Biomedical subjects

G Mamelle

Publications and source records attributed to G Mamelle.

At least 19 recordsLinked to original sources

PubMed2006

[Role and perspectives of sentinel node biopsy in head and neck tumors].

PURPOSE: To evaluate the accuracy of sentinel node biopsy for assessing the neck status for those patients with squamous cell carcinoma T1T2N0 of oral cavity. PATIENTS AND METHODS: 55 patients were included in a prospective study between 2000 and 2003. 53 underwent a sentinel node biopsy (SNB) followed by an elective neck dissection (END). Pathological examination with stepped serial sectioning and immunohistochemistry of sentinel node (SN) has been compared with routine pathology examination of remaining END nodes. RESULTS: 12 patients had a positive SN. No false negative was found. Patient follow up on, at less of 3 years, did not show any node recurrence for those patients with negative SN. After that study, 44 patients had a SNB without END. 7 patients had a positive SN. Follow up showed a node recurrence for 3 patients. In two of these, pathological reexamination showed a micrometastase in SN. SN failure rate is less than 3% for those 99 patients. CONCLUSION: SNB is a liable procedure. Failure rate is the same as in END. We plan to use this procedure in orophyngeal tumors where it could be possible to reduce irradiation fields and treatment sequels for those patients with negative SN.

Adult↗

PubMed2006

[Clinical and genetic study in 22 patients with basal cell nevus syndrome].

BACKGROUND: Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by developmental abnormalities and cancer predisposition. The PTCH 1 gene, the human homolog of the Drosophila segment polarity gene patched, has been shown to be involved in the development of nevoid basal cell carcinoma syndrome. PTCH 1 is mapped to chromosome 9q22.3. The aim of the present study was to report on clinical and genetic characteristics in patients followed for nevoid basal cell carcinoma syndrome and to compare them to the data in the literature. PATIENTS AND METHODS: Screening for PTCH 1 mutations was done in 22 patients followed between 1981 and 2003 for clinical suspicion of nevoid basal cell carcinoma syndrome. Clinical and radiological data were reviewed retrospectively from records. Genetic analysis was performed using blood samples after patient informed consent was obtained. When possible, DNA was also analyzed from the parents of patients in whom PTCH 1 mutations were found. RESULTS: All patients had developed basal cell carcinomas: 45% palmar and plantar pitting, 62% jaw cysts and 66% calcification of falx cerebri. Medulloblastomas and meningiomas were the most common associated tumors. PTCH 1 mutations were identified in 13 patients: 6 familial cases, 3 sporadic cases and for 4 patients, it was not possible to conclude. Nine different new germ-line mutations were identified. DISCUSSION: Genetic analysis allows molecular confirmation of diagnosis in about half of all patients. Early diagnosis is essential for detection of clinical and radiological manifestations in young patients and for provision of advice concerning protection of the skin from the sunlight.

Adolescent↗

PubMed2006

Microcystic adnexal carcinoma: report of seven cases including one with lung metastasis.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare cutaneous neoplasm, with a high rate of local recurrences. OBJECTIVE: A series of MAC was analyzed and compared to previously published cases. METHODS: Seven cases of MAC were identified in the register of the institution. Medical and pathological records were reviewed. RESULTS: The primary MAC were located on the face in all patients, and 85% were initially misdiagnosed. The mean follow-up duration was 108 months. The recurrence rate was high: 4 patients developed recurrences. In 3 patients, the course of the disease was severe: one of them developed pathologically proven lung metastasis. CONCLUSION: The present study and review of the literature confirm the clinically aggressive evolution of MAC and its rare ability to give rise to metastasis. Long-term clinical follow-ups with imaging investigations are mandatory.

Adult↗

PubMed2003

[Significance of sentinel lymph node biopsy in Merkel cell carcinoma. Analysis of 11 cases].

