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Biomedical subjects

L Corti

Publications and source records attributed to L Corti.

At least 19 recordsLinked to original sources

Multimodal imaging of esophagus and cardia cancer before and after treatment.

PURPOSE: Prognosis and treatment of esophagus and cardia cancer (ECC) depend on the precision with which the disease is staged according to the American Joint Committee of Cancer (AJCC) criteria. Imaging modalities normally used in clinical staging are esophagography, esophagoscopy, endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography- CT fusion (CT-PET). The combination of these methods is crucial in determining not only the right diagnosis but also the stage and follow-up after multimodal treatment. The purpose of our investigation was to define the role of each imaging modality in determining the most appropriate treatment options in patients with ECC. MATERIALS AND METHODS: Fifty-six patients with ECC diagnosed by X-ray of the upper digestive tract, endoscopy and biopsy were staged using EUS, chest and abdomen CT scan, and CT-PET. Thirty-four patients in stage II and 18 patients in stage III underwent surgery after neoadjuvant chemotherapy; four patients in stage IV were treated with the positioning of an endoprosthesis after chemoradiotherapy. In the 52 patients who had surgery, follow-up included digestive tract X-ray, endoscopy and CT of the chest and abdomen every 6-8 months for the first 3 years. CT-PET was only performed in patients with a clinical suspicion of recurrence and/or CT findings suspicious of persistent disease (12 cases). RESULTS: In all 56 patients, endoscopy, EUS, CT and CT-PET in combination were crucial in determining the site of disease, locoregional extent and depth of esophageal wall penetration (T), and any involvement of the mediastinal lymph nodes (N1), extrathoracic lymph nodes (M1) or hepatic metastases. In the locoregional staging of ECC before chemotherapy, we were able to differentiate T2-T3 from T4 in 40 patients; T4 disease was found in 12 potentially resectable cases. We were able to distinguish N0 from N1 in 12 patients. In four cases, the presence of small lymph node and/or liver metastases prompted positioning of an endoprosthesis. The specificity of CT in detecting small lymph nodes in the mediastinum was less than 50% while for CT-PET, it was more than 80%; EUS revealed sensitivity higher than 90% but a low specificity in seven cases. Only CT-PET revealed metastatic subdiaphragmatic lymph nodes (diameter <15 mm) in three cases. Presurgical restaging of the 18 patients (stage III) who had chemotherapy was based on endoscopy, EUS, CT of the chest and abdomen and CT-PET (only in suspected cases) and was compatible with surgery. Anastomotic recurrence was diagnosed in 16 patients by endoscopy with associated biopsy; any intramediastinal spread from anastomotic recurrences was evaluated by chest CT, and CT-PET in suspected cases. CONCLUSIONS: X-ray of the upper digestive tract and chest and abdomen CT scan are useful in preliminary evaluation of ECC. Endoscopy is particularly indicated for evaluating tumour morphology, taking biopsies for a histological diagnosis and the early diagnosis of anastomotic recurrences. EUS is indicated mainly for evaluating T stage before and after chemotherapy or chemoradiotherapy. CT-PET is extremely useful in identifying small mediastinal metastatic lymph nodes (N1) or extrathoracic lymph nodes (M1) and hepatic metastases (</=1 cm), which may escape multislice CT. PET alone is useful for identifying residual or recurrent tumour in the esophageal wall when an endoprosthesis is in place.

Adult↗

Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model.

The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.

Animals↗

Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy.

Hypoxia inducible factor 1a and 2a (HIF-1a and HIF-2a) are key proteins regulating cellular response to hypoxia. Because the efficacy of photodynamic therapy (PDT) is dependent on the presence of oxygen, the assessment of HIF-1a and HIF-2a expression may be of value in predicting clinical response to PDT. Using recently produced MoAbs, we examined the expression of HIF1a and HIF2a in a series of 37 early-stage esophageal cancers treated with PDT and with additional radiotherapy in case of incomplete response after PDT. Strong expression of the HIF1a and of HIF2a proteins in all optical fields examined was noted in 51% and in 13% of cases, respectively. High expression was associated with a low complete response (CR) rate and with the absence of bcl-2 protein expression. On the contrary, bcl-2 expression was associated with a high CR rate. Combined analysis of HIF1a and bcl-2 protein expression revealed that of 16 cases with high HIF1a expression and the absence of bcl-2 reactivity, only 1 (7%) responded completely to PDT (P = 0.007). Bivariate analysis showed that HIF1a expression was independently related to response to PDT (P = 0.04; t ratio = 2.8), whereas bcl-2 approached significance (P = 0.07; t-ratio = 1.8). The final response to radiotherapy was high (70%) and independent of the HIF and bcl-2 status, which may be a result of reoxygenation after cellular depletion mediated by PDT. The present study suggests that assessment of HIF and of bcl-2 expression are important predictors of in vivo sensitivity to PDT. Modulation of PDT response with bioreductive drugs and/or drugs targeting bcl-2 (i.e., taxanes) may prove of significant therapeutic importance in a subgroup of patients with high HIF expression.

