Li-Fraumeni Syndrome With Six Primary Tumors-Case Report.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with a high, lifetime risk of a broad spectrum of cancers caused by pathogenic germline TP53 mutations. Numerous different germline TP53 mutations have been associated with LFS, which has an exceptionally diverse clinical spectrum in terms of tumor type and age of onset. Our patient has developed six asynchronous tumors to date: a phyllode tumor of the breast, a pheochromocytoma, a rosette-forming glioneuronal tumor (RGNT), an adrenocortical carcinoma (ACC), a ductal carcinoma of the breast, and a thymoma. The occurrence of such a number of rare tumors is sporadic even among in the population of patients living with cancer predisposition syndromes. In this instance, the omission of pretest genetic counseling and thorough family tree analysis prior to selecting the test led to the oversight of an underlying TP53 likely pathogenic mutation (classified as Class 4). This emphasizes the necessity for such counseling to prevent overlooking crucial genetic information. Neglecting this step could have had profound implications on the patient's treatment, particularly considering the early onset and occurrence of multiple tumors, which typically raise suspicion of a hereditary component. The implications for family members must be considered.

Sentinel lymph node biopsy in clinically node negative patients with papillary thyroid carcinoma.

PURPOSE: The incidence of histologically proven lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) reaches 80%. According to different guidelines surgical management in clinically N0 (cN0) patients with PTC remains controversial. The purpose of this study was to investigate if sentinel lymph node biopsy (SLNb) using methylene blue dye is accurate in the detection of LNM in the lateral neck compartment in cN0 patients with PTC. METHODS: Enrolled were 153 cN0 patients with PTC. All underwent total thyroidectomy with central neck dissection and SLNb in the lateral neck compartment, using methylene blue dye as marker. Selective modified radical neck dissection was performed in cases of metastatic SLNs. RESULTS: Neck LNMs were histologically verified in 40.9% of the cases. Predictive factors for LNM were: males, younger than 45 years, tumors greater than 1cm, capsular and vascular invasion. The central neck compartment of LNM was predictive for lateral LNM in 80.5% of the cases. LNM were confirmed in 24% of SLNs in the lateral neck compartment, which were over 56% predictive of LNM to other dissected lateral LN. SLN identification rate (IR) was 91.8%. Sensitivity, specificity, positive value (PPV) and negative predictive value (NPV) were 85.7, 96.7, 88.3 and 95.9%, respectively. The overall accuracy of the method was 94.3%, with probability of 91.2% (ROC AUC, 95% CI; 84.2-98.3). CONCLUSION: The proposed method of SLN biopsy using methylene blue dye is feasible, safe and accurate in the detection of LNM in the lateral neck compartment and may help in the decision to perform selective modified radical neck dissection in cN0 patients with PTC.

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.

Multifocality as independent prognostic factor in papillary thyroid cancer - A multivariate analysis.

PURPOSE: The incidence of multifocality of papillary thyroid carcinoma (PTC) ranges from 18 to 87.5% The mechanisms of multifocal spreading, correlation with tumor size, histology variants of PTC, lymph node metastases, and prognostic impact remains unclear. The purpose of this study was to clarify the prognostic significance of multifocality on relapse and survival rates of patients with PTC by analyzing the correlation of multifocality with patient age, gender, tumor size, histological variants of PTC, presence of lymph node metastases and extent of surgery. METHODS: 153 patients with PTC were included in this study. Patients with pT4 tumors or initially distant metastases were excluded from study. Total thyroidectomy was done in all 153 patients. Central and level III and IV lateral neck lymph node dissection was done in 76.5% of the patients, followed by modified radical neck dissection if positive. RESULTS: Multifocality was found in 43 (28%) whole thyroid gland specimens, and was significantly more frequent in patients older than 45 years and in tumors greater than 4 cm in diameter (p<0.01). Presence of multifocality didn't significantly correlate with gender, histology variants of PTC or lymph node metastases. In a median follow up of 84 months locoregional relapse occurred in 8.4% and 1.3% of the patients, while 7.2% patients died due to PTC. The incidence of relapse was significantly higher (p<0.01), and relapse free interval and survival were significantly shorter (p=0.0095, p=0.0004, respectively) in patients with multifocal PTC. Cox multivariate regression analysis showed that multifocality was independent prognostic factor for both disease-free interval (DFI) and cancer-specific survival (CSS) of patients with PTC. CONCLUSION: Due to high incidence of multifocality and potential prognostic impact, total thyroidectomy should be advocated in all patients with PTC, aiming to reduce relapse rate and improve DFI and CSS.

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.

Predictors of sentinel lymph node status of cutaneous melanoma in Serbian patients.

PURPOSE: Presence of metastasis in sentinel lymph node (SLN) is considered to be the most important factor in terms of patient survival. The main aim of this study was to identify predictors of positive SLN in Serbian patients with melanoma. METHODS: This retrospective study was conducted on 147 patients. Univariate chi-square and univariate logistic regression analyses were used to identify the association between prognostic factors and positive SLN. Receiver Operating Characteristics (ROC) was conducted to find the Breslow thickness cutoff point at which to perform SLN biopsy (SLNB). Kaplan-Meier analysis was used to evaluate disease-free survival (DFS), and log rank test was applied to compare differences between groups. RESULTS: Breslow thickness and Clark level (p≤0.05), presence of ulceration and a high mitotic rate (>6 mitoses/mm2) (p<0.001) were significant independent predictors of SLN metastasis. ROC curve showed that Breslow thickness of 2.8 mm was the most suitable cutoff point for SLN positivity (sensitivity 86%, specificity 67%). Furthermore, Breslow thickness and presence of ulceration were found to be associated with DFS (p<0.05). CONCLUSIONS: Patients with Breslow thickness ≥2.8 mm, ulceration, and high mitotic rate are at higher risk for SLN metastasis. In addition, high Breslow thickness and presence of ulceration are associated with decreased DFS. These results indicate that multiple selection criteria should be used when performing and predicting SLN metastasis and disease recurrence.

