Perioperative predictors of early surgical revision and flap-related complications after microvascular free tissue transfer in head and neck reconstructions: a retrospective observational series.

OBJECTIVES: The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer. MATERIALS AND METHODS: Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression. RESULTS: The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5). CONCLUSION: Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications. CLINICAL RELEVANCE: In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

Tumour budding is associated with the mesenchymal colon cancer subtype and RAS/RAF mutations: a study of 1320 colorectal cancers with Consensus Molecular Subgroup (CMS) data.

BACKGROUND: Tumour budding is an important prognostic factor in colorectal cancer (CRC). Molecular profiling of tumour buds suggests (partial) epithelial-mesenchymal transition and cancer stem-cell phenotype, similarly described in the "mesenchymal" Consensus Molecular Subtype 4 (CMS4), which identifies a particularly poor prognostic subgroup. Here, we determine the association of tumour budding with CMS classification, prognosis, and response to therapy. METHODS: AMC-AJCCII-90 cohort (n = 76, stage II) was evaluated for peritumoural budding on H&E slides. LUMC (n = 270, stage I-IV), CAIRO (n = 504, metastatic CRC) and CAIRO2 (n = 472, metastatic CRC) cohorts were investigated for intratumoural budding using pan-cytokeratin-stained tissue microarrays. Budding was scored as count/area, then classified as <5 or ≥5 buds. For all cohorts, CMS classifications were available (gene-expression/immunohistochemistry-based classifiers). RESULTS: High (≥5) budding predicted a worse outcome in multivariate analysis in AMC-AJCCII-90 (p = 0.018), LUMC (p < 0.0001), and CAIRO (p = 0.03), and in CAIRO2 (continuous variable, p = 0.02). Tumour budding counts were higher in CMS4 compared to epithelial CMS2/3 cancers (p < 0.01, all), and associated with KRAS/BRAF mutations (p < 0.01, AMC-AJCCII-90, CAIRO, CAIRO2). CONCLUSION: Tumour budding is an adverse prognostic factor across all CRC stages and is associated with the mesenchymal CMS4 phenotype. KRAS/BRAF mutations are strongly correlated with tumour budding suggesting their involvement in the regulation of this process.

High tumor budding stratifies breast cancer with metastatic properties.

Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

BACKGROUND: With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. METHODS: AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. RESULTS: AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). CONCLUSIONS: Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

Survival from Rhino-Orbital-Cerebral Mucormycosis in SARS-CoV-2-Positive Diabetic Patients: Two Case Reports.

Introduction: Rhino-orbital-cerebral mucormycosis (ROCM) is a rare angioinvasive fungal infection known to be associated with high morbidity and over 50% mortality. ROCM is becoming more common due to an increase in predisposing immunocompromising comorbidities as well as COVID-19. Case Presentations: We report 2 cases - a 75-year-old woman with diabetes and a 39-year-old man with recurrent diabetic ketoacidosis. Both presented initially with acute sinonasal symptoms, were positive for SARS-CoV-2, and diagnosed with acute ROCM. Both underwent mutilating surgical therapy as well as high-dose amphotericin B treatment. With continued oral antifungal treatment, patient 1 showed stable symptoms despite radiographically increasing disease and died of urosepsis 5 months after first surgery. With posaconazole treatment, patient 2 recovered from the disease and showed no clinical sign of disease progression after 1 year. Conclusion: Despite the rarity of the disease, ROCM should be considered if the findings of clinical and radiological examination fit, so that a delay in treatment initiation can be avoided. As our both cases show, survival from ROCM is possible - albeit at a high cost.

Alexander's Law During High-Speed, Yaw-Axis Rotation: Adaptation or Saturation?

Objective: Alexander's law (AL) states the intensity of nystagmus increases when gaze is toward the direction of the quick phase. What might be its cause? A gaze-holding neural integrator (NI) that becomes imperfect as the result of an adaptive process, or saturation in the discharge of neurons in the vestibular nuclei? Methods: We induced nystagmus in normal subjects using a rapid chair acceleration around the yaw (vertical) axis to a constant velocity of 200°/second [s] and then, 90 s later, a sudden stop to induce post-rotatory nystagmus (PRN). Subjects alternated gaze every 2 s between flashing LEDs (right/left or up/down). We calculated the change in slow-phase velocity (ΔSPV) between right and left gaze when the lateral semicircular canals (SCC) were primarily stimulated (head upright) or, with the head tilted to the side, stimulating the vertical and lateral SCC together. Results: During PRN AL occurred for horizontal eye movements with the head upright and for both horizontal and vertical components of eye movements with the head tilted. AL was apparent within just a few seconds of the chair stopping when peak SPV of PRN was reached. When slow-phase velocity of PRN faded into the range of 6-18°/s AL could no longer be demonstrated. Conclusions: Our results support the idea that AL is produced by asymmetrical responses within the vestibular nuclei impairing the NI, and not by an adaptive response that develops over time. AL was related to the predicted plane of eye rotations in the orbit based on the pattern of SCC activation.