Recombinant leptin administration improves early angiogenesis in full-thickness skin flaps: an experimental study.

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro, and angiogenesis in vivo. In addition, leptin seems to play an important role in angiogenesis as it promotes the formation of new blood vessels. OBJECTIVE: To determine the effect of local application of exogenous leptin on the survival of full thickness skin flaps in an experimental animal model. MATERIALS AND METHODS: Ninety Sprague-Dawley rats were used in this study. A full thickness dorsal flap (10 cm x 2 cm) with the pedicle located at the level of the iliac crest was designed. Animals were divided into ten groups of nine animals each. In the distal two thirds of the flap and by means of subdermal injection at 8 different locations, rats were injected with 100 ng/ml leptin, 250 ng/ml leptin, 500 ng/ml leptin, 1000 ng/ml leptin (groups A, B, C and D), 1 microg/ml VEGF (group E), or 1 ml saline (control group), respectively. For each of the four leptin doses used, another animal group was injected with a combination of leptin/antileptin: 100 ng/ml leptin with 150 ng/ml antileptin, 250 ng/ml leptin with 375 ng/ml antileptin, 500 ng/ml leptin with 750 ng/ml antileptin or 1000 ng/ml leptin with 1500 ng/ml antileptin (groups A1, B1, C1 and D1, respectively), in order to study the inhibition of the leptin factor. Nine rats served as controls and were injected with 1 ml saline solution. Rats were sacrificed 3, 7 and 9 days postoperatively. After sacrifice of the animals, the skin was grossly arranged on its appearance, colour and texture. Full thickness skin flaps were dissected for histological examination. A qualitative analysis of angiogenesis in the flap was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: Immunohistochemical staining revealed that more granulation tissue and improved angiogenesis were observed in group D (1000 ng/ml leptin) flaps compared to those in the VEGF, leptin/antileptin and saline groups. In addition, skin flap survival rate in group D (1000 ng/ml leptin) and group E (1 microg/ml VEGF) were significantly better than those of the other groups. The most impressive formation of new blood vessels was noted in the groups with the higher leptin doses. Surgical wounds in the control, as well as in the leptin/antileptin groups, did not demonstrate any new vessels. CONCLUSION: Exogenous administration of recombinant leptin increases early skin flap angiogenesis in an experimental animal model. Local application of leptin could efficiently improve survival of ischemic skin flaps.

Cavernous haemangioma of the left nasal cavity.

Cavernous haemangioma of the nose is a rare lesion but it has to be added to the differential diagnosis of an intra-nasal bleeding mass. A high index of suspicion, upon computed tomography delineation of the extent of the mass, including the presence of bone remodelling plus histological evaluation can be usefully employed to define an accurate diagnosis. In the present case of an adult female with a huge cavernous haemangioma arising from the mucosa of the left middle nasal meatus, the two most interesting points were the rarity as a site of occurrence of this tumour and the successful extirpation of this lesion with the minimally invasive trans-nasal endoscopic technique. We recommend the minimal invasive trans-nasal endoscopic technique for adequate exposure, sufficient control of bleeding and for complete removal of a nasal haemangioma reaching the nasopharynx and paranasal sinuses.

Exogenously-administered leptin increases early incisional wound angiogenesis in an experimental animal model.

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro, as well as angiogenesis in vivo. In addition, leptin seems to play an important role in clinical angiogenesis by promoting the development of new blood vessels. OBJECTIVE: To determine the effect of exogenously administered leptin on incisional wound healing in an experimental animal model. MATERIALS AND METHODS: Sixty-three Sprague-Dawley male mice were used for the study. Full thickness incisional wound was considered as the wound model. The mice were divided into seven groups of nine animals each. Surgical wounds were injected with murine recombinant leptin. Three different leptin doses of 100 pg/ml, 200 pg/ml and 500 pg/ml were used in different animal groups (A, B and C). For each of the three leptin doses used, another animal group was evaluated with a combined injection of leptin and antileptin: 100 pg/ml leptin with 50 pg antileptin, 200 pg/ml leptin with 100 pg antileptin, 500 pg/ml leptin with 250 pg antileptin (A1, B1, and C1), in order to study the inhibitory effect on the leptin factor. Nine mice served as controls. These were injected with 0.3 ml water for injection solution. Mice were sacrificed 3, 7 and 9 days postoperatively. After sacrifice of the animals, the skin was grossly assessed for appearance, colour and texture. Full thickness incisional wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the surgical wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant differences in microvessel density at seven or nine postoperative days among different groups treated with leptin. None of the wounds from the control group, or those from animal groups treated with the combined injection of leptin and antileptin developed any new vessels. CONCLUSION: Exogenous administration of leptin may increase early tissue angiogenesis in the incisional wound of an experimental animal model.

Dermatofibrosarcoma protuberans: clinicopathological aspects of an unusual cutaneous tumor.