BACKGROUND: Merkel cell carcinoma is an aggressive cutaneous neoplasm with a high propensity for nodal metastases. Regional lymph node involvement develops in 45 to 65 p. 100 of patients. We evaluated in Merkel cell carcinoma the use of sentinel lymph node biopsy which allows the identification of occult nodal metastases. PATIENTS AND METHODS: Eleven patients diagnosed with Merkel cell carcinoma without clinical nodal involvement underwent pre-operative lymphoscintigraphy followed by sentinel lymphadenectomy with histologic analysis. Identification of microscopic nodal metastases led to complete lymph node dissection and adjuvant radiation therapy to the lymph node basin. RESULTS: The sentinel lymph node was successfully identified in 9 patients. Two patients demonstrated metastatic disease in their sentinel lymph nodes. At subsequent complete node dissection, one of two patients had an additional metastatic lymph node. None of the eleven patients experienced recurrent disease at a follow-up varying from 1 to 42 months. One patient with a negative sentinel lymph node experienced lymphoedema. COMMENTS: Our results are consistent with the 14 published studies which totalled 93 patients with Merkel cell carcinoma and identified 29 patients (30 p. 100) with nodal involvement. Metastatic disease was identified only after immunohistochemical analysis in 20 p. 100 of these patients (n=6). Lymph node involvement appears to be a bad prognostic factor with 29.6 p. 100 of disease recurrence, as opposed to 3 p. 100 in patients with an uninvolved sentinel lymph node. Although the prognostic significance of this technique seems interesting, there is no optimal therapeutic approach to sentinel lymph node involvement.

Adult↗

PubMed2002

[Delayed cerebral radionecrosis following radiation therapy of cutaneous squamous cell carcinomas of the head].

INTRODUCTION: Three cases of cerebral radionecrosis occurring after radiation therapy for squamous cell carcinomas of the scalp are reported. This rare and poorly documented complication of radiotherapy is discussed. CASE REPORTS: Three patients presenting with squamous cell carcinomas of the scalp were treated with surgery and radiotherapy for recurrent or incomplete resection of squamous cell carcinomas of the head. X-ray doses range were 50 to 60 Grays in 22 to 24 fractions. Cerebral radionecrotic lesions were diagnosed 6 months to 14 years after irradiation, and were inconstantly associated with clinical symptoms. The patients were treated with systemic steroids, which were of limited efficacy in one of our patients. DISCUSSION: Little is known of cerebral radionecrosis following radiotherapy. This may be related to their rare occurrence and/or to the difficulties in establishing diagnosis. The delay of occurrence after radiotherapy can vary between a few months and several years, and the lesions are directly correlated with the doses and the fractionning of the X-rays. Intracerebral localization of the tumour is the main differential diagnosis. Localized and cystic forms of cerebral radionecrosis can be treated by surgery. Treatment otherwise relies on systemic steroids.

Aged↗

PubMed2001

Subtotal laryngectomy with cricohyoidopexy as first treatment procedure for supraglottic carcinoma: Institut Gustave-Roussy experience (146 cases, 1974-1997).

PATIENTS AND METHODS: Between 1974 and 1997, 297 patients underwent a subtotal laryngectomy at the Institut Gustave-Roussy; 146 of these patients underwent cricohyoidopexy (CHP) for a supraglottic primary as their first treatment. The majority of patients were men (137) aged from 33 to 78 years (median 54 years). The tumour stage at presentation was T1 in 2, T2 in 87, T3 in 53 (preepiglottic space involvement), and T4 (minimal thyroid cartilage invasion) in 4 patients. One hundred and twenty-five patients were N0 (86%) and 21 patients were Np (palpable); 98% had homolateral and 55% had bilateral neck dissections. RESULTS: One patient died postoperatively of a myocardial infarction and 68% patients had an uneventful course. Aspiration was the commonest complication (23 patients, 19%). The median time to removal of the tracheotomy cannula was 10 days and for the nasogastric tube 21 days during the past 10 years. Completion of subtotal laryngectomy into total laryngectomy was done in 21 cases (15%): eight times because of oncological events [five local failures, two second primary (hypopharynx), one positive margin] and 13 times because of aspiration (9%). There were six local failures (4%) and eight nodal failures (5%). The rates of distant metastases and second primaries were 6% and 16% respectively. Half of the local and nodal failures were subsequently sterilized. Findings at death were two local recurrences, four nodal recurrences, eight distant metastases, and 11 second primaries. The 3- and 5-year overall survival rates were 92% and 88% respectively, with an overall laryngeal preservation rate of 86%. CONCLUSION: When supraglottic laryngectomy is not feasible for supraglottic cancer, subtotal laryngectomy with CHP is a safe and effective oncological procedure, with preservation of satisfactory laryngeal function.

