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Objectives Carcinomas involving the cavernous sinus are challenging to resect without compromising important neurovascular structures. Given the morbidity and mortality of these operations, radiotherapy, chemotherapy, and immunotherapy are more often utilized. Although limited to case reports and small series, radical resection of the cavernous sinus has been proposed. We aimed to study surgeons' willingness to perform cavernous sinus exenteration (CSE) under different clinical scenarios. Design, Setting, Participants, Main Outcome Measures We conducted an online survey from April to July 2021 among members of the Skull Base Congress and the North American Skull Base Society. Descriptive statistics were used to analyze the main outcome measure of willingness to perform CSE . Results The analytic sample ( n = 112) included 54% otolaryngologists and 43% neurosurgeons. Eighty-six percent practiced in an academic setting. Surgeons' willingness to perform CSE was low (6-16% under different clinical scenarios), citing a belief that they could not obtain oncologic margins and the procedure's morbidity. Forty-five percent had at least one patient undergo CSE with 72% of patients surviving no more than 2 years. Complications included chronic intractable pain, cerebrospinal fluid leak, cerebrovascular accident, and/or intraoperative/postoperative death within 30 days. Sixty percent agreed that the availability of immunotherapy and genomic sequencing has affected their willingness to offer CSE. Conclusion Overall, most of the surgeons surveyed were unwilling to offer CSE for carcinomatous cavernous sinus invasion, whether for primary disease or recurrence. Given the rarity of these tumors and the limited data on CSE, these results may provide more information for clinicians and patients for these treatment decisions.
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Introduction Radiation-induced hypopituitarism (RIH) has long been recognized as one of the deleterious side effects of skull base radiation. This study aims to assess the quality of life (QoL) among patients with RIH compared with radiated patients who did not develop hypopituitarism using the validated Anterior Skull Base Questionnaire (ASBQ). Methods This was a single-institution retrospective cohort study. Included patients had a history of anterior skull base tumor, underwent at least one round of radiation to the skull base, and had filled out at least one ASBQ survey after their radiation treatment. Three statistical models were used to determine the effect of hypopituitarism and treatment on QoL scores. Results A total of 145 patients met inclusion criteria, and 330 ASBQ surveys were analyzed. Thirty-five percent (51/145) had evidence of RIH at some point after their radiation treatment. Those with hypopituitarism had significantly lower overall ASBQ scores across all three models even after adjusting for potential confounders and intraperson correlation (average decrease of 0.24-0.45 on a 5-point Likert scale; p -values ranging from 0.0004 to 0.018). The increase in QoL with hormonal replacement was modulated by time out from radiation, with long-term survivors (5+ years out from radiation) gaining the most benefit from treatment (increase of 0.89 on a 5-point Likert scale, p 0.0412), especially in the vitality domain. Conclusion This data demonstrates that hypopituitarism is an independent predictor of lower QoL. Early detection and appropriate treatment are essential to avoid the negative impact of hypopituitarism on QoL.
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Objectives Sinonasal neuroendocrine carcinomas (SNECs) are among the rarest paranasal sinus cancers. Consensus guidelines for therapy are difficult to develop due to limited data regarding the natural history and successful treatment of these tumors. This study presents 15 years of experience treating SNEC at a single institution and a review of the literature. Design Retrospective review. Setting Academic medical center in the United States. Participants Patients diagnosed with primary SNEC. Main Outcome Measures Overall survival. Results Thirteen patients were identified and included. Overall estimated survival was 74.6% at 5 years. Ten of 13 (76.9%) patients were diagnosed with high-grade neuroendocrine carcinoma and three (23.1%) with intermediate or low grade. All three patients with low- or intermediate-grade cancer survived more than 10 years from their initial diagnosis (median survival: 11.6 years) and are currently alive. The four patients who died had high-grade carcinoma, and estimated overall 5-year survival for all patients with high-grade carcinomas was 65.6%. Five patients, all with high-grade carcinoma, of seven who completed primary chemoradiation therapy (CRT) required salvage resection, and 60% are alive without disease. Conclusion This cohort has a higher overall rate of survival than many recent case series and reviews. There is consensus that multimodal therapy is preferred over monotherapy, but approaches to treatment vary widely. Our approach of surgical resection as primary therapy for low-grade tumors and primary CRT for high-grade SNEC has been successful, and could indicate hope for improved survival among these patients.
