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C De Cicco

Publications and source records attributed to C De Cicco.

At least 19 recordsLinked to original sources
PubMed2006

A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases.

BACKGROUND: Sentinel node biopsy (SNB) has become a standard treatment in staging axillary lymph nodes in early breast cancer. SNB, however, is an invasive procedure and is time-consuming when the sentinel node is analysed intra-operatively. Breast cancer is frequently characterised by increased 2-fluoro-2-deoxy-D-glucose uptake and many studies have shown encouraging results in detecting axillary lymph node metastases. The aim of this study was to compare SNB and -positron emission tomography (-PET) imaging, to assess their values in detecting occult axillary metastases. PATIENTS AND METHODS: In all, 236 patients with breast cancer and clinically negative axilla were enrolled in the study. 18-FDG-PET was carried out before surgery, using a positron emission tomography (PET)/computed tomography scanner. In all patients, SNB was carried out after identification through lymphoscintigraphy. Patients underwent axillary lymph nodes dissection (ALND) in cases of positive FDG-PET or positive SNB. The results of PET scan were compared with histopathology of SNB and ALND. RESULTS: In all, 103 out of the 236 patients (44%) had metastases in axillary nodes. Sensitivity of FDG-PET scan for detection of axillary lymph node metastases in this series was low (37%); however, specificity and positive predictive values were acceptable (96% and 88%, respectively). CONCLUSIONS: The high specificity of PET imaging indicates that patients who have a PET-positive axilla should have an ALND rather than an SNB for axillary staging. In contrast, FDG-PET showed poor sensitivity in the detection of axillary metastases, confirming the need for SNB in cases where PET is negative in the axilla.

Adult↗
PubMed2006

Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept.

PURPOSE: Cervical lymph node status is the most important pathological determinant of prognosis and decision making in head and neck squamous cell carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy (LS) can supply a complete map of the lymphatic drainage before surgery, allowing planning of the type of intervention and serving to guide lymphadenectomy. METHODS: The study population comprised 14 patients with T2-4 SCCs of the tongue and clinically negative lymph nodes in the neck (cN0) who were scheduled to undergo tumour resection and selective level I-IV neck dissection extended to level V. LS was performed in all patients following the injection of (99m)Tc-colloidal sulphide in three aliquots around the primary lesion. Dynamic, static and tomographic images of the head and neck were acquired. The operative specimens were subjected to lymphoscintigraphic evaluation. Preoperative and postoperative imaging results were compared with the pathological findings. All nodes were examined using haematoxylin-eosin staining. RESULTS: Preoperative LS was successful in all patients. Preferential pathways of lymphatic drainage were identified: level II of the neck was the most common lymphatic drainage pattern, followed by levels IV and III. Contralateral drainage occurred in 11 patients and in two of them metastatic nodes were found on the contralateral side. Metastases were observed only in radioactive lymph nodes. CONCLUSION: LS is able to supply a complete map of the lymphatic drainage before surgery, making it possible to tailor selective neck dissection to each individual patient based on the results of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing surgery-related morbidity.

Adult↗
PubMed2005

Preoperative determination of serum thyroglobulin to identify patients with differentiated thyroid cancer who may present recurrence without increased thyroglobulin.

Thyroglobulin is considered a reliable marker of recurrent disease in patients with well-differentiated thyroid carcinoma. However, some patients present recurrence with no increase in serum thyroglobulin. In the attempt to identify patients who might present recurrence with no such sign of the disease, thyroglobulin levels have been determined pre-operatively in 185 consecutive patients scheduled for primary treatment for well-differentiated thyroid carcinoma from June 1997 to May 2002 at the Head and Neck Division of the European Institute of Oncology. In 22 patients (11.9% of total), serum thyroglobulin was undetectable. In none of these 22 cases was thyroglobulin detected during follow-up, either during thyroxin suppressive therapy or during withdrawal for radioiodine scan. One of these low-thyroglobulin patients developed recurrent disease involving cervical lymph nodes, with positive radioiodine scan: thyroglobulin remained undetectable. On the contrary, in the patients with high or normal thyroglobulin presenting recurrence, the recurrence was indicated, in all cases, by increased thyroglobulin levels. From these findings it may be concluded that pre-operative assessment of serum thyroglobulin may identify patients who might present recurrence without increased thyroglobulin, and in whom standard follow-up by monitoring thyroglobulin serum levels is inadequate.

Adolescent↗
PubMed2004

Thyroid disease in northern Italian children born around the time of the Chernobyl nuclear accident.

