Local peritonitis as the first manifestation of Crohn's disease in a child.

Crohn's disease (CD) can occur anywhere in the gastrointestinal tract from the mouth to the anus and sometimes it presents in a nonspecific manner. Herein we describe a case of local peritonitis as the first manifestation of CD in an 11-year-old girl, and the subsequent method of treatment.

The use of a perimeatal-based penile skin flap to cover the repair of a tubularized incised plate urethroplasty: from experimental surgery to clinical practice.

OBJECTIVE: To prospectively evaluate the efficacy and safety of a perimeatal-based penile skin flap for neourethral coverage after repair of distal hypospadias with tubularized incised plate urethroplasty (TIPU). METHODS: In 12 New Zealand white rabbits a ventral urethral defect was created and reconstruction was accomplished with continuous suture. An epithelialized defect-based flap was harvested from the penile skin to cover the repaired defect. The animals were euthanized on the 28th postoperative day and their penises were processed for microscopic examination. In 32 children with distal hypospadias a TIPU was performed. A penile skin flap was created immediately below the distal end of the neourethra and used to cover the urethroplasty. RESULTS: Histological examinations revealed complete restoration of continuity of the stratified squamous epithelium without evidence of inflammation or fistula formation with full consistency with the underlying papillary reticular and corium. There were no cases of fistula formation. One patient developed meatal stenosis. All patients had a satisfactory cosmetic appearance and excellent functional results. CONCLUSION: The formation of a perimeatal-based skin flap is a simple and safe method of providing additional cover for the constructed neourethra after TIPU, minimizing the fistula rate.

Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study.

BACKGROUND: In this superiority study, pemetrexed was compared with erlotinib in pre-treated patients with metastatic non-small cell lung cancer (NSCLC). METHODS: Patients with stage IIIB/IV NSCLC who progressed after first-line or second-line treatment were randomized to receive either pemetrexed or erlotinib. In total, 21.7% of patients in the pemetrexed arm and 23.5% of patients in the erlotinib arm had squamous cell histology, and treatment was third line in 39.2% and 46.4% of patients, respectively. The primary study endpoint was time to tumor progression (TTP). Epidermal growth factor receptor/v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (EGFR/KRAS) mutation status also was investigated. RESULTS: There was no difference in terms of the TTP (P = .195), the objective response rate (P = .469), or overall survival (P = .986) between the 2 treatment arms. In patients who had squamous cell histology, erlotinib resulted in a superior TTP compared with pemetrexed (4.1 months vs 2.5 months, respectively; P = .006). The incidence of grade 3 and 4 neutropenia, thrombocytopenia, and asthenia was significantly higher in the pemetrexed arm, whereas the incidence of grade 3 and 4 skin rash was higher in the erlotinib arm. CONCLUSIONS: Both pemetrexed and erlotinib had comparable efficacy in pre-treated patients with metastatic NSCLC, and the current results indicated that genotyping of tumor cells may have an important effect on treatment efficacy.

Paclitaxel plus bevacizumab in patients with chemoresistant relapsed small cell lung cancer as salvage treatment: a phase II multicenter study of the Hellenic Oncology Research Group.

INTRODUCTION: Therapeutic options for patients with relapsed, chemo-resistant small-cell lung cancer (SCLC) are limited. Since paclitaxel has demonstrated single-agent activity in the second-line setting of SCLC and angiogenesis seems to play an important role in the pathogenesis of the disease, a phase II trial was conducted in order to evaluate the efficacy and the tolerance of their combination in patients with relapsed, chemo-resistant SCLC. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 who experienced relapse within 3 months after completion of 1st line chemotherapy for SCLC were eligible. Patients were treated with paclitaxel (90 mg/m(2), days 1, 8 and 15) along with bevacizumab (10mg per kg of body weight, days 1 and 15) in cycles of 28 days. RESULTS: Thirty patients (male/female: 27/3) with a median age of 64 years and ECOG performance status 0/1/2: 2/25/3 were enrolled. Nineteen patients (63.3%) had received at least two lines of prior treatment, 17 (56.7%) had undergone prior radiotherapy and nine (30%) had brain metastases at the time of study entry. The overall objective response rate was 20% (95% CI: 5.69-34.31%), including one complete remission, whereas the disease control rate was 36.7%. The median duration of response was 2.5 months (range, 1.5-5.7), the median progression-free survival 2.7 months (range, 0.5-9.2) and the median overall survival 6.3 months (range, 0.5-17.9). Grades 3 and 4 toxicities were limited in neutropenia, diarrhea and fatigue. There was one case of non-fatal pulmonary embolism. CONCLUSIONS: The combination of paclitaxel with bevacizumab was feasible and active in this poor prognosis and heavily pretreated population of patients with advanced, chemoresistant SCLC, representing a valid therapeutic alternative which merits further evaluation.

