Ultrasonography of Skin Changes in Legs with Chronic Venous Disease.

BACKGROUND: In daily practice, ultrasonography (US) is used only to designate the location and pattern of venous lesions. Skin US is not performed between routine venous investigations. METHODS: Skin morphology is evaluated by the same probes used for routine Duplex evaluation of superficial veins. US findings from evident skin lesions are comparatively evaluated with those from the surrounding apparently normal skin and from the contralateral leg. RESULTS: Inflammation and dermal edema can be found in the apparently normal skin of C2 legs. Swollen legs show thickening of the subcutaneous layer as a result of diffuse soaking or anechoic cavities, with or without dermal edema. Chronic hypodermitis is characterized by inflammatory edema in initial phases, and by liposclerosis in advanced cases. Recrudescence of inflammation provokes focal rarefactions of the subcutaneous layer, possibly related to ulcer opening. CONCLUSION: In legs with venous disorders, sonography refines clinical evaluation of the skin and may reveal changes not highlighted by inspection. Some of these changes could require further investigation because they have not yet been explained or described. Skin sonography should improve knowledge of the natural history of skin changes, as well as contribute to a better grading of venous diseases severity In particular, US evidence of cutaneous and subcutaneous changes in C2 legs should be considered to stratify the treatment in C2 legs, by identifying those in which varicose veins are not simply a cosmetic problem.

High level of TILs is an independent predictor of negative sentinel lymph node in women but not in men.

Factors that are most associated with positive lymph node status in melanoma are Breslow thickness and ulceration. However, there are other factors that have been little explored and could help in the identification of "at risk patients" harbouring occult metastasis. The objective of this study was to determine whether intensity of tumour-infiltrating lymphocytes (TILs) in a cohort study (N = 4133) is an independent predictor of sentinel lymph node (SLN) status in patients with primary cutaneous melanoma. Of the patients with cutaneous melanoma who resulted negative for nodal metastasis, 50.7% had moderate/marked TILs versus 27.7% among those patients who resulted positive for nodal metastasis. In the multivariate analysis, controlling for sex, age, mitotic rate, ulceration and Breslow, high levels of TILs in primary invasive melanoma was associated with a lower risk of developing SLN metastasis (OR 0.46; 95% CI 0.23-0.95, p = 0.037). When the analysis was stratified by sex, the protective effect of moderate/marked TIL remained only for women (OR 0.30; 95% CI 0.10-0.93, p = 0.037) but not for men (OR 0.51; 95% CI 0.19-1.34, p = 0.172). Other independent predictors of negative lymph node were low Breslow thickness (≤ 2.0 mm) and low mitotic rate. Besides predicting a negative lymph node response, TILs were also associated with a decreased risk of 10-year mortality among females with positive lymph node. Our findings suggest that high level of TILs is an independent predictor of negative SLN status among women. Further research is warranted to confirm our findings.

Skin iron deposition characterises lipodermatosclerosis and leg ulcer.

BACKGROUND: It is commonly reported that chronic venous disease (CVD) increases the skin iron content in which the excess is stored as haemosiderin. Despite increasing interest in the role of haemosiderin in venous ulceration, no study has systematically evaluated the occurrence of iron overload in the limbs of patients with CVD. PURPOSE: To evaluate skin haemosiderin deposition in relation to the presence and severity of skin changes in CVD legs designated according to the clinical, etiologic, anatomic and pathophysiologic (CEAP) classification. METHODS: A total of 85 skin biopsies were taken from the medial aspect of 49 limbs with CVD of CEAP clinical stages C2, C3, C4 and C6. The content of ferric ions was assessed by Perl's Prussian Blue (PPB) stain. RESULTS: No haemosiderin deposition was found in normal skin of C2, C3 and C4A legs, in less severe regions of pigmentation and in some parts of more severely affected limbs. Haemosiderin was always present in lipodermatosclerotic skin and ulcers. Occasionally, haemosiderin was found in the apparently normal perilesional skin of C4b and C6 legs. The regenerating dermis at the base of healing ulcers showed none or light haemosiderin deposition. CONCLUSION: Iron overload is not present in the less severe stages of skin damage due to CVD but lipodermatosclerosis and leg ulcers are always accompanied by haemosiderin deposition. In fact, no severe skin changes occur in CVD legs until iron overload occurs. Our results are in agreement with previous reports suggesting that a genetic inability to counteract skin iron overload is present in these patients. A more detailed analysis of disordered iron metabolism should be undertaken in CVD patients.

