Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy.

INTRODUCTION: Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2]. RESULTS: Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change. CONCLUSIONS: Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

Impact of the extent of pathologic complete response on outcomes after neoadjuvant chemotherapy.

BACKGROUND AND OBJECTIVE: With advances in systemic therapies for breast cancer, responses to neoadjuvant chemotherapy (NAC) have increased. Pathologic complete response (pCR) after NAC is an independent prognostic factor. We examined the impact of breast and/or lymph node (LN) pCR on survival. METHODS: From a prospectively maintained database, 202 women were identified with LN-positive breast cancer who underwent NAC then surgery. Clinicopathologic factors and survival were compared between four groups: breast/LNs pCR, node-only pCR, breast-only pCR, and residual disease (RD). RESULTS: Forty-eight (23.8%) patients had breast/LNs pCR, 43 (21.3%) node-only pCR, 5 (2.5%) breast-only pCR, and 106 (52.5%) had RD. There was no difference in age, stage, or breast operation between groups. With a median follow-up of 48.2 months, patients with any pCR had improved disease-free survival (DFS) (HR, 0.3; 95% CI, 0.157-0.572) and OS (HR, 0.192; 95% CI, 0.057-0.652) compared with RD patients. There were no significant differences in DFS (log-rank P = .18) and OS (log-rank P = 0.12) between patients with node-only pCR, breast-only pCR, and breast/LNs pCR. CONCLUSION: In node-positive breast cancer patients receiving NAC, any pCR was associated with improved survival vs RD. The anatomic site of pCR did not impact survival. This suggests that any favorable response to NAC has prognostic value.

Overuse of Preoperative Staging of Patients Undergoing Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Guidelines of the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) discourage the use of imaging to stage newly diagnosed early breast cancer (stages 1 and 2). This study aimed to evaluate preoperative staging imaging rates among patients with stage 1 or 2 breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: From a prospectively maintained database, 303 patients with stage 1 or 2 breast cancer who had NAC from 2008 to 2016 were identified. The main outcome measures were the rate and outcomes of staging imaging performed. RESULTS: The mean age of the 303 patients with stage 1 or 2 breast cancer was 51 years (range, 26-87 years). Of these 303 patients, 278 (92.4%) had invasive ductal cancer. 90 (30.2%) had estrogen receptor (ER)-positive disease, 79 (26.5%) had triple-negative disease, and 127 (42.6%) had human epidermal growth factor receptor 2 (HER2)-positive disease. Staging positron emission tomography (PET) or computed tomography (CT) scan was performed for 258 patients (85.2%), brain imaging for 94 patients (31%), bone scans for 117 patients (38.6%), and all three for 48 patients (15.8%). As a result, 15 patients (4.9%) with a positive PET/CT scan were upstaged to stage 4 breast cancer. No difference was observed among the ER-positive (p = 1.000), HER2-positive (p = 0.259), or triple-negative (p = 0.369) receptor profiles of the patients upstaged to stage 4 disease. One patient (1.1%) had positive brain imaging. Five patients (4.3%) had a positive bone scan, and three of these patients (60%) had bone metastasis also shown on the PET/CT scan. CONCLUSION: Despite guideline recommendations, a high rate of preoperative staging imaging is completed for patients with clinical stage 1 or 2 breast cancer who receive NAC, with few positive results.

Preoperative optimization for major hepatic resection.

PURPOSE: Major hepatic resections are performed for primary hepatobiliary malignancies, metastatic disease, and benign lesions. Patients with chronic liver disease, including cirrhosis and steatosis, are at an elevated risk of malnutrition and impaired strength and exercise capacity, deficits which cause increased risk of postoperative complications and mortality. The aims of this report are to discuss the pathophysiology of changes in nutrition, exercise capacity, and muscle strength in patient populations likely to require major hepatectomy, and review recommendations for preoperative evaluation and optimization. METHODS: Nutritional and functional impairment in preoperative hepatectomy patients, especially those with underlying liver disease, have a complex and multifactorial physiologic basis that is not completely understood. RESULTS: Recognition of malnutrition and compromised strength and exercise tolerance preoperatively can be difficult, but is critical in providing the opportunity to intervene prior to major hepatic resection and potentially improve postoperative outcomes. There is promising data on a variety of nutritional strategies to ensure adequate intake of calories, proteins, vitamins, and minerals in patients with cirrhosis and reduce liver size and degree of fatty infiltration in patients with hepatic steatosis. Emerging evidence supports structured exercise programs to improve exercise tolerance and counteract muscle wasting. CONCLUSIONS: The importance of nutrition and functional status in patients indicated for major liver resection is apparent, and emerging evidence supports structured preoperative preparation programs involving nutritional intervention and exercise training. Further research is needed in this field to develop optimal protocols to evaluate and treat this heterogeneous cohort of patients.

