Reconstruction with free flaps in robotic head-and-neck onco-surgeries.

AIMS AND OBJECTIVE: The aim of the present article is to highlight how reconstruction with free flaps is different and difficult in cases with robotic head-and-neck cancer surgery. It also highlights the technical guidelines on how to manage the difficulties. MATERIALS AND METHODS: Eleven patients with oropharyngeal cancer having undergone tumour excision followed by free-flap reconstruction been reviewed here. Nine patients had tumour excision done robotically through intraoral route while neck dissection done with transverse neck crease incision. There is a problem of difficult flap inset in this group of patient. Two patients had intraoral excision of tumour followed by robotic neck dissection via retroauricular incision. With no incision directly on the neck, microvascular anastomosis is challenging in this set of patients. Free flap was used in all the cases to reconstruct the defect. RESULTS: Successful reconstruction with free flap was done in all the cases with good outcome both functionally and aesthetically. CONCLUSION: Free-flap reconstruction is possible in robotic head-and-neck cancer surgery despite small and difficult access, but it does need practice and some technical modifications for good outcome.

Myofibrosarcoma of Maxilla - Case Report and Review of Literature.

Myofibrosarcoma is a distinct mesenchymal malignancy which commonly occurs in head and neck region. It has a high tendency for local recurrence and distant metastasis. 39-year-old male presented with epistaxis, nasal obstruction and left sided complete loss of vision. He underwent functional endoscopic sinus surgery and guided biopsy. MRI scan showed a lesion epicentred in the left maxillary sinus, superiorly extending into the orbit. He underwent Class 4b maxillectomy with neck dissection, tracheostomy and free flap reconstruction. Histopathological examination yielded final diagnosis as myofibrosarcoma of maxilla. The patient was planned for adjuvant radiotherapy and has been disease free for 3 years.

Robotic Neck Dissection in Head and Neck Cancer via Modified BABA Technique.

INTRODUCTION: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes. METHODS: A prospective observational study was conducted in our institute from 2020 March to 2022 March, where robotic-assisted neck dissections performed via the modified bilateral axillo-breast insufflation technique. RESULTS: Eighty-two patients underwent robotic neck dissections in our institute. Notably, 79 patients were treatment-naïve. The average docking time was 12 min and console time was 160 ± 15 min. The mean lymph node yield was 28.2. The average post-operative stay was 5.6 days. The average follow-up was noted to be 6.4 months. The mean cosmetic satisfaction score in our patients was 4.45. Only one patient presented with nodal recurrence, who was identified as a defaulter for adjuvant treatment. Robotic neck dissection gives similar functional and oncological outcomes as compared with conventional neck dissection. Patients had excellent cosmetic satisfaction following the procedure. The limitations of these techniques include high cost of procedure and longer operating time. This is a level IV evidence study. CONCLUSION: Although good oncological, functional, and cosmetic outcomes have been attained in robotic assisted neck dissection, further randomized controlled studies need to be conducted to justify the added costs, cosmetic advantage, and the time taken. LEVEL OF EVIDENCE: IV Laryngoscope, 134:4045-4051, 2024.

A Rare Case Report of Osteosarcoma of Maxilla with Double Free-Flap Reconstruction.

Osteosarcomas are rare and highly malignant bone tumours which are composed of malignant mesenchymal cells producing osteoid or immature bone. Maxillary osteosarcomas are rare tumours accounting for less than 1% of head and neck malignancies. Aggressive surgical resection is the main modality of treatment with good reconstruction. Due to the complex anatomy and location of maxilla as well as its proximity to the skull, resection with negative margins is always a challenge and so is the reconstruction so as to reduce the morbidity of the patient and to also give a good functional and cosmetic outcome. Clinical outcomes can be improved with administration of neoadjuvant or adjuvant chemotherapy in selected cases and radiotherapy in case of positive margins. A 41-year-old male patient presented to the outpatient department with complaints of a bulge over the hard palate for the past 1 year. CT scan showed a 6 × 5 × 4 cm osseous expansile lesion arising from the maxillary bone. Biopsy of the tumour showed features of conventional high-grade osteosarcoma. Plate-preserving maxillectomy with tracheostomy was done followed by reconstruction with a double free flap. On post-operative day 1, the flap showed signs of venous congestion and a new free anterolateral thigh flap was done. Patient was discharged on day 7 with a Ryles tube and a tracheostomy tube in situ. Final histopathological examination showed that the tumour was a high-grade chondroblastic osteosarcoma. After regular post-operative visits in the outpatient department and evaluation with flexible laryngoscopy, patient was started on oral feed by day 10 and decannulated by day 15. He has been on regular follow-up for the past 1 year and shows no signs of recurrence or residual disease on clinical examination as well as imaging. Maxillary osteosarcoma is a rare bone tumour which requires accurate imaging and biopsy for accurate surgical planning. The ideal treatment modality is radical resection with negative margins and appropriate reconstruction. With the advent of microvascular surgery, free flaps form the backbone for reconstruction of such large defects.

