Immunohistochemical Expression of Matrix Metalloproteinase-1 and Cyclooxygenase-2 in Cutaneous Squamous Cell and Basal Cell Carcinoma.

The most common nonmelanoma skin cancers (NMSC) are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of NMSC is 18-20 times higher than the incidence of melanoma. The Cyclooxygenase-2 (COX-2) and Matrix Metalloproteinase-1 (MMP-1) enzymes have both been linked to the development of these diseases but their exact significance is unknown. We conducted a retrospective analysis on 148 adult patients with cutaneous BCC and SCC. Cases were divided according to the sub-types of BCC and the degree of SCC differentiation. Immunohistochemical staining for COX-2 and MMP-1 was performed and analyzed to determine if the expression of these biomarkers were associated with BCC subtypes and the degree of SCC. differentiation. We did not find a significant association of the level of differentiation of SCC with the immunohistochemical expression for MMP-1 or COX-2. There was a significant association between BCC subtypes and immunohistochemical expression for MMP-1; positive expression of this enzyme reduces the odds for the infiltrative subtypes by 90%. A marginally significant association between BCC subtypes and immunohistochemical expression for COX-2 was also found. This enzyme was highly expressed in non-infiltrative basal cell carcinoma types (94%) compared with infiltrative types (71%). In conclusion, we did not find a significant predictor for SCC expression levels for either of two biomarkers, while the expression of MMP-1 in BCC was significantly inversely associated with the infiltrative type (moderate sensitivity and high specificity). Further research with larger sample sizes is needed to precisely determine the role these enzymes have in these diseases.

Tattoo Pigment within Regional Lymph Nodes Mimicking Cutaneous Melanoma Metastasis.

Dear Editor, The diagnosis of malignant melanoma accounts for 1-2% of all cancer diagnoses, around 4% of all malignant skin diseases, and 80% of all skin cancer deaths (1). The prognosis depends on several factors including tumor size, Clark level, Breslow thickness, location, ulceration, and presence of metastases. Detection of lymph node metastasis is initially accomplished by clinical examination and by operative evaluation for occult metastasis using sentinel lymph node biopsy (SLNB) when indicated (2). Lymph nodes (LN) with melanoma metastasis may appear normal in early stages, but eventually they become dark, firm, and enlarged (3). In 2017, a 32-year-old female patient was referred to our ward by a dermatologist following a biopsy excision of a nevus under her right breast that tested positive for a cutaneous melanoma grade T2aNx with a Breslow thickness of 1.9 mm, with no sign of ulceration and no history of previous illnesses or chronic diseases. Based on the American Joint Committee on Cancer (AJCC) guidelines, wide excision with a sentinel lymph node (SLN) biopsy was indicated (4). The patient was injected with 0.4 mL CiTc 99m Nanocoll in all four quadrants around the primary scar. A 2 cm wide elliptical excision was performed circumferentially around the scar and to the depth of the muscular fascia of the thorax. With the aid of a gamma probe, a single radioisotope positive lymph node was located in the ipsilateral axilla, but 5 dark pigmented lymph nodes situated behind the SLN were visualized during manual dissection and thought to be consistent with metastatic disease (Figure 1). Due to this new finding, an excisional biopsy of all pigmented nodes was performed. Histology of the excised skin did not demonstrate any further cancerous cells. The size of the SLN was 15 mm, and immunohistochemistry for Melan A was negative for metastatic melanoma. Histological analysis of the darkly pigmented nodes was negative for metastatic melanoma as the pigment was demonstrated to originate from the dermal tattoo on the patient's back that had been removed by dermabrasion 3 years before melanoma development (Figure 2, Figure 3). Dermal tattooing results in initial sloughing of the overlying epidermis, variable dermal inflammation, and gradual assimilation of pigment into macrophages. Much of the pigment is rapidly carried into regional draining LN, which was shown in 2010 on a SKH-1a mouse model, and causes lymphadenopathy which is thought to be a result of local inflammation (6). Importantly, even after removal of the offending cutaneous tattoo the tattoo pigment can persist in draining or distant nodes visible to the naked eye (7). In such cases, LN can mimic metastatic malignant melanoma and may prompt the surgeon to proceed with radical lymph node dissection which may not be necessary. Despite clear guidelines for melanoma treatment in the general population, there are several questions that need to be addressed: firstly, how should a physician approach a patient with unknown history of tattoo removal, a diagnosis of melanoma, and intraoperative darkly pigmented lymph nodes? Secondly, due to the lack of scientific data and treatment protocol, if the SLN is normally colored while other regional nodes are darkly pigmented, what should the treatment plan entail?

The influence of size, depth and histologic characteristics of invasive ductal breast carcinoma on thermographic properties of the breast.

