Adrenal Cysts: To Operate or Not to Operate?

Adrenal cysts are uncommon and usually asymptomatic, and therefore are usually incidentally discovered adrenal lesions. They have a broad pathohistological spectrum that includes pseudocysts and endothelial (vascular), parasitic, and epithelial (mesothelial) cysts. Although most adrenal cysts are benign and hormonally non-functional lesions, some can have ambiguous imaging appearances and mimic malignant adrenal neoplasms. On the other hand, the actual malignant neoplasms could undergo cystic transformation. Additionally, immune cell infiltrations, thrombosis, or haemorrhage seen in sepsis can frequently cause adrenal cyst development, raising a question about the possible connection between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and adrenal cystic lesions. Due to the disease's rarity, the likelihood of malignancy, and the lack of specific guidelines, the management of adrenal cysts is always challenging especially in a young person. This review discusses the important diagnostic and the current treatment possibilities for adrenal cystic lesions. Aiming to emphasize clinical dilemmas and help clinicians navigate the challenges when encountering a patient with an adrenal cyst in everyday practice, we based our review on a practical question-answer framework centred around the case of a young woman with an incidentally discovered large adrenal cyst.

The impact of different infusion solutions on postoperative recovery following colorectal surgery.

PURPOSE: The purpose of this study was to compare two groups in postoperative recovery, whether there were any complications and whether the length of their hospital stay differed. One group received intraoperatively a combination of crystalloids and a small colloid dose, while the other group received only the crystalloids intraoperatively. METHODS: This randomized prospective study included 80 patients with colorectal cancer prepared for major elective colorectal surgery. The patients were randomly assigned to either the control group (CG) which received only crystalloid solutions intraoperatively or to the research group (RG) which received a combination of colloid and crystalloid solutions. Regional and general endotracheal anesthesia techniques were combined in all patients. Goal-directed fluid therapy was administered to patients in both groups. After extubation, patients were transferred in the Intensive Care Unit (ICU). We measured the administered fluids, fluid balance, the volume of received red packed cells (RPC) and fresh frozen plasma (FFP). Recorded were the first bowel movement, the first flatus, the tolerance on oral food, complications by Clavian-Dindo classification, days of patient's recovery delay in the ICU, Surgery Department (SD) and the total length of hospital stay (LOS). RESULTS: Statistically significant differences were present in all parameters of postoperative recovery. RG patients showed better results relative to the CG patients. RG patients were faster in restoring bowel movement and peristalsis, get the first postoperative stool and re-acquire oral food tolerance. According to the Clavian-Dindo classification of complications, no significant difference between these two groups was noted. CONCLUSIONS: Goal-directed colloid-crystalloid therapy significantly improved postoperative recovery.

Goblet cell carcinoid of the appendix. Review of the literature a propos of a rare case of endometrial metastases.

BACKGROUND: Carcinoid tumors are rare tumors most commonly found in the gastrointestinal tract. They represent the most common malignancies of the appendix. As a distinct entity from both adenocarcinomas and carcinoids, Goblet cell carcinoid (GCC) was initially described in the literature in 1969. The GCC is almost exclusive to the appendix, but rarely can be found in rectum, ileum and colon. More than 50% of the patients at the time of diagnosis already have advancedstage disease. The most common metastatic sites are the peritoneal surfaces of the pelvis and abdominal cavity, and ovaries in women. Surgery is the main form of treatment in patients with GCC. CASE PRESENTATION: A 49-year-old woman was treated at the Institute of Oncology and Radiology of Serbia with histopathological findings of GCC. In a 8-year period the patient was treated with initial appendectomy and three more operations because of locoregional disease progression. The last operation was performed in March 2016 because of endometrial metastases. Since then the patient is on regular follow up without disease progression. CONCLUSION: GCC is a very rare entity. Multidisciplinary approach is necessary for adequate patient treatment.

Treatment outcome in patients with breast conserving surgery after neoadjuvant therapy for breast carcinoma - a single institution experience.