Extraskeletal Myxoid Chondrosarcoma of Floor of Mouth-A Rare Case Report and Review of Literature.

Introduction: Chondrosarcomas are rare malignancies of the cartilage and myxoid chondrosarcoma is its variant which commonly occurs in soft tissue of extremities. Extraskeletal chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin and is characterized by the presence of spindle cells admixed with well differentiated cartilage or chondroid stroma. They are mostly radioresistant tumours and surgical resections with adequate margins is considered as the ideal treatment modality with adjuvant radiotherapy in high grade tumours and add on chemotherapy, in case of presence of poor prognostic factors. Case Report: A 51-year-old diabetic, hypertensive female patient presented to our outpatient department with difficulty in chewing food for a duration of 6 months. On clinical examination, she had an ulceroproliferative growth involving right lower alveolus and floor of mouth. MRI face and neck with contrast showed a 4.1 × 2.9 × 4.5 cm lesion involving right lower alveolus extending to floor of mouth. Biopsy showed features of extraskeletal myxoid chondrosarcoma. She was planned for upfront surgery (Right composite resection with modified radical neck dissection with free fibula flap). Patient was stable post-surgery and was discharged in stable condition. Final histopathology report was high grade myxoid chondrosarcoma. The case was presented in tumour board and the patient was planned for adjuvant radiotherapy. She has been on regular follow up for the past 2 years and shows no signs of recurrence. Conclusion: Extraskeletal myxoid chondrosarcoma of oral cavity is a rare entity and very few cases are reported. It is a malignant neoplasm which is diagnosed with the help of immunohistochemistry. Surgery is the ideal modality of treatment accompanied by adjuvant radiotherapy in cases of high-grade tumours.

SS18-SSX Expression and Clinicopathologic Profiles in a Contemporary Cohort of Primary Paratesticular Synovial Sarcoma: A Series of Fourteen Patients.

Synovial sarcoma (SS) is a rare genitourinary malignancy with a specific SS18::SSX 1/2 gene fusion in majority of the instances. The paratesticular location of this neoplasm is extremely rare and only 4 cases are reported in the literature. Herein, we describe the clinicopathologic features and molecular profile of paratesticular SS in the largest case series to date and to the best of our knowledge, and the only series to use novel SS18-SSX antibody for immunohistochemistry. Clinicopathologic, immunohistochemical (IHC), molecular, treatment, and follow-up data of the patients were analyzed. There were 14 patients, ranging from 15 to 47 years (mean: 30 y). The tumor size ranged from 4​​​​​​ to 15 cm. The tumors were unilateral, solid, and homogeneous tan-white with monomorphic spindle cell histology. All 14 tumors expressed SS18-SSX and TLE1 IHC and harbored SS18 rearrangement. In addition, the tumor with multifocal SS18-SSX expression had lower break-apart signals in the FISH assay (38% of the tumor cells; range: 29% to 85%). Radical orchiectomy was performed in all 14 patients and adjuvant chemotherapy was administered in 9 patients. Follow-up was available in 9 patients. The follow-up duration ranged from 5 to 24 months (median=10 mo). Four patients died of metastatic disease (range: 5 to 16 mo) and 2 patients who are alive had metastatic disease at the last follow-up. Based on our experience with the largest series to date and aggregate of the published data, paratesticular SS has a poor prognosis despite aggressive therapy. Owing to its rarity, the differential diagnosis is wide and requires a systematic approach for ruling out key morphologic mimics aided with SS18-SSX IHC and molecular confirmation because this distinction carries important therapeutic and prognostic implications. Due to the excellent concordance of SS18-SSX IHC results with FISH results as observed in our study, we would like to suggest inclusion of SS18-SSX in the diagnostic immunohistochemistry panel of all spindle cell sarcomas where synovial sarcoma is considered as a morphologic differential. SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost.

Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients.

OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.