Invasive breast carcinoma is the most common oncologic disease worldwide. The existing diagnostic methods use morphologic changes in the breast to diagnose a carcinoma when it has reached a certain size. Therefore, it is important to augment the morphologic diagnostic examinations with a new method that focuses on characteristics other than morphology such as electromagnetic changes produced by cancer. 50 adult female patients with confirmed ductal carcinoma following a core biopsy due to a suspicious breast mass were included in the study. They underwent breast thermography using a specially designed infrared camera. The data collected was statistically analyzed to determine how the presence of a tumor and its histologic characteristics influence breast thermographic properties. Twenty eight [56 %] patients in the study had an abnormal thermogram. Following statistical analysis, it was found that temperature of the diseased breast was directly correlated to tumor volume [p=0.009] and negatively correlated to depth of tumor [p=0.042]. Tumors that were ER+ and PR+ tumors produced warmer temperatures [p=0.017 and p=0.038 respectively] than tumors without these receptors. HER2 status and Ki-67 index had no statistical correlation with breast temperature. Tumor size, distance from the skin surface and receptor status cause changes in breast thermographic properties. Despite technical advances in the field of thermography, there are still contradictory results associated with thermography. Its diagnostic abilities are generally poorer than conventional methods and its use in breast cancer screening or as an adjunctive tool for diagnostic purposes is not recommended.

Hepatocellular Carcinoma Surveillance-Experience from Croatian Referral Centre for Chronic Liver Diseases.

PURPOSE: For patients at high-risk of developing hepatocellular carcinoma (HCC), biannual ultrasound surveillance has long been recommended, in order to detect the tumor in the early, potentially curative stages. However, globally reported HCC surveillance rates vary greatly, ranging from as low as 1.7 to as high as 80%. Our aim was to assess the utilization of surveillance with biannual ultrasound in high-risk Croatian patients and to identify the factors that impact the implementation of the recommended protocol. METHODS: This retrospective study included 145 newly diagnosed HCC patients in the period from January 2010 to September 2015. We identified low-risk and high-risk patients. The latter were further subdivided into the regular biannual ultrasound surveillance group and the non-surveillance group. The groups were compared according to demographic characteristics and BCLC stage at the time of HCC diagnosis. RESULTS: Among 145 patients, 80 patients were classified as high-risk according to EASL criteria. During the relevant period, 28.7% underwent regular surveillance, while 71.25% did not. Younger patients were more likely to undergo surveillance (OR 0.935 CI 0.874-0.999; p = 0.05). The patients who underwent regular surveillance had a higher chance of being diagnosed at a curative stage (BCLC 0 or A) (OR 3.701 CI 1.279-10.710; p < 0.05).Gender was not a predictor of participation in the regular surveillance protocol. Among the high-risk patients who did not undergo regular surveillance, 56.1% were not aware of the chronic liver disease prior to the HCC diagnosis. CONCLUSION: HCC surveillance is still underutilized in high-risk Croatian patients despite its obvious benefits possibly due to the untimely diagnosis of the chronic liver disease.

Defect Reconstruction of an Infected Diabetic Foot Using Split- and Full-thickness Skin Grafts With Adjuvant Negative Pressure Wound Therapy: A Case Report and Review of the Literature.

INTRODUCTION: Any alteration or impairment to normal wound healing can result in the development of chronic wounds, which may lead to serious complications such as infection and loss of body fluid and proteins. Primary closure alone may not be sufficient to fulfill the criteria of successful defect reconstruction. Therefore, additional procedures such as skin grafting must be considered as an option. CASE REPORT: The case of a 43-year-old woman with diabetes who was admitted to the University Hospital Rebro (Zagreb, Croatia) due to an infected, nonhealing wound on her left foot. Skin grafts combined with negative pressure wound therapy (NPWT) before and after graft application improved wound healing in this patient. CONCLUSIONS: In this patient, the combination of skin grafts with NPWT before and after graft application reduced the comorbidities and complications often seen in the diabetic patient population. Herein, the authors utilized a quicker, cost-efficient, and safer technique of wound closure compared with traditional nonsurgical methods.

Management of a Complex Lower Limb Open Fracture in a Teenage Patient: A Case Report.

The challenges of managing Gustilo IIIB tibial fractures (ie, high energy trauma with a contaminated wound >10 cm in length, severe comminution ["crumbling"] or segmental fractures, and periosteal stripping) in children are unique in part because no clear guidelines exist and the injuries may cause short-term and long-term complications. Repeated wound debridement and secondary reconstruction are required in approximately 20% of these cases in both adults and children. A 13-year-old girl presented with severe polytrauma including an open Gustilo type IIIB fracture of the left lower leg. The patient declined limb amputation; a multidisciplinary team (plastic, pediatric, orthopedic-trauma surgeons, pediatrician, psychiatrist, clinical pharmacologist, anesthesiologist, physiotherapist, nurses) was assembled in order to give the patient the best chance of a successful outcome. Multiple limb salvage and reconstructive procedures including wound debridements, necrectomies, long-term negative pressure wound therapy, soft tissue reconstructions, external bone fixation, bone osteosynthesis, multiple skin grafts, and free-flap reconstruction were provided over a period of 6 months with great success. The patient is doing well 3 years after initial injury and is walking without complications. A multidisciplinary approach and structured treatment plan are important to minimize complications, avoid unnecessary delays in treatment, decrease morbidity, and provide the patient with the best result possible. Studies examining optimal treatment strategies for children and adolescents with these complicated fractures are needed.

