analogue lanreotide to women with advanced breast cancer and to colorectal carcinoma patients. Results confirmed that inhibition of the production of insulin-like growth factor-1, which plays an important role in neoplastic proliferation, could be obtained using the highest doses. Considering these data, we started a clinical trial of 58 patients affected by NE tumours, treated with two sequential doses (500 and 1,000 micrograms subcutaneously t.i.d.) of octreotide. Long-term disease stabilisation (> 6 months) was achieved in 43% of patients but an objective response in only 3%. Good control of clinical symptoms and markers was obtained in 73 and 77% of cases, respectively. Toxicity was negligible. Somatostatin analogues should be carefully evaluated at high doses for possible anti-proliferative effects. Studies are currently investigating their promising association with interferon.

Non-small-cell lung cancer: detection of mediastinal lymph node metastases by endoscopic ultrasound and CT.

In this prospective study endoscopic ultrasound (EUS) and computed tomography (CT) were evaluated to compare diagnostic accuracy of the two methods. They were performed for nodal staging in selected patients admitted to our institution for non-small-cell lung cancer (NSCLC). From February 1992 to July 1993, 45 patients were recruited for the study when N3 and N2 nodal involvement were excluded on standard chest X-ray. All the patients completed EUS and CT exams for staging before treatment. The results of sensitivity, specificity and accuracy were obtained in 30 patients who underwent surgical treatment with macroscopically radical resection of T and N, which allowed a complete surgical and histological comparison of CT and EUS findings. On a per-patient basis CT results were: sensitivity 63.6%, specificity 78.9% and accuracy of 73.3%; on a nodal station basis sensitivity, specificity and accuracy were 70.0%, 85.1% and 81.6%, respectively. The EUS evaluation showed, on a per-patient basis, values of sensitivity 45.5%, specificity 57.9% and overall diagnostic accuracy of 53.3%. On a nodal station basis the results were 50.0%, 86.6% and 78.2%, respectively. The results obtained in the 30 patients when both techniques were taken in association regarding sensitivity (90.9%), specificity (73.7%) and accuracy (80.0%) on a per-patient basis suggest that the association of EUS and CT offers the best approach for preoperative staging of NSCLC.

Blunt trauma of the spleen: the delayed rupture in computed tomography.

We retrospectively reviewed CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with the diagnosis of blunt splenic trauma. All patients underwent CT at different times after the trauma. The cases were divided into 2 groups: according to the time at which the CT was performed, the 1st group consisted of 11 patients scanned within 48 h after the trauma; the 2nd group consisted of 7 patients studied with CT at variable times after the traumatic event (mean time: 6.5 days; range 3-13 days). All lesions in the 1st group (11 patients) had indistinct margins, while lesions of patients in the 2nd group (7 patients) always showed clean-cut and regular edges. Early lesions were always hyperdense, late ones hypodense. CT diagnosis always matched the surgeon's diagnosis. We can confirm the diagnostic value of CT of splenic lesions in blunt abdominal traumas.

[An analysis of a case series of 342 short-stature patients examined by the Tanner-Whitehouse 2 (TW2) method]. / Analisi della casistica di 342 pazienti con bassa statura esaminati con il metodo Tanner-Whitehouse 2 (TW2).

342 short-stature patients were examined to assess the agreement between anagraphic and bone ages. 190 men and 152 women (age range: 0 to 17.5 years) underwent conventional radiographs of the left wrist. The radiographs were studied with the TW2 method which provides an index of the skeletal maturity of short and long bones and a global index of the hand. The bone ages thus obtained were compared with anagraphic ages. Patients' statures were compared with their parents' ones. Finally, radiation exposures were evaluated. Anagraphic and bone ages were in agreement in 199 patients and in disagreement in 220. Three patients were adult. The short stature in 78 patients was in agreement with their parents' one, while 253 patients had at least one parent with normal stature. No comparison could be made in 11 patients. In conclusion, TW2 is a simple method to calculate bone age (in months and years) and to select the patients to submit to further examinations and to hormone therapy.

[The radiodiagnosis of bone metastases from melanoma]. / Contributo alla radiodiagnostica delle metastasi ossee da melanoma.

The records of 3,795 cases of malignant melanoma treated at the INT (Milan) from 1975 to 1992 were reviewed. Histologic confirmation was obtained in all cases. Thirty-one patients (0.82%) with solitary or multiple skeletal metastases were identified. The review of conventional films, tomograms, CT, MR and bone scintigraphy images enabled us to detect 120 single bone lesions. The X-ray features were divided into two groups according to typical and atypical skeletal lesions. Typical bone metastases are osteolytic (87.5%), with medullary origin (91.6%), and they cannot be distinguished from other osteolytic metastases on the basis of imaging criteria alone. Lesion growth causes cortical erosion and destruction (46.6%), pathologic fractures (22.5%) and soft tissue involvement (12.5%). Lytic areas usually have ill-defined margins. Clear-cut outline is an uncommon finding. Atypical skeletal metastases exhibit a mixed osteolytic-osteoblastic pattern (10%), which is hardly ever completely osteoblastic (2.5%). Other unusual metastatic patterns include intense trabecular rarefaction with no detectable single lesion (3.3%), the presence of a well-defined sclerotic rim and periosteal reaction (12.5%). Atypical growth may cause extensive cortical destruction and periosteal production resembling osteogenic osteosarcoma. The various imaging methods show that conventional radiology has relatively poor sensitivity because of anatomical reasons, while MRI is the most sensitive method to detect skeletal localizations. Treatment changes the radiologic patterns of the lesions: recalcification, sclerotic rim, periosteal reaction are common response patterns. Finally, in spite of the above limitations, conventional radiology remains the method of choice to assess lesion evolution during the follow-up.