Intraoral anastomosis for primary microsurgical reconstruction in patients of oral cavity malignancies: Retrospective analysis of 30 cases from a tertiary care center in India.

INTRODUCTION: In patients undergoing either robotic neck dissection or no neck dissection, the neck recipient vessels for the free flaps remain unexposed. Intraoral vessels have been successfully used as microvascular recipients but their use in intraoral malignancies is uncommon. We describe our initial experience of using intraoral recipients in 30 patients with oral cavity malignancies. METHODS: For this retrospective observational study, the hospital records of all patients who underwent microvascular reconstruction using intraoral recipient vessels over a 14-month period at a tertiary care hospital in India were studied. Patient demographics, disease profile, details of oncosurgical resection, reconstructive procedure details, and postoperative recovery data were analyzed. RESULTS: Intraoral anastomosis was successfully performed in 30 patients. The average patient was middle-aged (mean age 54 years) and male (26/30). Location of the postexcision defect was the buccal mucosa in 16/30 and the tongue in 12/30 patients. Anterolateral thigh flap (ALT) was used in 28/30 patients. Recipient vessels were facial vessels in 24/30 patients and lingual vessels in 6/30 patients. Venous anastomotic coupler was used in 27/30 patients. Three patients underwent re-exploration for flap congestion with loss of flap in 2/30 patients. CONCLUSION: The intraoral approach offers consistent vascular anatomy and can be performed without any external incision and oro-cervical tunneling. Being technically challenging, it has an initial learning phase. Adequate mouth opening and preservation of recipient vessels during excision and neck dissection are important prerequisites. This approach can offer a scarless reconstruction, which can improve the psycho-social rehabilitation of the patients.

Adverse effects following botulinum toxin A injections in children with cerebral palsy.

The study aimed to analyze the adverse events associated with botulinum toxin A (BoNT-A) injections in children with cerebral palsy (CP). The literature search was completed using the Medline, PubMed, Google Scholar, Scopus, and Cochrane Library databases from the earliest date possible up to December 2021. Search terms included 'botulinum toxin', 'cerebral palsy', 'spasticity', 'adverse effects', 'side effects', 'undesirable effects', 'complications', 'lower limb', 'upper limb', and 'children' including combinations of index and free-text terms. Fifty-five studies were included in the study. Data on 6333 pediatric patients and more than 14 080 BoNT-A injections were collected. Respiratory symptoms and respiratory tract infections were the most frequently registered adverse events (AEs). Other common AEs included procedural/focal AEs, flu-like symptoms, and asthenia. Sentinel events including four cases of death were reported. AEs were more frequent and severe in high-dose patients; however, the capacity of BoNT-A to spread systemically remains unclear. Since severe adverse events are not common, further research is needed to collect more definitive clinical and homogeneous data to support the findings of the present research and clarify the safety profile of BoNT-A, especially regarding the incidence of respiratory issues and complications in GMFCS IV or V patients.

Multicystic Solitary Fibrous Tumor of the Kidney: A Case Report With Review of Literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm known to occur at various soft tissue and visceral locations. Kidney is one of the rare locations for these tumors with around 64 cases being available in the literature. Most of the renal SFTs are tan-white, solid, firm, unencapsulated, and lobulated masses. A predominantly cystic renal SFT has never been reported in the literature. Herein we describe a case of multicystic renal SFT in a 44-year-old male with the characteristic CD34 + /STAT6 + immunophenotype. A careful gross and microscopic examination is warranted while dealing with cystic spindle cell neoplasms of the kidney and SFT should always be considered in the differential diagnosis. STAT6 immunohistochemistry is quite specific for the diagnosis. Moreso, a detailed immunopanel is necessary to exclude other spindle cell neoplasms of the kidney because of significant therapeutic and prognostic implications.

Solitary Fibrous Tumor of the Kidney With Pure Round Cell Features: A Case Report With Review of Literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm known to occur at various soft tissue and visceral locations. Kidney is a rarely reported site for these tumors. Most of the SFTs described in the kidney exhibit a classical CD34-positive patternless spindle cell histology. Focal round cell morphology is seldom reported. Herein, we describe a 48-year-old male patient with renal SFT. This tumor had pure round cell morphology with a CD34-/STAT6+ immunophenotype. Fluorescent in situ hybridization and a multiplexed sequencing assay performed on an Illumina® HiSeq 4000 platform revealed NAB2 and STAT6 gene rearrangement. Renal tumors with round cell morphology are diagnostically challenging and SFT is not often considered in the differential diagnosis of a round cell tumor of the kidney. Moreover, a CD34-negative profile can be rather confounding while diagnosing such lesions. In such scenarios, a strong nuclear STAT6 immunostaining is extremely helpful in clinching the diagnosis. SFT should always be considered in the differential diagnosis of round cell tumors of the kidney due to significant diagnostic and therapeutic implications.