BACKGROUND: The Chernobyl nuclear accident of 1986 caused a dramatic increase in the incidence of thyroid cancers in exposed children in Belarus. Airborne radioactivity from the reactor spread over northern Italy, where rainout gave rise to low levels of radioactivity at ground level. PATIENTS AND METHODS: As the latency between exposure to ionising radiation and development of thyroid cancer is thought to be about 10 years, in 1996/1997 all children born in 1985 and 1986 and attending school in an area of Milan, Italy were examined for thyroid nodules. A total of 3949 children were examined by two physicians blinded to the examination and diagnosis of the other. The children were to be reassessed in 2001/2002. RESULTS: In total, 1% had palpable nodules. The nodule diagnoses were: Hurtle cell adenoma (one), thyroglossal duct cyst (one), thyroid cyst (four) and thyroiditis (four). The prevalence of thyroid disease in the cohort was indistinguishable from that of populations not exposed to radioactive pollution. Only 10 children re-presented for examination 5 years later; all were negative. The direct costs of the study were estimated at 21,200 Euros. CONCLUSION: The high cost of the study in relation to reassuring lack of increase in thyroid nodule prevalence suggests that further studies are not justified.

Chernobyl Nuclear Accident↗
PubMed2003

Optimised nuclear medicine method for tumour marking and sentinel node detection in occult primary breast lesions.

The aim of this study was to evaluate the feasibility of sentinel node (SN) biopsy in occult breast lesions with different radiopharmaceuticals and to establish the optimal lymphoscintigraphic method to detect both occult lesions and SNs (SNOLL: sentinel node and occult lesion localisation). Two hundred and twenty-seven consecutive patients suspected to have clinically occult breast carcinoma were enrolled in the study. In addition to the radioguided occult lesion localisation (ROLL) procedure, using macroaggregates of technetium-99m labelled human serum albumin (MAA) injected directly into the lesion, lymphoscintigraphy was performed with nanocolloids (NC) injected in a peritumoral (group I) or a subdermal site (group II). In group III, a sole injection of NC was done into the lesion in order to perform both ROLL and SNOLL. Overall, axillary SNs were identified in 205 of the 227 patients (90.3%). In 12/62 (19.4%) patients of group I and 9/79 (11.4%) patients of group III, radioactive nodes were not visualised, whereas SNs were successfully localised in 85 of 86 patients of group II ( P<0.001). Pathological findings revealed breast carcinoma in 148/227 patients (65.2%) and benign lesions in 79 (34.8%). A total of 131 axillary SNs were removed in 118 patients with breast carcinoma; intraoperative examination of the SNs revealed metastatic involvement in 16 out of 96 cases of invasive carcinoma (16.7%). It is concluded that the combination of the ROLL procedure with direct injection of MAA into the lesion and lymphoscintigraphy performed with subdermal injection of radiocolloids represents the method of choice for accurate localisation of both non-palpable lesions and SNs.

Adult↗
PubMed2002

Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study.

In a previous study we applied a three-step avidin-biotin pretargeting approach to target 90Y-biotin to the tumour in patients with recurrent high grade glioma. The encouraging results obtained in this phase I-II study prompted us to apply the same approach in an adjuvant setting, to evaluate (i) time to relapse and (ii) overall survival. We enrolled 37 high grade glioma patients, 17 with grade III glioma and 20 with glioblastoma, in a controlled open non-randomized study. All patients received surgery and radiotherapy and were disease-free by neuroradiological examinations. Nineteen patients (treated) received adjuvant treatment with radioimmunotherapy. In the treated glioblastoma patients, median disease-free interval was 28 months (range=9-59); median survival was 33.5 months and one patient is still without evidence of disease. All 12 control glioblastoma patients died after a median survival from diagnosis of 8 months. In the treated grade III glioma patients median disease-free interval was 56 months (range=15-60) and survival cannot be calculated as only two, within this group, died. Three-step radioimmunotherapy promises to have an important role as adjuvant treatment in high grade gliomas, particularly in glioblastoma where it impedes progression, prolonging time to relapse and overall survival. A further randomized trial is justified.

Adult↗
PubMed2002

Internal mammary node lymphoscintigraphy and biopsy in breast cancer.