Conventional radiographic follow-up in the irradiated lung.

AIMS: To highlight the different changes induced in lung tissues by various forms of radiotherapy (RT) according to tumor site and type. METHODS: A retrospective analysis of the roentgenographic evaluation of and long-term follow-up data on 2375 patients who received RT for various intrathoracic and extrathoracic tumors at the National Cancer Institute of Milan. RESULTS: The iconographic patterns of post-RT changes, grouped by site and type of tumor and RT procedure and described in detail, afford deeper insight into a little-known area of lung pathology. CONCLUSIONS: These descriptions of common and uncommon patterns of the irradiated lung as they appear on conventional chest roentgenograms enable the radiologist and radiotherapist to assess exactly the response of tumor and lung tissues and to plan the most appropriate clinical follow-up.

[Comparison of portal CT, arterial CT and CT with intravenous contrast media in the diagnosis of hepatocarcinoma]. / Confronto tra porto-TC, arterio-TC e TC con mezzo di contrasto per via endovenosa nella diagnosi dell'epatocarcinoma.

Sixty-nine patients underwent CT for hepatocellular carcinoma (HCC). All subjects were examined with CT before and after bolus injection of contrast medium: 42 HCCs were detected. 13/42 patients underwent also CT arteriography (contrast medium in the hepatic artery) and 29/42 were submitted to CT during arterial portography (contrast medium in the superior mesenteric artery). The results of the three techniques were compared with each other and with surgical and pathologic findings. CT during arterial portography detected other lesions in 5/29 patients while it confirmed CT diagnosis in the extant 24 cases; CT arteriography recognized other lesions in 2/13 subjects while in the extant 11/13 it confirmed CT diagnosis. Both CT arteriography and CT during arterial portography affected treatment protocol in 16.2% of cases. The results had surgical confirmation in all patients but 3 in whom intraoperative US showed some nodules undetected earlier. All the lesions were hypodense on CT during arterial portography. On CT arteriography, they were hyperdense in 4/13 cases and hypodense with an irregular hyperdense halo in 9/13 cases. To conclude, CT during arterial portography and CT arteriography are better diagnostic tools than CT: nevertheless, they are invasive techniques and should be employed in selected cases only.

Radiobiologic and pathologic characteristics of the irradiated lung and roentgenographic aspects.

AIMS: Experimental radiobiologic factors help to better understand and interpret the development of radiographic alterations in lung tissues due to radiant treatments. In this paper the authors summarize the radiologic factors and technical bases about radiotherapy of the lung. METHODS: The conventional radiologic iconography has been examined in a large series of patients (n = 2151) with iatrogenic pulmonary lesions determined by various types of antineoplastic radiant treatments at the Istituto Nazionale Tumori of Milan. RESULTS: A radiologic control and a long follow-up is essential to assess the successive phases of postactinic lesions due to "passive" irradiation therapy for any type of non-endothoracic tumor as well as those due to "necessary" lung radiotherapy for endothoracic neoplasms. CONCLUSIONS: A strict relation has been found between the aspects in conventional radiologic iconography and the corresponding lesions in the irradiated lung.

Adrenal gland metastasis in osteogenic osteosarcoma. A radiological case report.

Adrenal gland metastases from osteogenic sarcoma are rare and an unusual pattern of relapse. The recognition of solitary metastases, particularly when located in uncommon sites is very important for subsequent treatment. The authors describe the radiological features of an adrenal metastases from osteogenic sarcoma.

[Multidisciplinary radiological diagnosis of hepatic angioma in cancer patients]. / Diagnosi radiologica multidisciplinare degli angiomi epatici nel paziente neoplastico.

72 cases of hepatic angioma were examined. These were occasionally found during control investigations of patients treated for extrahepatic primary cancer, or revealed by ultrasound studies of patients not supposed to be affected by cancer. Prospective comparison in 18 cases was made between echotomographic, tomodensitometric and angiographic findings with purpose of pointing out possible correlations between the X-ray images and the anatomopathological pictures. Finally, the best diagnostic procedure was established for suspected hepatic angioma, in both a cancerous and a non cancerous patients.

Esophagogastroplasty and its radiological approach.

Sixty-six patients with tumor of the distal esophagus and/or the gastric fundus were admitted for intrathoracic esophagogastroplasty. Surgical mortality was 6% (4 of 66 cases). There were 3 early and 7 late complications among the 62 remaining patients. The authors suggest that radiological examinations of patients after esophagogastroplasty should include an early examination on the 7th-10th day after surgery with water-soluble contrast medium for detection of early complications and double-contrast studies before dismissal, at later check-ups and whenever clinical symptoms of late complications are developing.