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OBJECTIVE: Skull base osteomyelitis may rarely present in the sphenoid bone or clivus without an otologic source. This is referred to as central skull base osteomyelitis (CSBO). Knowledge regarding CSBO is limited to case reports and small case series. Here we present a case series to further describe typical patient characteristics, clinical presentation, and clinical course associated with this rare infection. METHODS: All patients treated at a single academic tertiary care institution for CSBO from 2016 through 2020 were identified. Inclusion criteria included culture proven CSBO without an otologic or iatrogenic source. Data were extracted via patient chart review and qualitatively analyzed. RESULTS: Seven patients were identified with CSBO, 5 male and 2 female. Age ranged from 63 to 87 (average 76). Risk factors included advanced age, diabetes, and history of radiation. The most common presenting symptom was headache (6), followed by otalgia (4). Two patients presented with cranial neuropathies. Diagnosis was facilitated by history and exam (including flexible laryngoscope exam), imaging (MRI), and labs (ESR). All patients received endoscopic biopsy and culture (most commonly polymicrobial, with diverse species). Treatment involved IV antibiotics, with a limited role for surgery. All patients survived and achieved resolution of infection. CONCLUSIONS: CSBO remains a diagnostic challenge due to its rarity and vague presenting symptoms that overlap with presentation of sinonasal malignancies. A high index of suspicion is required by the evaluating provider to ensure a timely diagnosis with early treatment in order to limit the significant morbidity which can be associated with this infection. LEVEL OF EVIDENCE: 4.
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Osteomyelitis , Skull Base , Humans , Male , Female , Tertiary Care Centers , Skull Base/diagnostic imaging , Skull Base/pathology , Biopsy , Osteomyelitis/therapy , Osteomyelitis/drug therapyABSTRACT
Poorly differentiated (PD) chordoma, a rare, aggressive tumor originating from notochordal tissue, shows loss of SMARCB1 expression, a core component of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. To determine the impact of SMARCB1 re-expression on cell growth and gene expression, two SMARCB1-negative PD chordoma cell lines with an inducible SMARCB1 expression system were generated. After 72 hours of induction of SMARCB1, both SMARCB1-negative PD chordoma cell lines continued to proliferate. This result contrasted with those observed with SMARCB1-negative rhabdoid cell lines in which SMARCB1 re-expression caused the rapid inhibition of growth. We found that the lack of growth inhibition may arise from the loss of CDKN2A (p16INK4A) expression in PD chordoma cell lines. RNA-sequencing of cell lines after SMARCB1 re-expression showed a down-regulation for rRNA and RNA processing as well as metabolic processing and increased expression of genes involved in cell adhesion, cell migration, and development. Taken together, these data establish that SMARCB1 re-expression in PD chordomas alters the repertoire of SWI/SNF complexes, perhaps restoring those associated with cellular differentiation. These novel findings support a model in which SMARCB1 inactivation blocks the conversion of growth-promoting SWI/SNF complexes to differentiation-inducing ones, and they implicate SMARCB1 loss as a late event in tumorigenic progression. Importantly, the absence of growth inhibition after SMARCB1 restoration creates a unique opportunity to identify therapeutic vulnerabilities.