PURPOSE: The aim of this study was to analyze outcomes of breast conserving surgery (BCS) after neoadjuvant treatment (NAT) in comparison to radical mastectomy (RM) after NAT in terms of disease-free survival (DFS), overall survival (OS) and patients' satisfaction with the esthetic outcomes of surgery. METHODS: This prospective study was conducted at the National Cancer Research Center of Serbia, Belgrade, from January 1st 2011 to December 31st 2015, on breast carcinoma patients receiving NAT. Treatment outcome was assessed by MDAPI (MD Anderson Prognostic Index). Female patients (n=52) with satisfactory clinical response to NAT and MDAPI scores 0 or 1 were included into the treatment group (NAT-BCS group). The control group (NAT-RM group) consisted of patients (n=52) with poorer clinical response and MDAPI scores 2 to 4. On check-ups, local or distant relapses were noted and both groups were asked to value their satisfaction with the esthetic outcomes of surgery using the Likert scale. RESULTS: OS was 100% in both groups. DFS was 96.1% in NAT-BCS group and 100% in NAT-RM group. Local recurrences were observed in two patients from the age group ≥60 years, with initial disease stage IIIA and "clear" resection margins on frozen section study. Patients in the NAT-BCS group were more satisfied with the esthetic outcome of surgery than the control group. CONCLUSIONS: BCS after NAT provides good esthetic outcome and is oncologically safe if adequate clinical response is achieved after NAT and if established criteria for patient selection are followed.

A Prospective, Randomized, Phase III Study to Evaluate the Efficacy and Safety of Fibrin Sealant Grifols as an Adjunct to Hemostasis as Compared to Cellulose Sheets in Hepatic Surgery Resections.

BACKGROUND: Local hemostatic agents have a role in limiting bleeding complications associated with liver resection. METHODS: In this randomized, phase III study, we compared the efficacy and safety of Fibrin Sealant Grifols (FS Grifols) with oxidized cellulose sheets (Surgicel®) as adjuncts to hemostasis during hepatic resections. The primary efficacy endpoint was the proportion of patients achieving hemostasis at target bleeding sites (TBS) within 4 min (T4) of treatment application. Secondary efficacy variables were time to hemostasis (TTH) at a later time point if re-bleeding occurs and cumulative proportion of patients achieving hemostasis by time points T2, T3, T5, T7, and T10. RESULTS: The rate of hemostasis by T4 was 92.8% in the FS Grifols group (n = 163) and 80.5% in the Surgicel® group (n = 162) (p = 0.01). The mean TTH was significantly shorter (p < 0.001) in the FS Grifols group (2.8 ± 0.14 vs. 3.8 ± 0.24 min). The rate of hemostasis by T2, T5, and T7 was higher and statistically superior in the FS Grifols group compared to Surgicel®. No substantial differences in adverse events (AE) were noted between treatment groups. The most common AEs were procedural pain (36.2 vs. 37.7%), nausea (20.9 vs. 23.5%), and hypotension (14.1 vs 6.2%). CONCLUSIONS: FS Grifols was safe and well tolerated as a local hemostatic agent during liver resection surgeries. Overall, data demonstrate that the hemostatic efficacy of FS Grifols is superior to Surgicel® and support the use of FS Grifols as an effective local hemostatic agent in these surgical procedures.

Hemodynamic stability achievement by application of goal directed fluid therapy with different infusion solutions in colorectal surgery.

PURPOSE: To determine whether there was a correlation between the type of administered infusion solutions intraoperatively with the quantity of administered infusion solutions, differences in values of cardiac output (CO) and cardiac index (CI) and need to use vasopressors and inotropes, between control and research groups. METHODS: This randomized prospective study included 55 patients with colorectal cancer. Subjects in the control group received only crystalloid solutions intraoperatively and postoperatively. The patients in the research group received a combination of colloid in dosage of 10mg/kg and crystalloid solutions. Patients in both groups were given goal directed fluid therapy. RESULTS: The control group received a significantly larger amount of crystalloid solution per kg of body weight during the entire surgical operation, in comparison with the volume of crystalloids in the research group (mean±SD 50.78±28.13 vs. 31.63±25.60 respectively, p=0.01). During the first hour of the surgery, the control group received a larger quantity of fluid in comparison with the research group (mean±SD 31.14±9.78 vs. 22.17±9.92 respectively, p=0.001). From the beginning of anesthesia until 6th postoperative hr the values of CI were significantly higher in the research group in comparison with the control group. CONCLUSIONS: Goal directed fluid therapy with colloids, followed by crystalloids during surgery, decreased the total intraoperative fluid volumes, and provided higher values of CI intraoperatively which were also maintained postoperatively.

Hyperthermic intrathoracic chemotherapy (HITHOC) in ovarian carcinoma - a propos of a case.

