Technical details for a robot-assisted hand-sewn esophago-gastric anastomosis during minimally invasive Ivor Lewis esophagectomy.

BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIILE) provides better outcomes than open techniques, particularly in terms of post-operative recovery and pulmonary complications. However, in addition to requiring advanced technical skills, thoracoscopic access makes it hard to perform esophagogastric anastomosis safely, and the reported rates of anastomotic leak vary from 5 to 16%. Several minimally invasive esophago-gastric anastomotic techniques have been described, but to date strong evidence to support one technique over the others is still lacking. We herein report the technical details and preliminary results of a new robot-assisted hand-sewn esophago-gastric anastomosis technique. METHODS: From January 2018 to December 2020, 12 cases of laparoscopic/thoracoscopic Ivor Lewis esophagectomy with robot-assisted hand-sewn esophago-gastric anastomosis were performed. The gastric conduit was prepared and tailored taking care of vascularization with a complete resection of the gastric fundus. The anastomosis consisted of a robot-assisted, hand-sewn four layers of absorbable monofilament running barbed suture (V-lock). The posterior outer layer incorporated the gastric and esophageal staple lines. RESULTS: The post-operative course was uneventful in nine cases. Two patients developed chyloperitoneum, one patient a Sars-Cov-2 infection, and one patient a late anastomotic stricture. In all cases, there were no anastomotic leaks or delayed gastric conduit emptying. The median post-operative stay was 13 days (min 7, max 37 days); the longest in-hospital stay was recorded in patients who developed chyloperitoneum. CONCLUSION: Despite the small series, we believe that our technique looks to be promising, safe, and reproducible. Some key points may be useful to guarantee a low complications rate after MIILE, particularly regarding anastomotic leaks and delayed emptying: the resection of the gastric fundus, the use of robot assistance, the incorporation of the staple lines in the posterior aspect of the anastomosis, and the use of barbed suture. Further cases are needed to validate the preliminary, but very encouraging, results.

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems.

BACKGROUND: A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. AIM: To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. METHODS: We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. RESULTS: One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha-fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients. CONCLUSIONS: Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients.

Seeding after radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis: a prospective study.

BACKGROUND: Neoplastic seeding of hepatocellular carcinoma may arise after radiofrequency ablation. AIMS: In order to clarify the real risk of seeding, we observed a prospective cohort of patients undergoing radiofrequency ablation. METHODS: Ninety-three (22.9%) out of 406 consecutive patients with hepatocellular carcinoma superimposed to cirrhosis diagnosed at our Liver Unit (2000-2005) were selected for radiofrequency ablation according to the Barcelona 2000 EASL guidelines. Seventy-one patients were treated by a percutaneous approach and 22 at laparotomy. After radiofrequency ablation ultrasound scan was repeated every 3 months and spiral-computed tomography every 6 months. RESULTS: Overall 145 sessions were performed in 93 patients: 113 (77.9%) by a percutaneous approach and 32 (22.1%) at laparotomy. The median follow-up was 23 months (range 1-60). Only 1 of the 71 patients (1.4%; 95% C.I. 0.25-7.56) treated percutaneously and none of the 22 (0%; 95% C.I. 0-14.8) treated at laparotomy showed neoplastic seeding. CONCLUSION: In our experience the risk of seeding of hepatocellular carcinoma after radiofrequency ablation was small (1.1% per patient, 95% C.I. 0.19-5.84; 0.7% per procedure, 95% C.I. 0.12-3.80). A stringent selection of patients for radiofrequency ablation and retraction of the needle with a hot tip may have been instrumental in obtaining this low frequency.

Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.

Radio-frequency thermal ablation (RFTA) of small hepatocellular carcinoma in patients with cirrhosis. Experience at a single tertiary referral center.

AIM: Radio-frequency thermal ablation (RFTA) may prolong the survival of patients with small hepatocellular carcinoma (HCC) associated with cirrhosis. The aim of this study was to evaluate efficacy and safety of RFTA. METHODS: We performed the Kaplan-Meier analysis to estimate the survival rate in 69 consecutive patients with HCC (mean age 66+/-6.5 years; 44/25 male/female; 56 Child-Pugh class A and 13 Child-Pugh class B) treated by RFTA. A single lesion was observed in 60/69 (87%), two lesions in 8/69 (11.6 %), and 3 lesions in 1/69 (1.4 %) of patients. The tumor size was = or <3 cm in 60/69 (87%). RESULTS: Twenty-two patients died during follow-up. Overall survival rates were 81%, 66%, and 46% at 1-, 2-, and 3-years, respectively. Cancer-free survival rates were 64% at 1 year, 30% at 2 years and 25% at 3 years. The 3-years rate of appearance of separate new lesions and local recurrence were 27.5% (19/69) and 26 % (18/69). CONCLUSIONS: Our study shows that patients with HCC and compensated cirrhosis may benefit from RFTA treatment, especially for tumors = or <3 cm. Nevertheless, the high rate of recurrence (both local and distant) points out the palliative role of this therapy.