Basic Helix-Loop-Helix Proteins↗

Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients.

This randomized phase II trial was performed to define the activity and toxicity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. Sixty patients with metastatic melanoma were randomly assigned to receive BCNU 150 mg/m2 intravenously (i.v.) on day 1, cisplatin 25 mg/m2 i.v. daily on days 1 to 3, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily for 7 days prior to chemotherapy (DBDT arm; arm A). Treatment cycles were repeated every 28 days, while BCNU was given every two cycles. The DTIC arm (arm B) patients received DTIC alone 1200 mg/m2 i.v. on day 1, repeated every 21 days. Patients were evaluated every two cycles; responding patients continued the treatment for a maximum of 12 cycles. The overall response rate was 26% in the DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for DTIC. The median progression-free survival and the median survival were 4 and 9 months, respectively for DBDT, and 2 and 7 months for DTIC. DBDT was associated with significant haematological toxicity: 33% of the patients experienced a grade III or IV neutropenia and 28% a grade III or IV thrombocytopenia. In conclusion, the overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival.

Adult↗

Photofrin II as an efficient radiosensitizing agent in an experimental tumor.

BACKGROUND AND OBJECTIVE: The use of ionizing irradiation as radiation therapy (RT) for tumor treatment represents a well-established method. The use of photodynamic therapy (PDT), especially with Photofrin II, for tumor treatment is also known. Chemical modifiers enhancing the action of radiation therapy are well known and widely used in medicine. None of these compounds, however, is a selective radiosensitizer. MATERIALS AND METHODS: Several series of animal experiments were performed. The highly differentiated human bladder cancer cell line RT4 was implanted subcutaneously in nude mice. The mice were injected 10 mg/kg Photofrin II and irradiated with 5 Gy. RESULTS: Photofrin II has proved to be a chemical modifier of ionizing irradiation, enhancing the tumor doubling time (tumor growth) from 6.2 to 10.9 days in the control group with the use of irradiation and injection of porphyrin. CONCLUSION: Photofrin II shows a high activity as radiosensitizer and, in the future, can be used as a selective radiosensitizer for tumor treatment with ionizing radiation.

Animals↗

Outcome of patients receiving photodynamic therapy for early esophageal cancer.

PURPOSE: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer. METHODS AND MATERIALS: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months). RESULTS: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy. CONCLUSION: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Antineoplastic Agents↗

Application of autoregressive methods to multigate spectral analysis.

Multigate analysis is known to be capable of detecting accurate blood velocity profiles from human vessels. Experimental systems so far presented in the literature use time-domain frequency estimations and, more recently, the fast Fourier transform (FFT) for real-time analysis of Doppler signals from multiple range cells. This experimental study is aimed at evaluating the application of an autoregressive (AR) method (Burg algorithm) to multigate Doppler analysis. Both in vitro and in vivo results were collected with a commercial Duplex scanner coupled with a prototype multigate unit developed in our laboratory. The same multigate signals are, thus, processed according to both the FFT and the Burg algorithms. The related spectral and maximum frequency profiles are reported and statistically compared. AR, implemented with the Burg algorithm, is demonstrated to be a way to perform multigate spectral analysis with reduced spectral variance, suitable for maximum velocity profile extraction through a simple threshold.

Artifacts↗

[Palliative treatment of esophageal and cardial carcinoma].

Recent series reported increasing incidence of esophageal and cardial cancers with prognosis still severe in spite of surgical progress. The late diagnosis reduces the chance of radical surgery; on the other hand about 80-90% of patients develop local or distant recurrence. Therefore the treatment of esophageal and cardial cancer is often palliative: surgical resection is reserved only to selected cases. Endoscopic palliation was the treatment of choice in a total of 265 patients 174 of which received laser therapy and 91 prosthesis intubation. The results it good in about 80% of cases.

