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Biomedical subjects

M A Climent

Publications and source records attributed to M A Climent.

At least 19 recordsLinked to original sources
PubMed2004

[Usefulness of serum markers in renal cell carcinoma].

OBJECTIVES: To select a group of useful serum markers in renal cell carcinoma (RCC) with investigational purpose in future. MATERIAL AND METHODS: Periodic determination in serum of 21 RCC patients of the following markers: EGR, RPC, hemogram and leucocyte differential count (LDC), standard biochemist parameters, beta-2 microglobuline, CEA, CA 12.5, CA 50, CA 15.3, ferritin, interleukin-6, serum interleukin-2 receptor, TNF-alpha and TPSA. RESULTS: Different elements within the LDC had relations with the presence of symptoms/signs, tumour size, pathological stage and disease progression. There was a significant increase of beta-2 microglobuline and sIL-2 receptor when disease progressed, as well as a similar statistical trend with RPC and alkaline phosphatases. Beta-2 microglobuline and sIL-2 receptor also decreased after treatment of the disease progression. CONCLUSIONS: We will keep analysing hemogram, LDC and standard byochemics, RPC, ferritin, beta-2 microglobuline and sIL-2 receptor only with investigational purposes, obviating the determination of the rest of the tested markers.

Biomarkers, Tumor↗
PubMed2004

A multicentre, randomised phase II study of weekly or 3-weekly docetaxel in patients with metastatic breast cancer.

BACKGROUND: A phase II randomised trial was conducted to evaluate the tolerability and activity of weekly or 3-weekly docetaxel in patients with metastatic breast cancer. PATIENTS AND METHODS: Eighty-three patients with histologically proven metastatic breast cancer were randomised to receive either docetaxel 40 mg/m2 weekly for 6 consecutive weeks followed by 2 weeks without treatment (n = 41), or docetaxel 100 mg/m2 on day 1 every 3 weeks (n = 42). RESULTS: The incidence of all grade 3-4 adverse events was higher in the 3-weekly group than in the weekly group (96 versus 44), and the number of patients with grade 3-4 adverse events was also greater in the 3-weekly group (31 versus 20). Analysis of individual adverse events tended to favour the weekly regimen. Intent-to-treat overall response rate was 34% and 33% in the weekly and 3-weekly groups, respectively. Median time to progression was 5.7 and 5.3 months after weekly and 3-weekly docetaxel, respectively, and median time to treatment failure was 4.1 and 4.9 months, respectively. CONCLUSION: Weekly docetaxel is an active regimen in metastatic breast cancer with comparable efficacy to 3 weekly docetaxel. Although both schedules were well tolerated, weekly docetaxel appears to have a more favourable toxicity profile.

Adult↗
PubMed2003

Conservative elective treatment of upper urinary tract tumors: a multivariate analysis of prognostic factors for recurrence and progression.

PURPOSE: We evaluate the safety and efficacy of conservative elective treatment of upper urinary tract tumors, and determine predictive factors for recurrence and progression to optimize indications of this type of treatment. MATERIALS AND METHODS: Since 1984 we have performed a prospective study of conservative treatment of single, low grade and stage, less than 3 cm. upper tract tumors. The study includes 54 patients with a normal contralateral kidney who had been followed for more than 36 months. Open conservative surgery was performed in 31 cases and endourological surgery in 23. Minimum followup was 36 months, maximum 210 and mean 84.8. Univariate and multivariate analyses of recurrence and progression were performed in relation to age, sex, association with a bladder tumor, bladder tumor stage and grade, sequence of bladder tumor in relation to upper urinary tract tumor, number of previous bladder tumor recurrences, association with bladder carcinoma in situ, upper urinary tract tumor grade, stage, location, size and therapy, and upper urinary tract cytology. RESULTS: Of the 54 patients 19 (35%) had recurrence, which was bilateral recurrence in 4, and progression occurred in 9 (16%). At the end of analysis 44 (62.9%) patients were disease-free and alive at a mean time of 92.88 months, 13 (24%) died disease-free at a mean of 72.7 months and 7 (12.9%) died of disease at a mean of 97.85 months. Cause specific mortality occurred in 7 (12.9% cases). Among the 54 initially conservatively treated units 42 (77.7%) kidneys were ultimately preserved. On univariate and multivariate analysis tumor location in the renal pelvis and association with a previous multi-recurrent bladder tumor were variables significantly related to recurrence and progression, as well as bilateral recurrence. CONCLUSIONS: Conservative treatment is an optional approach for select upper urinary tract tumors. The strongest risk factors for recurrence and progression were association with a previous multi-recurrent bladder tumor and tumor location in the renal pelvis but these conditions were also the strongest risk factors for bilateral recurrence. Conservative treatment can also be recommended in these cases but only with compliant patients and close followup.