The nature of skin pigmentations in chronic venous insufficiency: a preliminary report.

BACKGROUND: Chronic Venous Insufficiency (CVI) provokes skin pigmentation commonly seen in the gaiter region of the leg. The exact nature and pathogenesis of this are poorly understood. OBJECTIVE: To evaluate the presence of melanin and haemosiderin in histological sections of the skin of limbs with primary varicose veins. METHODS: Histological investigations were performed in 49 biopsies from pigmented and non-pigmented skin of limbs with varicose veins and control limbs. RESULTS: All samples from pigmented skin showed a higher content of melanin than controls. In contrast, haemosiderin was found in only a few biopsies taken from the more severely pigmented skin in areas of lipodermatosclerosis. Erythrocyte diapedesis was observed only where an intense inflammatory process was also present. CONCLUSIONS: Our findings suggest that in the initial phases of skin changes due to venous disease, pigmentation is attributable to melanin. Haemosiderin seems to play a role in the evolution of skin changes toward lipodermatosclerosis and ulceration. Erythrocyte diapedesis is likely to occur only during acute phases of the inflammatory process. Further investigations are needed to explain the cause and the exact cellular and molecular mechanisms responsible for hypermelanisation occurring in early phases of skin changes in CVI.

Inflammation in venous disease.

Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated.

Sentinel lymph node biopsy for high risk cutaneous squamous cell carcinoma: case series and review of the literature.

AIMS: Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. The metastatic potential is generally low. However, there are subgroups of patients at higher risk, for whom sentinel lymph node biopsy (SLNB) might be useful. SLNB might allow the timely inclusion of high risk patients in more aggressive treatment protocols, sparing at the same time node-negative patients the morbidity of potentially unnecessary therapy. Our aim was to introduce the concept of SLNB for patients with high risk cutaneous SCC. PATIENTS AND METHODS: We examined a consecutive series of high risk cutaneous SCC patients undergoing SLNB at our large dermatological hospital, and performed a literature review and pooled analysis of all published cases of SLNB for cutaneous SCC. RESULTS: Among the 22 clinically node-negative patients undergoing SLNB at our hospital, one patient (4.5%) showed a histologically positive sentinel node and developed recurrences during follow-up. Sentinel node-negative patients showed no metastases at a median follow-up of 17 months (range: 6-64). The incidence of positive sentinel nodes in previous reports ranged between 12.5% and 44.4%. Pooling together patients from the present and previous studies (total 83 patients), we calculated an Odds Ratio of 2.76 (95% CI 1.2-6.5; p=0.02) of finding positive sentinel nodes for an increase in tumor size from <2 cm to 2.1-3 cm to >3 cm. CONCLUSIONS: Our case series and the pooled analysis support the concept that SLNB can be performed for high risk cutaneous SCC. Prospective multicenter studies are needed to examine the role, utility and cost-effectiveness of SLNB for this population.

Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.

BACKGROUND: Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP). The aim was to obtain a consensus of international experts on the methodology to be used for assessment of anatomy of superficial and perforating veins in the lower limb by ultrasound imaging. METHODS: The authors performed a systematic review of the published literature on duplex anatomy of the superficial and perforating veins of the lower limbs; afterwards they invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the authors and the experts (text and images) were made available to all participants via the UIP website. The authors prepared a draft document for discussion at the UIP Chapter meeting held in San Diego, USA in August 2003. Following this meeting a revised manuscript was circulated to all participants and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually, all participants agreed the final version of the paper. RESULTS: The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination as well as the interpretation of images and measurements obtained. This document provides a detailed methodology for complete ultrasound assessment of the anatomy of the superficial and perforating veins in the lower limbs. CONCLUSIONS: The authors and a large group of experts have agreed a methodology for the investigation of the lower limbs venous system by duplex ultrasonography, with specific reference to the anatomy of the main superficial veins and perforators of the lower limbs in healthy and varicose subjects.

[Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs: UIP consensus document - Parte II: anatomy]. / Investigação eco-doppler das veias dos membros inferiores na doenca venosa cronica: Documento de Consenso da UIP - Parte II: anatomia.

OBJECTIVES: Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP), The aim was to obtain a consensus of international experts on the methodology to be used for assessment of anatomy of superficial and perforating veins in the lower limb by ultrasound imaging. DESIGN: Consensus conference leading to a consensus document. METHODS: The authors performed a systematic review of the published literature on duplex anatomy of the superficial and perforating veins of the lower limbs; afterwards they invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the authors and the experts (text and images) were made available to all participants via the UIP website. The authors prepared a draft document for discussion at the UIP Chapter meeting held in San Diego, USA in August 2003. Following this meeting a revised manuscript was circulated to all participants and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually all participants agreed the final version of the paper. RESULTS: The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination as well as the interpretation of images and measurements obtained. This document provides a detailed methodology for complete ultrasound assessment of the anatomy of the superficial and perforating veins in the lower limbs. CONCLUSIONS: The authors and a large group of experts have agreed a methodology for the investigation of the lower limbs venous system by duplex ultrasonography, with specific reference to the anatomy of the main superficial veins and perforators of the lower limbs in healthy and varicose subjects.

Sentinel node biopsy for malignant melanoma: analysis of a four-year experience.

AIMS AND BACKGROUND: Sentinel node (SN) biopsy has been introduced to solve the controversy concerning the effectiveness of prophylactic lymphadenectomy in intermediate thickness melanoma. The aim of this study was to evaluate the rate of metastases, the technical details of the procedure, and the main reasons of failure. METHODS: 235 patients affected by intermediate thickness melanoma (tumor thickness >0.75 mm and <4 mm) without clinical signs of systemic spread (N0M0) were submitted to sentinel node biopsy between 1996 and 2000. Preoperative lymphoscintigraphy was routinely performed in the last 184 patients. Intraoperative mapping with gamma probe was combined with the use of vital dye for identification of sentinel nodes in the last 113 patients. RESULTS: The SN detection rate was 95.6%, with significant differences depending on the site of dissection and the use of a gamma probe. The overall rate of micrometastases was 14.7%, but relevant differences were recorded between different subgroups of patients (T2, 5.1%; T3a, 19.6%; T3b, 29%). CONCLUSIONS: Sentinel node biopsy requires a multidisciplinary approach (surgery, pathology and nuclear medicine) for reliable results. The association of vital dye and intraoperative gamma probe for sentinel node harvesting has made the procedure more effective, less time-consuming and less invasive. Failures may be due not only to surgical mistakes, but also to improper nuclear medicine procedures or inaccurate histological evaluation of SNs. Methods for histological examination of the SN are still debated and not standardized but promising results have recently been obtained with molecular oncology techniques (RT-PCR).

Lymphatic mapping and sentinel node identification in squamous cell carcinoma and melanoma of the head and neck.

AIM: The aim of our study was to evaluate the role of scintigraphy in lymphatic mapping and in the identification of the sentinel lymph node (SLN) in patients with head and neck cancer. METHODS: Between September 1999 and February 2001 we enrolled 22 consecutive patients with cancer in the head and neck region: five squamous cell carcinomas, one Merkel cell tumor of the cheek, and 16 malignant melanomas. Lymphoscintigraphy was performed three hours before surgery after injection of 30-50 MBq of 99mTc -Nanocoll in 0.3 mL; the dose was fractionated by injecting the radiotracer at two points around the lesion. Static acquisition (anterior and/or lateral views, 512 x 512 matrix, 5 mins pre-set time) was started immediately after the injections so as to visualize the pathways of lymphatic drainage. The skin projection of the SLN was marked with ink. Intraoperative SLN detection was performed with perilesional injection of patent blue. RESULTS: SLNs were found with lymphoscintigraphy in all patients. Thirty-three SLNs were identified: one occipital node, three nodes at the base of the tongue, 10 superficial lateral nodes (external jugular), five submandibular nodes, five submental nodes, three mastoid nodes and six supraclavicular nodes. Biopsy was performed in 21/22 patients. In 20/22 patients the first lymph nodes were visualized in the proximal cranial regions (retroauricular, jugular and submandibular) at five minutes post injection. The SLN positivity rate was 13.6% (three patients). All patients with tumor-positive SLNs were submitted to radical dissection. Poor concordance in the detection of sentinel nodes was observed with patent blue. CONCLUSIONS: The flow of nanocolloid in the lymph vessels of the head is rapid. In our experience immediate scintigraphic imaging was essential to visualize the pathways of lymphatic drainage and the first SLN. Radioguided SLN biopsy is therefore recommended within three hours. Injection of patent blue is inadvisable because of the poor concordance with lymphoscintigraphy and the risk of permanent tattooing of the face.

