Design, synthesis, and biological studies of the new cysteine-N-arylacetamide derivatives as a potent urease inhibitor.

Inhibition of Helicobacter pylori urease is an effective method in the treatment of several gastrointestinal diseases in humans. This bacterium plays an important role in the pathogenesis of gastritis and peptic ulceration. Considering the presence of cysteine and N-arylacetamide derivatives in potent urease inhibitors, here, we designed hybrid derivatives of these pharmacophores. Therefore, cysteine-N-arylacetamide derivatives 5a-l were synthesized through simple nucleophilic reactions with good yield. In vitro urease inhibitory activity assay of these compounds demonstrated that all newly synthesized compounds exhibited high inhibitory activity (IC50 values = 0.35-5.83 µM) when compared with standard drugs (thiourea: IC50 = 21.1 ± 0.11 µM and hydroxyurea: IC50 = 100.0 ± 0.01 µM). Representatively, compound 5e with IC50 = 0.35 µM was 60 times more potent than strong urease inhibitor thiourea. Enzyme kinetic study of this compound revealed that compound 5e is a competitive urease inhibitor. Moreover, a docking study of compound 5e was performed to explore crucial interactions at the urease active site. This study revealed that compound 5e is capable to inhibit urease by interactions with two crucial residues at the active site: Ni and CME592. Furthermore, a molecular dynamics study confirmed the stability of the 5e-urease complex and Ni chelating properties of this compound. It should be considered that, in the following study, the focus was placed on jack bean urease instead of H. pylori urease, and this was acknowledged as a limitation.

Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase.

α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a-n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC50 values in the range of 49.0-668.5 µM were more potent than standard inhibitor acarbose (IC50 = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (Ki = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic.

Accuracy of fine-needle aspiration cytopathology to differentiate malignant and benign thyroid nodules with ≥4 cm diameter: A retrospective study.

BACKGROUND: Thyroid nodules (TN) are commonly present in the general population and are usually pathologically benign. An initial diagnosis with fine-needle aspiration (FNA) cytopathology could help clinical decision-making with fewer complications. As the previous studies suggest surgical procedures for >4 cm TNs, we aimed to investigate the accuracy of preoperative FNA cytology to predict malignancy risk in these nodules in a sample of the Iranian population. METHODS: Patients with ≥4 cm TNs who had preoperative FNA cytology, underwent nodulectomy and had a histopathological report were included. Each patient's preoperative demographic, ultrasonographic, and cytology data were gathered. After surgery, resected samples were assessed pathologically and diagnosed as benign or malignant. Finally, data were analyzed to evaluate the presurgical accuracy of the FNA cytology. RESULTS: We identified 41 (51.25%) patients with malignant legions among our study population (N = 80). The pathology reports were indeterminate in 3 patients with follicular neoplasm. Bethesda scores were substantially higher in patients with malignancy. The sensitivity, specificity, and false-negative rate of FNA cytology reports using the Bethesda system were 73.7%, 74.2%, and 26.3%, respectively. There was no association between malignancy and TNs' size, neither their volume nor their highest diameter. CONCLUSION: FNA cytology is not as sensitive and specific in nodules>4 cm as in smaller ones. However, it can still be used alongside other diagnostic procedures in malignancy screening. Clinicians should make more complex decisions considering various influential factors to avoid missing malignant lesions and reduce diverse probable complications of highly invasive diagnostic surgery. Further prospective research on >4 cm TNs and their multiple features' association with malignancy is required for more precise judgment.

Isoindolin-1-ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation.

Helicobacter pylori-induced ulcers and gastric cancer have been one of the main obstacles that the human community has ever struggled with, especially in recent decades. Several different attempts have been made to eradicate this group. One of the most widely used attempts is to inhibit the critical enzyme that facilitates its survival, the urease enzyme. Therefore, in this study, isoindolin-1-ones fused to barbiturates were designed, synthesized, and evaluated for their in vitro urease inhibitory activity as novel inhibitors for the urease enzyme. The synthesis route consisted of two steps. These steps increased the yield rate and decreased the percentage of byproducts while approaching green chemistry using ethanol and water as green solvents and microwave irradiation instead of conventional methods. In vitro urease inhibitory results indicated that all the compounds had higher inhibitory activity than the standard inhibitor, thiourea, and compound 5b proved to be the most potent inhibitor (IC50 = 0.82 ± 0.03 µM). A molecular docking study was performed to understand the interaction between compounds 5a-n and Jack bean urease enzyme. The results of the molecular docking study were also in harmony with the in vitro results, which are discussed in detail later in this study.