Adult↗
PubMed2002

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer.

A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m(-2) and cisplatin 75 mg m(-2) on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79-102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41-74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3-4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3-4 thrombocytopenia was rare (one patient). Other grade 3-4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation.

Adult↗
PubMed2002

Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG).

OBJECTIVE: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. METHODS: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). RESULTS: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. CONCLUSION: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.

Adolescent↗
PubMed2001

Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment.

HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.

Journal Article↗
PubMed2000

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group.

PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up. CONCLUSION: This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.

Adult↗
PubMed2000

[Cost of antibiotic therapy in neutropenic patients undergoing peripheral blood stem cell transplantation for breast cancer].

The increase in pharmaceutical costs, especially for expensive procedures such as bone marrow transplants, has led to the study of the economic impact of febrile neutropenia in peripheral blood stem cell transplantation (PBSCT). We analyzed 89 consecutive patients with breast cancer who underwent PBSCT. All patients developed febrile neutropenia and were administered an empirical intravenous regimen based on the combination of piperacillin-tazobactam and amikacin. We analyzed the direct costs of this treatment and grouped them into drug acquisition cost, administration costs (cost of the additional material), and preparation costs (time employed for the preparation and administration of the drug). We found that the overall cost was $1,110, 65% of which corresponded to the initial therapy and the rest (35%) to the use of additional antibiotics. This higher cost was especially related to the use of vancomycin or teicoplanin (50%). The acquisition costs accounted for 90% of the overall treatment costs. Thirty-six patients (40%) did not need additional antibiotics and the cost in this group was less ($663). We concluded that knowledge of the costs of pharmacological therapy for infection in PBSCT is indispensable for the appropriate development of treatment units, especially in terms of optimizing resources and comparing different therapeutic or prophylactic approaches.

Amikacin↗
PubMed1998

The antiemetic efficacy of granisetron plus dexamethasone, haloperidol and loracepam in breast cancer patients treated with high-dose chemotherapy with peripheral blood stem-cell support.

There has recently been a marked trend to increasing dose intensity in cancer chemotherapy, with or without peripheral blood stem-cell support, which has been associated with a higher frequency of nausea and vomiting. Antiemetic treatment in this setting has not been extensively analysed. From October 1995 to January 1997, prevention of emesis with granisetron 3 mg/12 h i.v., dexamethasone 12 mg/24 h i.v., haloperidol 0.5 mg/12 h p.o., and loracepam I mg/24 h p.o. was instituted in 30 breast cancer patients treated with high-dose chemotherapy (a 4-day intravenous continuous infusion of cyclophosphamide 1500 mg/m2 per day, thio-TEPA 125 mg/m2 per day and carboplatin 200 mg/m2 per day).A total of 30% of the patients (9/30) obtained complete or major protection on the 4 days of chemotherapy treatment (96.7% (29/30) on day 1, 86.7% (26/30) on day 2, 70% (21/30) on day 3, and 50% (15/30) on day 4). On the days following chemotherapy, 46.7% (14/30) presented fewer than two emetic episodes on day 5, 70% (21/30) on day 6, 83.4% (25/30) on day 7 and, 93.3% (28/30) on day 8. This energic antiemetic combination treatment has hardly any effect in the prevention of emesis, providing complete or major protection of 30% for the 4 days of chemotherapy treatment. Further investigation aimed at improving antiemetic treatment results is necessary.

Adult↗
PubMed1997

Prognostic value of S-phase fraction in lymph-node-negative breast cancer by image and flow cytometric analysis.