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Chordoma , Humans , Chordoma/genetics , Chordoma/pathology , Transcription Factors/metabolism , Cell Differentiation/genetics , Carcinogenesis , SMARCB1 Protein/geneticsABSTRACT
BACKGROUND: The goal of this study was to learn more about the potential impact of medical student mistreatment on patient safety and care. METHODS: A web-based survey was sent to members of the class of 2021 and 2022 who have completed their core clerkships at a single academic institution. Descriptive statistics were performed to understand how prior and future mistreatment impacted communication among students and team members. RESULTS: We received 290 of 376 responses (77.1%). 26% of respondents indicated that past mistreatment negatively impacted their communication with other team members. 30% of respondents reported that fear of future mistreatment negatively impacted their communication with other team members. CONCLUSION: Mistreatment of medical students has many sources and occurs throughout the clinical curriculum. Past and fear of future student mistreatment can negatively impact intrateam communication and therefore negatively impact patient care, with the potential of causing poor patient outcomes.
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Clinical Clerkship , Students, Medical , Humans , Surveys and Questionnaires , Communication , LearningABSTRACT
[This corrects the article DOI: 10.1055/s-0040-1722642.].
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Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.
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Background: Microaggressions are one form of gender bias contributing to gender disparities and mistreatment, but their prevalence during virtual residency interviews has not been explored. Objective: To explore applicants' recall of experiencing gender microaggressions during virtual residency interviews and whether these experiences affected programs' rank position on applicants' rank lists. Methods: Fourth-year medical students at a single institution who participated in the 2021 Match were surveyed after submitting their rank lists. Students were surveyed categorically on (1) their recall of the frequency they experienced 17 gender microaggressions during interviews, and (2) how these affected reported ranking of programs on their rank lists. Results: Sixty-one percent (103 of 170) of eligible students responded to the survey. Seventy-two percent (36 of 50) of women experienced at least one microaggression compared to 30% (9 of 30) of men. The largest difference was in the experience of environmental microaggressions, which are demeaning cues communicated individually or institutionally, delivered visually, or that refer to climate (P<.001). Women experienced more microaggressions than men in nonsurgical (P=.003) and surgical specialties excluding obstetrics and gynecology (P=.009). When microaggressions were experienced at 1 to 2 programs, 36% of applicants (26 of 73) reported significantly lowering program ranking, compared to 5% (1 of 19) when microaggressions occurred at more than 5 programs (P=.038). Conclusions: Women applicants experience more microaggressions than men do during nonsurgical and male-dominated surgical specialty residency interviews. Respondents who recalled experiencing microaggressions at fewer programs were more likely to report significantly lowering the rank of those programs compared to those who experienced them at more programs.
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Internship and Residency , Specialties, Surgical , Students, Medical , Female , Humans , Male , Microaggression , Sexism , Surveys and QuestionnairesABSTRACT
Objectives The role of surgery in management of sinonasal rhabdomyosarcoma (SNRMS) has traditionally been limited, owing to anatomic and technological challenges and the established role of systemic therapy. Herein, we report our institutional experience with surgical management of SNRMS, with a particular focus on operative approaches, extent and outcomes. Design This study is a retrospective cohort study. Setting This study was conducted at a single-institution, academic center. Participants Patients of any age with histologically confirmed RMS of the nasal cavity, maxillary, ethmoid, frontal, or sphenoid sinus, nasolacrimal duct, or nasopharynx presenting between 1994 and 2020 were included in this study. Main Outcome Measures Demographics, tumor characteristics, operative settings, complications and recurrence, and survival outcomes were the primary outcomes of this study. Results Our study cohort comprised of 29 patients (mean [range] age: 27.0 [3.1-65.7], n = 12 [41%] female). Tumors of the nasal cavity ( n = 10, 35%) and ethmoid sinuses ( n = 10, 35%) and those with alveolar histology ( n = 21, 72%) predominated. Patients who had surgery as part of their treatment ( n = 13, 45%) had improved distant metastasis-free survival (DMFS) overall (hazard ratio [HR]: 0.32, 95% CI: 0.11, 0.98, p = 0 .05 ) as compared with those who did not have surgery. Surgical approaches included open ( n = 7), endoscopic ( n = 4), and combined ( n = 2). Eight of these 13 patients (62%) had an R0 resection. Additionally, surgical salvage of recurrent disease was employed in five patients (17%). Conclusion SNRMS is an aggressive malignancy with a high rate of recurrence and spread requiring a multidisciplinary approach for optimal outcomes. Our data supports an expanding role for surgery for SNRMS given its feasibility, tolerability, and potential to improve outcomes.