Real-Time Mobile Teleophthalmology for the Detection of Eye Disease in Minorities and Low Socioeconomics At-Risk Populations.

PURPOSE: To examine the benefits and feasibility of a mobile, real-time, community-based, teleophthalmology program for detecting eye diseases in the New York metro area. DESIGN: Single site, nonrandomized, cross-sectional, teleophthalmologic study. METHODS: Participants underwent a comprehensive evaluation in a Wi-Fi-equipped teleophthalmology mobile unit. The evaluation consisted of a basic anamnesis with a questionnaire form, brief systemic evaluations and an ophthalmologic evaluation that included visual field, intraocular pressure, pachymetry, anterior segment optical coherence tomography, posterior segment optical coherence tomography, and nonmydriatic fundus photography. The results were evaluated in real-time and follow-up calls were scheduled to complete a secondary questionnaire form. Risk factors were calculated for different types of ophthalmological referrals. RESULTS: A total of 957 participants were screened. Out of 458 (48%) participants that have been referred, 305 (32%) had glaucoma, 136 (14%) had narrow-angle, 124 (13%) had cataract, 29 had (3%) diabetic retinopathy, 9 (1%) had macular degeneration, and 97 (10%) had other eye disease findings. Significant risk factors for ophthalmological referral consisted of older age, history of high blood pressure, diabetes mellitus, Hemoglobin A1c measurement of ≥6.5, and stage 2 hypertension. As for the ocular parameters, all but central corneal thickness were found to be significant, including having an intraocular pressure >21 mm Hg, vertical cup-to-disc ratio ≥0.5, visual field abnormalities, and retinal nerve fiber layer thinning. CONCLUSIONS: Mobile, real-time teleophthalmology is both workable and effective in increasing access to care and identifying the most common causes of blindness and their risk factors.

Detecting Common Eye Diseases Using the First Teleophthalmology GlobeChek Kiosk in the United States: A Pilot Study.

PURPOSE: The aim of this study was to assess the benefit and feasibility of the teleophthalmology GlobeChek kiosk in a community-based program. DESIGN: Single-site, nonrandomized, cross-sectional, teleophthalmologic study. METHODS: Participants underwent comprehensive evaluation that consists of a questionnaire form, brief systemic evaluation, screening visual field (VF), and GlobeChek kiosk screening, which included but not limited to intraocular pressure, pachymetry, anterior segment optical coherence tomography, posterior segment optical coherence tomography, and nonmydriatic fundus photography. The results were evaluated by a store-and-forward mechanism and follow-up questionnaires were obtained through phone calls. RESULTS: A total of 326 participatents were screened over 4 months. One hundred thirty-three (40.79%) participants had 1 condition in either eye, and 47 (14.41%) had >1 disease. Seventy (21.47%) had glaucoma, 37 (11.34%) narrow-angles, 6 (1.84%) diabetic retinopathy, 4 (1.22%) macular degeneration, and 43 (13.10%) had other eye disease findings. Age >65, history of high blood pressure, diabetes mellitus, not having a dental examination >5 years, hemoglobn A1c measurement of ≥5.6, predibates risk score of ≥9, stage 2 hypertension, and low blood pressure were found to be significant risk factors. As for the ocular parameters, all but central corneal thickness, including an intraocular pressure >21 mm Hg, vertical cup to disc ratio >0.7, visual field abnormalities, and retinal nerve fiber layer thinning were found to be significant. CONCLUSIONS: GlobeChek kiosk is both workable and effective in increasing access to care and identifying the most common causes of blindness and their risk factors.

Artificial Intelligence and Optical Coherence Tomography Imaging.

