Abstract
Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an ...emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case–control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (
P
= 0.024), lower body mass index (
P
= 0.023), left breast involvement (
P
= 0.001), N3 status (
P
= 0.004), diabetes (
P
= 0.016), and a family history of coronary artery disease (
P
= 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.
Gastric cancer is one of the most common malignancies worldwide and the fourth leading cause of cancer-related deaths. Gastric cancer is a multifactorial disease influenced by both environmental and ...genetic factors. Its most critical features include invasiveness and high metastatic potential. Metastasis is a complex process, and our understanding of the mechanisms involved remains incomplete. Growing evidence suggests that cancer-testis antigens (CTAs) play a crucial role in the metastatic potential of various tumors. Several studies have linked CTA expression with lower tumor differentiation, higher metastatic potential, and poor chemotherapy response. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen, part of the CTA group, is expressed in tumor tissues, while its expression in normal tissues is restricted to spermatogonia. This study aimed to determine the expression of NY-ESO-1 in primary adenocarcinoma of the stomach, both with and without metastasis in regional lymph nodes, and to compare it with TNM stage, age, gender, and survival. We analyzed gastric cancer tissue from 53 node-negative and 55 node-positive primary gastric carcinoma patients for NY-ESO-1 expression using immunohistochemical assay. The results were correlated with clinicopathological parameters and survival. Patients with positive NY-ESO-1 expression in primary tumors had a median survival of 19.0 months (range 14.1 - 24.0), in contrast to those with negative expression, who had a median survival of 52.0 months (range 0.0 - 133.3) (chi-square 7.99, P = 0.005). T status, N status, and NY-ESO-1 expression were all independently associated with shorter survival. No significant difference in NY-ESO-1 expression in primary tumors was observed concerning lymph node metastasis status. In summary, our findings suggest that increased expression of NY-ESO-1 could potentially serve as a prognostic biomarker for gastric cancer.
Tocilizumab is used in patients with severe COVID-19 pneumonia and high concentration of IL-6. We studied potential prognostic role of neutrophil and lymphocyte count regarding tocilizumab treatment.
...We enrolled 31 patients with severe COVID-19 pneumonia and higher serum IL-6 concentration. The samples were taken on the day of tocilizumab administration and five days later. We used ROC analysis to investigate the association between the analysed parameters and 30-day mortality in order to determine the best pre-treatment and post-treatment prognostic factor. Kaplan-Meier curves and log-rank test were used to present and to analyse the difference in survival.
Patients had a median age of 63 (55-67) years and were treated with a median tocilizumab dose of 800 mg. During the 30-day follow-up period, 17 patients died (30-day mortality 54%). Among pre-treatment variables, neutrophil count had the best prognostic accuracy (AUC 0.81, 95%CI: 0.65-0.96, P = 0.004), while neutrophil to lymphocyte ratio (NLR) had the highest accuracy among post-treatment variables in predicting 30-day mortality (AUC 0.94, 95%CI: 0.86-1.00, P < 0.001). Among post-treatment parameters, neutrophil count and NLR were equally good prognostic factors. Post-treatment NLR cut-off of 9.8 had the sensitivity of 81% and specificity of 93%. Patients with NLR ≥ 9.8 had the median survival of 7.0 (3-10) days
. median survival not reached in patients with NLR < 9.8 (P < 0.001).
Pre-treatment and post-treatment neutrophil count with post-treatment NLR may represent prognostic tools for patients with higher IL-6 concentration in severe COVID-19 pneumonia treated with tocilizumab.
Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy ...may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed.
Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity.
In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.
Spontaneous resolution of nonfunctioning pituitary adenoma after hemorrhagic apoplexy is a rare clinical entity of unknown etiology and is defined as disappearance of a tumor without any specific ...treatment. Here we present a 54-year-old male patient who presented with acute onset of severe headache, vomiting, photophobia, and sonophobia. He was referred to brain computed tomography, which showed a 16x12x16 mm tumor mass located in the sellar region with signs of hemorrhage. Endocrinologic evaluation was consistent with under-function of pituitary gonadotropic cells. Magnetic resonance imaging (MRI) performed ten days later was consistent with hemorrhagic apoplexy of the pituitary adenoma. The patient's symptoms resolved after conservative treatment with dexamethasone, but he was scheduled for elective pituitary surgery. Preoperative MRI was performed one month after the first one and disclosed normal pituitary gland without any signs of adenoma. Our case is remarkable due to the fact that spontaneous remission of pituitary adenoma occurred within the first month, which is the shortest interval reported to date. Our case highlights the importance of conservative therapy as the first-line treatment for pituitary apoplexy in the absence of neurological impairment, since spontaneous remission may occur in a short time interval. Key words: Pituitary neoplasms; Pituitary apoplexy; Adenoma; Empty sella syndrome; Neoplasm regression, spontaneous; Remission, spontaneous
- A rare case of necrotizing hypophysitis (NH) in a 52-year-old man presenting with pituitary apoplexy and sterile meningitis is described. This case indicates that the diagnosis of NH could be made ...without biopsy, based on concomitant presence of diabetes insipidus, hypopituitarism and radiologic features of ischemic pituitary apoplexy. Conservative management of pituitary apoplexy should be advised in NH. Additionally, this is the first report of a case of sterile meningitis caused by ischemic pituitary apoplexy.