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Background Inflammatory pseudotumor (IPT) of the skull base is a rare, locally destructive lesion managed with a variety of treatments. We explore the impact of treatment on outcome and assess the prognosis of IPT. Methods This is a retrospective review of IPT of the skull base at a tertiary academic medical center. The primary outcome was radiographic progression after treatment. Outcome versus tumor location was also examined and a prognostic model was developed using a logistic regression. Results The demographics of 21 patients with IPT are reported. Treatment consisted of corticosteroids (in 80.1% of patients), disease modifying antirheumatic drugs (DMARDs; 33.3%), surgical resection (28.6%), radiation (23.8%), antibiotics (14.3%), chemotherapy (rituximab; 9.5%), and antivirals (4.8%). At 50.7 months, 50.8% had radiographic progression. Local therapy trended toward having a better response than systemic therapy ( p = 0.60). IPT of the orbit required 2.4 treatment modalities, compared with 2.0 for pharyngeal IPT, and 1.3 for posterior skull base masses ( p = 0.14). A total of 75% orbital IPT underwent radiographic progression, compared with 71% of pharyngeal IPT and 50% of posterior skull base masses ( p = 0.62). Sixteen patients were used to create the logistic model of radiographic progression. The Cox-Snell R 2 was 0.71 ( p = 0.03). No individual variables were statistically significant. Conclusion To our knowledge, this is among the largest sample of cases describing the presentation, treatment, and prognosis of IPT of the skull base. Our data suggest that there may be an improved response with local therapy over systemic therapy and better prognosis among posterolateral skull base masses.
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Objectives Antibiotic use in lateral skull base surgery (LSBS) has not been thoroughly investigated in the literature. There is wide variability in antibiotic use and insufficient data to guide management. This study aims to describe the factors and patterns influencing antibiotic use in LSBS among the membership of the North American Skull Base Society (NASBS). Design An online-based survey was designed and distributed to the membership of the NASBS. Data was analyzed using bivariate analysis and logistic regression modeling. Setting Online-based questionnaire. Participants NASBS membership. Main Outcome Measures Use of intraoperative antibiotics and use of postoperative antibiotics. Results The survey response rate was 26% (208 respondents). Of the 208 total respondents, 143 (69%) respondents performed LSBS. Most respondents are neurosurgeons (69%) with the remaining being otolaryngologists (31%). The majority of respondents (79%) are fellowship-trained in skull base surgery. Academic or government physicians make up 69% of respondents and 31% are in private practice with or without academic affiliations. Bivariate analysis showed that practice setting significantly influenced intraoperative antibiotic use ( p = 0.01). Geographic location significantly affected postoperative antibiotic use ( p = 0.01). Postoperative antibiotic duration was significantly affected by presence of chronic otitis media, cerebrospinal fluid leak, and surgeon training ( p = 0.02, p = 0.01, and p = 0.006, respectively). Logistic regression modeling showed that the motivation to reduce infection significantly impacted postoperative antibiotic use ( p = 0.03). Conclusion This study demonstrates significant variations in intraoperative and postoperative antibiotic use in LSBS among the NASBS membership. Appropriate guidelines for optimal perioperative antibiotic use patterns should be determined with randomized studies in the future.
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Interdisciplinary teams have many potential and proven benefits, including decreased burnout, decreased medical errors, increased quality, and leveraging of competing values and skills. Pituitary Tumor Centers of Excellence must have adequate volumes and high-functioning teams in order to provide exceptional, high-value care. Organizational logistics, attentive operations management, facilitated collaboration, and clear communication are key teamwork tools in delivering that care.