Modern treatment of infected total knee arthroplasty with a 2-stage reimplantation protocol.

The purpose of this study was to determine if 2-stage reimplantation for the treatment of infected total knee arthroplasty (TKA) is still effective for treating contemporary pathogens, many of which are multidrug resistant (MDR). The medical records of all cases of infected TKAs from April 1998 to March 2006 were retrospectively reviewed for data on infecting organism and success of treatment. Of 72 patients (75 knees), with a minimum of 2 years of follow-up, who completed the protocol, the infection was eradicated in 90.7% (68/75 knees). Thirty-one (91.2%) of 34 of MDR infections and 42 (91.3%) of 46 of non-MDR infections were successfully treated. These results support previous studies that demonstrated the effectiveness of a 2-stage reimplantation protocol with a standard 1:8 minimal bactericidal titer for treating infections after TKA, including MDR organisms.

Can Radiologic Tumor Size Following Neoadjuvant Therapy Reliably Guide Tissue Resection in Breast Conserving Surgery in Patients with Invasive Breast Cancer?

Optimum tissue resection volume for patients with invasive breast cancer undergoing breast conserving surgery following neoadjuvant therapy (NAT) is not known. We compared positive margin and in-breast tumor recurrence (IBTR) between 2 groups that were created based on radiologic tumor size (RTS (cm3)) at diagnosis, RTS post-NAT, and volume of tissue resected (VTL): Pre-NAT group, patients with VTL closer to RTS at diagnosis, and post-NAT group, patients with VTL closer to post-NAT RTS. 82 patients with 84 breast cancers treated with NAT between 2007 and 2017 who had pre- and post-NAT imaging were identified from a prospectively maintained database. RTS at diagnosis, RTS post-NAT, and VTL were determined. Clinical and treatment characteristics, IBTR, and disease-free survival (DFS) were compared between pre-NAT (n = 51) and post-NAT (n = 33) groups. Compared to post-NAT patients, pre-NAT patients had smaller RTS at presentation (9.2 vs. 33.5 cm3, P < .001) and post-NAT (1.2 vs. 8.2 cm3, P = .024). At median follow-up of 4 years, there were no differences between groups in pathologic tumor size, positive margin rate, adjuvant therapy, IBTR, or DFS. Resection volumes that matched RTS on post-NAT imaging were not associated with increased positive margins or IBTR. It may be appropriate to use post-NAT imaging to guide lumpectomy volume.

Thirty-day postoperative morbidity in patients with breast cancer following neoadjuvant chemotherapy.

BACKGROUND: Early post-operative complications for patients having partial and total mastectomies after neoadjuvant chemotherapy have not been well defined. The objective was to compare post-operative complication rates among patients treated with partial mastectomy (PM), unilateral mastectomy (UM), and bilateral mastectomy (BM) after NAC. STUDY DESIGN: 398 patients with breast cancer who had NAC from 2008 to 2016 were identified from a prospectively maintained database. The primary outcome measure was 30-day post-operative morbidity. RESULTS: 125 patients (31.4%) underwent PM, 107 patients (26.9%) UM, and 166 (41.7%) BM. There was no significant difference among the 3 groups with respect to histology (ductal: 96.0% PM, 88.8% UM, 92.6% BM, p = 0.161). Groups were similar with respect to estrogen receptor positivity (overall 58.8%, p = 0.331) and triple negative biomarker status (overall 23.9%, p = 0.559). The PM group had a higher rate of HER2 positive disease (n = 58, 47.5%, p = 0.012). Patients who underwent PM had a lower clinical T Stage at presentation (p=<0.001), fewer axillary lymph node dissections (n = 32, 25.6%, p=<0.001), and a higher rate of pathologic complete response (n = 48, 38.4%, p = 0.037) compared with patients who underwent mastectomies. Overall, 52 patients (13.1%) had a complication within the 30 day post-operative period. 30-day complication rates were significantly higher in the BM group compared to the PM group: 6.4% (n = 8) for PM, 12.2% (n = 13) for UM, and 18.7% (n = 31) for BM, (p = 0.008). 30-day readmission rates were significantly higher in the BM group compared to the PM group (overall 4.5%; 0.8% PM, 2.8% UM, 8.4% BM, p = 0.004). CONCLUSION: Bilateral mastectomy is associated with higher rates of 30-day morbidity and re-admissions compared to partial mastectomy, but not unilateral mastectomy in patients who received neoadjuvant chemotherapy.