Adult↗

PubMed2001

Indium-111 octreotide scintigraphy of Merkel cell carcinomas and their metastases.

BACKGROUND: Somatostatin receptor scintigraphy (SRS) may be of interest for staging Merkel Cell Carcinoma (MCC). This study was undertaken to evaluate the sensitivity and specificity of SRS and to determine its role compared to conventional investigations. PATIENTS AND METHODS: From 1993 to December 2000, 20 patients (10 females and 10 males, aged from 38 to 88, mean 66 years) were included prospectively. At the time of SRS: 12 patients had been diagnosed as having stage I disease, 6 stage II and 4 stage III. Two patients had two SRS studies during the course of their disease. SRS was performed with Indium-111 pentetreotide (Octreoscan), a radiolabelled somatostatin analogue. Patients were treated according to the clinical stage. A regular follow-up was scheduled every three months. RESULTS: SRS depicted stage I and II MCC tumour sites with an overall sensitivity of 78% (95% confidence interval (CI): 40%-97%) and a specificity of 96% (81%-100%). The histopathological diagnosis was used as the gold standard. Sites visualised by SRS were compared to those detected with conventional modalities and to follow-up data for all stages: SRS visualised four out of five primary tumour sites, six out of eight lymph node sites, no skin metastases (14 sites in 2 patients), two out of three thoracic metastases and zero out of two hepatic metastases. SRS did not influence treatment decision-making in any of the cases. CONCLUSIONS: Although SRS seems highly specific in MCC and could be of help in difficult cases, it cannot be recommended for routine evaluation.

Adult↗

PubMed2000

Selective neck dissection and sentinel node biopsy in head and neck squamous cell carcinomas.

The Sentinel Node concept is now well established for HNSCC and gives us a strong basis to treat patients with N0 neck where the rate of occult node metastasis is high. At the present time, the most accurate method for staging N0 neck is pathologic examination of the neck content. In this way, sentinel node dissection (SND) and sentinel node biopsy (SNB) are complementary surgical procedures. SNB has limited indications in HNSCC because of the inaccessibility of most of the primary sites to local injection of Tc99m colloid. However it seems to be an encouraging approach for small tumors of the oral cavity. In other primary sites, except for small glottic tumors, patients must undergo an SND. Supraomohyoid neck dissection which removes levels I, II and III, is performed in oral cavity tumors. Lateral neck dissection which removes levels II, III and IV, is used by many authors for laryngeal, oropharyngeal and hypopharyngeal tumors. In our experience, SND could be limited to levels II and III for laryngeal and oropharyngeal tumors without more neck failures. SND is a reliable procedure, we report only 1.5% of skip nodal metastases in 464 patients who had this staging procedure.

Carcinoma, Squamous Cell↗

PubMed2000

[Cerebral magnetic resonance imaging (MRI) in the diagnosis of leptomeningeal carcinomatosis in melanoma patients].

OBJECTIVE: Meningeal involvement is frequent in metastatic melanoma, approximately 30% in autopsy series. Functional signs may be misleading and the neurological examination may be normal. Certain diagnosis requires identification of tumor cells in the cerebrospinal fluid. CSF cytology is however sometimes negative and magnetic resonance imaging (MRI) with gadolinium injection may provide the diagnosis. The aim of this retrospective study was to assess the role of imaging in the diagnosis of leptomeningeal carcinomatosis. PATIENTS AND METHODS: The diagnosis of leptomeningeal carcinomatosis was made in 8 patients between 1992 and 1998. All had signs of neurological function impairment, but the neurology examination was abnormal in only 2. RESULTS: Cytology examination of the cerebrospinal fluid provided the diagnosis of leptomeningeal carcinomatosis in 5 patients. One out of 5 brain CT scans were positive, showing meningeal enhancement confirmed by brain MRI. The spinal tap was not contributive in 2 cases and was not done in 1. In these three cases, the brain CT did not provide any diagnostic element while the brain MRI with gadolinium injection confirmed the diagnosis of leptomeningeal carcinomatosis. DISCUSSION: Forty-one percent of patients with autopsy proven leptomeningeal carcinomatosis have a normal ante mortem spinal tap. Brain MRI with gadolinium injection has better sensitivity than brain CT scan. All patients with nonspecific neurological signs and a normal spinal tap should be explored with a brain MRI.