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Medical Errors , Patient Care Team , Communication , Humans , Interdisciplinary CommunicationABSTRACT
Objectives Targeted inhibitors of the PI3 kinase (PI3K) pathway have shown promising but incomplete antitumor activity in preclinical chordoma models. The aim of this study is to advance methodology for a high-throughput drug screen using chordoma models to identify new combination therapies for chordoma. Study Design Present work is an in vitro study. Setting The study conducted at an academic research laboratory. Materials and Methods An in vitro study on automated high-throughput screening of chordoma cells was performed using a library of 1,406 drugs as both mono- and combination therapies with PI3K inhibitors. Combination indices were determined for dual therapies and synergistic outliers were identified as potential therapeutic agents. T (brachyury) siRNA knockdown in combination with PI3K pathway inhibition was also assessed. Results Fifty-nine combination therapies were identified as having potential therapeutic efficacy. Effective combinations included PI3K inhibitors with GSK1838705A (ALK/IGF-1R inhibitor), LY2874455 (VEGFR/FGFR inhibitor), El1 (selective Ezh2 inhibitor), and (-)-p-bromotetramisole oxalate (alkaline phosphatase inhibitor). The top ranking targets identified included ALK, PDGFR, VEGFR, aurora kinase, and BCL-2. T (brachyury) inhibition produced significant reduction in cell viability and growth; however PI3K inhibition in combination with T (brachyury) knockdown did not result in further reduction in growth and viability in vitro. Conclusion High throughput with in vitro combination screening is feasible with chordoma cells and allows for rapid identification of synergistic dual-therapies. Potential combination therapies and targetable pathways were identified. T (brachyury) knockdown produced significant reduction in cell viability, but did not show additional benefit with PI3K pathway inhibition in this model. Further in vitro and in vivo validation of these therapeutic combinations is warranted.
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OBJECTIVES: Phosphaturic mesenchymal tumor (PMT) is a rare, polymorphous neoplasm with a highly variable presentation and natural history and unpredictable clinical course. The primary objective was to describe our clinical experience with and management of 4 markedly different cases of sinonasal and skull base PMT. METHODS: A retrospective case series with chart review, and relevant literature review, was performed at a tertiary academic medical center between 1998 and 2020. Adult patients treated for PMTs of the sinonasal area and skull base were included. Our main outcome measures included postoperative laboratory findings and radiological evidence of disease remission. RESULTS: Four patients (2 Males, 2 Females; Mean Age: 63.5 years) with PMTs of the skull base have been managed at our institution since 1998. Patient presentations varied, ranging from severe phosphorus wasting and osteoporosis to symptoms secondary to mass effect, including nasal obstruction and rhinorrhea. All 4 patients were eventually found to have elevated levels of fibroblast growth factor 23. Tumors were located in the sinonasal area (right frontal sinus, right ethmoid sinus, and right nasal cavity, respectively) in 3 patients and in the lateral skull base (right jugular foramen) in 1 patient. All 4 patients underwent complete surgical resection of their tumors. PMT tissue pathology was confirmed in all cases. Gross total resection was achieved in all patients. There was no chemical or radiological evidence of disease recurrence in any patients at follow-up. CONCLUSIONS: The presentation of skull base PMT is variable, and it may mimic other mass pathologies of the head and neck. Complete surgical resection with negative margins is potentially curative.
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Mesenchymoma , Osteomalacia , Soft Tissue Neoplasms , Adult , Female , Humans , Male , Mesenchymoma/diagnosis , Mesenchymoma/pathology , Mesenchymoma/surgery , Middle Aged , Neoplasm Recurrence, Local , Osteomalacia/complications , Osteomalacia/diagnosis , Osteomalacia/surgery , Retrospective Studies , Skull Base/diagnostic imaging , Skull Base/pathology , Skull Base/surgeryABSTRACT
BACKGROUND: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. METHODS: We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. RESULTS: Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. CONCLUSION: Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.