Dermatofibrosarcoma protuberans is a rare cutaneous tumor with particular characteristics and a high frequency of recurrence after inadequate primary treatment. Its histopathological diagnosis might be difficult. Dermatofibrosarcoma protuberans can be safely distinguished from other similar neoplasms of mesenchymal origin based on the immunohistochemical expression of CD34 antigen and the genetic presence of specific chromosomal translocations. Although rarely metastatic, it is followed by a significantly high rate of locoregional failure due to an indolent subcuticular tissue spread. Aggressive surgical management is the therapeutic approach of choice. A wide resection with microscopically disease-free margins is always recommended. Mohs' micrographic surgery together with advanced reconstructive techniques provides satisfactory results even for tumors involving the face or distal extremities.

Merkel cell carcinoma: clinicopathological aspects of an unusual neoplasm.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous cancer that predominately affects elderly Caucasians with fair skin and has a propensity for local recurrence and regional lymph node metastases. It can occur on the face, the trunk, the genitalia, and the perianal region. The median age of the patients is 69 years, but it may occur earlier and more frequently in immunosuppressed patients. MCC usually arises in the dermis and extends into the subcutis. It may be difficult to accurately diagnose MCC by light microscopy alone and ancillary techniques, including electron microscopy and immunohistochemistry, may be necessary for a definitive diagnosis. The management of MCC is dependent on the stage of the disease and is hampered by its rarity and lack of randomized trials. Nonetheless, for localized disease most guidelines include wide local excision of the primary tumor either alone or followed by radiation therapy. Sentinel lymph node biopsy can be helpful in staging and prognosis, but its benefit in survival remains to be seen. Systemic chemotherapy may be considered as an adjuvant following surgery or to treat locoregional or distant disease. The prognosis of MCC is variable. In patients with localized disease the course is indolent and is well-controlled with local excision alone. On the other hand, many tumors are aggressive and have a tendency for locoregional recurrence and distant metastases. Such patients have a grim prognosis, with a median survival of 9 months. Successful outcome most often is seen in patients with early diagnosis and complete excision.

Malignant hidradenoma: a report of two cases and review of the literature.

INTRODUCTION: Malignant tumors of the sweat glands are very rare. Clear cell hidradenoma is a lesion with histopathological features resembling those of eccrine poroma and eccrine spiradenoma. The biological behavior of the tumor is aggressive, with local recurrences reported in more than 50% of the surgically-treated cases. MATERIALS AND METHODS: Two patients are presented, the first with tumor in the right axillary region, the second with a recurrent tumor of the abdominal wall. The first patient underwent wide excision with clear margins and axillary lymph node dissection and the second patient underwent wide excision of the primary lesion and bilateral inguinal node dissection due to palpable nodes. RESULTS: The patients had uneventful postoperative courses. No additional treatment was administered. However, sixteen months after surgery, patient 2 developed extensive and massive recurrence involving almost the whole abdominal wall. Although he had received several chemotherapeutic agents, the disease had a relentless course and the patient succumbed two and a half years following surgery. CONCLUSION: Malignant tumors of the sweat glands are very rare neoplasms with no discrete clinical characteristics. It is necessary to suspect any lesion which shows evidence of enlargement and to verify its status by histological evaluation. Additional resection is generally required, with at least 2-cm clear margins, since surgery is the only effective treatment.

Mucocele of the appendiceal stump due to benign mucinous cystadenoma.

Mucocele of the appendix is a rare lesion, characterized by distension of the lumen due to accumulation of mucus material. Correct preoperative diagnosis is seldom achieved. If left untreated, the mucocele may rupture producing a potentially fatal peritoneal spread. The type of surgical treatment is related to the dimensions and histology of the mucocele. In this paper, the case of a 49-year-old woman, with a previous appendectomy, suffering from a painful mass in the right lower quadrant of the abdomen, is reported. Imaging showed a large, cystic structure at the base of the cecum. Surgery revealed a 8x5.5 cm calcified tumor, which was excided together with the appendiceal remnant. Pathological diagnosis was that of a mucocele arising from the appendiceal stump due to the development of a benign mucinous cystadenoma.

Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer.

BACKGROUND AND AIMS: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (5x5 Gy) not only reduces the risk of local recurrence but also improves overall survival rate. An increase in postoperative mortality and morbidity has also been observed, however. We therefore evaluated early postoperative complications in patients treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma. PATIENTS/METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on CT scan and, in several cases, on endorectal ultrasonography. They were 55 men and 30 women, with a median age of 68 years. They were retrospectively divided into two groups: Group A, which included 40 patients undergoing preoperative radiotherapy (25 Gy in five fractions) followed by surgery within 1 week, and Group B, which included 45 patients with rectal cancer receiving surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of the disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. RESULTS/FINDINGS: No postoperative deaths were recorded in either group. Low anterior resection with total mesorectal excision was performed in all group A patients, whereas eight patients in group B underwent abdominoperineal resection (P<0.05). Diverting stoma was performed in seven patients of group A and it was closed 3-6 months later on every occasion. Postoperative morbidity was not statistically significant between the two groups (40 vs 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection, and delayed ileus was similar. The percentage of major anastomotic leak was also equivalent (5 vs 6.6%). INTERPRETATION/CONCLUSION: Short-term preoperative radiotherapy does not increase the rate of postoperative complications and is a safe therapeutic adjunct for the treatment of locally advanced rectal cancer.