[Esophageal digital videofluorography with water siphon test in the post-operative evaluation of the anti-reflux laparoscopic surgery]. / La videofluorografia esofagea digitale con water siphon test nella valutazione postoperatoria della chirurgia antireflusso laparoscopica.

BACKGROUND: In recent years digital videofluorography (VFG) with water siphon test (WST) has been proposed just for diagnosing hiatal hernia and/or gastroesophageal reflux. PATIENTS AND METHODS: Fifteen patients undergone Laparoscopic Nissen (LN) for complicated GERD associated to hiatal hernia, were referred for VFG and WST in order to evaluate the functional results of surgery. At one-month videofluorographic control thirteen patients had just a minimal prolonged esophageal transit time but only six of these had an early postoperative dysphagia, whereas at six months control the prolonged esophageal transit time was present in three patients two of which complained a very light dysphagia. One patient at one month control had a severe dysphagia, her videofluorography showed a very prolonged esophageal transit time and she had to redo surgery. She had a complete resolution of dyspagia and at the six months videofluorographic control she had a normal esophageal and esophagogastric transit time. One patient, underwent surgery in another hospital, complained a persistent and moderate dysphagia and at one month videofluorografic control was evident a malposition of wrap around the upper part of the stomach and a WST positive for reflux and at six months control clinical finding was worst. He will be evaluated for further endoscopic or surgical treatment. CONCLUSIONS: In our experience we believe that VFG is a valid test to identificate the postoperative outcomes giving the surgeons a visual evaluation of their work.

Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-small-cell lung cancer.

Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib.

Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.

BACKGROUND: Gefitinib (Iressa(TM), ZD1839) is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I studies showed that it is well tolerated, with evidence of tumor regression in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the antitumor activity and tolerability of gefitinib in a series of patients with previously treated, advanced NSCLC, as a part of a compassionate use program. PATIENTS AND METHODS: To be eligible, all patients were required to have histologically or cytologically proven advanced or metastatic NSCLC, prior chemotherapy with at least one cisplatin-containing chemotherapy regimen or contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group performance status < or =2, and adequate hematological, renal and hepatic parameters. All patients provided signed informed consent. Patient re-evaluation was performed every 4-6 weeks. RESULTS: Seventy-three consecutive patients were enrolled. Response rate, including complete and partial response, was 9.6%; an additional 43.8% of patients achieved stable disease, for an overall disease control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25 patients. According to EGFR1 immunoreactivity all responses were observed with medium/strong imunoreactivity while three out of four responses were observed in high expressive patients. Median survival for all patients was 4 months while it reached 6 months for patients with disease control. The 1-year survival rate was 13.1% for the entire series and 23.2% for patients with disease control. Non-hematological toxicity was generally mild. CONCLUSION: Gefitinib has promising activity with a good toxicity profile in patients with progressive NSCLC who have received one or two prior chemotherapy regimens. A possible relationship within response and EGFR1 expression is suggested.

[Cutaneous ascites as complication of the placement of a totally implantable arterial system]. / Filtrazione ascitica cutanea come complicanza del posizionamento di un sistema totalmente impiantabile arterioso.

The Authors report the case of a patient with intrahepatic colangiocarcinoma, operated on for totally implantable arterial device (TIAD) implant in view of hepatic chemotherapy. The postoperative course was characterized by cutaneous drainage of ascites fluid from the wound of the TIAD implant. Its aetiology and therapy are discussed.

DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.

PURPOSE: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. METHODS: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. RESULTS: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P<0.05) and DNA aneuploid tumors (P<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. CONCLUSIONS: Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.

Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose density of doxorubicin and cyclophosphamide.

