Clinical Utility of Neoadjuvant MRI in Early-Stage Breast Cancer Patients

Background With the increasing use of neoadjuvant treatment (NAT) for patients with early-stage breast cancer (ESBC), adequate clinical staging is essential to inform treatment. While the use of MRI with NAT has been proposed to help with accuracy of pre-treatment clinical staging, its impact in clinical practice remains controversial. Methods A prospective institutional database of patients with ESBC treated with NAT between May 2012 and December 2020 was analyzed in order to compare the management of patients who received an MRI prior to NAT to those who did not. The indications for MRI and correlation of MRI findings to conventional breast imaging were evaluated. The impact of MRI on management was compared between the MRI and non-MRI groups. Results A total of 530 patients met inclusion criteria. Of these, 186 (35.1%) had an MRI and 344 (64.9%) did not. The most frequent indication for MRI was the determination of disease extent (54.5%). Patients who had an MRI prior to neoadjuvant treatment were significantly more likely to be younger (47 years versus 57 years; p<0.001) and have multifocal disease (32.3% versus 22.1%; p<0.05). When compared to conventional imaging, MRI reported a greater extent of disease in the breast (37.6%), more nodal involvement (18.8%) and multifocal disease (15.1%). Additional diagnostic interventions were advised in 52.2% of patients. who underwent MRI. Rates of mastectomies were greater in the MRI group (80.0% versus 58.9%; p<0.05) in addition to more axillary dissections (28.0% versus 17.4%; p<0.01). Rates of locoregional recurrences were low in both groups, with similar disease-free survival outcomes at 5 years. Conclusions MRI identified significantly more disease in contrast to conventional imaging and lead to more aggressive surgical management. Prospective studies evaluating the role of neoadjuvant MRI and its impact on long term outcomes are needed.

Preoperative Ultrasonography in the Evaluation of Suspected Familial Non-Medullary Thyroid Cancer: Are We Able to Predict Multifocality and Extrathyroidal Extension?

Family history of thyroid cancer increases the risk of harboring thyroid malignancies that end up having extrathyroidal extension (ETE) and multifocality on histology; some authors suggest a more aggressive surgical approach. Their pre-operative identification could allow more conservative surgical procedures if none of these features are suspected. Our aim was to assess if neck ultrasonography could identify or exclude multifocality or ETE in these patients to tailor the extent of surgery. This retrospective study included patients with previous thyroid surgery, ≥1 first-grade relative with thyroid cancer, and who had undergone pre-surgical ultrasound. ETE was suspected in the case of thyroid border interruption or gross invasion of perithyroidal tissues. Multiple suspicious nodules were defined as suspicion of multifocal cancer. The cohort consisted of 45 patients (median age 49 years, 40 with thyroid cancer, 30 females). The positive predictive value of ultrasonography in predicting multifocality and ETE was 57.14% (25.25–84.03) and 41.67% (21.5–65.1%), respectively, while the negative predictive values were 63.2% (56.4–69.4%) and 72.7% (63.3–80.5%). Pre-operative ultrasound examination is unable to reliably identify or exclude multifocal disease or extrathyroidal extension. In patients scheduled for surgery and with a first-degree relative affected by DTC, a “negative” pre-operative US report does not exclude the potential finding of multifocality and ETE at final histopathology.

Multifocality, Multicentricity, and Bilaterality of Breast Cancer

Multifocal, multicentric, and bilateral breast tumours are either benign, precursor lesions or malignant neoplasms.A multidisciplinary review of these entities can offer clinicians a practical guidance for diagnostic and treatment procedures. Multiple synchronous (multifocal or multicentric) ipsilateral breast cancers (MSIBC) with heterogeneous histopathology require particular attention, since MSIBC tends toward more aggressive biology and higher rates of nodal positivity. Being independent of laterality, domination of the invasive carcinoma was observed in the bilateral and multifocal disease type. The TNM staging system for breast cancer does not include multifocality and multiplicity. Only the tumour with the largest diameter is considered for the pT category, neglecting the secondary foci which can make the treatment decision more difficult. MSIBC has a similar prognosis to unifocal cancers, but sometimes they might be negative prognostic parameters. Likewise, in comparison with unifocal breast cancer, MSIBC presents a different genetic pathway.