Phase III study comparing sequential versus alternate administration of cisplatin-etoposide and topotecan as first-line treatment in small cell lung cancer.

AIM: To compare the efficacy and tolerance of sequential versus alternate front-line administration of cisplatin-etoposide (PE) and topotecan (T) in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients were randomized to receive either 4 cycles PE (cisplatin 80 mg/m(2) i.v. day 1 and etoposide100 mg/m(2)/d i.v. days 1-3 every 21 days) followed by 4 cycles T (1.5 mg/m(2)/d i.v. days 1-5 every 21 days) (arm A, 183 patients) or the same regimens using an alternate sequence (arm B, 181 patients). RESULTS: There was no significant difference in terms of compliance with treatment, overall response rates (51.4% vs. 55.2%; p=0.458), median response duration (4.3 vs. 5.2 months; p=0.780), median time to tumour progression (5.7 vs. 6.4 months; p=0.494), median overall survival (10.9 vs. 9.8 months; p=0.186) and 1-year survival (43.8% vs. 36.5%) between the two arms. The incidence of severe grade 3-4 haematological and grade 2-4 non-haematological (asthenia, mucositis, diarrhoea and neurotoxicity) toxicity was comparable between the two arms. CONCLUSION: The comparison of sequential versus alternate administration of cisplatin-etoposide and topotecan as front-line treatment of patients with extensive stage SCLC revealed no clinically meaningful differences in terms of efficacy and tolerance.

Pooled analysis of elderly patients with non-small cell lung cancer treated with front line docetaxel/gemcitabine regimen: the Hellenic Oncology Research Group experience.

INTRODUCTION: Thirty to 40% of patients with non-small cell lung cancer (NSCLC) are older than 70 years and rarely are enrolled in clinical trials. Moreover, in clinical practice, > 75% of patients older than 65 years with metastatic NSCLC never receive any kind of chemotherapy. PURPOSE: To retrospectively evaluate the impact of age on efficacy and toxicity of chemotherapy regimens in patients with advanced NSCLC treated with the docetaxel-gemcitabine combination. PATIENTS AND METHODS: Pooled data from six clinical trials of the Hellenic Oncology Research Group were analyzed. According to their age, patients were divided into two groups: those with age < 70 years and those with > or = 70 years. RESULTS: A total of 858 patients were included in this analysis. Six hundred sixty-six (77.6%) patients were younger than 70 years, whereas 192 (22.4%) patients where > or = 70-year-old. Overall response rate was 30.3% and 30.2% for patients < 70 years and > or = 70 years, respectively (p = 0.974). The median time to tumor progression was 4.1 and 4.5 months for patients < 70 years and > or = 70 years, respectively (p = 0.948). Median overall survival was 9.9 and 9.2 months for patients < 70 and > or = 70, respectively (p = 0.117). The multivariate analysis revealed performance status (PS) (p = 0.0001) and stage (p = 0.0001) as independent factors with significant impact on the hazard of death. Chemotherapy was well tolerated, but the incidence of grade III/IV mucositis was significantly higher in elderly patients (0.2% versus 1.5% for patients < 70 versus > or = 70 years, respectively; p = 0.011). CONCLUSION: The docetaxel/gemcitabine regimen has a comparable efficacy and tolerance in young (< 70 years) and elderly (> or = 70 years) patients.

Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial.