Adenocarcinoma↗

Photodynamic therapy in gynaecological neoplastic diseases.

Since 1982, our department has used photodynamic therapy (PDT) in the treatment of loco-regional recurrences of gynaecological cancers. We have treated 26 patients in this time. In the majority of cases the site of vaginal recurrences was the vaginal vault. The light sources were an Argon-dye laser (Meditec) and, in some cases, a CO2 laser. The light dose ranged between 60 and 500 J cm-2. The photosensitizing drug used was Hematoporphyrin (HP) (Monico Farmaceutici) at the dose of 5 mg kg-1 body weight. Patients were evaluated 45 days after the treatment with a gynaecological examination and after 75-90 days with a vaginal smear. The results were divided into 2 groups: objective and symptomatic. The symptomatic response concerned only the patients treated with a palliative aim and, in this case, a complete response (CR) was a complete absence of symptoms at least for 60 days. In this group the complete response rate was 66%. In the curative group, the complete response was a cytological and/or histological absence of lesions. In this group we had 12 CR (70.58%). The survival rate was also evaluated. A significant review of the photodynamic therapy in gynaecological neoplasms has also been done.

Adenocarcinoma↗

Gynecologic cancer recurrences and photodynamic therapy: our experience.

The incidence of locoregional recurrences of gynecological tumors is still a major problem. Many authors suggest that it is the major cause of death in patients affected by cervical-endometrial cancers. The results achieved by retreating these patients with conventional therapies are still unsatisfactory. Since 1982, in our department, we have been using photodynamic therapy (PDT) for treatment of locoregional recurrences in gynecological cancers. We have treated 26 patients. In the majority of the cases, vaginal recurrences were on the vaginal vault. Out of 26 cancers, 17 were epidermoid cancers. Lasers used were the argon dye laser (Meditec) and, in some cases, the CO2 laser. Light dose ranged between 60 and 500 J/cm2. The photosensitizing drug used was hematoporphyrin (HP) (Monico Farmaceutici, Venezia, Italy) at a dose of 5 mg/kg body weight. Patients were evaluated 45 days after treatment with gynecological examination and again after 75-90 days with a vaginal smear. Results were divided into 2 groups: objective and symptomatic. The symptomatic response concerned only patients treated with a palliative aim and, in this case, a complete response (CR) was a complete absence of symptoms for at least 60 days. In this group the complete response rate was 66.6%. In the curative group, the complete response was a cytological and/or histological absence of lesion. In this group we had 12 CR (70.58%). The survival rate of patients treated only with PDT ranged between 3 and 92 months (mean 50.7 months). No major acute or side effects were recorded.

Female↗

Patterns of dyspepsia in patients with no clinical evidence of organic diseases.

We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between "related" and "associated" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis.

Adolescent↗

Oesophageal cancer treated by photodynamic therapy alone or followed by radiation therapy.

Photodynamic therapy (PDT) with porphyrins and red light is receiving increasing attention in the management of malignant tumours. At present PDT is primarily indicated for the treatment of superficial or early-stage lesions. At the Department of Radiotherapy and the First Institute of Surgery in Padova (Italy) more than 150 cases of tumours of different types have been treated using this technique. This paper briefly describes 21 cases of superficial oesophageal cancer. A complete response was observed in 11 of 21 cases. Radiation therapy appeared to be very effective as a salvage treatment of non-response patients.

Antineoplastic Agents↗

Trophic response and morphological changes in pancreas of caerulein treated rats: dose and time dependent effects.

The present study was performed to determine the effect of the duration of chronic caerulein administration given at different doses, on the rat pancreas. Four groups of rats, one treated with 0.9% NaCl (control) and the others with caerulein 2, 5 and 10 micrograms/Kg twice a day i.p. were used. After a treatment period of 15, 30 and 60 days, 6 rats from each group were anesthetized, the pancreas was removed, and growth and composition of pancreatic tissue were determined. Small samples were taken for histological examination. Caerulein induced pancreatic hyperplasia and hypertrophy. The dose of caerulein used and the length of the treatment did not significantly modify the trophic effect. Focal perivascular and periductular lymphomonocytic infiltrates associated with cellular abnormalities were seen at 30 and 60 days. The results suggest that 1) the trophic effect of caerulein is not dose-and-time dependent and 2) morphological abnormalities can appear during long term treatment with CCK analogous.

Amylases↗