A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology.

Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer.

Preoperative multimodal protocol reduced postoperative nausea and vomiting in patients undergoing mastectomy with reconstruction.

BACKGROUND: Mastectomy with immediate reconstruction is a high-risk cohort for postoperative nausea and vomiting (PONV). Known risk factors for PONV include female gender, prior PONV history, nonsmoker, age < 50, and postoperative opioid exposure. The objective of this observational, cohort analysis was to determine whether a standardized preoperative protocol with nonopioid and anti-nausea multimodal medications would reduce the odds of PONV. METHODS: After IRB approval, retrospective data were collected for patients undergoing mastectomy with or without a nodal resection, and immediate subpectoral tissue expander or implant reconstruction. Patients were grouped based on treatment: those receiving the protocol - oral acetaminophen, pregabalin, celecoxib, and transdermal scopolamine (APCS); those receiving none (NONE), and those receiving partial protocol (OTHER). Logistic regression models were used to compare PONV among treatment groups, adjusting for patient and procedural variables. MAIN FINDINGS: Among 305 cases, the mean age was 47 years (21-74), with 64% undergoing a bilateral procedure and 85% having had a concomitant nodal procedure. A total of 44.6% received APCS, 30.8% received OTHER, and 24.6% received NONE. The APCS group had the lowest rate of PONV (40%), followed by OTHER (47%), and NONE (59%). Adjusting for known preoperative variables, the odds of PONV were significantly lower in the APCS group versus the NONE group (OR=0.42, 95% CI: 0.20, 0.88 p = 0.016). CONCLUSIONS: Premedication with a relatively inexpensive combination of oral non-opioids and an anti-nausea medication was associated with a significant reduction in PONV in a high-risk cohort. Use of a standardized protocol can lead to improved care while optimizing the patient experience.

Perioperative antibiotics should be used for placement of implanted central venous ports: A propensity analysis evaluating risk.

OBJECTIVE: To quantify risk for CRI based on PABX use in CVAP placement for cancer patients. SUMMARY BACKGROUND DATA: Central venous access ports (CVAP) are totally implanted devices used for chemotherapy. There is a temporal risk for catheter related infection (CRI) to insertion and perioperative prophylactic antibiotics (PABX) use is a contested issue among practitioners. METHODS: Data was collected from a single center, academic oncology center. Treatment with a perioperative PABX was compared to non-treatment, to examine the incidence of 14-day CRI. Propensity scores with matched weights controlled for confounding, using 15 demographic, procedural and clinical variables. RESULTS: From 2007 to 2012, 1,091 CVAP were placed, where 59.7 % received PABX. The 14-day CRI rate was 0.82%, with 78% of those not receiving PABX. While results did not achieve statistical significance, use of PABX was associated with a 58% reduction in the odds of a 14-day CRI (OR = 0.42, 95% CI: 0.08-2.24, p = 0.31). CONCLUSION: The findings suggest a reduction in early CRI with the use of PABX. Since CRI treatment can range from a course of oral antibiotics, port removal, to hospital admission, we suggest clinicians consider these data when considering PABX in this high-risk population.

Surgical Outcomes for Mastectomy Patients Receiving Neoadjuvant Chemotherapy: A Propensity-Matched Analysis.

OBJECTIVE: To evaluate the risk of neoadjuvant chemotherapy for surgical morbidity after mastectomy with or without reconstruction using 1:1 matching. BACKGROUND: Postoperative surgical complications remain a potentially preventable event for breast cancer patients undergoing mastectomy. Neoadjuvant chemotherapy is among variables identified as contributory to risk, but it has not been rigorously evaluated as a principal causal influence. METHODS: Data from American College of Surgeons National Surgical Quality Improvement Program (2006-2012) were used to identify females with invasive breast cancer undergoing planned mastectomy. Surgical cases categorized as clean and undergoing no secondary procedures unrelated to mastectomy were included. A 1:1 matched propensity analysis was performed using neoadjuvant chemotherapy within 30 days of surgery as treatment. A total of 12 preoperative variables were used with additional procedure matching: bilateral mastectomy, nodal surgery, tissue, and/or implant. Outcomes examined were 4 wound occurrences, sepsis, and unplanned return to the operating room. RESULTS: We identified 31,130 patient procedures with 2488 (7.5%) receiving chemotherapy. We matched 2411 cases, with probability of treatment being 0.005 to 0.470 in both cohorts. Superficial wound complication was the most common wound event, 2.24% in neoadjuvant-treated versus 2.45% in those that were not (P = 0.627). The rate of return to the operating room was 5.7% in the neoadjuvant group versus 5.2% in those that were not (P = 0.445). The rate of sepsis was 0.37% in the neoadjuvant group versus 0.46% in those that were not (P = 0.654). CONCLUSIONS: This large, matched cohort study, controlled for preoperative risk factors and most importantly for the surgical procedure performed, demonstrates that breast cancer patients receiving neoadjuvant chemotherapy have no increased risk for surgical morbidity.