Synthesis, molecular docking, and cytotoxicity of quinazolinone and dihydroquinazolinone derivatives as cytotoxic agents.

BACKGROUND: Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a-e and dihydroquinazolinone 10a-f compounds were designed, synthesized as cytotoxic agents. METHODOLOGY: All derivatives (5a-e and 10a-f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software. RESULTS AND DISCUSSION: Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87-205.9 µM against HCT-116 cell line and 14.70-98.45 µM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 µM after 72 h, respectively, indicated the plausible activities of the synthesized compounds. CONCLUSION: The compounds quinazolinone 5a-e and dihydroquinazolinone 10a-f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.

Synthesis, Molecular Docking, and Biological Evaluation of 2,3-Diphenylquinoxaline Derivatives as a Tubulin's Colchicine Binding Site Inhibitor Based on Primary Virtual Screening.

BACKGROUND: Tubulin inhibitors have proved to be a promising treatment against cancer. Tubulin inhibitors target different areas in microtubule structure to exert their effects. The colchicine binding site (CBS) is one of them for which there is no FDA-approved drug yet. This makes CBS a desirable target for drug design. METHODS: Primary virtual screening is done by developing a possible pharmacophore model of colchicine binding site inhibitors of tubulins, and 2,3-diphenylquinoxaline is chosen as a lead compound to synthesis. In this study, 28 derivatives of 2,3-diphenylquinoxalines are synthesized, and their cytotoxicity is evaluated by the MTT assay in different human cancer cell lines, including AGS (Adenocarcinoma gastric cell line), HT-29 (Human colorectal adenocarcinoma cell line), NIH3T3 (Fibroblast cell line), and MCF-7 (Human breast cancer cell). RESULTS: Furthermore, the activity of the studied compounds was investigated using computational methods involving molecular docking of the 2,3-diphenylquinoxaline derivatives to ß-tubulin. The results showed that the compounds with electron donor functionalities in positions 2 and 3 and electron-withdrawing groups in position 6 are the most active tubulin inhibitors. CONCLUSION: Apart from the high activity of the synthesized compounds, the advantage of this report is the ease of the synthesis, work-up, and isolation of the products in safe, effective, and high-quality isolated yields.

Repeat injection following sentinel node nonvisualization on lymphoscintigraphy images can decrease axillary dissection rate in breast cancer patients.

AIM: Sentinel node biopsy is considered the standard of care in early-stage breast cancer patients. In the current study, we evaluated the effect of radiotracer reinjection in the case of sentinel node nonvisualization on preoperative lymphoscintigraphy. MATERIALS AND METHODS: Between March 2017 and March 2020, 1850 early-stage breast cancer patients were referred for sentinel node mapping. All patients received a single injected activity of Tc-99m Phytate intradermally in the periareolar area of the index lesion using an insulin syringe. Lymphoscintigraphy images of the patients were done 1-2 h postinjection. Between March 2017 and September 2017, sentinel node nonvisualization was reported to the surgeon, and for the rest of the study period, the patients received another injected activity of the radiotracer, and immediately, other lymphoscintigraphy images were taken (with the same parameters). RESULTS: A total of 255 patients entered our study. Fifty-five patients were in group I without any reinjection. The remainder of the patients were in group II. In 155 out of 200 patients of group II, a sentinel node could be visualized following reinjection of the radiotracer. The detection rate was 15 out of 45 and 15 out of 55 in group I and patients without sentinel node visualization even after reinjection, respectively. Axilla was involved in 5 out of 40 (12.5%) patients in group I with intraoperative sentinel node mapping failure. On the other hand, axilla was involved in 27 out of 30 (90%) group II patients with sentinel node nonvisualization. CONCLUSION: Reinjection of the tracer in cases of no sentinel node visualization in lymphoscintigraphy for breast cancer increases the detection rate of sentinel nodes, and therefore a high number of unnecessary axillary lymph node dissections can be avoided.

Platelet-rich plasma fibrin glue for treatment of chylothorax following cavopulmonary connections.

OBJECTIVES: The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation. METHODS: Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10-15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years. RESULTS: Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications. CONCLUSIONS: Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.

Investigating the prevalence of risk factors of papillary thyroid carcinoma recurrence and disease-free survival after thyroidectomy and central neck dissection in Iranian patients.