Adolescent↗

PubMed1999

[Midface reconstruction with free flaps].

STUDY AIM: Midface is situated between the occlusal plane and the transverse midorbital plane. The aim of midface reconstruction is to restore the bony and soft tissue contour of the face, to obtain a rigid support for the velum, to allow oronasal separation, and to allow support for the orbit and obliteration of the maxillary sinus in order to restore the main functions: respiration, speech, deglutition, mastication, olfaction, vision. PATIENTS AND METHODS: Between 1988 and 1997, 65 patients with defects to the midface in relation with cancer (n = 60), gunshot (n = 3), or congenital malformation (n = 2), underwent reconstruction with one or more transplants: forearm (n = 21), latissimus dorsi (n = 23), scapula (n = 12), composed subscapula (n = 10), and fibula (n = 4). Forty-seven of the patients were men and 18 were women. The mean age was 56 years (12-90 years). In patients with cancer, tumoral resection was immediately followed by midface reconstruction in the last 43 cases. Free flaps were selected for reconstruction of each part of the midface: cheek, nose, orbit floor, maxillary and palate. RESULTS: One post-operative death occurred (1.5%). The morbidity rate (18.7%) included necrosis of the free flaps in four cases. Average resumption of oral intake was ten days. The mean time to discharge was 17 days. Aesthetic and functional results were rated good or excellent in 53 patients. After one year, 52 patients were alive. Oral intake was normal in 48 patients, and mixed in four. Speech was excellent or good in 49 patients. From amongst the patients, 80% were able to find a job. CONCLUSION: Free flaps with micro surgery provides an optimal, functional, morphological and aesthetic outcome. Patients with advanced cancer of the midface are best managed through a multidisciplinary team approach. Microsurgical reconstruction represents the technical state of the art in case of extensive and complex midface defect.

Adolescent↗

PubMed1999

Prognostic value of high-frequency sonography and color Doppler sonography for the preoperative assessment of melanomas.

OBJECTIVE: The purposes of this study were to determine the efficacy of high-frequency sonography for the preoperative assessment of melanomas and to determine the prognostic value of tumor vascularity measured by color Doppler sonography. SUBJECTS AND METHODS: Twenty-seven patients with melanomas were prospectively examined using high-frequency sonography before they underwent surgery. For each tumor, morphologic evaluation (20-MHz probe), including the measurement of maximum tumor thickness, and color Doppler sonography analysis (13-MHz probe), including the measurement of intratumor vascularity, were performed. Diagnosis was confirmed by histologic findings, tumor thickness was measured using the Breslow index, and vascularity was assessed by immunochemical findings. RESULTS: Each of the 27 melanomas was depicted on high-frequency sonography as a homogeneous hypoechoic structure with well-defined margins. Tumor thickness was measured using high-frequency sonography as ranging from 0.3 to 8.0 mm, whereas it was measured using the Breslow index as ranging from 0.26 to 8.0 mm. Sonography measurements and Breslow index values were strongly correlated (r > .95). In the cases in which the Breslow index value exceeded 1 mm (n = 11), surgical reexcision was necessary but could have been avoided if surgery had been planned on the basis of high-frequency sonography measurements. Intratumor vessels were depicted on color Doppler sonography (n = 10). Color Doppler sonography data and histologic findings were significantly correlated. CONCLUSION: High-frequency sonography is a simple, reliable, noninvasive, and accurate method for the preoperative measurement of melanoma thickness. In fact, surgical planning could be adapted according to this measurement. The prognostic value of vascularization evaluated with color Doppler sonography is comparable with that determined by the Breslow index.

Aged↗

PubMed1999

[Primary synovial sarcoma of head and neck. Materials of The Gustave Roussy Institute. Report of 13 cases].