Image-guided placement of long-term central venous catheters reduces complications and cost.

BACKGROUND: The goals of this study were to evaluate the complication rate for intraoperative placement of a long-term central venous catheter (CVC) using intraoperative ultrasound (US) and fluoroscopy and to examine the feasibility for eliminating routine postprocedure chest X-ray. METHODS: Retrospective data pertaining to operative insertion of long-term CVC were collected and the rate of procedural complications was determined. RESULTS: From January 2008 to August 2013, 351 CVCs were placed via the internal jugular vein using US. Of these, 93% had a single, successful internal jugular vein insertion. The complications included 4 arterial sticks (1.14%). Starting in October 2012, postprocedure chest radiography (CXR) was eliminated in 170 cases, with no complications. A total of $29,750 in charges were deferred by CXR elimination. CONCLUSIONS: This review supports the use of US for CVC placement with fluoroscopy in reducing the rate of procedural complications. Additionally, with fluoroscopic imaging, postprocedural CXR can be eliminated with associated healthcare savings.

Optimal utilization of a breast care advanced practice clinician.

BACKGROUND: Incorporation of "lean" business philosophy within health care has the goal of adding value by reducing cost and improving quality. Applying these principles to the role of Advance Practice Clinicians (APCs) is relevant because they have become essential members of the healthcare team. METHODS: An independent surgical breast care clinic directed by an APC was created with measurements of success to include the following: time to obtain an appointment, financial viability, and patient/APC/MD satisfaction. RESULTS: During the study period, there was a trend toward a decreased median time to obtain an appointment. Monthly APC charges increased from $388 to $30,800. The mean provider satisfaction score by Press Ganey was 96% for the APC and 95.8% for the surgeon. Both clinicians expressed significant satisfaction with clinic development. CONCLUSIONS: Overall, initiation of an APC breast clinic met the proposed goals of success. The use of lean philosophy demonstrates that implementation of change can result in added value in patient care.

A survey of American College of Surgery fellows evaluating their use of antibiotic prophylaxis in the placement of subcutaneously implanted central venous access ports.

BACKGROUND: Currently, there is no standard of care for prophylactic antibiotics (PABX) at the time of placement of fully implanted central venous access ports (CVAPs). A survey of fellows of the American College of Surgeons was undertaken to determine the current practice pattern of PABX in CVAP placement. METHODS: A survey was mailed to 5,000 fellows of the American College of Surgeons. RESULTS: The response rate was 21.7%, with 73.1% of respondents nonacademic surgeons. PABX were given by 88.2% of the respondents. Of those who did not use PABX, the primary reasons were "not justified" or "not standard of care." General comments regarding reasons for use of PABX included "medicolegal," "required by hospital," and "liability." CONCLUSIONS: In this survey, the overwhelming majority of responding American College of Surgeons fellows indicated that they use preoperative antibiotic prophylaxis for CVAP placement, despite there being no accepted standard of care or definitive evidence regarding PABX use for fully implanted CVAPs.

Local recurrence of breast cancer 52 years after halsted mastectomy: is there a role for more aggressive ipsilateral surveillance?

We present the longest reported case of breast cancer recurrence, 52 years after initial diagnosis, in a patient initially treated with Halsted mastectomy. Observation and palpation of the chest wall resulted in late presentation, and this patient went on to demonstrate metastatic disease. Current surveillance guidelines lack specific recommendations regarding monitoring of the ipsilateral chest wall. In addition, the growing utilization of breast reconstruction poses an additional challenge to surveillance strategies of the ipsilateral breast. However, the emergence of MRI may present a new opportunity to identify ipsilateral recurrence. The changing landscape of breast cancer therapy warrants guidance from groups of national import such as ASCO, in the surveillance of breast cancer patients.

Success in sentinel lymph node procedures in obese patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy for axillary staging in breast cancer is technically more demanding but of added benefit in obese patients. This retrospective review compares variables and outcomes of SLN staging in obese and nonobese women. METHODS: From 235 total SLN cases, demographics and clinical and procedural variables were collected and compared in obese (body mass index [BMI] of ≥ 35, n = 28) and nonobese (BMI ≤ 25 [n = 84]) patients. RESULTS: Overall, the intraoperative false-negative rate was 13.6% and failure to identify SLN occurred in 2 cases (.85%). Although no differences in patient or tumor characteristics were found, obese patients had significantly lower external hotspot counts, first sentinel node counts, and fewer sentinel nodes recovered when compared with the nonobese. CONCLUSIONS: SLN procedures are successful and accurate for axillary staging in obese women and avoid the added morbidity of axillary lymph node dissection in this higher risk population.