Background: Papillary thyroid carcinoma (PTC) is considered the most frequent thyroid malignancy (85-90%) with a good prognosis. However, its frequent recurrence increases mortality and morbidity. In this inquiry we investigated the prevalence of risk factors of PTC recurrence and disease free survival after thyroidectomy and central neck dissection. Method: In this retrospective study, all patients with confirmed PTC who underwent total thyroidectomy and central neck dissection in Imam Reza and Omid hospitals of Mashhad University of Medical Sciences from 2004 to 2011 were included. Total locoregional and distant recurrence rate, 5-year disease free survival rate (DFS) and contributing factors of recurrence were investigated after at least 5 years. Results: In this study 289 patients were included with a mean follow-up of 72.90 ± 11.02 months. 70.6% were female and 29.4% were male. Recurrence occurred in 58 cases from which 10 were distant and 48 were loco-regional. 5-year DFS was 80% and total-survival-rate was 99%. Our analysis showed that primary tumor size, vascular-invasion, extra-thyroid extension, and lymph node ratio (LNR) were significantly related to DFS.

Design, synthesis, and biological evaluation of selective and potent Carbazole-based butyrylcholinesterase inhibitors.

Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE might be a useful therapeutic target for AD. A new series of Carbazole-Benzyl Pyridine derivatives were designed synthesized and evaluated as butyrylcholinesterase (BChE) inhibitors. In vitro assay revealed that all of the derivatives had selective and potent anti- BChE activities. 3-((9H-Carbazol-9-yl)methyl)-1-(4-chlorobenzyl)pyridin-1-ium chloride (compound 8f) had the most potent anti-BChE activity (IC50 value = 0.073 µM), the highest BChE selectivity and mixed-type inhibition. Docking study revealed that 8f interacted with the peripheral site, the choline binding site, catalytic site and the acyl pocket of BChE. Physicochemical properties were accurate to Lipinski's rule. In addition, compound 8f demonstrated neuroprotective activity at 10 µM. This compound could also inhibit AChE-induced and self-induced Aß peptide aggregation at concentration of 100 µM and 10 µM respectively. The in-vivo study showed that compound 8f in 10 mg/kg increased the time spent in target quadrant in the probe day and decreased mean training period scape latency in rats. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD.

Efficacy and Safety of Pleurodesis Using Platelet-Rich Plasma and Fibrin Glue in Management of Postoperative Chylothorax After Esophagectomy.

INTRODUCTION: Chylothorax is by definition a collection of lymphatic fluids in the pleural cavity because of leakage from main thoracic duct or its tributaries. It is an uncommon but serious postoperative complication in esophageal cancer patients. There is no standard therapeutic algorithm for chylothorax because no prospective or randomized trials have yet been performed to evaluate the available treatment options. The aim of this study was to evaluate the efficacy of pleurodesis with a combination of platelet-rich plasma (PRP) and fibrin glue to the treatment of chylothorax after trans-hiatal esophagectomy. MATERIALS AND METHODS: We randomly allocated 52 consecutive esophageal cancer patients with postoperative chylothorax who did not respond to conservative management to either PRP fibrin glue pleurodesis or surgical thoracic duct ligation. 26 patients in each group were treated with PRP fibrin glue pleurodesis or surgical thoracic duct ligation in order to control chylothorax. Perioperative data, including success rate and complications of both interventions, were analyzed. RESULTS: Two groups were similar in terms of patients' demographics and tumor characteristics. All 26 patients in pleurodesis group (100%) and 20 patients in surgery group (76.9%) were successfully treated (p = 0.009). Seven patients (26.92%) in pleurodesis group required a second application of PRP fibrin glue after a week. The mean length of hospital stay was 53.50 ± 16.662 days in surgery group and 36.04 ± 8.224 days in pleurodesis group (p < 0.001). Although mortality rate in surgery group was higher than pleurodesis group, it was not statistically significant (p = 0.1621). There was no significant difference in complications between two groups either. No serious side effect occurred with PRP fibrin glue application. CONCLUSION: In conclusion, pleurodesis using PRP and fibrin glue for chylothorax after trans-hiatal esophagectomy was associated with significantly increased success rate, decreased ICU stay, decreased overall hospital stay, and decreased mortality compared with surgical thoracic duct ligation. No patient after PRFG required additional intervention including surgery. Thus, given the improved outcomes with PRFG pleurodesis, this technique may be considered in all patients with postoperative chylothorax after or during conservative management and before proceeding to more invasive interventions.

Minimally invasive radioguided parathyroid surgery using low-dose Tc-99m-MIBI - comparison with standard high dose.