The caliber of the human long saphenous vein and its congenital variations.

The purpose of the present study is to evaluate the caliber of the normal human long saphenous vein (LSV) in order to verify the occurrence of congenital narrowings. The LSV morphology was evaluated by the dissection of 32 cadaveric limbs, and by ultrasonography of 102 healthy living subjects. The LSV caliber was constant in most of the limbs, showing only a mild and progressive increase from the ankle to the groin. Furthermore, great individual variation in LSV caliber was found. A segmental narrowing of the LSV was present in 39.8% of limbs. The narrow segment was visible with the naked eye during dissection or by ultrasonography in 22.4% of cases (LSV hypoplasia). In the remaining 17.4% the caliber was so reduced that it could only be detected microscopically (LSV aplasia). In relation to the narrow segments, the main ascending flow was shunted in a collateral vein running within the superficial hypodermis. The narrow segments of the LSV had a weaker and less muscular wall than did those of normal caliber. Hypoplasia and aplasia of the LSV are probably due to segmental failure in the development of the vessel, and represent a risk factor for varicosis. In fact, the ascending flow is shunted from the LSV in a collateral vein that runs in the yielding superficial fatty layer of the hypodermis. Furthermore, the high incidence of LSV segmental hypoplasia and aplasia has also to be considered whenever this vein is used as an arterial graft, because of the marked anatomical remodelling.

Partial agenesis of the azygos vein: a case report.

In the cadaver of an 86 year old man the inferior segment of the azygos vein could not be found. Furthermore, a normally developed hemiazygos vein drained the right and left intercostal veins from T 10 to T 6. This vessel finally curved towards the right to reach the superior vena cava after having drained the right superior intercostal veins. The left superior intercostal vein ended in a short vessel draining into the left brachiocephalic vein. This condition may be represented in a standard chest radiograph by the so-called "aortic nipple". Agenesis of the azygos vein, suspected because of the presence of this radiological sign, should be confirmed in the living by means of computerized tomography. This can clarify the anatomy of the mediastinal vessels precisely. Embryological pattern of the azygos system accounting for its possible defects is discussed.

On a complex arrangement of the vascular pedicle of the left kidney.

During the dissection of an 83 year-old male cadaver, we observed that the left renal vein passed behind the aorta to follow an oblique course before draining into the inferior vena cava. The left renal vein was connected to the left suprarenal, spermatic, lumbar ascending and azygos veins. The left spermatic vein, after collecting the suprarenal vein, crossed in front of the abdominal aorta to reach the inferior vena cava directly. Furthermore, the arterial pedicle of the left kidney was composed of two tortuous and intermingled vessels. Variations in the number and arrangement of the vessels terminating in the renal veins are not uncommon, but so complex a vascular arrangement as this has not to our knowledge been previously described. The ontogenetic explanation and clinico-surgical implications of such a variation are reviewed and discussed.

[Use of pulsed expansion in lengthening of tubed cutaneous flaps. Experimental study]. / Sull'impiego dell'espansione pulsata per l'allungamento di lembi cutanei tubulati. Ricerca sperimentale.

The Authors describe an intermittent pulsed pressure methodic applied to bipedicle tubed flaps prepared on the back of the rabbit. Clinical, thermographic, and histological data have demonstrated the safety of the flaps and a microvascular bed increase larger than in inexpanded ones.

[Sentinel node biopsy for malignant melanoma. Technical details and clinical results on 390 patients]. / La biopsia del linfonodo sentinella nel melanoma maligno. Dettagli tecnici e risultati in 390 pazienti.