This review article aimed to highlight the application and use of artificial intelligence (AI) in optical coherence tomography (OCT) imaging in ophthalmology. Artificial intelligence programs seek to simulate intelligent human behavior in computers. With an abundance of patient data, especially with the advent and growing use of imaging modalities such as OCT, AI programs provide us with the unique opportunity to analyze this plethora of information and assist in making clinical decisions in the field of ophthalmology. Groups around the world have developed and evaluated AI programs that gather data from diagnostic modalities, such as OCT, that assist in the diagnosis and management of ophthalmological diseases with a high accuracy. Artificial intelligence programs using OCT have the potential to play a significant role in the diagnosis and management of ophthalmological disease in the near future. Incorporation of AI in medicine, however, is not without its pitfalls. Some limitations of AI in ophthalmology are also discussed in this review. These include the deskilling of physicians due to increase in reliance on automation, inability of AI programs to take a holistic approach to clinical encounters with patients, requirement of pre-existing strong datasets to train AI programs, and the inability of AI programs to incorporate the ambiguity and variability that is intrinsic to the nature of clinical medicine.

The current state of artificial intelligence in ophthalmology.

Artificial intelligence (AI) is a branch of computer science that deals with the development of algorithms that seek to simulate human intelligence. We provide an overview of the basic principles in AI that are essential to the understanding of AI and its application in health care. We also present a descriptive analysis of the current state of AI in various fields of medicine, especially ophthalmology. Finally, we review the potential limitations and challenges that come along with the development and implementation of this new technology that will likely play a major role in clinical medicine in the near future.

Evaluation of a Deep Learning System For Identifying Glaucomatous Optic Neuropathy Based on Color Fundus Photographs.

PRECIS: Pegasus outperformed 5 of the 6 ophthalmologists in terms of diagnostic performance, and there was no statistically significant difference between the deep learning system and the "best case" consensus between the ophthalmologists. The agreement between Pegasus and gold standard was 0.715, whereas the highest ophthalmologist agreement with the gold standard was 0.613. Furthermore, the high sensitivity of Pegasus makes it a valuable tool for screening patients with glaucomatous optic neuropathy. PURPOSE: The purpose of this study was to evaluate the performance of a deep learning system for the identification of glaucomatous optic neuropathy. MATERIALS AND METHODS: Six ophthalmologists and the deep learning system, Pegasus, graded 110 color fundus photographs in this retrospective single-center study. Patient images were randomly sampled from the Singapore Malay Eye Study. Ophthalmologists and Pegasus were compared with each other and to the original clinical diagnosis given by the Singapore Malay Eye Study, which was defined as the gold standard. Pegasus' performance was compared with the "best case" consensus scenario, which was the combination of ophthalmologists whose consensus opinion most closely matched the gold standard. The performance of the ophthalmologists and Pegasus, at the binary classification of nonglaucoma versus glaucoma from fundus photographs, was assessed in terms of sensitivity, specificity and the area under the receiver operating characteristic curve (AUROC), and the intraobserver and interobserver agreements were determined. RESULTS: Pegasus achieved an AUROC of 92.6% compared with ophthalmologist AUROCs that ranged from 69.6% to 84.9% and the "best case" consensus scenario AUROC of 89.1%. Pegasus had a sensitivity of 83.7% and a specificity of 88.2%, whereas the ophthalmologists' sensitivity ranged from 61.3% to 81.6% and specificity ranged from 80.0% to 94.1%. The agreement between Pegasus and gold standard was 0.715, whereas the highest ophthalmologist agreement with the gold standard was 0.613. Intraobserver agreement ranged from 0.62 to 0.97 for ophthalmologists and was perfect (1.00) for Pegasus. The deep learning system took ∼10% of the time of the ophthalmologists in determining classification. CONCLUSIONS: Pegasus outperformed 5 of the 6 ophthalmologists in terms of diagnostic performance, and there was no statistically significant difference between the deep learning system and the "best case" consensus between the ophthalmologists. The high sensitivity of Pegasus makes it a valuable tool for screening patients with glaucomatous optic neuropathy. Future work will extend this study to a larger sample of patients.

Safety and efficacy of percutaneous nephrolithotomy in the pediatric population.