Late-onset dysphagia lusoria assessed by 3-dimensional computed tomography of an aortic arch abnormality.

Symptomatic vascular rings causing late-onset dysphagia (dysphagia lusoria) are quite unusual in adults. We present a 42-year-old woman with a 1-year history of dysphagia from a right-sided aortic arch with an aberrant left subclavian artery and left-sided ligamentum arteriosum. Using a helical CT scan of the chest and a three-dimensional reconstruction software, her anatomic abnormality was completely delineated. Arch aortogram confirmed the anomaly. The patient underwent a left posteriolateral thoracotomy. Intraoperative findings correlated precisely with the preoperative reconstruction data. Division of the ligamentum resulted in a complete decompression of the esophagus and resolution of the patient's symptoms.

Short-term preoperative radiotherapy in locally advanced rectal cancer does not increase postoperative complications and improves the rate of sphincter-preserving surgery.

PURPOSE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (RT) (5x5 Gy) not only reduces the risk for local recurrence, but also improves the overall survival rate. However, an increase in postoperative mortality and morbidity has also been observed. We, therefore, evaluated the early postoperative complications in patients treated with neoadjuvant RT for locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on computed tomography (CT) scan and, in several cases, with endorectal ultrasonography. There were 55 men and 30 women, with a median age of 68 years. Patients were retrospectively divided into two groups: group A, which included 40 patients receiving preoperative RT (25 Gy in 5 fractions), followed by surgery within one week, and group B, which included 45 patients with rectal cancer undergoing surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. RESULTS: No postoperative deaths were recorded in either group. In group A, complete pathologic response was observed in 6 (15%) patients and microscopic residual cancer was found in 8 (20%). Low anterior resection (LAR) with total mesorectal excision (TME) was performed in all group A patients, whereas 8 patients in group B underwent abdominoperineal resection (APR) (p < 0.05). Diverting stoma was performed in 7 patients of group A; this was closed 3-6 months later in all cases. Postoperative morbidity was not statistically significant between the two groups (40% versus 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection and delayed ileus was similar. The percentage of major anastomotic leak was also similar in both groups (5 versus 6.6%). CONCLUSION: Short-term preoperative RT in locally advanced rectal cancer does not increase postoperative complications and improves the rate of sphincter-preserving surgery.

Tumor histology and stage but not p53, Her2-neu or cathepsin-D expression are independent prognostic factors in breast cancer patients.

BACKGROUND: Several factors are currently employed for prognosis assessment and treatment determination in breast cancer. An array of molecular parameters, such as p53, Her2-neu (c-erbB 2) and Cathepsin-D, are also examined to improve clinical patient management. We have conducted a statistically powerful study of the prognostic value of conventional factors and of the investigational factors p53, Her2-neu and Cathepsin-D in patients with invasive breast carcinoma, in order to compare their significance. Our analysis was extended to determine the associations of p53 and Her2-neu with risk of death and relapse among patients with and without lymph node metastases. MATERIALS AND METHODS: In a set of 125 primary breast tumors, p53 and Her2-neu expression were immunohistochemically evaluated. Cathepsin-D, estrogen and progesterone receptor concentrations were determined in cytosols by a standard immunoradiometric assay. RESULTS: Over a mean of 62 months, 49 patients (39%) had a relapse and 29 patients (23%) died. Overexpression of p53, Her2-neu and Cathepsin-D was observed in 31%, 46% and 88% of cases, respectively. Overall survival was associated with histology (hazard ratio 0.04, 95% confidence interval: 0.01, 0.49 for lobular tumors) and stage (hazard ratio 5.94, 95% confidence interval: 1.30, 27.15 for stage III samples). Disease-free survival was also related to histology (hazard ratio 0.23, 95% confidence interval: 0.08, 0.73 for lobular tumors) and stage (hazard ratio 4.27, 95% confidence interval: 1.36, 13.36 for stage III tumors). Patients with both negative nodal status and Her2-neu overexpression tended to display an elevated risk of death. CONCLUSION: Our results support the prognostic power of tumor histology and stage and emphasize the need for further studies on the prognostic impact of p53. Her2-neu and Cathepsin-D in breast cancer. Additionally, our analysis indicates that deregulation of Her2-neu might characterize a subgroup of node-negative patients with poor prognosis who could benefit from an aggressive adjuvant therapy.

Ovarian fibrothecoma associated with Meigs' syndrome and elevated serum CA 125.

Meigs' syndrome consists of a benign ovarian tumor accompanied by ascites and hydrothorax. Elevated serum CA 125 in postmenopausal women with a solid adnexal mass, ascites and pleural effusion is highly suggestive of a malignant ovarian tumor. We report on an unusual case of a benign fibrothecoma of the ovary associated with Meigs' syndrome and elevated CA 125 level in an 62-year-old white female. Although rarely, a benign ovarian tumor should be considered in the differential diagnosis of an adnexal mass associated with Meigs' syndrome and elevated serum CA 125 levels.