McLaughlin, Sarah A.

Abstract Purpose: Patient-derived xenografts (PDX) are a research tool for studying cancer biology and drug response phenotypes. While engraftment rates are higher for tumors with more aggressive characteristics, it is uncertain whether engraftment is prognostic for cancer recurrence. Patients and Methods: In a prospective study of patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with taxane ± trastuzumab followed by anthracycline-based chemotherapy, we report the association between breast cancer events and PDX engraftment using tumors derived from treatment naïve (pre-NAC biopsies from 113 patients) and treatment resistant (post-NAC at surgery from 34 patients). Gray test was used to assess whether the cumulative incidence of a breast cancer event differs with respect to either pre-NAC PDX engraftment or post-NAC PDX engraftment. Results: With a median follow-up of 5.7 years, the cumulative incidence of breast cancer relapse did not differ significantly according to pre-NAC PDX engraftment (5-year rate: 13.6% vs. 13.4%; P = 0.89). However, the incidence of a breast event was greater for patients with post-NAC PDX engraftment (5-year rate: 50.0% vs. 19.6%), but this did not achieve significance (P = 0.11). Conclusions: In treatment-naïve breast cancer receiving standard NAC, PDX engraftment was not prognostic for breast cancer recurrence. Further study is needed to establish whether PDX engraftment in the treatment-resistant setting is prognostic for cancer recurrence.

Background: Lymphangiogenic growth factors, such as vascular endothelial growth factor (VEGF)-D, are subjects of interest in studies of targeted therapies in lymphedema treatment. Methods and Results: We conducted a systematic review assessing the use of VEGF-D as a targeted therapy in lymphedema treatment. We hypothesized that VEGF-D was a promising therapy to induce lymphangiogenesis. Our search yielded 90 studies in the literature, but only 4 articles fulfilled our study eligibility criteria, and they were all experimental studies using viral gene transfer. The majority of the studies were conducted on small animals (mice) and investigated the effects of VEGF-D on lymph node transfer. All authors agreed about VEGF-D's lymphangiogenic potential, but they noticed that VEGF-C induced a superior lymphangiogenesis, and one study noticed that VEGF-D induced seroma. Conclusions: The publications assessing the use of VEGF-D as a targeted therapy in lymphedema treatment were able to demonstrate its lymphangiogenic potential. Nonetheless, further studies are still necessary to investigate VEGF-D's efficacy and safety in lymphedema treatment on patients.

BACKGROUND: Bioimpedance spectroscopy has been suggested as a useful tool for early diagnosis of breast cancer–related lymphedema (BCRL). We aimed to describe the outcomes of published studies that evaluated bioimpedance analysis as a method for prospective surveillance and early diagnosis of BCRL. METHODS: We queried the PubMed, Ovid Medline, and EMBASE databases to identify studies that evaluated use of bioimpedance spectroscopy as a diagnostic tool. We used the keywords “bioimpedance” AND (“lymphedema” OR “lymphoedema”) in the search. Only English-language studies that reported quantitative outcomes for patients with BCRL were included. RESULTS: Of 152, 235 and 116 identified articles in PubMed, Ovid Medline and EMBASE databases, only 22 were included. Use of bioimpedance analysis for prospective surveillance has been shown to prevent chronic BCRL. All the cross-sectional and retrospective studies that evaluated bioimpedance for diagnosis of BCRL reported significantly different L-Dex scores between lymphedema patients and healthy participants; in addition, bioimpedance scores were positively correlated with volume of lymphedema. CONCLUSION: Bioimpedance analysis is a potential tool with demonstrated benefits for prevention of chronic BCRL and may be an economic and great alternative for early diagnosis of BCRL.

Controversy exists regarding the influence of breast cancer–related lymphedema (BCRL) in the development of peripheral neuropathies. Our aim was to evaluate the association of secondary lymphedema with peripheral neuropathies in patients with breast cancer. We performed a systematic review by querying PubMed, EMBASE, Ovid Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Cochrane Central Register of Controlled Trials databases. The keywords “lymphedema” AND (“neuropathy” OR “carpal tunnel syndrome” OR “cubital tunnel syndrome” OR “neuropathic pain”) and synonyms in titles and abstracts were used to perform the search. Seventeen articles met the inclusion criteria. Discrepancies were found in studies that analyzed whether a cause-effect association exists between carpal tunnel syndrome (CTS) and secondary lymphedema. No evidence indicated that lymphedema predisposes to developing peripheral neuropathies such as CTS or brachial plexopathy. No studies found an association between patients with breast cancer at risk of or with lymphedema and the development or worsening of CTS. Carpal tunnel release can be safely performed in patients with BCRL. Neuropathic pain worsens with lymphedema, and treatment seems to improve the pain. Our study did not find enough evidence to conclude that BCRL is associated with the development of peripheral neuropathies. Carpal tunnel release is a safe procedure that can be performed in patients with BCRL and does not influence the development or worsening of lymphedema. Neuropathic pain seems to worsen after development of lymphedema, and treatment has been found to improve neuropathic pain.