PURPOSE: We reviewed our experience with percutaneous nephrolithotomy (PCNL) in patients in the pediatric age group and compared its efficacy and safety over a 5-year period. PATIENTS AND METHODS: We studied retrospectively and prospectively 31 patients who were treated with PCNL for renal stones larger than 1.5 cm. Variables assessed were stone bulk, size, location, and type. Metabolic and anatomic factors were also assessed. PCNL punctures and number of tracts were recorded. Clearance with PCNL and ancillary procedures was recorded. RESULTS: There were 31 renal units. Mean age of the patients was 9.6 years (range 1.5-15 years). Fifteen (48.4%) patients had single calculi; eight (25.8%) patients had staghorn calculi. Lower-pole access was the preferred route of entry, and upper-pole access was used only when necessary. We used a 22F nephroscope for the procedure. We dilated the tract to 30F in the majority of patients, but limited dilation to 24F when appropriate. If needed, we used a ureteroscope. Complete clearance was achieved in 83.9% of patients after PCNL and in 90.32% of patients after dual therapy (PCNL + shockwave lithotripsy). Average hemoglobin drop was less than 1 g/dl. Factors responsible were the size of the tract (larger than 24F) and the number of tracts. Six patients were treated for an anatomic abnormality. A metabolic abnormality was diagnosed in three patients. CONCLUSION: PCNL is effective in children, with a clearance rate of 83% and, with dual therapy, more than 90%. We recommend that tract dilation be restricted to 24F or smaller whenever possible. Approximately 40% of patients had either an anatomic or metabolic abnormality.

Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia.

INTRODUCTION: High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), but serious infections are frequent. Recently published data suggested that high-dose dexamethasone might be equally effective as HDMP despite a lower cumulative dose. MATERIAL AND METHODS: We performed retrospective analysis of 60 patients with relapsed/refractory CLL (median age: 66 years; range: 37-86) treated with rituximab plus dexamethasone (R-dex) at a single tertiary center between September 2008 and October 2012. The schedule of R-dex consisted of rituximab 500 mg/m(2) i.v. day 1 (375 mg/m(2) in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13 repeated every 3 weeks for a maximum of 8 cycles. Unfavorable prognostic features were frequent (Rai stages III/IV in 67%, unmutated IgVH 82%, del 11q 43%, TP53 mutation/deletion 23%, bulky lymphadenopathy 58% of patients). RESULTS: Overall response (OR)/complete remission (CR) was achieved in 75/3%. At the median follow-up of 21 months, median progression-free survival (PFS) was 8 months, median time to next treatment 12.9 months and median overall survival 25.5 months. Refractoriness to fludarabine (p = 0.04) and age ≥ 65 years (p = 0.03) were significant predictors of shorter PFS. R-dex was successfully used for debulking before allogenic stem cell transplantation in 7 patients (12%). Serious (CTCAE grade III/IV) infections occurred in 27% of patients; 20% of patients developed steroid diabetes requiring temporary short-acting insulin. CONCLUSIONS: Our results show that R-dex is an active and well-tolerated regimen for patients with relapsed/refractory CLL; however, major infections remain frequent despite combined antimicrobial prophylaxis.

Selective Patch Angioplasty and Intraoperative Shunting in Carotid Endarterectomy: A Single-Center Review of 141 Procedures.

OBJECTIVE: Open surgical treatment of carotid artery stenosis, namely, carotid endarterectomy (CEA), has evolved since its inception in 1953. Despite improvements in the treatment of carotid occlusive disease through technological and surgical innovations, the use of patch grafting in CEA's remains controversial. We evaluate the durability of the primary closure and the safety of selective shunting during carotid endarterectomy (CEA) as determined by intraoperative EEG and postoperative outcomes. METHODS: A consecutive series of CEA's performed by the senior author at a single academic medical center from 2001 to 2012 were reviewed. All cases were performed under continuous intraoperative electroencephalography (EEG). Patch angioplasty was used in cases where there was tortuosity of the vessel within the region of the endarterectomy and narrow vessel diameter at the distal end of the arteriotomy. Shunting was used when intraoperative EEG showed a > 50% reduction in a waveform in any lead. Patients were evaluated for restenosis via imaging or ultrasound at six months and subsequently annual follow-up. RESULTS: One hundred and forty-one CEA's were performed on 132 (76 male, 56 female) patients with an average age of 71 years (range: 40-95 years). Four (3%) cases required patch angioplasty and three (2%) required intraoperative shunts. The cross-clamp time ranged from 22 to 74 minutes, and the duration increased with the use of shunts and patches. Complications were rare and included recurrent stenosis (n=2), postoperative transient ischemic attack (n=1), ischemic stroke in (n=1), temporary hypoglossal nerve weakness (n=2), temporary marginal mandibular nerve weakness (n=6), and neck hematoma (n=1). CONCLUSION: Intraoperative EEG data suggests that primary closure and selective shunting in CEA can result in outcomes comparable with routine patch angioplasty and shunting.

Birt-Hogg-Dubé syndrome and intracranial vascular pathologies.

Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome. We present three cases (three female; age range 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. We hypothesize that increased transcription of hypoxia-inducible factor 1-alpha, resulting from a mutated form of the protein folliculin transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.