Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: a Kaplan-Meier-derived patient data meta-analysis.

PURPOSE: Partial breast irradiation (PBI) and intraoperative radiation (IORT) represent alternatives to whole breast irradiation (WBI) following breast conserving surgery. However, data is mixed regarding outcomes. We therefore performed a pooled analysis of Kaplan-Meier-derived patient data from randomized trials to evaluate the hypothesis that PBI and IORT have comparable long-term rates of ipsilateral breast tumor recurrence as WBI. METHODS: In February, 2023, PubMed, EMBASE and Cochrane Central were systematically searched for randomized phase 3 trials of early-stage breast cancer patients undergoing breast-conserving surgery with PBI or IORT as compared to WBI. Time-to-event outcomes of interest included ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and distant disease-free survival (DDFS). Statistical analysis was performed with R Statistical Software. RESULTS: Eleven randomized trials comprising 15,460 patients were included; 7,675 (49.6%) patients were treated with standard or moderately hypofractionated WBI, 5,413 (35%) with PBI and 2,372 (15.3%) with IORT. Median follow-up was 9 years. PBI demonstrated comparable IBTR risk compared with WBI (HR 1.20; 95% CI 0.95-1.52; p = 0.12) with no differences in OS (HR 1.02; 95% CI 0.90-1.16; p = 0.70) or DDFS (HR 1.15; 95% CI 0.81-1.64; p = 0.43). In contrast, patients treated with IORT had a higher IBTR risk (HR 1.46; 95% CI 1.23-1.72; p < 0.01) compared with WBI with no difference in OS (HR 0.98; 95% CI 0.84-1.14; p = 0.81) or DDFS (HR 0.91; 95% CI 0.76-1.09; p = 0.31). CONCLUSION: For patients with early-stage breast cancer following breast-conserving surgery, PBI demonstrated no difference in IBTR as compared to WBI while IORT was inferior to WBI with respect to IBTR.

Influence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy.

OBJECTIVE: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A total of 29 female dogs with mammary tumors. METHODS: Premedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 µg kg-1 loading dose (LD) and 1 µg kg-1 hour-1; lidocaine 2 mg kg-1 LD and 3 mg kg-1 hour-1; ketamine 1 mg kg-1 LD and 0.6 mg kg-1 hour-1; n = 14] or FLK (fentanyl 5 µg kg-1 LD and 9 µg kg-1 hour-1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (Fe'Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann-Whitney test. RESULTS: More dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and Fe'Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. CONCLUSIONS AND CLINICAL RELEVANCE: Based on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively.

Impact of multifocal or multicentric disease on local recurrence and survival in breast cancer patients with or without BRCA1/2 variants.

PURPOSE: Multifocal or multicentric (MFMC) breast cancer is mainly focused on breast cancer patients with unknown BRCA status, the incidence and clinical relevance of MFMC disease in BRCA1/2 carriers is less explored to date. Our study was to investigate the incidence of MFMC disease in BRCA1/2 carriers and whether MFMC disease influences local recurrence and clinical outcomes. METHODS: In this retrospective study, 479 breast cancer patients with BRCA1/2 variants and 1437 age-matched noncarriers were enrolled and patients received either breast-conserving therapy (BCT) or mastectomy with or without radiotherapy. RESULTS: The rates of MFMC disease in BRCA1 and BRCA2 carriers, and noncarriers were 33.0% (61 of 185), 37.4% (110 of 294), and 31.2% (449 of 1437), respectively. MFMC disease in BRCA2 carriers was significantly higher than that in noncarriers (P = 0.039). After a median follow-up of 8.1 years, among patients treated with BCT, BRCA2 carriers with MFMC disease experienced a significantly higher rate of ipsilateral breast tumor recurrence (IBTR) than those with unifocal disease (16.7% vs 4.1%, P = 0.044). Moreover, BRCA2 carriers with MFMC disease had a significantly worse RFS (unadjusted hazard ratio [HR], 3.65 [95% CI 1.40-9.52]; P = 0.008), DRFS (unadjusted HR, 3.07 [95% CI 1.07-8.80]; P = 0.037), and OS (unadjusted HR, 4.96 [95% CI 1.18-20.02]; P = 0.029) than those with unifocal disease when treated with BCT. CONCLUSION: MFMC breast cancer is more common in BRCA2 carriers, and BRCA2 carriers with MFMC disease treated with BCT exhibit a higher rate of IBTR and may have a poor survival.