Treatment of infected total hip arthroplasty with a 2-stage reimplantation protocol: update on "our institution's" experience from 1989 to 2003.

Infection is a devastating complication of total hip arthroplasty (THA). This study aimed to determine whether 2-stage reimplantation is still effective for treating contemporary pathogens, including multidrug-resistant organisms. Records of all cases of infected THAs from 1989 to 2003 were reviewed for data on organism, presence of drug resistance, use of an antibiotic-impregnated spacer, type of reimplant, and success of treatment. Of the 87 protocol patients with 2 years of follow-up, 94.3% (82) underwent reimplantation. The original infection was eradicated in 80 of the 84 hips (78/82 patients), a success rate of 95%. All 21 multidrug-resistant infections were eradicated. There were no major differences in eradication rates when the period was split into 3 sections. These results support previous studies from our institution which demonstrated the effectiveness of a 2-stage reimplantation protocol with a standard 1:8 minimal bactericidal titer for treating infections after THA, including those due to methicillin-resistant organisms.

Pathology results of architectural distortion on detected with digital breast tomosynthesis without definite sonographic correlate.

BACKGROUND: Digital breast tomosynthesis (DBT) is a mammographic technique which improves the detection of breast cancer. Architectural distortion of malignancy may be occult on 2D mammography and ultrasound but detected by DBT. METHODS: 110 patients who underwent 116 DBT-guided needle biopsies for architectural distortion were identified between June 2014 and August 2017 and underwent review of medical records. RESULTS: 59 of 116 biopsies (51%) revealed lesions warranting further consideration or excision. These included 21 specimens with invasive carcinoma, 2 ductal carcinoma in situ (DCIS), 5 atypical ductal hyperplasia, 4 atypical lobular hyperplasia, and 2 other lesions. 46 lesions were excised. Surgical pathology demonstrated 22 malignant lesions (20 invasive carcinomas and 2 DCIS). 11 patients continued surveillance and two patients were lost to follow up. 94 lesions (87%) were not visible on ultrasonography. CONCLUSIONS: DBT-guided biopsy for architectural distortion detected a malignancy in 19% of lesions, demonstrating the importance of pathologic diagnosis for lesions without correlating ultrasound findings.

The use of spiral computed tomography scans for the detection of pulmonary embolism.

Total joint arthroplasty carries a risk of symptomatic pulmonary embolism (PE). This study examined symptoms and risk factors of patients who underwent postoperative spiral computed tomography (CT) scans. The presenting symptoms and risk factors of total hip arthroplasty and total knee arthroplasty patients who had a postoperative CT scan were reviewed and the location of PE/deep vein thrombosis (DVT) was noted for positive scans. Of the 10209 patients who had total hip or total knee arthroplasty, 478 (4.7%) underwent a spiral CT scan to rule out PE and 136 (1.3%) had scans positive for PE. Twenty-two and four tenths percent of scans were positive for PE only, 2.1% for proximal DVT only, and 6.1% for PE and proximal DVT. Patients taking estrogen and patients presenting with low oxygen saturation postoperatively were significantly (P = .010, P < .001) more likely to have a positive scan. Spiral CT is the gold standard for detection of PE. Thirty-one and one half percent of scans were positive for PE and/or DVT, yet only 19.2% of patients had a predisposing risk factor for PE. Total knee arthroplasty carried a greater risk for PE than THA.