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Carboxylic Ester Hydrolases/genetics , Carcinoma/genetics , Maxillary Sinus Neoplasms/genetics , Neoplasm Recurrence, Local/epidemiology , Oncogene Proteins, Fusion/genetics , Protein Serine-Threonine Kinases/genetics , Receptors, Cell Surface/genetics , Adult , Aged , Aged, 80 and over , Carcinoma/mortality , Carcinoma/therapy , Cell Line, Tumor , Chemoradiotherapy, Adjuvant , Disease-Free Survival , Female , Follow-Up Studies , Gene Knockdown Techniques , Humans , Kaplan-Meier Estimate , Male , Maxillary Sinus Neoplasms/mortality , Maxillary Sinus Neoplasms/therapy , Middle Aged , Neoplasm Recurrence, Local/genetics , Retrospective Studies , Young AdultABSTRACT
Cerebrospinal fluid (CSF) leak is a complication of endoscopic endonasal pituitary adenoma resection. Previous studies examining complications of pituitary adenoma resection have not examined associations of an exhaustive list of clinical and financial variables with CSF leak. We designed a retrospective analysis of 334 consecutive patients that underwent endoscopic endonasal pituitary adenoma resection at a single institution over 5 years, analyzing associations between CSF leak and demographic data, operative data, comorbidities, clinical complications and outcomes, costs, charges, and payments. Of the 20 preoperative variables studied, none were positively associated with CSF leak in between-groups comparison, although multivariate analysis revealed an association with a history of radiation to the skull base (odds ratio [OR], 8.67; 95% confidence interval [CI], 0.94-57.03; p < 0.05). CSF leak was associated with a significantly higher rate of postoperative diabetes insipidus (Δ = 33.4%, p = 0.040) and increased length of stay after operation in between-groups comparison. Multivariate analysis on postoperative variables revealed significant associations between CSF leak and intracerebral hemorrhage (OR, 17.44; 95% CI, 0.65-275.3; p < 0.05) and postoperative intracranial infection (OR, 28.73; 95% CI, 2.04-438.7; p < 0.05). Also, CSF leak was associated with significantly higher costs (Δ = $15,643, p < 0.05) and hospital charges (Δ = $46,026, p < 0.05). Operating room time, room and board, and supplies and implants were the strongest cost drivers. This study highlights the difficulty of utilizing preoperative variables to predict CSF leak, the clinical complications and outcomes of leak, and the financial subcategories that drive the costs, charges, and payments associated with this complication.
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Background Management of anterior cranial base malignancies requires multidisciplinary care. Radiation therapy remains a mainstay of definitive or adjuvant treatment. Apart from primary hypothyroidism, the effects of radiation on the hypothalamic-pituitary axis after high-dose treatment of head and neck malignancies remain poorly described. We describe a comprehensive screening protocol for surveillance and characterize the incidence of pituitary dysfunction after radiation for anterior cranial base malignancies. Methods A review of patients prospectively enrolled in a skull base registry at an academic center was performed. Included patients had a history of anterior skull base malignancy and external beam radiation to the primary site, with comprehensive post-treatment pituitary serologies and at least 1 year of post-radiation follow-up. Routine hormonal screening was initiated during the study period for all patients with anterior skull base irradiation. Results Eighty-one patients met inclusion. Fifty-eight patients (71%) demonstrated some laboratory abnormality. Thirty patients (37%) demonstrated evidence of hypopituitarism. Twenty-four (29%) demonstrated central hypogonadism, and 16% of patients showed central hypothyroidism. Ten patients (12%) displayed central adrenal insufficiency with six patients demonstrating panhypopituitarism. Primary tumor location and maximum dose of radiation to the gland appeared to correlate with incidence of hypopituitarism. Conclusion Radiation for malignancies of the anterior skull base resulted in a 37% incidence of hypopituitarism in our study. Given the potential morbidity of hypopituitarism, we recommend annual post-treatment screening in these patients. We describe a comprehensive set of serologies that can be utilized, and recommend updating clinical guidelines to reflect the necessity of this screening.
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Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2. In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.