Effect of anaesthesia on cell-mediated immunity in dogs undergoing mastectomy for mammary cancer.

OBJECTIVE: To investigate if anaesthesia for canine cancer mastectomy further influences host cell-mediated immunity (CMI) promoting cancer progression. STUDY DESIGN: A randomized, controlled, blinded clinical study. ANIMALS: A total of 20 bitches with malignant mammary tumours of clinical stage II or III undergoing the same type of mastectomy (regional mastectomy). METHODS: Dogs were randomly allocated to one of two anaesthetic groups (10 per group). The anaesthetic protocol of group A used minimally immunosuppressive drugs (tramadol, robenacoxib, propofol), whereas that of group B (control) used more immunosuppressive drugs (morphine, fentanyl, thiopental, isoflurane). For each animal, measurements of white blood cells (WBCs), neutrophils and lymphocytes, and flow cytometric assessment of T cells (CD3+), helper T cells (CD4+), cytotoxic T cells (CD8+) and CD5low+ T cells were performed prior to anaesthesia (day 0) and on days 3 and 10 postsurgery. Data were analysed using a General Linear Model for repeated measures and presented as mean ± standard deviation, p ≤ 0.05. RESULTS: In all animals, on day 3, WBCs and neutrophils were significantly increased (p < 0.0005), while flow cytometry revealed significantly decreased relative percentages of T cells (CD3+) (p = 0.003) and their subpopulations CD4+ (p = 0.006), CD8+ (p = 0.029) and CD5low+ (p = 0.031). Specifically, on day 3, the cytotoxic T cells (CD8+) were significantly decreased (p = 0.05) only in group B, whereas the CD4+ (p = 0.006) and CD5low+ (p = 0.008) T cells in group A. The only significant difference between groups was found preoperatively in the CD4+/CD8+ ratio, which was higher in group A (p = 0.006). CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with mammary cancer undergoing regional mastectomy, a significant decrease in components of CMI was observed on day 3 postsurgery in both anaesthetic groups. Some indication, however, for better preserved cellular immunity by less immunosuppressive anaesthetic/analgesic drugs was detected, rendering their use advisable.

Correlation of Cytokine Content in the Lymph with the Morphological Parameters of the Mesenteric Lymph Nodes in Adjuvant Therapy of Experimental Breast Cancer with the Use of Fragmented Human DNA.

We studied the relationship between the level of cytokines in the lymph of the thoracic duct and the morphometric parameters of the mesenteric lymph nodes after surgical treatment of breast cancer, chemotherapy, and administration of fragmented (double-stranded, dsDNA) human DNA. In comparison with surgical treatment and with chemotherapy alone, administration of a human dsDNA has a stimulating effect on the T-cell link of the immune response. In the paracortical zone, the relationship between the chemokine MCP-1 and increased content of small lymphocytes in this zone was revealed. Interrelations of IL-2 cytokines with small lymphocytes and of IL-4 with medium lymphocytes were revealed in germinal centers. We also observed interrelations of IL-7 with small lymphocytes and IL-4 with macrophages in the medullary cords, chemokine MIP-1α with immature and mature plasma cells (the number of these cells is reduced), and of MCP-1 with immunoblasts (the number of which is also reduced) in the medullary sinuses.

Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease.

BACKGROUND: There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. METHODS: This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively). RESULTS: In the RENCAluc model, adjuvant sunitinib plus anti-PD-L1 improved overall survival compared to either drug alone, while the same combination was ineffective as early therapy for unresected primary tumours or late-stage therapy for advanced metastatic disease. In the EMT-6/CDDP model, anti-PD-L1 was highly effective as an adjuvant monotherapy, while its combination with paclitaxel chemotherapy (with or without anti-VEGF) was most effective as a neoadjuvant therapy. CONCLUSIONS: Our preclinical data suggest that anti-PD-L1 plus sunitinib may warrant further investigation as an adjuvant therapy for RCC, while anti-PD-L1 may be improved by combining with chemotherapy in the neoadjuvant but not the adjuvant setting of treating breast cancer.

Bcl-2 expression and prognostic significance in feline invasive mammary carcinomas: a retrospective observational study.