To compare the overall survival (OS) of patients with advanced non-small cell lung (NSCLC) treated with either docetaxel plus gemcitabine or single-agent docetaxel. Chemotherapy-naive patients with advanced/metastatic NSCLC were randomly assigned to receive either DG [n=157; gemcitabine 1100mg/m(2) on days 1 and 8], docetaxel 75mg/m(2) on day 8 or D [n=155; docetaxel 100mg/m(2) on day 1] every 3 weeks. A total of 312 patients were evaluable for toxicity and response. A predefined interim intention-to-treat analysis showed significantly longer median OS (p=0.037) in favor of the DG regimen (9.4 months versus 8.3 months for DG and D regimens, respectively), resulting in the premature termination of the study. The DG regimen was also associated with a significantly higher response rate compared to D (26.8% versus 11.6%, p<0.001). TTP were 3.5 and 2.3 months for the DG and D regimen, respectively (p=0.054). Although there were two treatment-related deaths in the DG arm, the toxicity profiles of the two regimens were comparable. The DG regimen was associated with a significantly better quality of life. The efficacy of the docetaxel plus gemcitabine combination is superior to single-agent docetaxel in chemonaive patients with advanced NSCLC.

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer.

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.

Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group.

BACKGROUND: This trial was designed to compare the efficacy and toxicity of sequential versus alternating administration of cisplatin/etoposide and topotecan in patients with previously untreated extensive-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: Two hundred eighty-four chemotherapy-naive patients were randomized between the sequential therapy arm (n=142; 4 cycles of cisplatin 75 mg/m2 intravenously [I.V.] on day 1 with etoposide 100 mg/m2 per day I.V. on days 1-3 followed by 4 cycles of topotecan 1.5 mg/m2 per day I.V. on days 1-5) and the alternating arm (n=142; same doses of cisplatin/etoposide on cycles 1, 3, 5, and 7 and topotecan on cycles 2, 4, 6, and 8). Treatment cycles for both regimens were administered every 3 weeks. RESULTS: At this preliminary analysis, no statistically significant difference in the overall response rate, duration of response, time to disease progression, or median survival was observed between the 2 arms. A total of 756 cycles of the sequential therapy and 830 cycles of the alternating therapy were administered, with a median numbers of 6 and 7 cycles per patient, respectively. Topotecan was administered in 85 patients on the sequential arm and 132 patients on the alternating arm. Dose reductions for toxicity were similar in both arms. Grade 3/4 toxicities in the sequential and alternating arms, respectively, included neutropenia (51% and 52%; P=NS), anemia (12% and 11%; P=NS), febrile neutropenia (7% and 9%; P=NS), thrombocytopenia (19% and 20%; P=NS), and asthenia (8% and 2%; P=0.02). There were 4 toxicity-related deaths in the sequential arm versus 3 in the alternating arm. CONCLUSION: Our preliminary conclusion is that the sequential and alternating regimens resulted in comparable activity and tolerability in previously untreated patients with extensive-stage SCLC.

Combination of vinorelbine plus gemcitabine in previously treated patients with small cell lung cancer: a multicentre phase II study.

PURPOSE: To evaluate the efficacy and toxicity of the gemcitabine plus vinorelbine combination in pretreated patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-five pretreated patients (median age 59 years, PS: 0--1 in 97% and 2 in 3%) were treated with gemcitabine (1100 mg/m(2)) and vinorelbine (25mg/m(2)) on d1 and d8 every 3 weeks. Seven (20%) patients were treated with two prior regimens and 20 (57%) were refractory to front-line chemotherapy. RESULTS: In an intention-to-treat analysis two (6%) partial responses (PR) were observed with a duration of 5.6 and 11.1 months. Stable disease (SD) was documented in 8 (23%) patients and progressive disease (PD) in 25 (71%). The overall median survival was 4.5 and the 6 months survival rate was 42.6%. Grades 3--4 neutropenia and thrombocytopenia were observed in 25 and 14% of the patients, respectively. Non-hematological toxicity consisted of grade 2 neurotoxicity occurring in 14% of the patients and grades 2--3 fatigue in 17%. Febrile neutropenia was observed in three (8.6%) patients and one of them died from sepsis. CONCLUSION: The combination of gemcitabine plus vinorelbine cannot be considered as an effective salvage treatment in pretreated patients with SCLC.

Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial.

PURPOSE: To compare the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone. PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m(2) on day 1, cisplatin 80 mg/m(2) on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 microg/m(2)/d on days 3 to 9) or D (n = 152; 100 mg/m(2) on day 1 without rhG-CSF) every 3 weeks. RESULTS: The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P =.004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P =.200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P =.580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P =.0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P =.0001), diarrhea (P =.007), neurotoxicity (P =.017), and nephroroxicity (P =.006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P =.098). CONCLUSION: DC regimen resulted in a higher response rate but without improvement in median time to tumor progression or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.