BACKGROUND: The purpose of this paper is to present personal experience with sentinel node biopsy for the treatment of malignant melanoma. Technical details influencing the efficacy of the procedure are presented and the clinical, therapeutic and prognostic advantages of this technique discussed. METHODS: A total of 390 consecutive patients with primary skin melanoma (T2-3,N0,M0) underwent sentinel node biopsy between March 1996 and May 2001. All patients underwent previous excisional biopsy of the primary lesion and clinical and radiographic examination to exclude lymphatic or systemic macroscopic spreading of the disease. Preoperative lymphoscintigraphy (99mTc nanocoll) was routinely performed in the last 315 patients. Intraoperative detection of the sentinel nodes was performed by perilesional, intradermical, injection of blue dye associated with a g probe (Neoprobe(R) 2000) in the last 315 patients. Sentinel nodes, serially sectioned, were all Haematoxylin-Eosin and immunohistochemically stained. All patients positive for micro-metastasis underwent radical lymphadenectomy. Comparative analysis between the incidence of metastasis in sentinel and non-sentinel nodes, according to the clinical stage of the disease, was done. RESULTS: The overall detection rate of sentinel nodes was 97.4%. Relevant differences were found according to the site of dissection and the use of a g probe. The g-probe makes the procedure more effective, less invasive and less expensive. Timing and accuracy of the preoperative lymphoscintigraphy is a basic step of the procedure. The overall incidence of positive sentinel nodes was 14.7% with differences correlated with thickness of primary lesion (0.75-1.5 mm: 5,8%; 1.5-3 mm:18%; 3-4 mm: 24.6%). Metastasis in other non-sentinel nodes was found only with primary tumour thickness exceeding 2 mm. CONCLUSIONS: Sentinel node biopsy is a procedure requiring a multidisciplinary approach (surgery, nuclear medicine and pathology). A specific learning phase (>30 patients) is recommended to obtain reliable results.

Island chondromucosal flap from the nose in reconstruction of the eyelid. A light and scanning electron microscopic study.

Specimens from the reconstructed eyelids of two out of 15 patients operated on using an island chondromucosal flap from the nose were observed under light and scanning electron microscopy (EM) to study the histological and ultrastructural features of nasal epithelium transferred as a flap to the lids, the microscopic appearance of the other tissues of the flap, and its vascularisation. Both light and scanning EM images showed that nasal epithelium, when transferred as part of a flap for reconstruction of the eyelid, maintains its differentiation for many months. The lumen of arteries and veins can be observed in sagittal sections within the flap, suggesting that their course is parallel to its long axis. The absence of fibrosis or muscle fibre degeneration together with a highly cellular cartilage are indirect indications of good vascularity. These data support the reliability of the island chondromucosal flap from the nose in reconstruction of the eyelid.

Nipple reconstruction by local flaps: a long-term comparative study between star and skate techniques.

Nipple reconstruction often gives the highest satisfaction to the patient despite being just a minor procedure. During the last 50 years, many techniques have been described in order to improve the cosmetic appearance. Star and skate flaps are two of the most frequently reported procedures. The aim of this study was to compare the personal experience of two plastic surgery departments that have been using these two different methods. Thirty patients have been included in this study. Nipple projection and cosmetic appearance have been evaluated by both patients and surgeons. Follow-up ranged between 1 and 5 years. Results have been compared. Both techniques proved to be versatile and valid. The skate flap seemed to keep projection for a longer time, while the star technique gave a better cosmetic appearance.

[Anatomo-surgical study on a new technique of nephropexy]. / Studio anatomo-chirurgico su di una nuova tecnica di nefropessi.

The Authors carried an autoptic study on ten cadavers in order to clarify and if necessary modify some aspects of the nephropexy technique which was modified and improved by them. Two main conclusions are reported. First, the approach is better obtained by a prolonged incision to the twelfth rib. Second, possible damage to the diaphragm and to the lung are avoided with this technique. Furthermore, the study provides information about the preparation and suture of the capsule.

[Diverticula of the cecum. Our experience]. / I diverticoli del cieco. La nostra esperienza.

On the basis of their experience in right colonic emergencies, the Authors report two cases of diverticular disease presenting with acute abdomen. Pointing out the difficulty of a correct pre- and intraoperative diagnosis, different surgical procedures are analysed.