BACKGROUND: Following our previous study of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) intensification in non-Hodgkin's lymphoma (NHL), in the present report we attempted to further increase dose intensity by shortening the between-course intervals with the support of growth factors. PATIENTS AND METHODS: A total of 67 patients were enrolled. With a fixed dose of doxorubicin 75 mg/m(2), cyclophosphamide (CTX) was started at a dose of 1750 mg/m(2) and increased by 250 mg/m(2) in consecutive cohorts of patients provided that no dose-limiting toxicity occurred. After the maximal tolerated dose (MTD) had been identified, this was used to treat more patients in order to confirm the feasibility of the regimen on a large scale, with the number of cycles being varied on the basis of disease extension. RESULTS: Twenty-three cases were enrolled in the CTX dose finding phase. Dose-limiting non-hematological toxicity occurred at 2250 mg/m(2). As the intermediate level of 2000 mg/m(2) had a borderline toxicity profile, a CTX dose of 1750 mg/m(2) was defined as the MTD. A total of 53 patients then received the MTD during the course of the study as a whole. At the MTD, toxicity was acceptable. Only 10 of 189 cycles (4%) required hospitalization due to infection or febrile neutropenia. Seventy-four percent of the patients achieved complete remission. Freedom from progression and overall survival at 12 months were 71% and 86% in the whole series, and 58% and 71% for high-risk cases, respectively. CONCLUSIONS: This intensified CHOP regimen is feasible on an outpatient basis. It can be safely considered a definitive treatment in patients at low and intermediate risk, and as induction before high-dose consolidation in high-risk cases.

Efficacy and safety of elective laparoscopic cholecystectomy in elderly: a case-controlled comparison with the open approach.

BACKGROUND: Minimally invasive laparoscopic surgery is the method of choice for the surgical treatment of gallbladder disease. However, surgery of the biliary tract in the elderly is often associated with high morbidity and mortality. PATIENTS AND METHOD: To evaluate the efficacy and safety of the laparoscopic cholecystectomy in the elderly with symptomatic, uncomplicated gallbladder disease, we retrospectively compared the records of 24 consecutive patients over 70 years of age with symptomatic uncomplicated gallbladder disease, who underwent elective laparoscopic cholecystectomy, with a similar cohort of patients who underwent elective open cholecystectomy for the same indications. RESULTS: In the laparoscopic group we found a significantly low incidence of postoperative complications, low analgesics and antibiotics administration, rapid recovery, short length of stay and considerable cost savings. CONCLUSION: We conclude that elective laparoscopic cholecystectomy in elderly with uncomplicated gallbladder disease is safe and effective and we suggest that it may become the surgical procedure of choice.

Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study.

BACKGROUND: The cisplatin and gemcitabine (GC) regimen is usually administered as a 4- or 3-week schedule; however, the best schedule to use is still unclear. We therefore started a randomized phase II trial to compare toxicity and dose intensity (DI) between these two GC schedules. PATIENTS AND METHODS: Ninety-six patients with non-small-cell lung cancer (NSCLC) and an additional 11 patients with an advanced epithelial neoplasm [bladder (n = 5), head and neck (n = 3), cervix (n = 1), esophageal (n = 1) or unknown primary carcinoma (n = 1)] were randomized to receive cisplatin 70 mg/m(2) intravenously on day 2 plus either gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle or gemcitabine 1000 mg/m(2) on days 1 and 8 of a 21-day cycle. Planned DI (PDI) for the 4-week schedule was 750 mg/m(2)/week for gemcitabine and 17.5 mg/m(2)/week for cisplatin; for the 3-week regimen PDI was 666 mg/m(2)/week and 23 mg/m(2)/week for gemcitabine and cisplatin, respectively. RESULTS: From July 1998 to March 2000, 107 patients were randomized. Grade 3/4 neutropenia was observed in 27.8% of patients in the 3-week versus 22.5% in the 4-week arm (P = 0.69), while grade 3/4 thrombocytopenia was higher in the 4-week arm (29.5% versus 5.5% of patients; P = 0.14). A total of 398 cycles of therapy were delivered. Overall, 51% of cycles were modified in dose, timing or both in the 4-week arm, and 19% in the 3-week arm. The 21-day schedule of GC leads to a similar received DI of gemcitabine and higher cisplatin DI. Both regimens had activity in NSCLC, with a response rate of 39% (38% for the 4-week arm, and 42% for the 3-week arm). CONCLUSIONS: The 3-week schedule has similar DI to the 4-week schedule. However the 3-week regimen has a better compliance profile and a comparable response rate in NSCLC, supporting the use of such a schedule.

Extravascular migration of the catheter. A rare complication of the totally implantable venous device.