A female patient aged 42, started chemotherapy for advanced ovarian carcinoma in June 2016. Considering intraoperative findings, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) were performed, followed by adjuvant chemotherapy. In March 2018, computed tomography (CT) examination showed disease progression in the form of pleural carcinomatosis with increased levels of tumor markers. In April 2018, total parietal pleurectomy, partial visceral pleurectomy, and then hyperthermic intrathoracic chemotherapy (HITHOC) with cisplatin were performed. The procedure was uneventful, as was the postoperative course. The patient was discharged on the 13th postoperative day with no major postoperative complications. Three months after surgery, CT showed no signs of disease relapse. Since this is a relatively new method of treating pleural carcinomatosis, real results are to be expected with larger series of patients and longer postoperative follow-up.

Immunohistochemical study of cyclin A and p16 expression in patients with renal cell carcinoma.

PURPOSE: Renal cell carcinoma (RCC) is the most common malignant kidney tumor in adults. Dysregulation of the cell cycle can lead to cancer development. In this study, the mitosis-associated cyclin A and p16, a negative controller, were investigated as potential key points in the RCC development. METHODS: This retrospective study included 74 patients with RCC. The expression of cyclin A and p16 and their correlation to histopathological parameters (TNM stage, histological subtype, nuclear grade, tumor size), gender, age, and clinical outcome were studied and analyzed. RESULTS: The highest median value for cyclin A (40%; range 0-70)) and for p16 (57.5%); range 35-80) were found in the papillary histological subtype. Survival analysis showed that in the group of patients that had died before September 2015, the median value for cyclin A was 20% (range 0-60), which was significantly higher than 5% (range 0-70), found in the group of patients that survived (p=0.019). CONCLUSIONS: In relation to the histological subtype, the papillary type of RCC was associated with a significantly higher expression of cyclin A and p16 compared to other subtypes of RCC. High expression of cyclin A indicated worse prognosis, therefore cyclin A could be considered to be a significant prognostic marker.

Prognostic factors and outcomes of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer - A single tertiary institution experience.

PURPOSE: Ovarian cancer (OC) ranks fifth in mortality among females cancer patients. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have radically changed the treatment of OC. The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in our patient population after the application of combined CRS and HIPEC treatment. METHODS: The study included patients who met defined inclusion and exclusion criteria and had undergone CRS of peritoneal carcinomatosis from 2006 to 2011. Tumor extension was intraoperatively calculated using peritoneal cancer index (PCI). After CRS had been performed, selected patients underwent closed HIPEC. Assessment of successful surgery was estimated with the completeness of cytoreduction score. RESULTS: The study involved 31 patients. The median DFS was 19 months. The DFS for 1 and 2-year period were 69.2 and 35.2%, respectively. The mean OS was 51 months. The 1-, 2- and 5-year OS was 85.4, 63.3 and 56.3%, respectively. PCI ranged from 1 to 24 and the majority (77.4%) of the patients had PCI score below 13. The most frequent carcinomatosis was observed in the omentum (80.6%), followed by adnexae (61.3%), uterus (58.1%), colon (58.1%). spleen (25.8%), diaphragm (25.8%), small intestine (19.4%), bursa omentalis 19.4, liver (9.7%), and pancreas (3.2%). CONCLUSION: The results of the current study are in concordance with the literature which clearly favors combined the CRS and HIPEC treatment. The reported data suggest that this method could be successfully applied in our region and outline the necessity of future multicentric studies that will involve major regional hospitals.

Diabetes mellitus and coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries.

BACKGROUND AND AIM: Coronary flow reserve is impaired in asymptomatic patients with aortic stenosis and has a prognostic value. We investigated whether the type II diabetes mellitus additionally impairs microvascular circulation assessed by coronary flow reserve in patients with asymptomatic severe aortic stenosis, normal left ventricular ejection fraction and nonobstructed coronary arteries. METHODS: A total of 128 patients, mean age of 66.35 ± 10.51 (58.6% males), with severe aortic stenosis and normal left ventricular ejection fraction were enrolled in this study. Patients with diabetes mellitus, those who were treated for diabetes mellitus or had documentation confirming the diagnosis of diabetes mellitus, were considered. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter), standard transthoracic Doppler-echocardiographic study and adenosine stress transthoracic echocardiography for coronary flow reserve measurement. RESULTS: Diabetes mellitus was present in 26 patients (20.31%). There was no significant difference in aortic stenosis severity between diabetic and non-diabetic patients [aortic valve area (0.81 ± 0.18 vs 0.85 ± 0.15 cm(2)) and Vmax (4.20 ± 0.57 vs 4.21 ± 0.48 m/s)]. Mean coronary flow reserve in diabetic patients was 1.98 ± 0.48, while mean coronary flow reserve in non-diabetic patients was 2.64 ± 0.54 (p < 0.01). Diabetes mellitus was independent predictor of coronary flow reserve [B = -0.636, 95% confidence interval (-0.916 to -0.368), p < 0.001]. CONCLUSION: Diabetes mellitus additionally impairs coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries.

