Surgical management of continuous and mixed type of OPLL in cervical spine: Experience in tertiary level hospital.

Background: Ossification of the posterior longitudinal ligament (OPLL) is a chronically progressive disease of ectopic enchondral and membranous ossification of posterior longitudinal ligament (PLL). Controversy still persists over the superiority of various surgical approaches for cervical OPLL management. Purpose: To see the efficacy of expansive laminoplasty for the management of continuous and mixed type of cervical OPLL retrospectively. Methods: Records of 20 male and 8 female aged 36-72 years (mean, 56.64 years), who underwent surgical treatment posteriorly for continuous and mixed type OPLL by laminoplasty were obtained from the year 2004 - 2020. Clinical features along with imaging studies, which included X -ray/CT /MRI, were done for the diagnosis of OPLL. Multiple variables were studied, including demographics, surgical parameters, complications and functional outcomes. Results: They were followed on an average of 59.86 ± 20.95 months (range, 24 -108 months). The average operative duration was 95 ± 15.52 min (range: 70 - 140), and the intraoperative blood loss was 199.29 ± 33.55 ml. The cervical curvature index reduced to 8.81 ± 1.96 from 11.00 ± 2.49 and the VAS score decreased from 4.25 ± 0.75 to 2.43 ± 1.40. mJOA score improved from 8.64 ± 1.03 to 13.96 ± 1.26 on the last follow-up after surgery (p < 0.01), with average recovery rate of 65.5 %. Conclusions: The management for cervical myelopathy with multilevel stenosis due to continuous and mixed type of OPLL by Laminoplasty is safe and effective.

Reappraisal of Grading in Intestinal-Type Sinonasal Adenocarcinoma: Tumor Budding as an Independent Prognostic Parameter

Since sinonasal intestinal-type adenocarcinomas (ITAC) show resemblance to colorectal adenocarcinomas, we aimed to investigate novel prognostic factors of outcome, with particular focus on the role of tumor budding (TB). Retrospective clinico-pathological single-institution study on consecutive ITAC patients between 1996 and 2020. Histopathological parameters including conventional subtypes and TB features (low, intermediate, high) were evaluated with the aid of pancytokeratin (AE1/AE3) immunohistochemical staining. Parameters were correlated to clinical data and outcome. A total of 31 ITAC patients were included. Overall, 19/31 patients (61.3%) presented with stage III/IV disease. Presence of lymph node or distant metastases was rare (1/31 patient, 3.2%). Treatment protocols consisted of tumor resection in 30/31 patients (96.8%) and primary radiochemotherapy in 1/31 patient (3.2%). Adjuvant radiation therapy was conducted in 20/30 surgically treated patients (66.7%). The 3- and 5-year overall survival (OS) was 83.9% and 78.3% and the 3- and 5-years disease-specific survival (DSS) 83.7% % and 78.5%, respectively. The presence of intermediate/high TB (defined as ≥ 5 buds) was associated with both, worse DSS (log rank p = 0.03) and OS (log rank p = 0.006). No patient with low TB revealed progressive disease or died of the disease. No association between TB and tumor stage or conventional tumor subtype was found. Tumor budding seems to be an independent prognostic factor of worse outcome in ITAC.

Changes in Serum Growth Factors during Lenvatinib Predict the Post Progressive Survival in Patients with Unresectable Hepatocellular Carcinoma

Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1–4 p = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.

Cognitive dysfunction and mortality in multiple sclerosis: Long-term retrospective review

Background: Cognitive dysfunction as a predictor of clinical progression and mortality in multiple sclerosis (MS) is still a matter of debate. Objective: The aim of this study was to explore the long-term outcome associated with neuropsychological performance in a cohort of patients with MS. Methods: A series of 408 MS patients had previously undergone a comprehensive neuropsychological assessment and a contemporaneous neurological evaluation (T1). A retrospective review of the clinical records was conducted 102–192 months after T1. Demographic and clinical data regarding the last clinical appointment with EDSS measurement (T2) were collected and the date of the last clinical contact or death (TS) was recorded. Results: This review revealed that cognitive dysfunction (T1) was associated with higher odds of transitioning from relapsing–remitting course to a progressive disease course (adjusted odds ratio (OR) = 2.29, p = 0.043) and higher hazard of death in the total sample (adjusted hazard ratio (HR) = 3.07, p = 0.006) and the progressive disease course subgroup (adjusted HR = 3.68, p = 0.007), even when adjusting for other covariates. Discussion: The study results demonstrate that cognitive dysfunction in MS is predictive of poorer prognosis and mortality.