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.

Factors related to local recurrence of non small cell lung cancer and its operability.

PURPOSE: To analyze the correlation of primary tumor (PT) pathological characteristics (size, stage, type and grade) and the extent of initial surgical treatment of non small cell lung cancer (NSCLC) with the incidence and time to local recurrence (LR) and disease-free survival (DFS), as well as to determine in what way these parameters and LR localizations affect the possibility for surgical retreatment. METHODS: The research was conducted on 114 patients with NSCLC and LR that had initial surgery in two reference institutes in Serbia from January 2002 to December 2010. PT size and disease stage were defined according to the revised 2004 WHO classification. PTs were grouped by size into 3 categories. Due to great diversity, surgical procedures were sorted into 6 operation types. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analyses showed significant difference in DFS and LR reoperability that were related to PT size, disease stage and the extent of initial surgery. LR localization on the chest wall was favorable for secondary surgery due to LR. CONCLUSIONS: Squamous cell lung carcinoma relapses locally more frequently than other lung tumor types, and the commonest LR site is the chest wall. This localization provides high possibility for surgical retreatment. Adequate staging, proper indications for surgical treatment and quality surgery provide longer DFS in patients with NSCLC. All these suggest that the surgeon may be considered as the most significant factor of prognosis.

Correlation of tumor size as independent factor and disease stage with local recurrence of non-small cell lung carcinoma and its operability.

PURPOSE: To analyze the correlation of non-small cell lung carcinoma (NSCLC) primary tumor size, independently, and the initial disease stage with the incidence of local recurrence (LR) and disease-free survival (DFS), as well as the LR operability. METHODS: The research was conducted on 114 patients operated due to NSCLC at the Institute for Lung Diseases of the Clinical Center of Serbia and the Institute for Oncology and Radiology of Serbia from January 2002 to December 2010, who developed LR during the 5-year follow-up. Diagnostic methods and surgical approaches were standard, defined by protocols. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analysis showed significant difference in DFS and LR incidence in first 2 postoperative years related to primary tumor size and stage. Patients with T1 tumors (vs T2 vs T3), as well as in earlier disease stage, had significantly longer DFS. LR in the first and second year after primary tumor operation occurred more frequently with larger primary tumors. Significant correlation was registered between LR operability and primary tumor size, as well as LR operability and primary tumor stage. CONCLUSIONS: This research highlights size of the primary tumor as independent prognostic factor for patients with NSCLC. The likelihood of LR increases with larger primary tumor and higher primary tumor stages, while DFS decreases. Because larger tumors are more frequently understaged, with occult mediastinal metastases, their LR is not possible to be surgically treated.

[Treatment of postoperative pain in elderly oncology patients with intravenous administration of a 50% glucose solution]. / Lecenje postoperativnog bola u starih onkoloskih pacijenata intravenskom primenom 50% rastvora glikoze.

Postoperative pain is the most important factor od so called "tumor-promotive effect of surgery" i.e. of endocrine-metabolic changes having the consequence drop in immune, antiinfective and antitumor defense. Due to presence of organic involutive changes, old people (= 65 years), often have serious side effects during application of usual analgetics. Since hypertonic glucose (33%) given i.v. or per os, works analgesically in small children there is assumption that it can be used in treatment of postoperative pain in old oncology patients. We tested the hypothesis that postoperative pain in old oncology patients can be treated with i.v. application of 50% of glucose solution. 37 oncology patients over 65 years, 26 females and 11 males, operated for breast cancer and soft tissue cancer, were investigated. Average age of the patients was 72 +/- 4 years. 50% Glucose solution was given in two boluses of 20 ml each: the first bolus was given to all patients at the end of anesthesia, and the other bolus was given individually after appearance of post-operative pain. Pain intensity (in coefficients of the visual analogue scale VAK = 1-100) and its characteristics were tested by oral testing of operated patients; after weakening from anesthesia, after the first appearance of the pain and 15 minutes after giving of the second glucose bolus. None patient had pain weakening from anesthesia. All tested patients experienced pain during the first 70 minutes and it could be categorized as very strong pain (= 82 VAK). The pain was decreased with another glucose bolus by approximately (= 56% VAK) so it was classifies in category of bearable pains (= 36 VAK). In 9 patients (24.3%) the pain had neuropathic component (filing of "burning") which could not be eliminated by hypertonic glucose, but only with application of tramadol. Activation of the central cholinergic transmission is the most significant mechanism of analgesic glucose effect, but, probably there is another one: facilitation of entrance of formerly given analgesics in the brain cells. As energetic substrate, entering all organism cells, glucose could make easier intracell breakthrough of any other analgesic drug, of the peripheral or central action, and final antipain effect could be potential or additional one. It was concluded that 40 ml of 50% glucose solution given in two identical boluses, has good analgesic effect in treatment of postoperative pain in old oncology patient: the pain was not completely eliminated, but it was significantly decreased and became tolerable. Hypertonic glucose neither eliminates, nor decreases neuropathic component of the pain, so, when the pain appears the therapy should be supplemented with other drugs, which may completely eliminate all pain components.