Post-transplant lymphoproliferative disorders in liver transplanted patients: a single-centre experience.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after solid organ transplantation. Reduction of immunosuppression (RI) is accepted as a first step treatment with a long-term complete response rate observed in 23-50% of patients. Chemotherapy for diseases refractory to RI is based on small cohorts treated with different regimens. This paper reports on 10 consecutive cases of PTLD after liver transplantation. The median time from transplantation to PTLD diagnosis was 5 years. PTLD was frequently extranodal involving the transplanted liver. Seven monomorphic PTLD, 2 polymorphic and one Hodgkin disease were observed. Epstein Barr virus was present in tumour tissue only in one case. Initial therapy included RI in all patients. Chemotherapy was used in eight patients. No treatment-related mortality was observed and no patient developed graft rejection during chemotherapy. At a median follow-up period of 25 months, 6 of the 10 patients were alive and without evidence of disease.

Post-transplant lymphoproliferative disorders after heart or kidney transplantation at a single centre: presentation and response to treatment.

Post-transplant lymphoproliferative disorders (PTLD) is a serious complication after solid organ transplantation. Reduction of immunosuppression (RI) alone is not able to control the disease. We report a prospective analysis of 30 patients with PTLD after heart or kidney transplantation. Only 5 of 30 patients, treated solely with RI, obtained a complete response. Five patients were treated heterogeneously; in the remaining 20, the efficacy and safety of a weekly anthracycline-based chemotherapy were assessed. Sixteen patients obtained a complete remission. One death was related to treatment. With a median follow-up of 36 months, 3-year overall survival was 63.3% and 57% for the entire group and the chemotherapy-treated group, respectively. Moreover, 4 second neoplasms were observed in the chemotherapeutic group. In this study, we demonstrated that most PTLD need other treatment than RI and a weekly regimen is manageable and has a favourable impact on long-term survival.

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer.

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m(-2), cisplatin 75 mg m(-2) on day 1 and fluorouracil 750 mg m(-2) day(-1) on days 2-5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m(-2) week(-1) for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week(-1)). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2-66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1-12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3-4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

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.

[First-line chemo-radiotherapy neoadjuvant treatment in locally advanced (T4) epidermoid carcinoma of the esophagus]. / Il trattamento neoadiuvante con chemio-radioterapia di prima linea nei carcinomi epidermoidi localmente avanzati (T4) dell'esofago.

In the period 1993-1997 we performed two phase II pilot studies of first-line chemo-radiotherapy in patients with locally advanced (T4) SCC of the esophagus. The first protocol (3 cycles of DDP-VP16 + 45 Gy) was used in 37 patients: toxicity was not negligible; a clinical tumor downstaging was obtained in 54% of cases; an R0 resection surgery was performed in 40% of patients. The overall median survival of the whole group of 37 patients was 11 months, while it was > 36 months for patients undergoing R0 resection. The second protocol (4 cycles of DDP-5FU + 45 Gy) was used in 25 patients: a clinical tumor downstaging was obtained in 55% of cases, and R0 resection surgery was performed in 45% of patients. The overall median survival of the whole group was 11 months. To date, all patients but one (who died after 13 months) are alive with a median follow up of 13 months. The prognosis of both groups of patients was improved compared to patients with T4 SCC of the esophagus who did not undergo chemo and/or radiotherapy. The survival advantage was especially evident for those who were able to undergo an R0 resection. First line chemo-radiotherapy should be considered the standard treatment for locally advanced esophageal SCC.

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.

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.