BACKGROUND: Cats spontaneously develop invasive mammary carcinomas with high clinical aggressiveness, and are considered relevant animal models for human breast cancer. Bcl-2 is an anti-apoptotic pro-survival protein, whose expression is associated with a favorable outcome in human breast cancer. The aim of our study was to determine the frequency of Bcl-2 expression in feline invasive mammary carcinomas (FMCs), its relationship with other clinicopathologic variables, and its prognostic value. This retrospective study included 180 FMCs, diagnosed in female cats treated by surgery only, with a 2-year follow-up post-mastectomy. Bcl-2, ER, PR, Ki-67, HER2, and CK5/6 expression were determined by automated immunohistochemistry. A receiver-operating-characteristic curve was used to set the threshold for Bcl-2 positivity. RESULTS: The cohort comprises 32% (57/180) luminal FMCs defined by ER and/or PR positivity, and 68% (123/180) triple-negative FMCs (negative for ER, PR, and HER2). Bcl-2 expression was considered as positive when at least 65% of tumor cells were immunohistochemically stained. Thirty-one out of 180 FMCs (17%) were Bcl-2-positive. There was no significant association between Bcl-2 expression, and the tumor size, nodal stage, histological grade, or ER, PR, Ki-67, HER2, and CK5/6 expression. By multivariate survival analysis (Cox proportional-hazards regression), Bcl-2 positivity in FMCs was associated with longer disease-free interval (p = 0.005, HR = 0.38), overall survival (p = 0.028, HR = 0.61), and cancer-specific survival (p = 0.019, HR = 0.54) independently of other powerful prognostic factors such as pathologic tumor size, pathologic nodal stage, and distant metastasis. The positive prognostic value of Bcl-2 was confirmed in both luminal FMCs, of which 9/57 (16%) were Bcl-2-positive, and in basal-like triple-negative (ER-, PR-, HER2-, CK5/6+) FMCs, of which 14/76 (18%) were Bcl-2-positive. CONCLUSIONS: Compared to human breast cancer, Bcl-2 positivity in feline invasive mammary carcinomas is also associated with better outcome, but is less common, and not associated with ER, PR, and HER2 expression. Cats with spontaneous Bcl-2-positive FMCs could be useful in preclinical trials evaluating anti-Bcl-2 strategies for chemoresistant luminal or triple-negative breast cancers.

Lipid and metabolic profiles in female dogs with mammary carcinoma receiving dietary fish oil supplementation.

BACKGROUND: Dyslipidemias induce angiogenesis and accelerate the development and in vitro growth of breast tumors. The aim of this study was to assess the lipid and metabolic profile of female dogs with mammary carcinomas and their correlations with body condition score and degree of tumor malignancy, as well as to study the effect of dietary fish oil supplementation on these animals. RESULTS: Overweight or obese dogs had more aggressive carcinomas and higher triglyceride (p = 0.0363), VLDL (p = 0.0181), albumin (p = 0.0188), globulin (p = 0.0145) and lactate (p = 0.0255) concentrations. There was no change in the lipid profile after supplementation with fish oil at any concentration. However, in relation to the metabolic profile, glucose (p = 0.0067), total protein (p = 0.0002) and globulin (p = 0.0002) concentrations were increased when 90% omega-3 fish oil was used as a dietary supplement. CONCLUSION: Obese dogs showed altered lipid and metabolic profiles and more aggressive tumors, suggesting an important relationship between dyslipidemia and tumor aggressiveness. Supplementation with fish oil, rich in omega-3 fatty acids, may alter metabolic parameters in cancer patients.

Canine invasive mammary carcinomas as models of human breast cancer. Part 1: natural history and prognostic factors.