BACKGROUND: In patients with breast cancer, sentinel nodes (SNs) are detected outside the axilla in 1-2% of cases after superficial injection of radiocolloid in the breast. We investigated whether deep injection of tracer visualized internal mammary chain lymph (IMC) nodes more often, and assessed the impact of IMC status on disease staging. METHODS: A total of 400 patients were enrolled in this trial. The study group included 200 patients with T1-T2 N0 breast cancer in an inner quadrant. Radio tracer was injected superficially in 100 (group A), and deeply under the tumor in the others (group B). If an IMC took up tracer in group B patients it was biopsied. An additional 200 patients with outer quadrant lesions were also studied lymphoscintigraphically following superficial (100 patients) or deep (100 patients) injection, but IMC nodes were not biopsied as this would have required an additional surgical excision. RESULTS: An SN was visualized in the IMC in 65.6% of inner quadrant patients after deep injection and in 2.1% after superficial injection. In outer quadrant patients, deep injection visualized an SN in the IMC in 10% of cases. The IMC SN was located mainly in the 2nd and 3rd intercostal spaces. Radioguided IMC biopsy was performed in 62 patients. Node removal proved simple and risks insignificant. Stage migration occurred in 8% of cases. CONCLUSIONS: Deep injection allows SN localization in the IMC in 65% of inner quadrant breast lesions. Biopsy of the axillary plus IMC resulted in stage migration in 8% of patients. It is unclear whether this additional information can lead to better survival.

Adult↗
PubMed2002

Radioguided occult lesion localisation (ROLL) and surgical biopsy in breast cancer. Technical aspects.

BACKGROUND: The surgical management of non-palpable breast lesions remains controversial. At our Institute we have introduced a new technique, radioguided occult lesion localisation (ROLL) to replace standard methods and overcome their disadvantages. In this paper technical aspects of ROLL and results on a large series of patients are reported. METHODS: We analysed 812 consecutive patients with 816 non-palpable breast lesions detected mammographically or ultrasonically. (99m)Tc-labelled particles of human serum albumin (7-10 MBq) in 0.2 ml saline were injected into the lesion under stereotactic mammographic or ultrasonic guidance. Mammography and scintigraphy were then performed. With ultrasound guidance only scintigraphic control was necessary. The excision biopsy was carried out with the aid of a hand-held gamma-detecting probe, and entire removal of the lesion was verified by X-ray of the specimen. RESULTS: The tracer was correctly positioned initially in 772/816 (94.6%) cases and at second attempt in another 2. In 42/816 (5.1%) cases, lesion localisation had to be repeated using a traditional approach. X-ray demonstrated the lesion was entirely removed in 770/774 (99.5%) cases. Pathological examination revealed 367 (47.4%) benign lesions and 407 (52.6%) cancers. The cancers were treated by conservative breast surgery in 99.5% of cases. CONCLUSIONS: We concluded that ROLL enables the surgeon to remove occult breast lesions easily and reliably.

Adult↗
PubMed2001

Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide.

A newly developed somatostatin radioligand, DOTA-[D-Phe1-Tyr3]-octreotide (DOTATOC), has been synthesised for therapeutic purposes, because of its stable and easy labelling with yttrium-90. The aim of this study was to determine the dosage, safety profile and therapeutic efficacy of 90Y-DOTATOC in patients with cancers expressing somatostatin receptors. We recruited 30 patients with histologically confirmed cancer. The main inclusion criterion was the presence of somatostatin receptors as documented by 111In-DOTATOC scintigraphy. 90Y-DOTATOC was injected intravenously using a horizontal protocol: patients received equivalent-activity doses in each of three cycles over 6 months. The first six patients received 1.11 GBq per cycle and the four successive groups of six patients received doses increasing in 0.37-GBq steps. Toxicity was evaluated according to WHO criteria. No patient had acute or delayed adverse reactions up to 2.59 GBq 90Y-DOTATOC per cycle (total 7.77 GBq). After a total dose of 3.33 GBq, one patient developed grade II renal toxicity 6 months later. The maximum tolerated dose per cycle has not yet been reached, although transient lymphocytopenia has been observed. Total injectable activity is limited by the fact that the maximum dose tolerated by the kidneys has been estimated at 20-25 Gy. Complete or partial tumour mass reduction occurred in 23% of patients; 64% had stable and 13% progressive disease. It is concluded that high activities of 90Y-DOTATOC can be administered with a low risk of myelotoxicity, although the cumulative radiation dose to the kidneys is a limiting factor and requires careful evaluation. Objective therapeutic responses have been observed.

Adult↗
PubMed2000

Sentinel node localization by lymphoscintigraphy: a reliable technique with widespread applications.

