Interleukin 17 in early invasive breast cancer.

Introduction: Interleukin 17 (IL-17) has a key role in inflammatory responses. Increased serum concentrations of IL-17 have been reported in patients with different types of cancer. Some studies suggest antitumor activity of IL-17 while others speak in favor of its association with poorer prognosis. The lack of data on IL-17 behavior in vivo hinders the efforts to clarify the exact role of IL-17 in breast cancer patients and precludes the usage of IL-17 as potential therapeutic target. Methods: The study included 118 patients with early invasive breast cancer. The serum concentration of IL-17A was measured before surgery and during adjuvant treatment and compared with healthy controls. The correlation of serum IL-17A concentration and different clinical and pathological parameters, including IL-17A expression in the corresponding tumor tissue samples, was analyzed. Results: Significantly higher serum concentrations of IL-17A were found in women with early breast cancer before surgery, but also during adjuvant treatment in comparison to healthy controls. No significant correlation to tumor tissue IL-17A expression was observed. There was a significant postoperative decrease of serum IL-17A concentrations even in patients with relatively lower preoperative values. A significant negative correlation was found between serum IL-17A concentrations and the tumor estrogen receptor expression. Conclusion: The results suggest that the immune response in early breast cancer is mediated by IL-17A, particularly in triple-negative breast cancer. IL-17A-mediated inflammatory response subsides postoperatively, but IL-17A concentrations remain elevated compared to the values in healthy controls, even after the removal of the tumor.

The role of interleukin­7 serum level as biological marker in breast cancer: a cross­sectional, observational, and analytical study.

BACKGROUND: The important role that the immune system plays in malignant diseases is well known. The action of interleukin-7 (IL-7) as a cytokine has been observed in many cellular processes, both in normal cells of the immune system and in some cancer cells. The aim of this study has been to explore whether there is any elevation of interleukin-7 serum levels in early invasive breast cancer (EIBC) patients in comparison with healthy controls. In addition, the correlation between the IL-7 serum level and the histopathological characteristics of the tumor has been evaluated. METHODS: This cross-sectional, observational, and analytical study included 213 consecutive patients with EIBC (113 from Croatia and 100 from Kosovo) and 62 healthy participants as the control group (30 from Croatia and 32 from Kosovo). Blood samples have been taken from patients confirmed with breast cancer (BC) by biopsy, prior to surgical intervention and other oncological treatments, as well as from healthy participants. A serum IL-7 level has been measured, using the "Sandwich" ELISA Immunoenzyme test. In addition, after the surgical intervention, histopathological specimen examinations and immunohistochemistry have been performed and analyzed. The differences in the distribution of the numerical variables have been analyzed with the Mann-Whitney U test and Kruskal-Wallis ANOVA test. Correlations have been tested with Pearson coefficients. A P-value < 0.05 has been accepted as statistically significant. RESULTS: The serum level of IL-7 in EIBC patients was significantly higher than in control cases (P 0.001). Patients with invasive lobular carcinoma (ILC) seem to have a lower IL-7 serum level compared to other histological subtypes, and the difference has been significant (P = 0.043). There has been no correlation between IL-7 serum level and histopathological characteristics of the tumor, with neither age nor menopausal status of the patients. CONCLUSIONS: Noting the significant increase in the IL-7 serum level in the EIBC patients as compared to the healthy control group, the use of IL-7 as a potential diagnostic indicator for BC, as well as in the follow-up of the patients after treatment, can be assumed. The lack of correlation with tumor size, lymph node metastasis, and all other histopathological characteristics of the tumor questions its use as a prognostic indicator.

THE EFFECT OF REGIONAL VS. GENERAL ANESTHESIA ON THE IMMUNE RESPONSE IN BREAST CANCER SURGERY: A NARRATIVE REVIEW OF THE LITERATURE.