Cellular DNA content and proliferation rates have been suggested as prognostic factors in breast carcinomas. A series of 271 lymph-node negative breast carcinoma patients without adjuvant therapy was reviewed (mean follow-up, 108 mo). Tumor cells from the same paraffin-embedded block tissue (Hedley's method) were analyzed by image analysis (IA) in Feulgen-stained smears and by flow cytometric analysis (FC). Clinicopathologic features, ploidy, S-phase fraction, and percentage of tumor cells with more than 5n DNA content (in diploid tumors, by IA) were related to outcome. The results of IA and FC were compared in 115 cases. Tumor size, histologic grade, desmoplasia and S-phase fraction were significant predictors of survival in multivariate analysis (Cox proportionate regression) (P < or = 0.03). Ploidy by the two methods showed agreement in 100 carcinomas (87%). Of the 15 discordant cases, FC detected 6 multiploid and 4 aneuploid-peridiploid. In contrast, IA detected more tetraploid carcinomas. Tumor size, histologic grade, desmoplasia, and S-phase fraction were independent predictors of long-term prognosis in our patients. Ploidy and percentage of tumor cells with more than 5n DNA content were not prognostic indicators. FC detected aneuploidy more frequently than did IA.

Adult↗
PubMed1995

A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer.

One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m2) or mitoxantrone (12 mg/m2) associated with 5-fluorouracil (600 mg/m2) and cyclophosphamide (600 mg/m2) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m2 day 1, Vbl 5 mg/m2 days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer. M-Vbl treatment is useful as second-line treatment in patients with prior adriamycin exposure.

Adult↗
PubMed1995

Endometrial cancer stages I and II. Analysis of survival and prognostic factors.

BACKGROUND: Endometrial cancer is the most frequent gynaecologic neoplasia in women. Stages I and II account for 75% of endometrial cancers. METHODS: Diagnostic features, treatment and outcome based on therapy with surgery and/or irradiation of 185 endometrial cancer patients in Stage I and II were analysed retrospectively. RESULTS: There were 148 patients (80%) in Stage I and 37 (20%) in Stage II. Twenty-nine patients (16%) relapsed and 18 have died of cancer. The 5 and 10 year specific actuarial survival was 89% and 81% respectively. The 5 and 10 years disease free survival was 82% and 78% respectively. In our analysis of prognostic factors we observed a significantly worse survival for postmenopausal and Stage II patients, high grade tumors (grade III) and greater myometrial penetration (outer 2/3). CONCLUSIONS: Endometrial cancer has a relatively good prognosis partly because of its early diagnosis. There is general consensus that surgery is the optimal treatment in Stages I and II. While it is well documented that complementary irradiation improves survival in Stage II, there is no general agreement regarding the value of complementary irradiation in Stage I. Further studies are needed to delimit Stage I patients who would benefit from complementary irradiation.

Adult↗
PubMed1993

Treatment of stage I testicular tumours.

Between 1980 and 1989, 138 patients with stage I carcinoma of the testes were treated and followed up; 81 patients had seminoma and 57 had non-seminomatous tumours. Between January 1980 and December 1983, patients with seminoma were treated by orchiectomy, followed by complementary radiotherapy to aortic and ipsilateral pelvic nodes. Retroperitoneal lymph node dissection (RPLND) was performed in patients with non-seminomatous tumours. After January 1984 the treatment strategy was changed and orchiectomy was followed by a surveillance policy in all histological types. In seminoma patients, 1 of 36 patients (3%) treated with complementary radiotherapy and 5 of 45 (11%) on the surveillance policy relapsed. All achieved a complete response after chemotherapy. In non-seminomatous tumours, 3 of 21 patients (14%) treated with complementary lymphadenectomy relapsed, in contrast to 11 of 36 (31%) surveillance policy patients. All patients who relapsed obtained a complete response with chemotherapy. All patients are currently free of disease. There were no differences in survival between both treatment policies. We conclude that a wait and see policy in stage I testicular tumours is feasible and provides the same results as more interventionist practices.

Combined Modality Therapy↗
PubMed1992

Malignant ovarian germ cell tumors: the experience at the Hospital de la Santa Creu i Sant Pau.