The concept of the sentinel lymph node (SN) represents an important contribution to guide appropriate surgery of cancer. Diagnostic non-invasive or minimally invasive procedures that provide accurate preoperative staging of the lymph node status are badly needed. The technique of SN biopsy, first developed with the purpose to select melanoma patients for regional node dissection, has been extended to other malignancies. Initial studies in breast carcinoma, conducted with vital blue dye, showed that the SN concept was biologically valid, although SN was missed in up to 30%-40% of cases. If a radioactive tracer is injected close to the tumor, then the SN can be identified by lymphoscintigraphy (LS), and a gamma ray detecting probe (GDP) can be used to locate the skin projection of SN and assist biopsy. These techniques are already used successfully in melanoma and breast carcinoma where the various parameters involved, such as the size of the radioactive particles, the injection site and injection volume, have recently been optimized. In a large series of breast cancer patients, the overall predictive value of the SNs biopsy guided by LS and GDP was 96.8%; in patients with small carcinomas (< 1.2 cm diameter), the concordance between SN and axillary status was 98.6%. In patients with melanoma, LS combined with GDP showed itself to be superior to the blue dye mapping. LS associated with GDP allowed the detection of SN in 98% of cases and 72 SNs in 54 basins were localized. Using blue dye instead, SN was stained only in 80% of patients (50 SNs in 40 basins). Lymphoscintigraphic techniques have shown promising results also in tumors such as vulva and tongue. In conclusion, LS is a simple nuclear medicine technique, relatively inexpensive and well accepted by patients. SN biopsy guided by a GDP is becoming widely adopted for a variety of neoplasms, contributing significantly to the search for less aggressive treatments in patients with early stages of cancer.

Axilla↗
PubMed2000

Use of technetium-99m-labeled colloid albumin for preoperative and intraoperative localization of nonpalpable breast lesions.

BACKGROUND: Management of clinically occult breast lesions is still a major point of debate. Several techniques (eg, skin projection, guidewire localization) have been proposed, but all of them have technical limitations. STUDY DESIGN: The aim of this study was to assess the efficacy of a new method to locate occult breast lesions using technetium-99m (99mTc)-labeled colloid particles of human serum albumin (radioguided occult lesion localization). We studied 647 consecutive patients (mean age 51.3 years; range 25 to 77 years) with nonpalpable breast lesions detected mammographically or by ultrasonography. Within 24 hours before operation, 3.7 MBq (0.1 mCi) of 99mTc-labeled colloid was injected directly into the center of the lesion using stereotactic mammographic guidance (when only microcalcifications were present) or ultrasonographic guidance (for opacities). Excision biopsy was performed with a gamma-detecting probe. After excision, the area was checked for residual radioactivity and the specimen was radiographed to verify complete removal of the lesion. The material was then sent for pathologic examination. The absorbed dose to the inoculated area and the external irradiation to staff were also determined. RESULTS: In all 647 patients, the "hot spot" was located easily and quickly. X-ray and scintigraphy of the specimen verified the presence and centricity of the lesion in all patients but three (99.5%). Pathologic examination revealed 340 cancer lesions (52.6%). Of these patients, 339 (99.7%) were treated by breast-conserving operations and one (0.3%) received a modified radical mastectomy. No major surgical or postoperative complications were encountered. No recurrences were documented during follow-up. The absorbed dose to the breast and other tissue was negligible (0.03 +/- 0.02 mGy/MBq), as was the dose to the surgeon's hands (7.5 +/- 5.0 microSv/h). The latter dose represents 0.015% and 0.002% of the recommended limits of the European Community for the general population and for exposed workers, respectively. CONCLUSIONS: Radioguided occult lesion localization seems to offer a simple and reliable method to locate occult breast lesions with a gamma-detecting probe, allowing complete removal of the lesion in 99.5% of patients. Because of the small quantity of radioactivity, the procedure is safe for both patients and medical staff.

Adult↗
PubMed2000

Sentinel node biopsy in early vulvar cancer.

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1-T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node was positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer.

Adult↗
PubMed1999

Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series.

BACKGROUND: Axillary lymph node dissection is an established component of the surgical treatment of breast cancer, and is an important procedure in cancer staging; however, it is associated with unpleasant side effects. We have investigated a radioactive tracer-guided procedure that facilitates identification, removal, and pathologic examination of the sentinel lymph node (i.e., the lymph node first receiving lymphatic fluid from the area of the breast containing the tumor) to predict the status of the axilla and to assess the safety of foregoing axillary dissection if the sentinel lymph node shows no involvement. METHODS: We injected 5-10 MBq of 99mTc-labeled colloidal particles of human albumin peritumorally in 376 consecutive patients with breast cancer who were enrolled at the European Institute of Oncology during the period from March 1996 through March 1998. The sentinel lymph node in each case was visualized by lymphoscintigraphy, and its general location was marked on the overlying skin. During breast surgery, the sentinel lymph node was identified for removal by monitoring the acoustic signal from a hand-held gamma ray-detecting probe. Total axillary dissection was then carried out. The pathologic status of the sentinel lymph node was compared with that of the whole axilla. RESULTS: The sentinel lymph node was identified in 371 (98.7%) of the 376 patients and accurately predicted the state of the axilla in 359 (95.5%) of the patients, with 12 false-negative findings (6.7%; 95% confidence interval = 3.5%-11.4%) among a total of 180 patients with positive axillary lymph nodes. CONCLUSIONS: Sentinel lymph node biopsy using a gamma ray-detecting probe allows staging of the axilla with high accuracy in patients with primary breast cancer. A randomized trial is necessary to determine whether axillary dissection may be avoided in those patients with an uninvolved sentinel lymph node.