PURPOSE: Dogs have been proposed as spontaneous animal models of human breast cancer, based on clinicopathologic similarities between canine and human mammary carcinomas. We hypothesized that a better knowledge of the natural history and prognostic factors of canine invasive mammary carcinomas would favor the design of preclinical trials using dogs as models of breast cancer. METHODS: The 2-year outcome of 350 female dogs with spontaneous invasive mammary carcinoma was studied. The investigated prognostic factors included age at diagnosis, pathologic tumor size, pathologic nodal stage, lymphovascular invasion, histological grade, and expression of Estrogen Receptor alpha (ERα), Progesterone Receptor, Ki-67, Human Epidermal Growth Factor Receptor 2, basal cytokeratins 5/6, and Epidermal Growth Factor Receptor. Multivariate survival analyses were performed using the Cox proportional hazards model. RESULTS: The overall survival after mastectomy was 11 months. Within 1 year post mastectomy, 41.5% of dogs (145/350) died from their mammary carcinoma. By multivariate analysis, the significant prognostic factors for overall survival included a pathologic tumor size larger than 20 mm [HR 1.47 (95% confidence interval 1.15-1.89)], a positive nodal stage [pN+, HR 1.89 (1.43-2.48)], a histological grade III [HR 1.32 (1.02-1.69)], ERα negativity [HR 1.39 (1.01-1.89)], a high Ki-67 proliferation index [HR 1.32 (1.04-1.67)], and EGFR absence [HR 1.33 (1.04-1.69)]. CONCLUSION: The short natural history of spontaneous canine invasive mammary carcinomas and high rate of cancer-related death allow for rapid termination of preclinical investigations. The prognostic factors of invasive mammary carcinomas are remarkably similar in dogs and humans, highlighting the similarities in cancer biology between both species.

MAMMARY FIBROADENOMATOUS HYPERPLASIA IN A JUVENILE CALIFORNIA SEA LION ( ZALOPHUS CALIFORNIANUS).

A juvenile female California sea lion ( Zalophus californianus) presented with a firm subcutaneous mass in the right caudoventral pelvic region, measuring approximately 15 × 15 cm, and edema in the right hind flipper. The initial diagnostic workup included an ultrasound, blood analysis, and fine-needle aspirate of the mass under manual restraint. While the blood analysis was within normal limits, the ultrasound revealed a large discrete hyperechoic homogeneous mass with anastomosing hypoechoic fluid pockets that, when aspirated, was suggestive of a reactive lymph node. Short-term empiric antibiotic therapy prescribed to address possible lymphadenitis yielded no response, and edema of the right hind flipper and perianal region worsened. The sea lion was anesthetized to facilitate a more thorough exam, repeat blood analysis, obtain survey radiographs, evaluate with ultrasound, and perform biopsy of mass. The thoracic radiographs were normal; however, the large radiopaque mass was observed cranial to the pelvis on lateral abdominal view and appeared solitary on ultrasound. An exploratory surgery was performed to completely excise the mass. On histopathologic review, the mass demonstrated diffuse fibrous hyperplasia of lobular ducts of the mammary gland and mild mastitis, characterizing it as a mammary fibroadenoma. The surgical wound healed within 6 wk, and there was no recurrence of mammary hyperplasia.

MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

Photoacoustic and fluorescence image-guided surgery using a multifunctional targeted nanoprobe.

PURPOSE: A complete surgical excision with negative tumor margins is the single most important factor in the prediction of long-term survival for most cancer patients with solid tumors. We hypothesized that image-guided surgery using nanoparticle-enhanced photoacoustic and fluorescence imaging could significantly reduce the rate of local recurrence. METHODS: A murine model of invasive mammary carcinoma was utilized. Three experimental groups were included: (1) control; (2) tumor-bearing mice injected with non-targeted nanoprobe; and (3) tumor-bearing mice injected with targeted nanoprobe. The surgeon removed the primary tumor following the guidance of photoacoustic imaging (PAI), then inspected the surgical wound and removed the suspicious tissue using intraoperative near-infrared (NIR) fluorescence imaging. The mice were followed with bioluminescence imaging weekly to quantify local recurrence. RESULTS: Nanoprobe-enhanced photoacoustic contrast enabled PAI to map the volumetric tumor margins up to a depth of 31 mm. The targeted nanoparticles provided significantly greater enhancement than non-targeted nanoparticles. Seven mice in the group injected with the targeted nanoprobes underwent additional resections based upon NIR fluorescence imaging. Pathological analysis confirmed residual cancer cells in the re-resected specimens in 5/7 mice. Image-guided resection resulted in a significant reduction in local recurrence; 8.7 and 33.3 % of the mice in the targeted and control groups suffered recurrence, respectively. CONCLUSIONS: These results suggest that photoacoustic and NIR intraoperative imaging can effectively assist a surgeon to locate primary tumors and to identify residual disease in real-time. This technology has promise to overcome current clinical challenges that result in the need for second surgical procedures.

Retrospective clinical evaluation of ultrasound guided transverse abdominis plane block in dogs undergoing mastectomy.