627 Background: With more centers using MRI to aid in initial staging, there is apprehension that the highly sensitive MRI exam may lead to “unnecessary” mastectomies. We evaluated whether a negative contralateral MRI could be used to rule out a synchronous contralateral carcinoma and hence avoid a prophylactic contralateral mastectomy (CPM) at initial breast cancer diagnosis. Methods: Data of women with a new diagnosis of breast cancer (invasive or DCIS) from February 2003-November 2007 at our institution were reviewed. Women who had a negative MRI of the contralateral breast and who subsequently underwent CPM were included. A CPM was one in which there was no histological confirmation of cancer in the contralateral breast before surgery. All mastectomy specimens were analyzed pathologically. True negatives were mastectomy samples which contained no cancer following pathologic examination. False negatives were mastectomy samples which were found to have cancer after pathologic review. Results: 538 women were identified. 51 women met the study criteria. Median patient age was 56 years (range, 33–77). Of the 51 women who underwent a CPM, 2 were found to have pathologic confirmation of cancer. One occult cancer was a 0.3 cm grade 1, invasive lobular carcinoma; the second a 0.5 cm, low grade DCIS. The overall prevalence of synchronous occult contralateral cancer after a negative MRI was 3.9% (95% CI 0.5 - 13.5%). The negative predictive value of MRI was 96.1% (95% CI 86.5 - 99.5%). Conclusions: This study provides pathologic data regarding the utility of a negative contralateral breast MRI in women with newly diagnosed breast cancer. The prevalence of a synchronous occult contralateral cancer after a negative MRI in women with newly diagnosed breast cancer is very low. Physicians and patients can be assured that the risk of occult cancer is low in the setting of a normal contralateral MRI, an important fact when considering CPM after a diagnosis of unilateral breast cancer. No significant financial relationships to disclose.

Breast cancer treatment-related lymphedema (BCRL) is a common comorbidity in breast cancer survivors. Although magnetic resonance imaging (MRI) is widely used to evaluate therapeutic response of patients with various medical conditions, it is not routinely used to evaluate lymphedema patients. We conducted a systematic review of the literature to identify studies on the use of MRI to evaluate therapy for BCRL. We hypothesized that MRI could provide information otherwise not possible through other examinations. On October 21, 2019, we conducted a systematic review on the PubMed/MEDLINE and Scopus databases, without time frame or language limitations, to identify studies on the use of MRI to evaluate therapy for BCRL. We excluded studies that investigated other applications of MRI, such as lymphedema diagnosis and surgical planning. Of 63 potential articles identified with the search, three case series fulfilled the eligibility criteria. In total, 53 patients with BCRL were included and quantitatively evaluated with MRI before and after manual lymphatic drainage. Authors used MRI or MR lymphagiography to investigate factors such as lymphatic vessel cross-sectional area, tissue water relaxation time (T2), and chemical exchange saturation transfer. The only study that compared MRI measurement with standard examinations reported that MRI added information to the therapy evaluation. MRI seems to be a promising tool for quantitative measurement of therapeutic response in patients with BCRL. However, the identified studies focused on only manual lymphatic drainage and were limited by the small numbers of patients. More studies are necessary to shed light on the topic.

Pneumatosis intestinalis, or air within the wall of the gastrointestinal tract, has been documented from the esophagus to the rectum. Its presence can suggest gangrenous changes of the stomach or colon and represents a surgical emergency. However, pneumatosis intestinalis can also occur as a result of a benign, nongangrenous condition. We report the conservative management of a patient with nongangrenous gastric and esophageal pneumatosis.

AbstractPurposeStudy objectives were to examine: (a) biomarker trajectories (change from presurgical baseline values of Lymphedema index (L‐Dex) units and arm volume difference) and symptom cluster scores 24 months after breast cancer surgery and (b) associations of these objective biomarkers and symptom cluster scores. Patient/treatment characteristics influencing trajectories were also evaluated.MethodsA secondary analysis of data from the published interim analysis of a randomized parent study was undertaken using trajectory analysis. Five hundred and eight participants included in the prior analysis with 24 months of postsurgical follow‐up were initially measured with bioelectric impedance spectroscopy (BIS) and tape measure (TM) and completed self‐report measures. Patients were reassessed postsurgery for continuing eligibility and then randomized to either BIS or TM groups and measured along with self‐report data at regular and optional* visits 3, 6,12,15*,18, 21*, and 24‐months.ResultsThree subclinical trajectories were identified for each biomarker (decreasing, stable, increasing) and symptom cluster scores (stable, slight increase/decrease, increasing). Subclinical lymphedema was identified throughout the 24‐month period by each biomarker. An L‐Dex increase at 15 months in the BIS group was noted. The self‐report sets demonstrated contingency coefficients of 0.20 (LSIDS‐A soft tissue, P = .031) and 0.19 (FACTB+4, P = .044) with the L‐Dex unit change trajectories.ConclusionsThese data support the need for long‐term (24 months) prospective surveillance with frequent assessments (every 3 months) at least 15 months after surgery. Statistically significant convergence of symptom cluster scores with L‐Dex unit change supports BIS as beneficial in the early identification of subclinical lymphedema.