Albumins↗
PubMed1999

Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin.

While the incidence of brain tumours seems to be increasing, median survival in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatment. We have developed an avidin-biotin pre-targeting approach for delivering therapeutic radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems potentially effective for treating these tumours. We treated 48 eligible patients with histologically confirmed grade III or IV glioma and documented residual disease or recurrence after conventional treatment. Three-step radionuclide therapy was performed by intravenous administration of 35 mg/m2 of biotinylated anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2nd step), and 18-24 h later by 1-2 mg of yttrium-90-labelled biotin (3rd step). 90Y doses of 2.22-2.96 GBq/m2 were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m2. Tumour mass reduction (>25%-100%), documented by computed tomography or magnetic resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration of response of at least 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a minor response and four with stable disease. Median survival from 90Y treatment is 11 months for grade IV glioblastoma and 19 months for grade III anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well tolerated at the dose of 2.2 GBq/m2, allowing the injection of 90Y-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in patients no longer responsive to other therapies.

Adolescent↗
PubMed1999

Radiation protection in radioguided surgery of breast cancer.

The protocols for sentinel lymph node biopsy and radioguided occult lesion localization could potentially be of great value in the management of breast cancer patients. Both involve the injection of a 99Tcm-labelled radiopharmaceutical close to or into the lesion, localization of the sentinel lymph node or occult lesion by scintigraphy, and surgical removal with the aid of a hand-held gamma-ray detector. We present dosimetric data on patients and hospital personnel involved in these procedures. For evaluation of radiation protection, we measured the absorbed dose and air kerma rate. Activity levels in excised tissues and surgical instruments were also determined. For patients, the mean absorbed dose to the abdomen was 0.45 mGy, which is low compared to doses received from other diagnostic examinations. For surgeons after 100 operations, the mean absorbed dose to the hands was 0.45 mGy and the mean effective dose 0.09 mSv. Absorbed doses to all hospital personnel involved in the procedures were very low compared to recommended annual limits stipulated by the International Commission on Radiological Protection. We conclude that these procedures, performed according to protocols laid down by the European Institute of Oncology, Milan, are safe from the point of view of radiological protection and that only routine precautions are necessary.

Breast Neoplasms↗
PubMed1998

Intraoperative localization of the sentinel node in breast cancer: technical aspects of lymphoscintigraphic methods.

Axillary lymph node dissection is an important part of the surgical treatment of breast cancer as a staging procedure. Recent progressive advances in early detection have led to the treatment of small primary carcinomas; thus, a great number of axillary dissections show completely negative lymph nodes. The sentinel node (SN) concept, developed for melanoma patients, seems to be similarly valid in breast cancer and has the potential to change the standard surgical approach in these patients. To verify the accuracy of lymphoscintigraphic method associated with radioguided biopsy of the sentinel node in a large series of patients, we studied 382 patients with operable breast cancer. Lymphoscintigraphy (LS) was performed the day before surgery; three different-sized ranges of 99mTechnetium-labeled colloid particles were injected either by subdermal or peritumoral administration. Planar scans were registered in anterior and oblique projections, and a cutaneous marker was placed over the skin corresponding to the SN as visualized. SNs were localized and removed during surgery, using a gamma-detecting probe (GDP); total axillary dissection was then performed. In 54 patients, blue dye was also administrated in the tumor bed immediately after excision of the primary. LS identified at least one SN in 377 of 382 cases (98.7%). Axillary SN was localized in 371 cases (97.1%). The overall concordance between SN status and other axillary nodes was 96.8% (359 of 371). Localization of the SN was easier when large-size particles of colloidal albumin were injected in a volume of 0.4 ml. GDP successfully localized SN in 54/54 cases (100%), while blue dye identified SN in 37/54 patients (68.5%). In 33 of 37 cases (89%) the dye and LS identified the same node. LS and GDP-guided surgery provide accurate identification and removal of the SN, particularly when large-size radiolabeled colloids are injected in a small volume.

Axilla↗