For breast cancer patients, surgery remains the cornerstone in treatment. Perioperative and postoperative period is associated with impaired immune function that can have profound implications for cancer patients in terms of tumor recurrence and metastases. The three main factors include surgery and related neuroendocrine stress response, anesthetic drugs, including opioid analgesics and postoperative pain. The most investigated immune cells are natural killer (NK) cells that are affected by both anesthesia and surgery. It has been demonstrated that ketamine, thiopental, volatile anesthetics, fentanyl and morphine, but not propofol, remifentanil or tramadol reduce the number of circulating NK cells and depress their toxicity. The level of NK cells' cytotoxicity is inversely proportional to the stage and spread of cancer. Regional anesthesia and its potential beneficial effects on the perioperative immune response and long-term outcome after surgery has been investigated as an alternative to general anesthesia in patients undergoing breast cancer surgery. In this paper, we present a review of literature aimed to assess the impact of regional anesthesia techniques on the immune response in patients undergoing breast cancer surgery and how it compares to general anesthesia.

PROGNOSTIC VALUE OF TOPOISOMERASE 2-ALPHA AND B-MYB IN EARLY BREAST CANCER TREATED WITH ADJUVANT CHEMOTHERAPY.

Breast cancer is the most common malignancy in females. Despite its well-established prognostic factors, our prognostic ability at an individual patient level remains limited. In this study, the immunohistochemical expression of B-Myb and DNA topoisomerase 2-alpha (Topo2a) was analyzed in primary tumors to identify patients with a higher risk of disease recurrence after adjuvant chemotherapy for early invasive breast cancer. We analyzed a cohort of 215 early invasive breast cancer patients having undergone surgery from 2002 to 2003 at the Zagreb University Hospital Centre, including 153 patients treated with adjuvant chemotherapy. All of them were followed-up prospectively for at least ten years according to routine institutional practice. Statistically significant correlations were found between B-Myb and Topo2a expression levels and particular well-established prognostic factors. B-Myb expression was lower in estrogen receptor (ER)-positive tumors (p=0.0773), whereas larger tumors and those with positive lymphovascular invasion displayed a statistically significantly higher B-Myb expression (p=0.0409 and p=0.0196). Higher tumor grade indicated higher Topo2a values (p=0.0102 and p=0.0069). The subgroup with the expression of both proteins above the median value had an almost statistically significantly (p=0.0613) inferior prognosis compared to the rest of the cohort. Study results showed the B-Myb and Topo2a expression to have a prognostic value in breast cancer patients after adjuvant chemotherapy, which should be additionally explored in future studies in a larger patient cohort.

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.

The Acceptance of Cosmetic Surgery Scale (Acss) and Its Correlations with Psychological Characteristics among the Croatian Population.

BACKGROUND: This study aimed to examine the results of Acceptance of Cosmetic Surgery Scale among the Croatian population and its correlations with other scales and demographic data. SUBJECT AND METHODS: The sample consisted of 420 people who voluntarily filled out an online questionnaire. They completed demographic questions and four scales: Acceptance of Cosmetic Surgery Scale (ACSS), Rosenberg Self-Esteem Scale (RSES), Satisfaction With Life Scale (SWLS), and Body Appreciation Scale-2 (BAS-2). RESULTS: ACSS scale showed five statistically significant differences between genders and a higher overall score in women, but no significant differences were recorded in three ACSS subscales and the overall ACSS score. In contrast to men, women respondents recorded a significant negative correlation between ACSS subscales score (Social, Consider) and BAS-2 and Satisfaction with life score, while a positive correlation was recorded with BMI. CONCLUSION: The ACSS score among the Croatian population was higher than the results among the Italian and Serbian population, and similar to the original American study, which tells us that the Croatian population accepts and considers cosmetic surgery a lot. Furthermore, our results are important for practitioners and patients because they revealed correlations between ACSS scores and the self-thinking scale.

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?

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.

LAPAROSCOPIC APPENDECTOMY DOES NOT INCREASE THE RATE OF NEGATIVE APPENDECTOMY along with a lower rate of perforated appendicitis - RESULTS IN 1899 PATIENTS at Zagreb UHC.