Diagnosing a Rare Cutaneous Presentation of Anaplastic Large Cell Lymphoma

Anaplastic Large Cell Lymphoma (ALCL) is a rare aggressive neoplasm. Rapid and progressive lymphadenopathy is common. Due to its aggressive nature, two-thirds of initial presentations are in stage III or IV. Multifocal disease that is primarily cutaneous is rare and extracutaneous spread of the cancer occurs in up to 13 percent of cases. In this case, a patient with systemic ALCL went undiagnosed for two months across three hospitalizations. A 33-year old male presented with multiple cutaneous lesions that had erupted bilaterally on his lower extremities and a fever which was unresponsive to over the counter medication. The patient required three hospitalizations and extensive work up before a diagnosis of Anaplastic Lymphoma Kinase (ALK) -negative CD30+ T-cell lymphoma was made by skin and lymph node biopsy. Diagnosis was delayed due to this patient’s uncommon presentation, the broad list of differential diagnoses, inaccuracies in biopsy, and communication delays from multiple hospital visits. This patient had aggressive ALCL and passed away during the first week of chemotherapy treatment. When there is a concern for malignancy, properly performed biopsies are important to collect from appropriate sites with non-necrotic tissue. Additionally, this case demonstrates the consequences of inadequate communication during handoff between transfer centers. It is important to have a broad differential diagnosis as well as prompt investigation and constant communication between all providers involved when a patient presents with abnormal and aggressively progressing symptoms.

Surgical management of complex ileocolonic Crohn’s disease: a survey of IBD colorectal surgeons to assess variability in operative strategy

Introduction To explore the reported variability in the surgical management of ileocolonic Crohn’ s disease and identify areas of standard practice, we present this study which aims to assess how different colorectal surgeons with a subspecialty interest in inflammatory bowel disease (IBD) surgery may act in different clinical scenarios of ileocolonic Crohn’s disease. Methods Anonymous videos demonstrating the small bowel walkthrough and anonymised patients’ clinical data, imaging and pathological findings were distributed to the surgeons using an electronic tool. Surgeons answered on operative strategy, bowel resections, management of small bowel mesentery, type of anastomosis and use of stomas. Results Eight small bowel walkthrough videos were registered and 12 assessors completed the survey with a questionnaire completion rate of 87.5%. There was 87.7% agreement in the need to perform an ileocolonic resection. However, the agreement for the need to perform associated surgical procedures such as strictureplasties or further bowel resections was only 57.4%. When an anastomosis was fashioned, the side to side configuration was the most commonly used. The preferred management of the mesentery was dissection close to the bowel. Conclusions The decision on the main procedure to be performed had a high agreement amongst the different assessors, but the treatment of multifocal disease was highly controversial, with low agreement on the need for associated procedures to treat internal fistulae and the use of strictureplasties. At the same time, there was significant heterogeneity in the decision on when to anastomose and when to fashion an ileostomy.

Special Situations in the Management of Diverticular Disease

Diverticular disease affects a large percentage of the US population, affecting over 30% among those older than 45 years old. It is responsible for ∼300,000 hospitalizations per year in the United States and can lead to serious complications such as hemorrhage, obstruction, abscess, fistulae, or bowel perforation.2 It is an extremely common reason for emergency room and outpatient visits and evaluations by general and colorectal surgeons. In the US, patients usually present with sigmoid diverticulitis in the setting of a normal immune system so surgeons will follow well-established practice guidelines for treatment. However, there may be special circumstances in which the management of diverticulitis is not as straightforward. In this article, we will address patients who present with multifocal disease, giant colonic diverticulum, right-sided diverticulitis, and diverticulitis in the setting of immunosuppression and hopefully provide guidance for treatment in these special circumstances.

Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors

BackgroundDespite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence of multifocal/disseminated disease in patients increases their mortality risk. Hence, the development of novel strategies to effectively treat patients with melanomas that are resistant to anti-PD1 mAb (αPD1) and/or Brafi, particularly those with multifocal/disseminated disease remains a major unmet clinical need.MethodsMice developing induced/spontaneous BrafV600E/Pten−/− melanomas were treated by cutaneous immunization with a DNA vaccine encoding the melanoma-associated antigen TRP2, with Brafi or αPD1 alone, or with a combination of these treatments. Tumor progression, tumor-infiltration by CD4+ and CD8+ T cells, and the development of TRP2-specific CD8+ T cells were then monitored over time.ResultsVaccination led to durable antitumor immunity against PD1/Brafi-resistant melanomas in both single lesion and multifocal disease models, and it sensitized PD1-resistant melanomas to salvage therapy with αPD1. The therapeutic efficacy of the vaccine was associated with host skin-resident cells, the induction of a systemic, broadly reactive IFNγ+CD8+ T cell repertoire, increased frequencies of CD8+ TIL and reduced levels of PD1hi/intCD8+ T cells. Extended survival was associated with improved TIL functionality, exemplified by the presence of enhanced levels of IFNγ+CD8+ TIL and IL2+CD4+ TIL.ConclusionsThese data support the use of a novel genetic vaccine for the effective treatment of localized or multifocal melanoma refractory to conventional αPD1-based and/or Brafi-based (immune)therapy.