Inflammatory cytokines prime adipose tissue mesenchymal stem cells to enhance malignancy of MCF-7 breast cancer cells via transforming growth factor-ß1.

Mesenchymal stem cells from human adipose tissue (hASCs) are proposed as suitable tools for soft tissue engineering and reconstruction. Although it is known that hASCs have the ability to home to sites of inflammation and tumor niche, the role of inflammatory cytokines in the hASCs-affected tumor development is not understood. We found that interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro. IFN-γ and/or TNF-α-primed hASCs produced conditioned media (CM) which induced epithelial to mesenchymal transition (EMT) of MCF-7 cells by reducing E-Cadherin and increasing Vimentin expression. Induced EMT was accompanied by increased invasion, migration, and urokinase type-plasminogen activator (uPA) expression in MCF-7 cells. These effects were mediated by increased expression of transforming growth factor-ß1(TGF-ß1) in cytokines-primed hASCs, since inhibition of type I TGF-ß1 receptor on MCF-7 cells and neutralization of TGF-ß1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFN-γ and/or TNF-α primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-ß1-Smad3 signalization, with potentially important implications in breast cancer progression.

Case with triple-negative breast cancer shows overexpression of both cFOS and TGF-ß1 in node-positive tissue.

We present herein a case report style article on a rare advanced triple-negative breast cancer (TNBC) patient with 6-month disease-free interval, and 10-month overall survival. Our results demonstrate that the poor clinical outcome of this patient was associated with pronounced, more than fivefold higher, overexpression of both cFOS and TGF-ß1 proteins in its metastatic nodal tissue extracts, when compared with the values of the two non-TNBC controls (with 'zero' disease-free interval and overall survival). This original observation suggests, for the first time, that both the cFOS and TGF-ß1 may be considered as a pair of biomarkers for an early assessment of poor prognosis for TNBC patients. The possible clinical implication of this observation is discussed.

Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?

PURPOSE: To evaluate the accuracy of intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLNs) mapped using methylene blue dye (MBD) and its usefulness for selecting patients with breast carcinomas and positive axillary lymph nodes (ALNs) for one-time axillary dissection. METHODS: 152 female patients with T1/T2 breast carcinomas and clinically negative ALNs were selected for mapping using MBD (1%) from October 2010 to December 2011. Patients underwent FSA of mapped SLNs and ALN dissection. The accuracy of SLN-FSA was tested by comparing these findings with the definite histopathology (HP) of SLNs, as well as of other ALNs. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: There was a 98%-match between FSA and definite HP findings of SLNs, suggesting high accuracy of FSA in this series. None of 3 patients with false-negative SLNs on FSA had additional axillary nodal metastases. One out of 20 (5%) patients with metastases in other ALNs had "clear" SLNs, both on FSA and definite HP (false-negative). Accuracy reached 94.1%. CONCLUSIONS: SLN-FSA enables adequate selection of patients for one-time axillary node dissection. MBD mapping technique is cheap, feasible and enables easy and precise detection of the first draining ALNs. Using FSA of SLNs mapped with MBD, patients with breast carcinoma benefit from complete surgical treatment during one hospitalization, the risk of undergoing anaesthesia twice is reduced, as well as the treatment cost, which is important in developing countries.

Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy: a single institution experience.

PURPOSE: The aim of this research was to examine overall (OS) and disease-free survival (DFS) in patients with colorectal peritoneal carcinomatosis (CRC-PC), treated with cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), as well as to analyse factors of prognostic significance. METHODS: We included 61 patients with pathological/and computerized tomography (CT) confirmation of CRC-PC, treated with CRS+HIPEC from 2005 to 2012. Peritoneal Cancer Index (PCI) score was used for quantitative assessment of the CRC-PC extent. We performed CRS following the Sugarbaker's principles in all patients with PCI ≤20 and only in 3/61 (4.92%) patients with PCI >20. HIPEC (oxaliplatin 410 mg/m(2) in 2000mL isotonic solution and 41?C) was performed using RanD Performer® HT perfusion system during 30-60 min. Cox proportional hazard regression was used to determine significant factors for OS and DFS. RESULTS: The follow-up ranged from 1 to 83 months (median 22). Median OS was 51 months (95% confidence interval/ CI 22+). Median DFS for patients without residual disease (57/61, 93.44%) was 23 months (95% CI 16+). One-, 2- and 6-year OS (DFS) were 78.6% (68.3%), 58.7% (46.7%) and 50.5% (38.1%), respectively. By the end of the study, 55.74% of the patients were still alive. Cox multivariate analysis indicated PCI score as a parameter of highly prognostic significance for patients treated with CRS+HIPEC (p<0.001). Patients with PCI (13 (vs PCI ≥13) had significantly longer OS and DFS (p<0.001), also confirmed for PCI subcategories (PCI <7 vs 7≤ PCI <13 vs PCI ≥13). All patients with PCI <7 are still alive. CONCLUSION: Our study indicates that CRS+HIPEC significantly improves the survival of CRC-PC patients. This treatment modality should be considered as the most suitable in well-selected patients with this disease.