From 1979 to 1990, 33 patients with pathologically confirmed malignant ovarian germ cell tumors (MOGCT) were referred after initial surgical procedure at the Department of Oncology, Hospital de la Santa Creu i Sant Pau. The median age was 22 years (range, 10 to 39). Stage distribution was as follows: stage I, 12 patients; stage II, 6 patients; stage III, 11 patients; stage IV, 3 patients; and unstaged, 1 patient. The histologic diagnoses were 10 dysgerminomas, 4 endodermal sinus tumors, 11 immature teratomas, and 8 mixed germ cell tumors. Twenty-eight out of the thirty-three patients received postoperative chemotherapy with POMB-ACE-PAV or other platinum-containing regimens. One patient with stage IV disease failed to respond to chemotherapy and she died. Sixteen out of the twenty-eight treated patients had second-look laparotomy, which showed mature teratoma in six and persistent malignant teratoma in one patient. This last patient had complete remission with second regimen. No patient has developed recurrence. With a median follow-up of 66 months (range, 10 to 133), 32 patients (97%) are alive without evidence of disease. These data confirm that platinum-containing regimens have dramatically improved the prognosis for patients with MOGCT. This paper discusses primary chemotherapy and the role of the second-look in these patients.

Adolescent↗
PubMed1991

[Lymphomas originating in the otorhinolaryngeal region: 10 years' experience].

BACKGROUND: Non-Hodgkin's lymphomas (NHL) originated in the otorhinolaryngological (ORL) area are rare diseases and its therapy is poorly established. METHODS: The diagnostic features, treatment and outcome based on therapy of 34 NHLs originated in the ORL area and seen in the Oncology Service from the Hospital de la Santa Creu i Sant Pau during a ten year period were reviewed. RESULTS: The predominant primary localization was the tonsil (17 patients), followed by rhinopharynx (8), massive involvement of Waldeyer's ring (4), and oropharynx, maxillary sinus and larynx in the remaining cases. In 26 patients the diagnosis was high-grade lymphoma. The stage distribution was 8 patients (24%) in stage I, 16 in stage II (47%), 3 in stage III (9%), and 5 in stage IV (16%). The treatment was heterogeneous and consisted in chemotherapy in 29 patients (38%), radiotherapy in 5 (15%) or the combination of both in 16 (47%). Eleven patients relapsed (38%), more commonly those treated with radiotherapy. The specific actuarial survival was 69%. CONCLUSIONS: NHL originated in the ORL area are uncommon neoplastic diseases, with a commonly dramatic response to chemotherapy. This should be the initial therapeutic modality in all cases.

Adult↗
PubMedDate not supplied

[Experience in the treatment of 98 carcinomas of the nasopharynx. Long-term follow-up and analysis of prognostic factors].

This was a retrospective study of 98 patients (pts.) with histologically confirmed nasopharyngeal carcinoma. The clinico-demographic characteristics were: median age of 53 years (11-83); 74 males and 24 females (ratio 3:1); histology subtype OMS 2-3 in 89 pts. (90.8%); cranial nerve deficits in 11 pts. (11.2%); 50 (51%) were stage T3T4; 68 pts. (69.4%) N2N3 and 77 pts. (78.6%) stage IV. The therapeutic modalities were: radical radiotherapy (RT) alone in 42 pts., chemotherapy (CT) alone in 4 pts., RT + adjuvant CT in 10 pts. and neoadjuvant CT + RT in 42 pts. RT was delivered in wide fields, doses between 50-75 Gy with conventional fractionation. CT consisted in cisplatinum-based schedules (PF in 34 pts., BEC in 9 and others in 13 pts.). Analyzed by treatment, more males and stages N2N3 and IV were accrued in neoCT + RT arm (p < or = 0.05). For the entire population, the overall complete response was achieved in 65 pts. (66.3%); in 27/35 pts. (77.1%) of the RT group and 30/51 pts. (58.8%) of CT + RT group (p 0.07) of pts. with III-IV stages. With a median follow-up of 74.5 months, 32 pts. (32.65%) are alive and free of disease. The projected OS for all pts. was 40 months (m), 51.4% at 3 years (y) and 45.5% at 5 y with a disease free survival of 37 m (0-236). No differences between treatment arms were found (p 0.4). In univariant analysis for OS in stage III-IV pts., age > 50 y, histology OMS1, cranial nerve deficits, stage T3T4 and N2N3, were considered adverse prognostic factors (p < or = 0.05). In multivariant analysis, only age > 50 y and stages T3-T4, N2-N3 were significant (p < or = 0.05). In conclusion, we demonstrated good long term survival without any differences among treatment modalities in pts. with advanced nasopharyngeal carcinomas. New therapeutic approaches are warranted in order to improve the outcome of this patients.

Adolescent↗