INTRODUCTION: Surgery remains the most effective treatment for primary hyperparathyroidism (PHPT). Minimally invasive radioguided parathyroidectomy (MIRP) is a common technique for detecting and excising abnormal parathyroid glands. The aim of this study was to compare injections of low-dose and high-dose (99m) Tc methoxy isobutyl isonitrile (MIBI) for intraoperative localisation of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). MATERIAL AND METHODS: Thirty patients with PHPT and a preoperative diagnosis of parathyroid adenoma were enrolled between 2010 and 2012. They were considered as Group B and underwent MIRP using 5 mCi Tc-99m MIBI, and their perioperative data were compared with twenty patients treated with conventional 20 mCi Tc-99m MIBI previously (Group A). RESULTS: Group A was made up of 20 patients (mean age, 41.55 years; 14 women and 6 men), and group B included 30 patients (mean age, 40.43 years; 19 women and 11 men). The mean serum parathyroid hormone (PTH) and calcium values were recorded pre- and postoperatively. The mean follow-up period for the patients in the two groups was 18.4 and 16.5 months, respectively. Pre-operative evaluation demonstrated that the groups were statistically similar. Intraoperative data and success rate of surgery showed no difference between the two groups. No significant complication was detected after surgeries and no recurrence happened in either of the two groups during the follow-up period. CONCLUSIONS: A new protocol of MIRP using low doses of Tc-99m-MIBI resulted in an excellent success rate. Comparing results of the study, we conclude that low-dose Tc-99m-MIBI may be preferred for identification of parathyroid adenomas intraoperatively by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose Tc-99m-MIBI.

Feasibility and safety of minimally invasive radioguided parathyroidectomy using very low intraoperative dose of Tc-99m MIBI.

BACKGROUND: Surgical resection of the abnormal parathyroid glands is the only curative treatment for primary hyperparathyroidism (PHPT). Radioguided parathyroidectomy with technetium-99m (TC-99m) sestamibi has been successfully used in patients with PHPT. This study was designed to evaluate the results of a series of patients with PHPT who underwent minimally invasive radioguided parathyroidectomy (MIRP) using very low dose (1 mCi) of TC-99m sestamibi (MIBI) without application of intraoperative parathyroid hormone (PTH) assay or frozen section analysis. METHODS: Eighty-seven patients with PHPT were prospectively studied from November 2012 to January 2015. Following neck ultrasound (US) and MIBI scan concordant for single gland disease, patients underwent MIRP using a handheld gamma probe. The technique involved injecting of 1 mCi MIBI in the operative room before the beginning of the intervention. All patients were followed up for a minimum of 6 months postoperatively. RESULTS: MIRP was successfully performed in 86 out of 87 patients (98.85%). The Gamma probe was particularly useful in detection of ectopic parathyroid adenomas in upper mediastinum. Mean operative time was 23.95 ± 7.982 min and mean hospital stay was 1.44 ± 0.604 days. No major surgical complications were recorded. CONCLUSIONS: The MIRP technique using very low dose (1 mCi) of Tc-99m MIBI without intraoperative PTH assay and frozen section analysis resulted in excellent cure rate for PHPT. This technique involves a radiation exposure to patients and surgical staffs 20 times lower than conventional MIRP using 20 mCi Tc-99m MIBI. Besides, patients with PHPT due to ectopic parathyroid adenoma may especially benefit from MIRP.

Internal mammary sentinel lymph node biopsy in clinical practice.

Almost all recent studies confirmed internal mammary sentinel lymph node biopsy (IM-SLNB) as an accurate and valuable technique to determine stage, prognosis, and best treatment option in breast cancer patients. Decision about local treatment of internal mammary lymph nodes (IMLN) is still being made based on Axillary lymph node (ALN) status. According to study results, there will be patients in positive ALN subgroup who just face complications of an unnecessary radiation to IMLNs and there will be patients in negative ALN subgroup who do not receive adjuvant radiation therapy they really need, if we insist to continue planning IMLN treatment based on ALN status. It seems that patients with bonafide drainage to IMLNs will benefit from IM-SLNB regardless of their ALN status.

Evaluation and Comparison of the Early Outcomes of Open and Laparoscopic Surgery of Liver Hydatid Cyst.

BACKGROUND AND AIM: Surgery is the mainstay for treatment of liver hydatid cyst. Different surgical procedures have been suggested, but it is important to select the most appropriate treatment to obtain the best results with the lowest rate of recurrence and minimal morbidity and mortality. The aim of this study was to evaluate the early outcomes of open and laparoscopic surgery of hydatidosis. MATERIALS AND METHODS: In this study, 75 patients with uncomplicated liver hydatid cyst were assigned prospectively to either groups of laparoscopic surgery (37, 50.68%) or open procedure (36, 49.32%) during the period of 2007 to 2012. Conversion to open surgery was required in 2 patients (2.67%), who were excluded from the study. Patients were followed for about 17.86±17.64 months. RESULTS: Participants included 73 patients: 49 (67.12%) female and 24 (32.88%) male patients, with the mean age of 38.97±16.48 years. There was no statistically significant difference between the 2 groups with regard to the sex, the occupation, and the mean diameter of the cysts. Bilious staining of the cyst content was observed in 23 (35.94%) patients during surgery, and a maximum diameter of 91 mm was considered as a cut point for predicting postoperative fistula with 69.2% sensitivity and 41.1% specificity. The mean duration of operation, postoperative pain, the hospitalization time, and the time to return to work were significantly lower in the laparoscopic group. Postoperative biliary fistula, cyst cavity infection, and wound infection were not different between the 2 groups. CONCLUSIONS: Laparoscopic surgery seems to be effective and safe, with low morbidity rates for uncomplicated cysts in accessible segments of the liver.