Antibiotic prophylaxis in the placement of totally implanted central venous access ports.

BACKGROUND: Antibiotic prophylaxis during placement of implanted central venous access ports (CVAP) has not been studied. This retrospective review compared the rate of catheter-related infections (CRIs) with and without perioperative antibiotics. METHODS: This was a single-center study that compared patients treated with and without a single dose of antibiotics during CVAP placement. CRIs were defined as a patient treated with antibiotics for port site induration, positive blood cultures, or suspicion of infection that led to port removal within 30 days of placement. RESULTS: CVAP were placed in 459 patients, 103 of whom (22.4%) received antibiotic prophylaxis. Surgical technique and patient demographics were similar to those patients not receiving antibiotics (356). All 9 (2%) CRIs occurred in the non-prophylactic antibiotic group (P = .218), with 5 infections resulting in port removal. CONCLUSIONS: Single-dose perioperative antibiotics may decrease CVAP infection rates and should be studied further in a prospective randomized trial.

Selective use of intraoperative sentinel lymph node pathological evaluation in breast cancer.

BACKGROUND: In breast cancer staging, the need for intraoperative sentinel lymph (SLN) evaluation is not well established. This study compares intraoperative use of touch preparation (TP), frozen section (FS), and factors that may influence the selective use of intraoperative SLN analysis. METHODS: Breast cancer patients (1998-2007) undergoing SLN evaluation were retrospectively reviewed. RESULTS: Of 205 SLN procedures, 157 cases underwent intraoperative evaluation, 43% (FS) and 57% (TP) with positive pathology in 21% and 20%, respectively. The false negative case rate was 16% for TP versus 12% for FS. Of T1, low-grade tumors, 9% were intraoperatively positive, versus 43% of T2-3, moderate- to high-grade tumors (P = .006). Additional positive axillary nodes were found in 43% of the higher risk patients versus 0% in the lower risk groups. CONCLUSIONS: Both TP and FS are accurate for intraoperative SLN evaluation and can be selectively applied to breast cancer staging in low- and high-risk groups.

Plasma cell neoplasms. Review of disease progression and report of a new variant.

Plasma cell neoplasms are generally categorized into four groups; multiple myeloma (MM), solitary plasmacytoma of the bone (SPB), plasma cell leukemias, and extramedullary plasmacytomas (EMP). A plasmacytoma is defined as any discrete, usually solitary mass of neoplastic plasma cells, either in the bone marrow or in various soft tissue sites. Each manifestation of a plasma cell neoplasm differs in terms of tumor recurrence and progression to MM. A gastric plasmacytoma (GP) is a rare presentation of extramedullary plasmacytoma and has not been previously reported as a site of recurrence for a SPB. This pattern of tumor recurrence is unique and the management of gastric plasmacytoma as part of this complex disease is discussed. The continuum of progression between various sites and manifestations of plasma cell manifestations is reviewed including a previously undiscovered sequence of bone disease, gastric disease, and finally multiple myeloma.

Desmoid tumor: a case of mistaken identity.

Desmoid tumors are rare tumors accounting for only 0.03% of all neoplasms. Mainly occurring in the fourth and fifth decades of life, these tumors originate in musculoaponeurotic tissues of the limbs, neck, trunk, abdominal wall, and mesentery. We present a rare case of a chest wall desmoid tumor that was mistaken for breast cancer on both physical examination and mammography, which highlights the unique risk these tumors present for confusion with other malignant processes. Although past literature contains numerous reports of other misdiagnoses, this case is unique in reporting the potential for misdiagnosis between chest wall desmoid tumors and breast cancer. In cases where suspicious breast findings do not correlate to usual diagnostic measures, such as fine-needle aspiration or core needle biopsy, the possibility of another pathology such as a chest wall desmoid tumor mimicking breast cancer should be considered in the differential diagnosis.

Transplantation of crossed fused ectopic kidneys into a single recipient.

BACKGROUND: Crossed renal ectopia is a rare (1 in 1000 live births) congenital anomaly in which both renal masses are located on one side of the abdomen and in 90% of cases are fused. Although this condition is not typically associated with underlying renal pathology or symptoms, complex vascular anatomy is commonly encountered. STUDY DESIGN: A report of the successful transplantation of crossed fused ectopic kidneys as a single allograft. RESULTS: With careful attention to the complex anatomy presented by this anomaly, the course of the patient's transplantation and postoperative convalescence were uncomplicated and resulted in excellent longterm graft function. We report the first successful transplantation and longterm function of crossed fused ectopic kidneys as a single allograft. CONCLUSIONS: Given the shortage of cadaveric renal allografts, patients with this anomalous condition should not be excluded as potential organ donors. Transplant surgeons should have an understanding of this anomaly and its anatomic variants to ensure proper utilization of this limited but valuable resource.