- Laparoscopic appendectomy is the method of choice of many professional societies owing to its many advantages. The question arises whether surgeons urge more easily to laparoscopic exploration due to its less invasiveness, faster recovery and adequate exploration of the entire abdominal cavity than to observation in unequivocal cases. This retrospective analysis (2009-2016) included 1899 patients undergoing laparoscopic (lap) or gridiron intra-abdominal approach treated at Zagreb University Hospital Centre. The analysis included total negative appendectomy, negative-negative appendectomy (normal appendix and no other pathology found), and negative-positive appendectomy (normal appendix but another pathology found) in children (≤16 years) and adults. There was no statistically significant difference in the rates of negative appendectomy (children) - lap vs. open (p=0.24); negative appendectomy (adults) - lap vs. open (p=0.15); negative-negative appendectomy (children) - lap vs. open (p=0.36); negative-negative appendectomy (adults) - lap vs. open (p=0.21); negative-positive appendectomy (children) - lap vs. open (p=0.53); negative-positive appendectomy (adults) - lap vs. open (p=0.56); and laparoscopy group negative appendectomy in children vs. adults (p=0.56). There was a statistically significantly higher perforation rate with the open approach in total (p<0.0001), in children (p<0.0001) and in adults (p=0.02). There was no statistically significant difference between adults and children in the perforation rate with laparoscopic approach (p=0.24) and perforation rate with open approach (p=0.29). Results confirmed that there was no statistically significant difference in the rate of negative appendectomy in all subgroups. It is concluded that laparoscopic appendectomy should be offered as the method of choice in any patient population with suspicion of acute appendicitis.

Quality of Life and Depression Among Female Patients Undergoing Surgical Treatment for Breast Cancer: A Prospective Study.

BACKGROUND: Breast carcinoma is the most common malignant disease in women in the majority of developed countries. The development of depression as well as the quality of life (QoL) in these patients depends not only on the result of oncologic treatment, but on the cosmetic outcome as well. The primary aim of this prospective study was to investigate the changes in QoL and depressive symptoms among patients undergoing surgical treatment for breast cancer. SUBJECTS AND METHODS: We conducted a prospective study that included 100 female patients (mean age 60.26 years) who underwent surgical and oncological treatment for breast carcinoma at the University Hospital Center Zagreb, Croatia. The patients were photographed before and after treatment and were required to fill out a standardized quality of life questionairres QLQ - C30 and QLQ - BR23, Beck Depression Inventory (BDI) and a questionnaire on breast asymmetry. RESULTS: Our results show that patients had significantly higher QoL levels compared with their pre-surgical results. Statistical trend of a lower degree of depression was also observed. A worse cosmetic outcome (i.e., postoperative assymetry) was associated with a lower QoL, but there was no association with depression. Depression was significantly related to the level of pain and lower financial status. CONCLUSION: QoL improved after surgical treatment of breast cancer and was dependant on postoperative asymmetry, whereas the findings for depressive symptoms remained less clear. Future research should investigate more factors that may contribute to the QoL and degree of depression in this patient population.

[CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND FOLLOW-UP OF PATIENTS WITH MELANOMA]. / KLINICKE PREPORUKE HRVATSKOG DRUSTVA ZA INTERNISTICKU ONKOLOGIJU HLZ-A ZA DIJAGNOZU, LIJECENJE I PRACENJE BOLESNIKA/CA OBOLJELIH OD MELANOMA KOZE.

Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma.

Abdominal Wall Defect Reconstructed by Breast Flaps Using a Mercedes Closure Pattern.

BACKGROUND: Surgery of the abdominal cavity may lead to postoperative defects to the ventricular segment of the abdominal wall. The reconstruction of these defects, especially in the area of the median line, represents an issue during the course of healing due to the role of the abdominal cavity in respiratory processes. METHODS: Reconstructive surgical procedure was performed on an infected vast defect to the ventral segment of the abdominal wall in a 77-year-old woman by a modified "Mercedes closure pattern," i.e., by combining three fasciocutaneous flaps: bipedicle flap of the upper segment of the abdominal wall and two sliding breast flaps. RESULTS: Application of a modified complex Mercedes closure pattern was successful and positively affected the redistribution of pressure forces at the places where the edges of the wound were in contact. CONCLUSIONS: The applied and described technique of closing the abdominal cavity decreased the possibility of infection to the prosthetic material, because direct contact between the sutures and the prosthetic no longer existed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[CANCER PATIENTS FOLLOW-UP ­ CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES Part V: melanoma, sarcomas, central nerve system tumors, lung cancer].

Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert's opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures' algorithm in follow­up of oncological patients after primary treatment, in patients with melanoma, sarcomas, central nerve system tumors and lung cancer.

Anatomical Prediction for Surgical Positioning of the Umbilicus in a Croatian Population.

AIM: The umbilicus is an essential esthetic landmark on the abdominal wall in women and men. There are only few models published for predicting exact localization of the umbilicus. The aim of our study was to develop a mathematical model for predicting correct umbilical positioning in a sample of young women and men and in a sample of middle-aged women. In addition, we wanted to develop a predictive model applicable to both sexes. We applied our models with distinct anthropometric characteristics such as body mass index (BMI) and waist circumference (WC)/hip circumference (HC) to further expand our findings. METHODS: In this study, 98 Croatian women and men randomly selected from the University of Zagreb and 46 female patients awaiting abdominoplasty procedure at our institution were included. Anthropometric data and measurements between the umbilicus and fixed bony points around the anterior abdomen were collected. The data collected were body mass (BM), body height (BH), BMI, WC and HC, and waist-hip ratios (WHR). All collected data were subjected to standard statistical analyses. RESULTS: This study developed 2 different regressive equations for the most accurate prediction of exact umbilical localization. In women, the best prediction of the position of the umbilicus was based on the distance from the interanterior hypochondrium line to the umbilicus using the following regressive equation: u-i-hy = BM × 0.5799 + BH × -0.5051 + BMI × -1.8230 + WHR × -10.6364 + 89.6411. In men, the best prediction of the position of the umbilicus was based on the distance from the umbilicus to the interspinous line using the following regressive equation: u-i-is = age × 0.2033 + BM × 0.6445 + BH × -0.5692 + BMI × -2.2802 + WC × -0.0911 + 101.9408. METHODS: We found that age and anthropometric dimensions have a significant influence on the position of the umbilicus on the anterior abdominal wall. The naturally occurring anthropometric variations between women and men made the results of a unique predictive model for umbilical position inaccurate. We found that using 2 distinct predictive models, 1 for both subgroups of women and 1 for men, generated the most accurate predictive results. This quantitative tool should be applied to both women and men for the correct positioning of the umbilicus in reconstructive and esthetic procedures in which the original umbilical location is affected.

Hair transplantation on a free microvascular latissimus dorsi flap: case report.

Large scalp defects can present as a challenging clinical problem for a reconstructive surgeon. We present a patient with a large scalp defect following an infection after neurosurgical treatment. Reconstruction of a defect was performed using a free latissimus dorsi flap with split-thickness skin graft. For achieving good aesthetic result, we transplanted 1000 minigrafts in 3 sessions on the latissimus dorsi flap. In our opinion, hair transplantation on a free microvascular flap is a viable and easy procedure with good aesthetic outcome for treating residual alopecia after reconstructing large scalp defects.

Perforated ascending colon cancer presenting as colocutaneous fistula with abscess to the anterior abdominal wall at the site of a cholecystectomy scar treated with biologic mesh.

Ascending colon cancer as a colocutaneous fistula to the abdominal wall at the site of a previous postoperative scar is extremely rare. A 69 year old male presented with five day history of pain and foul smelling discharge from right subcostal scar from elective cholecystectomy performed 8 years ago. Last three days, he had fever up to 39 degrees C, with mild pain in right upper abdominal quadrant without vomiting, diarrhea, bloody stools or weight loss. Computed tomography, with peroral contrast, revealed extralumination into abdominal wall with several fistulas reaching the skin. Emergency median laparotomy found infiltrating tumor of ascending colon into abdominal wall. A right hemicolectomy and complete thickness abdominal wall excision (7 x 10 cm) was performed. The abdominal wall defect was too extensive for primary closure and two 20 x 20 cm moist gauzes were placed to cover the defect and were fixed with stitches to the skin. On second postoperative day, due to contamination, porcine dermal collagen implant was placed intraperitoneally. Such emergency presentations and therapeutic options are discussed.