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.

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.

Prognostic importance of steroid receptor status for disease free and overall survival after surgical resection of isolated liver metastasis in breast cancer patients.

PURPOSE: Breast cancer (BC) is the most common malignancy among women, while isolated operable liver metastases (LMs) from BC are very rare and occur in only 1-5% of the patients. Besides, positive steroid receptor (SR) status for oestrogen and/or progesterone is known as a factor which improves disease free survival (DFS) and overall survival (OS). The primary aim of this study was to examine the impact of SR status on DFS and OS after liver metastasectomy in female patients with primary BC. METHODS: We analyzed 32 medical records of female patients diagnosed and treated for primary BC with LMS as the first and only site of disease progression, at the Institute of Oncology and Radiology of Serbia (IORS), during 2006- 2009. All of them underwent primary BC surgery as well as LMs resection. RESULTS: Patients with metachronous BC and LMs and positive SR status in both BC and LM (BC+/LM+) had a median time from BC to LM occurrence (TTLM) of 36 months, compared to BC+/LM- and BC-/LM- subgroups, whose medians for TTLM were 30.5 and 14.5 months, respectively (p<0.01). For all patients, positive SR status showed high correlation with longer DFS and OS after LM resection (medians according survival analysis for DFS/OS in subgroups BC-/LM-, BC+/LM- and BC+-LM+ were 10/19, 25/45, 50/not reached months respectively; p<0.01 for DFS/ OS). Cox regression analysis confirmed that the subgroup of patients with BC-/LM- had 10.8 and 18.8 higher risk of events for DFS (disease relapse or death) and event for OS (death only), respectively, compared to BC+/LM+ subgroup of patients. CONCLUSION: Positive SR status in BC and LM has a high impact not only on time from BC to LM occurrence, but also on longer DFS and OS after LM resection.

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.

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.

The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.

PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma. METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed. RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001). CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

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.

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.

Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.

BACKGROUND: The St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference. In this respect, the authors of this paper have conducted a retrospective analysis of breast cancer subtypes, related to Ki-67 and involvement of the axillary lymph nodes (ALNs). The analysis was performed only in the cases of invasive breast cancer in the pT2 stages. The research and results of the paper have shown that investigating the value of these parameters could be of great benefit in future treatment strategies of invasive breast cancer. METHODS: A retrospective analysis of breast cancer subtypes, tumor nodal metastatic staging, and histopathological grading of 108 cases has been performed according to the methods recommended and provided by the St. Gallen International Expert Consensus Report, 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 108 tumor samples were all investigated by immunohistochemistry according to the methods used to classify breast cancer subtypes as proposed in the St. Gallen Consensus Report, 2011. Invasive breast cancers (n = 108) were immunohistochemically classified as follows: 28 (25.92%) as Luminal A, 51 (47.22%) as Luminal B (HER2 negative), 21 (19.44%) as Luminal B-like (HER2 negative), 2 (1.85%) as HER2 positive, and 6 (5.55%) as being a triple-negative subtype. RESULTS: The conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs. The chi-square test shows the difference to be significant (chi-square = 4.757; P = 0.029). Luminal B subtypes had the highest percentage (54.9%) of involvement of lymph nodes when compared to the other four subtypes. The Luminal B subtype had a higher percentage (51.4%) of involvement of lymph nodes than did Luminal A (10.7%). The chi-square test also shows the difference to be significant (P < 0.05). CONCLUSION: A combination of the Ki-67 index, HER negative tumors, PR negativity, and a low value that can be used to segregate ER positive pT2 tumors into prognostically significantly different clinical outcomes may be utilized clinically to guide patient management in accordance with these tumor characteristics.

Three Cases of Combined Therapy in Primary Breast Lymphoma (PBL) with Successful Outcomes.

Primary malignant lymphoma of the breast is a rare tumor, defined as a tumor localized in the breast with or without axillary lymph-node metastases. Such a tumor is mainly found in female patients and located more frequently in the right breast. It is difficult to make primary breast lymphoma (PBL) diagnosis before operation, and PBL diagnosis is mainly based on pathological biopsy and immunohistochemical staining. In this paper, the cases of three patients who had PBL, and who were treated for it at the Institute for Oncology and Radiology of Serbia between 2008 and 2012, are reviewed and discussed. These cases of PBL had no recorded reoccurrence of the disease and were originally treated by surgery, radiotherapy R-CHOP, and/or chemotherapy. While there is no consensus to the question of how to best treat PBL (ie, with chemotherapy, radiotherapy, or combined therapy), it is hoped that this review will offer insight into successful treatment procedures for tumors of this category.

Rare localisation of breast cancer metastasis to thyroid gland.

INTRODUCTION: Metastases to the thyroid gland are very rare. They are usually seen in malignant melanoma, kidney, breast cancer and lung cancer. CASE REPORT: We presented a 54-years-old female patient with breast cancer diagnosed in 2002. The adequate surgical procedure was done and the tumor and axillary lymph nodes were removed. The patient also received adjuvant postoperative chemotherapy. After seven years of a disease free period, the first relapse of the disease was detected as thyroid gland tumor with axillary lymphadenopathy. The patient had a good response to systemic treatment so the surgical removal of thyroid gland and enlarged lymph nodes was performed. Histopathological analysis confirmed metastasis with breast cancer origin. Radical mastectomy was also preformed. Second relapse of the disease was detected 10 months later, while the patient was on hormonal therapy. It was manifested as the appearance of bone and skin metastases, pleural effusion and lymphadenopathy. CONCLUSION: This case report emphasized the importance of detailed examination of any new onset of thyroid swelling in a patient with previous history of malignancy.

Sentinel lymph node biopsy may be used to support the decision to perform modified radical neck dissection in differentiated thyroid carcinoma.

BACKGROUND: The prognostic significance of lymph node metastases (LNM) in follicle cell-derived differentiated thyroid carcinoma (DTC) is still controversial. The management of cervical lymph nodes varies from "berry picking" to modified radical neck dissection (MRND). The incidence of LNM in papillary thyroid carcinoma varies from 27% to 80%. The importance of sentinel lymph node (SLN) biopsy for decisions about the surgical management of lymph nodes in DTC has been the subject of several previous studies. PATIENTS AND METHODS: In 40 patients with DTC methylene blue dye was applied peritumorally. Both SLN and non-SLN in the lower third of the jugulo-carotid chain were dissected prior to total thyroidectomy and routine dissection of the central neck compartment and examined by frozen-section and standard histology. MRND was performed in 9 cases of LNM in the lateral neck compartment. RESULTS: The SLN identification rate was 92.5%. Metastases in SLNs were revealed by frozen-section histology in 7 cases, leading to immediate MRND. The findings were confirmed on standard HE examination. In 2 false-negative cases SLN metastases were revealed on standard histology and MRND was performed 1 week later. The specificity of the method was 100%, sensitivity 77.7%, negative predictive value 94%, positive predictive value 100%, with overall accuracy of 95%. CONCLUSION: Our results seem to imply that SLN biopsy in the jugulo-carotid chain using methylene blue dye mapping may be a feasible and valuable method for estimating lymph node status in the lateral neck compartment. It may be helpful in the detection of true-positive but nonpalpable lymph nodes, and in such cases may support the decision to perform MRND in patients with DTC.

[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.