Since the first report of TIVD implantation, many authors have published immediate and post-operative complications. The Authors report the first case in which the catheter, implanted via the cephalic vein by cutdown technique, has migrated completely out of the vein. In order to avoid extravascular migration, during the surgical procedure, the catheter should be fixed at the vein with nonabsorbable sutures, taking care to avoid narrowing the catheter lumen. This case report discusses the possibility of catheter migration when a TIVD fails to function properly and considers how to avoid more disastrous effects.

[External oblique muscle-cutaneous flap use of the in the reconstruction of large chest wall defects after mastectomy]. / Utilizzazione del lembo muscolo-cutaneo di obliquo esterno nella ricostruzione della parete toracica dopo mastectomia allargata.

The use of an external oblique muscle-cutaneous flap in the reconstruction of large chest wall defects after mastectomy is described. The flap is drown as a V-Y advancement-rotation flap, laterally based, on the ipsilateral abdominal wall. The flap extends from the posterior axillary line to the linea alba, vascular supply is provided by the musculo-cutaneous perforating arteries of the intercostal vessels. Mobilization starts medially including the anterior rectus sheath, décollement continues between the external and the internal oblique muscles as far as the posterior axillary line. The abdominal wall, after flap mobilization, is reinforced by the plication of the internal oblique sheath. The flap was used in 13 patients with major anterior chest-wall defects after mastectomy. In one patient a marginal skin necrosis of about 2 cm was observed. The flap described differs from other external oblique flaps already described in several technical innovations that allow to obtain better functional and esthetic results.

Colorectal endometriosis: aggressive surgical management and practical considerations in a patient with advanced disease.

The aim of this study was to evaluate the results of bowel resection in a patient with obstructive colorectal endometriosis. The presentation will acquaint the physician with the signs and symptoms, evaluation, and surgical treatment of colorectal endometriosis. We emphasize that our findings strongly support an aggressive surgical approach with resection for all visible cases of colorectal endometriosis in women with advanced disease.

[Cystic lymphangioma of the pancreas: clinical case and review of the literature]. / Linfangioma cistico del pancreas: caso clinico e revisione della letteratura.

Cystic lymphangioma is a rare benign tumor that occurs more often in children with different localizations. Abdominal localization and its development may produce symptoms and clinical features of acute abdomen leading to problems in the differential diagnosis. The Authors report a rare case of pancreatic lymphangioma in a nine years old child resolved by surgical treatment. A review of the literature concerning problems of diagnosis and treatment is also presented.

Totally implantable venous access devices implanted surgically: a retrospective study on early and late complications.

BACKGROUND: The techniques used for the implantation of totally implantable venous access devices (TIVADs) are the percutaneous approach and surgical cutdown; however, the choice is still controversial. HYPOTHESIS: The surgical cutdown approach may be beneficial to reduce the rate of complications. DESIGN: Retrospective review. SETTING: A university hospital and a tertiary referral center. PATIENTS: Patients undergoing a TIVAD implant at the First Surgical Clinic of the University of Catania in Catania, Italy, between January 1995 and December 1999, were considered for the study. All of the devices were implanted in an operating room under fluoroscopic control. The vein of choice was the cephalic vein. When the cephalic vein was not suitable for implantation, the external jugular vein or the axillary vein and its branches were used. The percutaneous approach to the subclavian vein or internal jugular vein was considered a last resort to implant a catheter. RESULTS: During the study period, 346 TIVADs were implanted in 344 patients. The procedure was performed with local anesthesia in 341 cases (98.5%), and only 2 patients (0.6%) required sedation for psychological reasons. Three patients (0.9%) had their TIVAD placed during a laparotomy. In 326 patients (94.2%), the devices were implanted in the cephalic vein. In the remaining cases, other veins were used with surgical cutdown. The mean time for the procedure was 15 minutes. Percutaneous access was never used, and no early mechanical complications were recorded. Only 6 patients (1.8%) in our study group had late complications (1 case of migration of the catheter, 2 cases of infection, and 3 cases of withdrawal occlusion). The catheter life ranged from 6 to 1487 days (mean time, 348 days). CONCLUSION: Our results confirm the safety, speed, and low cost of the open cutdown technique. This surgical procedure avoids both early and late complications that frequently occur with percutaneous access. Surgical cutdown should be considered the technique of choice to implant the TIVAD, especially in cancer patients.

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).

BACKGROUND: The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial. METHODS: From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. RESULTS: Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively. CONCLUSIONS: This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.