Imidazo[2,1-b]thiazole derivatives as new inhibitors of 15-lipoxygenase.

A series of 3,6-diphenylimidazo[2,1-b]thiazol-5-amine derivatives was synthesized and evaluated as potential inhibitors of 15-lipoxygenase. Among the synthesized compounds, 5i bearing 2,4,4-trimethylpentan-2-yl pendent group was the most active compound, being two times more potent than reference drug quercetin. Also, the docking study revealed that 5i interacts properly with target enzyme 15-LOX and hydrophobic interactions have important role in the binding process. Besides, the protective effect of 5i against oxidative stress-induced cell death in differentiated PC12 cells was evaluated. The results showed that compound 5i significantly protected PC12 cells against H2O2-induced cell death at concentrations less than 10 µM.

The Stromal Overexpression of CD10 in Invasive Breast Cancer and its Association with Clincophathologic Factors.

BACKGROUND: Breast carcinoma is the most common non-skin malignancy in women. More recently, it has been suggested that extracellular proteinase has also regulated growth factors and cytokines that might contribute to tumor progression. CD10 is a 90-110kd cell surface zinc-dependent metalloproteinase. Since CD10 is structurally similar to matrix metalloproteinase and stromelysin, it might facilitate cancer cell invasion and/or metastasis. The aim of this study was investigation the rate of CD10 expression in the stromal cells of invasive ductal breast carcinomas, Immunohistochemical aspects, then any other aspects to be able to clarify its correlation with other clinicopathological factors of this disease. METHODS: One hundred patients with histopathologic diagnosis of invasive ductal carcinoma and 50 patients with fibroadenoma of breast (as the control group) have selected, then 150 paraffin blocks have obtained. The stained slides by immunohistochemistry method for CD10 marker have examined separately by two pathologists, and discrepancies have reviewed in common session to get the final result. RESULTS: Stromal CD10 has detected in 28% of the IDC. No kind of immunoreactivity has identified in the stromal cells of normal breast. Stromal CD10 expression in IDC has significantly correlated with increasing tumor size (p<0.001), increasing histologic grade (p<0.001), the presence of nodal metastases (p<0.001) and estrogen receptor negative status (p=0.003). CONCLUSION: Stromal CD10 expression in IDC has closely correlated with invasion and metastasis and it might play an important role in the pathogenesis of IDC.

Axillary concordance between superficial and deep sentinel node mapping material injections in breast cancer patients: systematic review and meta-analysis of the literature.

It is still unclear whether the deep and superficial lymphatics of the breast always drain into the same nodes and which route best simulates the spread of breast cancer. In the current study, we systematically searched the available literature to find the studies evaluated the sentinel node locations of deep and superficial injections in the same patients simultaneously or serially. We searched SCOPUS, and PUBMED for relevant studies. Patient basis concordance rate was defined as the ratio of patients with at least one identified axillary sentinel node by both deep and superficial injections to all patients with identified axillary sentinel nodes using either methods. Sentinel node basis concordance was defined as the ratio of the number of axillary sentinel nodes identified by both deep and superficial injections to the sum of all identified axillary sentinel nodes using either methods. Pooled sentinel node detection rates were 94 % [92.1-95.5], 91.2 % [87.1-94.1], and 97.2 % [96-98] for superficial, deep, and combined (superficial and deep) injections. Pooled patient basis and sentinel node basis concordance rates were 90 % [86.7-92.4] and 73 % [63.3-80.9]. Pooled false negative rates were 9.1 % [5.9-14], 8.6 % [3.7-18.8], and 6.5 % [3.4-11.9] for superficial, deep, and combined (superficial and deep) injections, respectively. Axillary lymphatic drainage concordance between superficial and deep sentinel node mapping material in breast cancer patients is fairly high and clinically acceptable. However, both injection techniques can complement each other and the combined superficial/deep injection technique seems to be more successful clinically and can decrease the overall false negative rate.