HISTORY: Eleven female dogs of different breeds undergoing unilateral radical (n = 7) or regional abdominal mastectomy (n = 4) received an ultrasound guided transverse abdominis plane block (TAP-block). PHYSICAL EXAMINATION: Subjects showed single or multiple mammary tumours. Serum biochemistry, CBC and electrocardiogram were unremarkable. Eight animals were classified as ASA physical status II and 3 as ASA III. MANAGEMENT: Dogs were premedicated with methadone [0.1 or 0.2 mg kg(-1) intravenously (IV) or intramuscularly respectively] or fentanyl (2.5 µg kg(-1) IV). Anaesthesia was induced with propofol and maintained with isoflurane or sevoflurane. Unilateral ultrasound guided TAP blocks were performed in the caudal and cranial abdomen with bupivacaine 0.25% (0.3 to 0.35 mL kg(-1) ). Intercostal nerve blocks (T4 to T11 ) with bupivacaine 0.25% (0.013 to 0.04 mL kg(-1) ) completed the blocked area in dogs undergoing radical mastectomy. FOLLOW UP: The median (range) of end-expired isoflurane and sevoflurane necessary to maintain anaesthesia was 1.15 (1.07-1.22) and 2.07 (2.05-2.2) vol% respectively. A single administration of fentanyl (2.5 µg kg(-1) , IV) was administered to control nociception (defined as an increased heart rate or mean arterial blood pressure above 20% of the pre-incisional value) in four of 11 dogs. All dogs received carprofen (2 mg kg(-1) subcutaneously) at the end of surgery. Post-operative pain, assessed for 120 minutes using the short form of Glasgow Composite Pain Scale (0-24), was always lower than 3. No rescue analgesia (allowed by the protocol) was required in this time. CONCLUSION: Transverse abdominis plane block combined with intercostal nerve blocks may be useful to produce intraoperative anti-nociception and short term post-operative analgesia in dogs undergoing unilateral mastectomy.

Treatment of mammary gland tumors in bitches: effects of sodium dichloroacetate as neoadjuvant therapy.

Mastectomy is the standard treatment for mammary gland tumors in dogs. In addition to traditional therapy, sodium dichloroacetate (DCA) can act as target therapy, as it may promote autophagy, reduce metastatic potential, and tumor proliferation in mammary tumor cell lines. This study aimed to analyze the effects of DCA as preoperative therapy for mammary tumors in bitches. Nineteen animals were selected, and they received DCA at a dose of 10 mg/kg orally every 12 hr, for 15 days. The periodic evaluation included hematological analysis (complete blood count and biochemical markers), evaluation of gastrointestinal adverse effects, evaluation of tumor volume, histopathological analysis, and immunohistochemical evaluation (Ki67 and cyclooxygenase-2/COX-2 markers). After treatment, there was a significant reduction in hematocrit (P=0.02) and leukocyte (P=0.04) means. Despite the variations for these two hematological parameters, the means remained within the reference range for the species. There were two cases of vomiting and one case of diarrhea. Most cases were classified as carcinoma in mixed tumor (n=7, 36.8%), followed by solid carcinoma (n=6, 31.6%). Nine cases (47.4%) showed reduced tumor volume, nine (47.4%) had stable disease, and one showed progressive disease. While there was no sample with a COX-2 score higher than 6, tumor samples with COX-2 scores 3 and 4 were significantly associated with stable disease or progression. DCA preoperative treatment for bitches with mammary gland tumors showed safety and potential cytoreduction in some cases.

The role of lymph nodes and their drainage in canine mammary gland tumours: Systematic review.

Mammary gland tumours are the most common neoplasms in intact bitches. Over the last decades, veterinary oncology has evolved in detecting and determining the lymph nodes to be removed in these patients for an accurate staging and prognosis, as well as to achieve better disease control and higher overall survival time. Our objective was to describe recent advances related to lymphatic drainage in bitches with mammary gland tumours, focusing on surgery, diagnosis, and prognosis. Through a systematic review using PubMed as the database, a thorough multi-step search reduced 316 studies to 30 for analysis. Vital dyes appear to be crucial in reducing the overall surgery time through transoperative staining of the lymph nodes. Imaging contrasts provide information regarding specific tumour drainage; however, there is still little evidence for their use. The axillary and superficial inguinal lymph nodes are well-established as regional lymph nodes of the cranial and caudal mammary glands. In sequence, accessory axillary, medial iliac, popliteal, and sternal lymph nodes should receive attention if they demonstrate contrast drainage, even considering that the literature has not shown a relationship between drainage and metastasis in these cases. In conclusion, recent studies have provided us with more support in regional lymph node excision regarding the TNM staging system. Studies are highly heterogeneous and method comparisons do not fit due to the non-uniformity of samples, materials, and procedures. We suggest further studies with a larger sample size, complete follow-up of patients, contrast use, and lymph node morphological and immunohistochemical analysis.