LMO2 (LIM domain only) is a member of transcription factor family of proteins characterized by their cysteine-rich, zinc-binding LIM domains. Its expression in prostate cancer cells, as well as in ...adjacent stroma, is described in a study in a cohort of 83 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. Authors found that LMO2 overexpression in prostate cancer was strongly associated with features indicative of worse prognosis (higher preoperative PSA, higher Gleason score, positive surgical margins, and extraprostatic extension of disease). Expression of LMO2 was also associated with biochemical disease progression. We analysed immunohistochemical expression of LMO2 in prostate cancer epithelial and stromal cells, as well as in adjacent parenchyma. Significant negative correlation between glandular expression of LMO2 in carcinoma and stromal expression in BPH (ρ = -0.238, P = 0.033) was found, but also be-tween stromal expression in carcinomas and glandular expression in BPH (ρ = -0.255, P = 0.021). Positive correlation was found between stromal expression in BPH and stromal expression in carci-nomas (ρ = 0.306, P = 0.005). Study results support the potential role of LMO2 in prostatic carcino-genesis and cancer progression.
Internal hernias have an overall incidence of less than 1% and are difficult to diagnose clinically due to their nonspecific presentation. Most internal hernias present as strangulating closed-loop ...obstruction and delay in surgical intervention is responsible for a high mortality rate (49%). We present a case of ileal herniation through the foramen of Winslow. A 29-year-old previously healthy female presented with acute onset right upper quadrant pain, abdominal fullness, and nausea. The pain was sudden in onset and began shortly after a dinner party where she consumed larger portions of food. Laboratory investigations revealed mild leukocytosis with left shift. Dual-phase multi-detector computed tomography disclosed herniation of the small bowel into the lesser sac. The patient underwent an emergency median laparotomy that revealed ileal herniation through the foramen of Winslow. Adhesiolysis and manual reduction of the bowel was performed, and the reduced bowel showed only congestive changes. The postoperative recovery was uneventful and the patient was discharged on the third postoperative day. Risk factors for internal herniation still remain unclear, although excessively mobile bowel loops and an enlarged foramen of Winslow have been described. Our case demonstrated that overeating could be an additional risk factor for internal herniation. We describe our clinical and radiology findings, as well as surgical management. Due to the high rates of morbidity and mortality, it is imperative that clinicians be aware of the possible risks factors for internal herniation. Internal hernias should be included in the differential diagnosis of small bowel obstruction so that appropriate steps can be made in the work-up of these patients, followed by timely surgical intervention.
Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of ...primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.
Purpose. In low-income countries, prolactinomas are difficult to manage with dopamine agonists (DA). We compared the effectiveness of DA in microprolactinomas as a first line treatment and as ...adjuvant therapy for residual macroprolactinomas treated surgically. Methods. Our retrospective study analyzed 78 patients, 38 with microprolactinomas and 40 with macroprolactinomas. Microprolactinomas were treated with DA. Macroprolactinomas were treated with microsurgical or endoscopic adenomectomies and adjuvant DA. Surgical remission was defined as normoprolactinemia three months postoperatively, and long-term remission as normoprolactinemia at the last control. Results. Surgical remission was achieved in 9 patients (23%). Postsurgical tumor mass was reduced by 50% (34–68). Residual macroprolactinoma size was greater than microprolactinoma size prior to treatment (10 mm versus 4 mm, P < 0.001 ). Both groups received similar doses of DA. Long-term remission occurred in 68% of microprolactinomas and 43% of macroprolactinomas ( P = 0.102 ). Prolactin (PRL) levels at the last control were similar in both groups (23.1 versus 32.9 mcg/L, P = 0.347 ). Conclusion. Comparable remission rates and PRL levels were reached in microprolactinomas and macroprolactinomas using similar doses of DA. Although complete tumor resection is the goal of surgery, our study suggests that even partial surgical removal has a role in treatment of prolactinomas since it may enhance the response to DA.
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