Characteristics of human adipose mesenchymal stem cells isolated from healthy and cancer affected people and their interactions with human breast cancer cell line MCF-7 in vitro.

Adipose tissue is an attractive source of mesenchymal stem/stromal cells (MSCs) with potential applications in reconstructive plastic surgery and regenerative medicine. The aim of this study was to characterise human adipose tissue MSCs (ASCs) derived from healthy individuals and cancer patients and to compare their interactions with tumour cells. ASCs were isolated from adipose tissue of healthy donors, breast cancer-adjacent adipose tissue of breast cancer patients and tumour-adjacent adipose tissue of non-breast cancer patients. Their proliferation, differentiation, immunophenotype and gene expression were assessed and effects on the proliferation of human breast cancer cell line MCF-7 compared. ASCs from all sources exhibited similar morphology, proliferative and differentiation potential, showing the characteristic pattern of mesenchymal surface markers expression (CD90, CD105, CD44H, CD73) and the lack of HLA-DR and hematopoietic markers (CD11a, CD33, CD45, Glycophorin-CD235a), but uneven expression of CD34. ASCs also shared a common positive gene expression of HLA-DR, HLA-A, IL-6, TGF-ß and HIF-1, but were negative for HLA-G, while the expression levels of Cox-2 and IDO-1 varied. All ASCs significantly stimulated the proliferation of MCF-7 tumour cells in direct mixed co-cultures and transwell system, although their conditioned media displayed antiproliferative activity. Data obtained showed that ASCs with similar characteristics are easily isolated from various donors and sites of origin, although ASCs could both suppress and favour tumour cells growth, emphasising the importance of cellular context within the microenvironment and pointing to the significance of safety studies to exclude any potential clinical risk of their application in regenerative medicine.

Quantification of transforming growth factor beta 1 levels in metastatic axillary lymph node tissue extracts from breast cancer patients: a new specimen source.

OBJECTIVE: To use cytoplasmic tissue extract as a new specimen source to quantify transforming growth factor beta 1 (TGFbeta1) protein in metastatic axillary lymph node tissue (ALNT) of breast cancer (BC) patients and to confirm the feasibility of this approach in a prospective pilot study on a subgroup of patients with invasive BC. STUDY DESIGN: The 6 selected malignant and autologous nonmalignant pairs of ALNT were fractionated, under special preanalytical, nonaggressive/nondenaturing conditions, to obtain respective cytoplasmic extracts for TGFbeta1 detection by the Quantikine (R&D Systems Inc., Minneapolis, Minnesota, U.S.A.) enzyme-linked immunosorbent assay kit. RESULTS: The data indicated a highly significant (r = 0.973054) positive linear correlation between the TGFbeta1 concentration and total protein concentration in cytoplasmic extract of metastatic ALNT. The subsequent patients' pilot study, performed strictly before any clinicopathologic factors were accessible, revealed significantly (p < 0.01) elevated TGFbeta1 in malignant ALNT (median value: 1.05 ng/mg protein, range: 0.67-3.6 ng/mg protein, n = 6) vs. autologous nonmalignant ALNT controls (median value: 0.48 ng/mg protein, range: 0.29-0.90 ng/mg protein, n = 6). This elevation was correlated with the number of metastatic axillary lymph nodes with respect to the total and was consistent with an increase in size of tumor deposits in axillary lymph nodes. CONCLUSION: Our data provide for the first time suggestive evidence that the TGFbeta1 level in cytoplasmic extracts of metastatic ALNTs may be a promising biomarker of invasiveness for BC patients. Confirmatory, large-scale studies are needed to evaluate possible implications of this putative biomarker in BC diagnosis and treatment.