Description of postoperative complications and bacterial contamination of wound soaker catheters used to administer postoperative local analgesia after mastectomy in 11 dogs: case series.

Mastectomy is a common and painful procedure in dogs. Wound soaker catheters (WSC) are frequently used to reduce postoperative pain, including pain after mastectomy. The objectives of this case series were to describe the use of WSC for owner administration of postoperative local analgesia in dogs with mammary tumors treated surgically, to identify complications associated with WSC and to determine the frequency of bacterial colonization of the catheters. Twelve WSC were placed in 11 dogs during mastectomy surgery, left in place for three days, protected by a dressing and successfully managed by owners at home. No postoperative antibiotics were administered. No complications were identified in any cases. No bacterial growth was identified on bacteriological analysis of the twelve WSC. These results suggest that the use of WSC is a safe alternative for postoperative analgesia administration following mastectomy in dogs. Future studies comparing dogs with or without WSC with a larger number of dogs are needed to further evaluate efficacy and complications.

Three-dimensional optical coherence tomography for optical biopsy of lymph nodes and assessment of metastatic disease.

BACKGROUND: Numerous techniques have been developed for localizing lymph nodes before surgical resection and for their histological assessment. Nondestructive high-resolution transcapsule optical imaging of lymph nodes offers the potential for in situ assessment of metastatic involvement, potentially during surgical procedures. METHODS: Three-dimensional optical coherence tomography (3-D OCT) was used for imaging and assessing resected popliteal lymph nodes from a preclinical rat metastatic tumor model over a 9-day time-course study after tumor induction. The spectral-domain OCT system utilized a center wavelength of 800 nm, provided axial and transverse resolutions of 3 and 12 µm, respectively, and performed imaging at 10,000 axial scans per second. RESULTS: OCT is capable of providing high-resolution label-free images of intact lymph node microstructure based on intrinsic optical scattering properties with penetration depths of ~1-2 mm. The results demonstrate that OCT is capable of differentiating normal, reactive, and metastatic lymph nodes based on microstructural changes. The optical scattering and structural changes revealed by OCT from day 3 to day 9 after the injection of tumor cells into the lymphatic system correlate with inflammatory and immunological changes observed in the capsule, precortical regions, follicles, and germination centers found during histopathology. CONCLUSIONS: We report for the first time a longitudinal study of 3-D transcapsule OCT imaging of intact lymph nodes demonstrating microstructural changes during metastatic infiltration. These results demonstrate the potential of OCT as a technique for intraoperative, real-time in situ 3-D optical biopsy of lymph nodes for the intraoperative staging of cancer.

Perioperative evaluation of tumescent anaesthesia technique in bitches submitted to unilateral mastectomy.