This report presents the result of our experience with 13 primary synovial sarcoma of the head and neck. The 9 males and 4 females had a median age of 32 years. The predominant location of the tumor was the pharynx, treatment consist of surgical excision alone or associated with post-operative radiotherapy or chemotherapy. Mean follow-up was 48 month. Local recurrence occurred in 2 patient, 4 patient died of pulmonary metastasis. The five year survival rate was 55%. Favorable prognostic findings included age < 20 years and complete initial resection.

Academic Medical Centers↗

PubMed1998

Circumferential pharyngolaryngectomy with total esophagectomy for locally advanced carcinomas.

BACKGROUND: Forty-nine cases of circumferential pharyngolaryngectomy with total esophagectomy (PLTE) done between 1982 and 1996 were studied retrospectively. These procedures were performed for advanced squamous cell tumors of the superior esophageal sphincter (n = 23), for hypopharyngeal tumors with synchronous esophageal carcinoma (n = 15), and for hypopharyngeal tumors extensively invading the cervical esophagus (n = 11). METHODS: Ninety-six percent of the patients had T3-4 lesions, and it was impossible to use a free jejunal graft reconstruction. Patients underwent primary surgery in 70% of the cases, and salvage surgery (after failure of chemoradiotherapy) in 30%. In most patients, esophagectomy was performed without thoracotomy (n = 45). Resection was curative (R0) in 70% of the cases, in spite of lymph node invasion in 94%. Reconstruction of the digestive tract was achieved with the stomach in 33 patients (67%) or with the colon in 16 patients (33%). RESULTS: Before 1989, postoperative mortality was high, was correlated with the high frequency of palliative surgery, and resulted in unsatisfactory survival results (overall 5-year survival rate of 7%). After 1989, as a result of better selection of patients and appropriate training of our team, postoperative mortality decreased from 33% to 10%, R1-2 resections decreased from 39% to 26%, and a 3-year overall survival rate of 28% was obtained for the last 25 patients, all of whom were able to eat without difficulty. These results are superior to the survival rates and functional results obtained with radiochemotherapy alone for such advanced tumors, even though the voice is preserved with radiochemotherapy alone. CONCLUSIONS: PLTE for advanced pharyngeal or cervical esophageal tumors is the best treatment currently available, but it is indicated only in very selected cases: when it is technically impossible to perform reconstruction with a free jejunal graft after circumferential pharyngolaryngectomy; as primary surgery, rather than as salvage surgery following chemoradiotherapy; after careful preoperative morphologic and endoscopic assessment of the extent of the tumor; and in patients able to tolerate a thoracotomy for an esophagectomy with lymphadenectomy. Selection according to these guidelines should improve results.

Adult↗

PubMed1998

Combined transfacial and neurosurgical approach to malignant tumours of the ethmoid sinus.

In order to understand the risks and benefits of a combined transfacial and neurosurgical procedure for neoplasms of the ethmoid sinus, we reviewed all patients who underwent this surgical approach in our department between 1986 and 1994. The study included 41 patients. Pathological diagnoses included adenocarcinoma (31 patients), squamous cell carcinoma (three patients), aesthesioneuroblastoma (three patients), other (four patients). The overall morbidity rate was 39 per cent, and the post-operative mortality rate was 2.5 per cent. Complications were statistically more likely in patients with bone skull base reconstruction. The main carcinologic failures were local recurrences (24 per cent) and metastases (22 per cent). The one-year, three-year and five-year Kaplan Meir survival rates were respectively 84 per cent, 53 per cent and 36 per cent. In conclusion, the mortality and morbidity were acceptable, especially when no bone skull base reconstruction was performed. Better local control justifies a combined procedure with post-operative radiotherapy when tumours involve or reach the skull base.

Adenocarcinoma↗

PubMed1998

Prognostic value of histological and biological markers in pharyngeal squamous cell carcinoma: a case-control study.

Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal tumours in patients who developed distant metastasis and in patients without metastasis, matched on tumour site, node site and size, and year of diagnosis. Tumour differentiation, keratinization, vascular emboli, immunohistochemical expression of p53, c-erb-B2, Rb and bcl2 were first assessed in 31 pairs of patients. Factors of potential interest were then determined in 32 additional pairs of patients. Statistical analysis showed that the risk of distant metastasis was halved in patients with tumours expressing c-erb-B2 compared with patients with c-erb-B2-negative tumours (P = 0.05). The significance of c-erb-B2 expression and its potential value as a prognostic factor is discussed.