A Synchronous Occurrence of Hepatocellular Carcinoma and Echinoccocal Liver Cyst - Can Parasite Promote Carcinogenesis? Literature Review and Classification Proposal.

Concomitant presence of hydatid cyst and hepatocellular carcinoma is a very rare clinical scenario especially in a previously non-diseased liver. Including our case here reported, there are 12 cases of synchronous HCC and hydatid cyst found in the scientific literature and 3 of them were found in a patient with non-diseased liver. We provide detailed review of all reported cases with additional highlights on etiology, pathogenesis, diagnosis, treatment and outcomes of both HCC and echinococcal disease. Although there is a small number of patients, possible relation between these 2 liver lesions should be investigated and standardized classification should be established. This will help us to understand the nature of HCC carcinogenesis, identify diagnostic features of liver lesions and choose the most appropriate type of treatment.

Detection of Epstein-Barr virus in inflammatory pseudotumour of the spleen: a case report.

BACKGROUND: Various types of benign and malignant splenic tumours including hemangiomas, lymphagiomas, hamartomas, hemangiosarcomas, malignant lymphomas and metastatic carcinomas share radiological characteristics making it impossible for a physician to determine the definite aetiology of splenic masses noninvasively without histopathological evaluation. It is important that physicians recognize the importance of a careful and continuous follow-up since inflammatory pseudotumours (IPT) are considered to be tumours with an intermediate malignant potential based on their behaviour when they arise in other locations. METHODS: Our patient, a 60-year-old woman was evaluated using laboratory, gastroscopy, computed tomography and surgical methods. The resected tumour was evaluated using immunohistochemical methods. RESULTS: The patient presented with weight loss, nausea and vomiting, symptoms lasting over a course of a few months. The splenic mass was found incidentally at the time of work up for gastritis and cholelithiasis. Histologically, the tumour differed from typical splenic architecture being composed of atypical spindle cells with inflammatory elements; numerous plasma cells, macrophages, eosinophils and lymphocytes. CONCLUSIONS: Although very difficult to diagnose at initial presentation, it is very important for the physician to be aware of the importance of a careful diagnosis since IPT of the spleen are rare and considered to be tumours with an intermediate malignant potential.

Current trends in breast reduction.

Results of our study describe the long term effects of reduction mammaplasty. Many women with excessively small or large breasts have an altered personal self-image and often suffer from low self-esteem and other psychological stresses. This procedure is designed to reduce and reshape large breasts, and since the size, shape, and symmetry of a woman's breasts can have a profound effect on her mental and physical well-being it is important to observe the patient's long-term outcome. Currently, breast reduction surgery is safe, effective and beneficial to the patient. In Croatia, reduction mammoplasty is often excluded from the general health care plan. The distinction between "reconstructive" versus "cosmetic" breast surgery is very well defined by the American Society of Plastic Surgeons Board of Directors. Unfortunately, the Croatian Health Society has yet to standardize such a distinction. There is an imperative need for evidence-based selection criteria. We retrospectively analyzed data of 59 female patients suffering from symptomatic macromastia who underwent reduction mammaplasty over a 16 year period (1995 until 2011). Our aim was to compare and contrast the various techniques available for reduction mammaplasty and to determine, based on patient outcome and satisfaction, which technique is most suited for each patient. The results of our study generally reinforce the observation that reduction mammaplasty significantly provides improvements in health status, long-term quality of life, postsurgical breast appearance and significantly decrease physical symptoms of pain. A number of 59 consecutive cases were initially treated with the four different breast reduction techniques: inverted-T scat or Wisa pattern breast reduction, vertical reduction mammaplasty, simplified vertical reduction mammaplasty, inferior pedicle and free nipple graft techniques. The average clinical follow-up period was 6-months, and included 48 patients. The statistical analysis of the postoperative patient complications revealed a significant positive relationship in regards to smoking. The majority of these complications were wound related, with no significant relationship between patient complications and variables such as age, BMI, ASA score, resection weight of breast parenchyma, nipple elevation, duration of surgery, and type of pedicle. The higher number of complication correlated with a lower volume of parenchyma resection (rho=-0.321). Overall satisfaction with the new breast size (79%), appearance of the postoperative scars (87%), overall cosmetic outcome score (91%), overall outcome (100%), psychosocial outcome (46%), sexual outcome (85%), physical outcome (88%), satisfaction with preoperative information data (92%), and finally satisfaction with overall care process (96%) was calculated. As expected, the physical symptoms disappeared or were minimized in 88% of patients. Each method of breast reduction has its advantages and disadvantages. The surgeon should evaluate each patient's desires on the basis of her physical presentation. Breast reduction surgery increases the overall personal and social health; not only for the patient, but for their family and friends as well. It is an imperative that every surgeon is aware of this, in order to provide the highest level of care and quality to their patients.