Custom total femur spacer and second-stage total femur arthroplasty as a novel approach to infection and periprosthetic fracture.

Total femur arthroplasty procedures have previously been used after tumor excision and as a last resort for failed revision arthroplasty. The patient in this case presented with massive loss of femoral bone stock, a periprosthetic fracture, and recurrent Staphylococcus epidermidis infection. A specially designed total femoral spacer impregnated with antibiotics was created for a 2-stage revision procedure that successfully restored functional ability and eradicated the infection. Although 2-stage protocols with spacers have been used to treat persistent infections after hip and knee arthroplasty, this is the first reported instance of the creation of a total femur antibiotic-impregnated cement spacer and subsequent total femoral arthroplasty as a 2-stage protocol at our institution.

Use of integrative services is associated with maintenance of work schedule during and after cancer treatment.

INTRODUCTION: Cancer diagnosis affects employment status. Our health network offers supportive services to cancer patients. We hypothesized patients who used these services were more likely to continue to work during and after treatment. METHODS: A mailed survey was used to assess employment before, during, and after treatment, and support services used. Chi-square analysis was performed. RESULTS: The response rate was 34% (273/782). 87% of patients worked full or part time before cancer diagnosis, 68.8% continued to work during treatment, and 73.9% returned to work after treatment. 61% of patients used at least one type of support service. Patients who had no change in work status during treatment and who returned to work less than one month after treatment were more likely to use services. CONCLUSIONS: Most patients used support services, continued to work during treatment, and returned to pre-cancer employment status. Physicians should encourage patients to pursue supportive therapies.

Resection of the largest reported hepatic small vessel neoplasm.

Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the adult liver. The neoplastic cells are positive for markers of vascular lineage (CD31, CD34, FLI-1). The distinctive morphology and infiltrative borders separate HSVN from benign vascular tumors such as cavernous hemangioma, while lack of atypical morphologic features, low to absent mitotic activity and low proliferation index distinguish it from malignant vascular tumors such as epithelioid hemangioendothelioma and angiosarcoma. Due to its infiltrative nature and lack of adequate follow-up information, the benign versus low-grade nature of this tumor is currently uncertain. We present a patient with resected HSVN involving all but the right posterior section of the liver, making this case the largest reported in the current literature.

Tailored treatment of patients with hepatocellular carcinoma with portal vein invasion: experience from a multidisciplinary hepatobiliary tumor program within a NCI comprehensive cancer center.

BACKGROUND: Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) has a poor prognosis with limited treatment options. Intra-arterial brachytherapy (IAB) and transarterial chemoembolization (TACE) yield local control but risk accelerating liver dysfunction. The outcomes, survival, and safety of selective liver-directed treatment are reported. METHODS: Thirty-seven consecutive patients with HCC and PVI treated between 2009 and 2015 were reviewed from a prospectively collected database. Univariate analysis, Kaplan-Meier plots using the log-rank method, and multivariate analyses were performed. Statistical significance was defined as P<0.05. Overall survival was reported in months (median; 95% CI). RESULTS: Most patients (59%) had PVI identified at initial HCC diagnosis. The liver-directed therapy group (n=22) demonstrated a survival advantage versus the systemic/supportive care group (n=14) [23.6 (5.8, 30.9) vs. 6.0 (3.5, 8.8) months]. Patients indicated for liver directed therapy had unilateral liver involvement (100% vs. 43%, P<0.0001), lower median alkaline phosphatase (105.5 vs. 208.0, P=0.002), and lower mean Child-Turcotte-Pugh (CTP) score (5.9 vs. 7.2, P=0.04) and tolerated treatment without serious complications. CONCLUSIONS: In HCC patients presenting with PVI, liver-directed therapy was safely performed in patients with limited venous involvement and preserved liver function. Liver-directed therapy extended survival for these patients indicated for palliative chemotherapy by traditional guidelines.

Symptomatic labral tear post femoral shaft fracture: case report.