Biomarkers, Tumor↗

PubMed1998

Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients.

PURPOSE: To review our experience using full-dose external reirradiation given with a curative intent for patients with unresectable head and neck carcinoma (HNC). PATIENTS AND METHODS: Between January 1980 and December 1996, 169 patients who presented with unresectable nonmetastatic HNC in a previously irradiated area were included in this series. The median time between the first and the second irradiation was 33 months. Reirradiation protocols were as follows: radiotherapy alone (65 Gy over 6.5 weeks at 2 Gy/d), 27 patients; Vokes protocol, ie, five to six cycles of radiotherapy (median total dose, 60 Gy; 2 Gy/d) with simultaneous fluorouracil (5-FU) and hydroxyurea, 106 patients; and bifractionated radiotherapy (median total dose, 60 Gy; 2 x 1.5 Gy/d) with concomitant mitomycin, 5-FU, and cisplatin, 36 patients. The median cumulative dose of the two irradiations was 120 Gy. Eighty-five percent of the tumors were squamous cell carcinoma, 14% undifferentiated carcinoma of nasopharyngeal type, and 1% adenocarcinoma. Forty-four percent were local recurrences, 23% nodal recurrences, 14% both local and nodal, and 19% second primary tumors. RESULTS: Mucositis grade 3 (World Health Organization [WHO]) was found in 32% and grade 4 in 14% of cases. Four patients presented with neutropenia or thrombocytopenia (grade 3 or 4 WHO). Late toxicities (> 6 months) were as follows: cervical fibrosis (grade 2 to 3 Radiation Therapy Oncology Group [RTOG]), 41%; mucosal necrosis, 21%; osteoradionecrosis, 8%; and trismus, 30%. Five patients died of carotid hemorrhage, apparently in complete remission. Six months after the onset of reirradiation, 37% of patients were in complete response. Patterns of failure were local only (53%), nodal only (20%), metastatic only (7%), and multiple (20%). Median follow-up time was 70 months. Overall survival rate (Kaplan-Meier) was 21% (95% confidence interval [CI], 15% to 29%) at 2 years and 9% (95% CI, 5% to 16%) at 5 years. Median survival time was 10 months for the entire population. Thirteen patients, of whom 12 were treated with the Vokes protocol, were long-term disease-free survivors. In a multivariate analysis, the volume of the second irradiation was the only factor significantly associated with the risk of death: relative risk=1.8 (95% CI, 1.13 to 5.7) (P=.01). CONCLUSION: Full-dose reirradiation combined with chemotherapy was feasible in patients with inoperable HNC. The incidence and severity of late toxicity was markedly increased in comparison to that observed after the first irradiation. Median survival was better than that generally obtained using palliative chemotherapy alone. A small proportion of patients were long-term disease-free survivors.

Adult↗

PubMed1998

[Isolated mandibular metastasis of cancer of the thyroid. Mandibulectomy and reconstruction using a free vascularized peroneal graft].

Isolated mandibular metastasis from a thyroid cancer is exceptional. In our observation, it was revealed 13 years after the thyroid cancer (papillo-vesicular carcinoma which was treated with total thyroidectomy, nodes resection and I 131). Treatment included interruptive mandibulectomy and reconstruction with a free composed vascularized fibular transplant. Follow-up was uneventful. Functional and morphological results were excellent. Isolated cases are reported in the literature. Surgical resection must be achieved. The originality of our observation is the mandibular reconstruction with a free vascularized fibular transplant.

Adenocarcinoma↗

PubMed1997

[Isolated mandibular metastases. Therapeutic strategy. Apropos of 7 cases].

Among the mandibular tumours, the secondary malignant tumours are uncommon. We relate 7 cases observed between 1977 and 1995. Two cases have revealed the original cancer (rectum, prostate). The five other cases were discovered during the evolution of the original cancer (colon, lung, kidney, thyroid, breast). These 7 mandibular metastases were isolated. The treatment included a mandibular resection in 6 cases. In one of these cases, the reconstruction was performed with a free vascularized fibular transplant with success. Among the seven cases, two patients are alive, at the present time, with a mean follow-up of 3 years. This justifies a curative treatment.

Adult↗