BACKGROUND: Tumescent anaesthesia (TA) is a widely used technique in oncologic surgeries necessitating large resection margins. This technique produces transoperative and postoperative analgesia, reduces surgical bleeding, and facilitates tissue divulsion. This prospective, randomised, blind study evaluated the use of TA in bitches submitted to mastectomy and compared the effect of TA with an intravenous fentanyl bolus. A 2.5-mcg/kg intravenous fentanyl bolus (n = 10) was compared with TA using 0.275% lidocaine (n = 10) in bitches submitted to unilateral mastectomy. Sedation was performed by intramuscular (IM) injection of 0.05 mg/kg of acepromazine combined with 2 mg/kg of meperidine. Anaesthesia was induced with 5 mg/kg of intravenous propofol and maintained with isoflurane/O2. Heart and respiratory rates; systolic, mean, and diastolic arterial blood pressures; central venous pressure; SpO2; ETCO2; inspired and expired isoflurane concentrations; and temperature were measured transoperatively. Visual analogue scales for sedation and pain and the Glasgow composite and Melbourne pain scales were used for postoperative assessment. The surgeon investigated the quality of the surgical approach, considering bleeding and resection ability, and the incidence of postoperative wound complications. RESULTS: The heart rate was lower and the end-tidal isoflurane concentration was higher in dogs treated with fentanyl than in dogs treated with TA. A fentanyl bolus was administered to 8 of 10 dogs treated with fentanyl and to none treated with TA. Intraoperative bleeding and the mammary gland excision time were lower in dogs treated with TA. The maximal mean and individual plasma lidocaine concentrations were 1426 ± 502 ng/ml and 2443 ng/ml at 90 minutes after infiltration, respectively. The Glasgow Composite Pain Scale scores were higher in dogs treated with fentanyl than in dogs treated with TA until 2 hours after extubation. CONCLUSIONS: Compared with intravenous fentanyl, TA in bitches: may be easily performed in non-inflamed, ulcerated, adhered mammary tumours; has an isoflurane-sparing effect; improves transoperative and immediate postoperative analgesia; is apparently safe for use in clinical conditions as evidenced by the fact that it did not produce any adverse signs or lidocaine plasma concentrations compatible with toxicity; does not modify the recovery time; and facilitates the surgical procedure without interfering with wound healing.

Prognostic value of different forms of serum MMP-2 and MMP-9 in dogs with mammary tumors; a longitudinal study.

Gelatinases (MMP-2 and MMP-9) are related to tumor invasion and metastasis. In humans, the diagnostic value of serum levels of gelatinases has been confirmed in breast cancer, but their diagnostic value in canine mammary tumors is still unknown. This study aimed to determine the serum level of gelatinases in dogs with mammary tumors in order to determine their value in the diagnosis of malignancy or benign tumors and also in predicting the possibility of metastasis and recurrence. Frequent measurement of MMP-2 and MMP-9 by gelatin zymography in serum before and after surgical treatment has not previously been studied for monitoring mammary tumors in dogs. Thus, the serum levels of MMP-2 and MMP-9 in 26 dogs with mammary tumors before surgical treatment and then 1, 4 and 12 months after surgery were evaluated by gelatin zymography. Serum samples of 26 healthy dogs with normal conditions were used as control. Dogs with benign and malignant mammary tumors showed bands of pro-MMP-2, pro-MMP-9 and active MMP-9. However, only pro-MMP-2 and pro-MMP-9 bands appeared in the serum of control group. Our results showed that the presence of active MMP-9, regardless of its level, was prognostically important for metastasis and or recurrence (M/R). However, the presence of active MMP-2 band was more important for M/R than active MMP-9, as its presence coincides with definitive M/R. It seems that serum gelatin zymography could possibly be used at regular intervals before and after surgery to evaluate the probability of M/R in dogs with mammary tumors. More research is needed in this regard.

Microwave ablation for the control of bleeding from disintegrated mammary tumours in two dogs.

A 16-year-old intact female Miniature Dachshund (dog 1) and a 13-year-old intact female American Cocker Spaniel (dog 2) presented with a chief complaint of bleeding from a mammary gland tumour ulceration. Dog 1 was transferred to hospital from a local hospital in a haemorrhagic shock state with uncontrolled continuous bleeding. Thoracic radiographs revealed multiple nodular shadows suspected to be pulmonary metastasis. Dog 2 presented with intermittent bleeding from a mass lesion in the right fifth mammary gland. Due to high anaesthetic risk secondary to severe mitral valve insufficiency (ASA status III), the owner declined surgical excision of the tumour. Therefore, microwave ablation (MWA) under local anaesthesia was chosen in order to achieve adequate haemostasis. Both dogs received local anaesthesia around the bleeding mass lesion, and the disintegrated site was microwave-ablated; dog 1 underwent MWA after blood transfusion to improve the haemorrhagic shock. The ablation site was protected using a non-adhesive dressing. Scarring of the ulcerated site led to complete haemostasis in both cases. Dog 1 underwent tumorectomy on the 31st hospital day to prevent rebleeding; histopathology results were consistent with mammary adenocarcinoma with the ablation site covered by a capsule structure. To the authors' knowledge, this is the first case report describing the use of MWA to stop bleeding from mammary tumours in veterinary medicine. MWA is a feasible and potentially effective palliative treatment modality to stop bleeding from disintegrated mammary tumours in dogs under local anaesthesia.