Fracture of the femoral shaft is a common injury that is often treated with closed locked intramedullary nailing. Associated injuries such as ipsilateral femoral neck fracture, neurological or vascular compromise, and soft tissue injury of the knee are well known, but surprisingly little information exists regarding soft tissue injury of the hip in the setting of a femoral shaft fracture. In this case a 35-year-old man status-post closed femoral shaft fracture fixation was found to have a symptomatic ipsilateral labral tear and was successfully treated with arthroscopic debridement.

Acute acalculous cholecystitis after gastrointestinal surgery.

Acute acalculous cholecystitis has been identified as a rare but potentially devastating entity after trauma, and burns, as well as in critically ill patients, and in the postoperative period. Gastrointestinal surgery is most frequently implicated in postoperative acute acalculous cholecystitis, especially after gastric and colorectal procedures. Review of the English literature identified 28 articles reporting 76 cases of acute acalculous cholecystitis after gastrointestinal operations, which included a case from Tulane University Medical Center of a 64-year-old man who developed postoperative acute acalculous cholecystitis after elective left hemicolectomy. A total of 52.4 per cent of the patients developed gangrenous acute acalculous cholecystitis, with a mortality rate of 21.1 per cent, much higher than that reported in postoperative calculous cholecystitis. This emphasizes the need for a high level of suspicion and early detection in the postoperative period to avoid devastating consequences.

Thromboembolic Complications Following Spine Surgery Assessed with Spiral CT Scans: DVT/PE Following Spine Surgery.

Spine surgery is associated with a significant risk of postoperative pulmonary embolism (PE) and/or deep vein thrombosis (DVT). The goal of this study was to determine which symptoms and risk factors were associated with spiral CT scans positive for PE and/or DVT in the postoperative spine surgery patient. We conducted a retrospective review of all spine patients who underwent a postoperative CT to rule out PE during the period of March 2004-February 2006. The type of surgical procedure, risk factors, symptoms prompting scan ordering, anticoagulation, and treatment were recorded. Logistic regression models were used to determine significant predictors of a positive CT in this patient population. Of the 3,331 patients that had spine surgery during the study period, 130 (3.9%) had a spiral CT scan to rule out PE and/or proximal DVT. Thirty-three of the 130 (25.4%) CT scans were positive for PE only, five (3.8%) for PE and DVT, and three (2.3%) for DVT only. Only 24.5% (32) patients had risk factors for thromboembolic disease, and of these, a history of PE and/or DVT was the only significant risk factor for a positive scan (p = 0.03). No presenting symptoms or demographic variables were noted to have a significant association with PE and/or DVT. The type of surgical procedure (i.e., anterior, posterior, and percutaneous) was not associated with an increased risk for PE and/or DVT. Patients who are undergoing spine surgery with a history of thromboembolic disease should be carefully monitored postoperatively and may benefit from more aggressive prophylaxis.

Detection of Pulmonary Embolism in the Postoperative Orthopedic Patient Using Spiral CT Scans.

Orthopedic surgery is associated with a significant risk of postoperative pulmonary embolism (PE) and/or deep vein thrombosis (DVT). This study was performed to compare the clinical presentations of a suspected versus a documented PE/DVT and to determine the actual incidence of PE/DVT in the post-operative orthopedic patient in whom CT was ordered. All 695 patients at our institution who had a postoperative spiral CT to rule out PE/DVT from March 2004 to February 2006 were evaluated and information regarding their surgical procedure, risk factors, presenting symptoms, location of PE/DVT, and anticoagulation were assessed. Statistical analysis was performed using an independent samples t test with a two-tailed p value to examine significant associations between the patient variables and CT scans positive for PE. Logistic regression models were used to determine which variables appeared to be significant predictors of a positive chest CT. Of 32,854 patients admitted for same day surgery across all services, 695 (2.1%) had a postoperative spiral CT based on specific clinical guidelines. The incidence of a positive scan was 27.8% (193/695). Of these, 155 (22.3%) scans were positive for PE only, 24 (3.5%) for PE and DVT, and 14 (2.0%) for DVT only. The most common presenting symptoms were tachycardia (56%, 393/695), low oxygen saturation (48%, 336/695), and shortness of breath (19.6%, 136/695). Symptoms significantly associated with DVT were syncope and chest pain. A past medical history of PE/DVT was the only significant predictor of a positive scan. Patients who have a history of thromboembolic disease should be carefully monitored in the postoperative setting.