What’s the difference between hyperprogressive disease and progressive disease for patients with treated immune checkpoint inhibitors?

Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. Some of the patients in this group, which is considered to have hyperprogressive disease (HPD), have a shorter overall survival compared to progressive disease (PD). Therefore, biomarkers are needed to differentiate between HPD and PD. Here, we evaluated PILE score to differentiate HPD from PD in patients treated with ICI. Methods Ninety-five patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any type of cancer with progression according to RECIST criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system was calculated, including PIV (< median vs. ≥ median), LDH (normal and > normal), and ECOG performance status (0 vs. ≥ 1). The relationship between PILE score and HPD was examined. Results The median follow-up was 6.6 months and the median OS of all cohort were 11.18 ± 1.36 months. The patients in the HPD group had decreased OS (4.77 ± 0.89 vs. 13.94 ± 1.80 months, p <0.001) and PFS (1.89 ± 0.11 vs. 3.16 ± 0.12 months, p <0.001) compared to PD group. The risk of HPD was higher than the risk of PD in patİents with a high PILE score (p:0.001). Conclusion In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. If prospective studies confirm our results, the PILE score may be a biomarker to differentiate HPD from PD.

An Unusual Early Oral Presentation of Acromegaly: A Case Report

Acromegaly is a devastating chronic slowly progressive disease. Its early diagnosis is a challenging issue that necessitates clinical suspicion of signs and symptoms as a first step. This report introduces an unusual early sign in the oral cavity that lead to the early diagnosis of an acromegaly case. A case of a healthy 40-year-old male patient presented with progressively growing multiple hard swellings in the upper and lower jaws. Clinical examination revealed bony hard multiple small spiky exostosis-like swellings, located at the maxillary and mandibular alveolar bones. An array of investigations revealed a 2-mm diameter pituitary tumour in MRI of sella. To the best of the author’s knowledge, this is the first report of spiky exostosis-like growths in the alveolar bone as an early sign of acromegaly. In this case, thorough examination of oral signs and symptoms was the first step for early diagnosis and hence, better prognosis for acromegaly.

Temozolomide non-responsiveness in aggressive prolactinomas and carcinomas: management and outcomes

Purpose Temozolomide is endorsed as the treatment of choice in aggressive or malignant pituitary adenomas. Herein we describe a case of an aggressive prolactinoma which was resistant to temozolomide and performed a literature review of similar non-responsive aggressive prolactinomas. Methods A 40-year-old female presented with a giant prolactinoma which required cabergoline, transsphenoidal surgery and radiotherapy to achieve near-normal prolactin and apparently no residual tumour. A year later, she presented with multiple cranial nerve involvement due to recurrent tumour extending to the infratemporal fossa. She underwent transfrontal surgery, second radiotherapy and was started on temozolomide. Despite 8 cycles of temozolomide (200mg/m 2, 5/28 day cycle), she had progressive disease and ultimately succumbed to the disease. Pubmed/MEDLINE, Google scholar and prior review articles were searched for manuscripts with aggressive prolactinomas who had been treated with temozolomide. Data on demography, duration of therapy and management outcomes were analysed in those with progressive disease. Literature review We identified 94 cases of aggressive/malignant prolactinomas in the literature who had received temozolomide. Progressive disease despite temozolomide was present in 36 cases (38%). There was a male preponderance (65%) and 40% had aggressive prolactinomas while the rest had carcinomas. Patients received a median of 8 cycles (IQR 3.5-11.5) of temozolomide. MGMT immunostaining was negative in 35%. Overall mortality at the time of publication was 40%, at a duration varying from 2 to 20 years from diagnosis. Conclusion Temozolomide resistance in aggressive/malignant prolactinomas is challenging. Progressive disease on optimal temozolomide treatment entails the use of newer agents.