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Objective: The choice of treatment modality for optic pathway gliomas (OPGs) is controversial. Chemotherapy is widely regarded as first-line therapy; however, subtotal resections have been reported for decompression or salvage therapy as first- and second-line treatment. The goal of this study was to further investigate the role and efficacy of resection for OPGs., Methods: A retrospective chart review was performed on 83 children who underwent surgical treatment for OPGs between 1986 and 2014. Pathology was reviewed by a neuropathologist. Clinical outcomes, including progression-free survival (PFS), overall survival (OS), and complications, were analyzed., Results: The 5- and 10-year PFS rates were 55% and 46%, respectively. The 5- and 10-year OS rates were 87% and 78%, respectively. The median extent of resection was 80% (range 30%-98%). Age less than 2 years at surgery and pilomyxoid features of the tumor were found to be associated with significantly lower 5-year OS. No difference was seen in PFS or OS of children treated with surgery as a first-line treatment compared with children with surgery as a second- or third-line treatment. Severe complications included new disabling visual deficit in 5%, focal neurological deficit in 8%, and infection in 2%. New hormone deficiency occurred in 22% of the children., Conclusions: Approximately half of all children experience a long-term benefit from resection both as primary treatment and as a second-line therapy after failure of primary treatment. Primary surgery does not appear to have a significant benefit for children younger than 2 years or tumors with pilomyxoid features. Given the risks associated with surgery, an interdisciplinary approach is needed to tailor the treatment plan to the individual characteristics of each child.

Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options. Optic gliomas contain various amounts of myxoid matrix, which can represent most of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on optic gliomas, which varied in the amount of myxoid matrix. We found that although subtypes of optic gliomas are indistinguishable on imaging, the microvascular network of pilomyxoid astrocytoma, a subtype of optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. These tumors show normal perfusion by clinical imaging and lack histological evidence of hemorrhage organization or thrombosis. The myxoid matrix is composed predominantly of the proteoglycan versican and its linking protein, a vertebrate hyaluronan and proteoglycan link protein 1. We propose that pediatric optic gliomas can maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed primitive myxoid vascularization. Enzymatic targeting of the proteoglycan versican/hyaluronan and proteoglycan link protein 1 rich myxoid matrix, which is in direct contact with circulating blood, can provide novel therapeutic avenues for optic gliomas of childhood., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

In a single-institution retrospective cohort study, 230 patients were treated for stage III primary ovarian cancer and 175 became eligible for second-look operations by virtue of a complete clinical response after primary surgical cytoreduction and platinum-based combination chemotherapy. Of these, 109 underwent a second-look operation. Optimal primary cytoreduction was defined as residual disease < or =1 cm. Median follow-up was 68.3 months. Five-year survival for all the 230 stage III ovarian cancers was 43.4%. Among all eligible patients (n = 175), there was no survival difference (P = 0.67) in those having second look (57.3%, 5-year survival) versus no second look (48.7%). In those patients with optimal primary cytoreduction (n = 118), there was no survival advantage to second look (69% versus 61%, P = 0.7). However, in those with suboptimal primary cytoreduction (n = 47), 5-year survival was 36% in those having second look versus only 13% in those refusing second look (P < 0.05). Multivariate analysis identified second-look surgery as the only significant independent prognostic variable affecting survival (RR = 0.321, P < 0.04). Patients with suboptimal debulking at primary surgery for stage III ovarian cancer appear to achieve a survival benefit from second-look surgical procedures, presumably from the early identification and treatment of residual disease.

A case of clear cell ovarian cancer and endometriosis in a postmenopausal patient following adjuvant tamoxifen for breast cancer is presented. Immunohistochemistry demonstrated the tumor to be positive for progesterone receptor protein but not estrogen receptor protein; the endometriosis was positive for both proteins. Literature review reveals this to be the first report of both clear cell ovarian cancer and endometriosis following tamoxifen use, and the third report of epithelial ovarian cancer associated with tamoxifen.

Objective: To evaluate the impact of integration of operative laparoscopy on length of stay (LOS) and complication rates on an academic gynecologic oncology service., Methods: Retrospective analysis of all admissions to our gynecologic oncology service was performed for the academic years 1990/1991 and 1993/1994. Primary endpoints were frequency of complications and LOS., Results: In 1990/1991, there were 785 total admissions, of which 287 were surgical and 3% were approached laparoscopically. In 1993/1994, there were 973 admissions of which 436 were surgical and 23% were approached laparoscopically. Operative laparoscopy was applied equally regardless of age and reproductive status; the utilization of laparoscopy was increased by 14-fold for patients with cancer, 4. 5-fold for patients with benign disease, and 12-fold for patients with adnexal masses. No change in the mean LOS of nonsurgical admissions was noted, yet overall LOS for all patients decreased from 6.3 to 4.8 days (P < 0.0001). Mean LOS in surgical patients decreased from 9.4 to 6.0 days (P < 0.0001). After correction for complications, decreases in LOS only occurred in procedures for which laparoscopy was significantly integrated. No reductions in LOS were noted with like surgical approaches; i.e., there was no change in the LOS of patients undergoing laparotomy in both years. Surgical complications were not increased by laparoscopy., Conclusions: Aggressive utilization of operative laparoscopy, even only for selected patients, into the surgical practice of a gynecologic oncology service demonstrates significant improvements in LOS without adversely affecting surgical complication rates., (Copyright 1998 Academic Press.)

Purpose: To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment of locally advanced cervical carcinoma., Materials and Methods: Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500 cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months)., Results: The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed 5 to 11.5 months (median, 8 months) after completion of treatment., Conclusion: Combination IFN-alpha and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin, or RT can increase tumor control with more acceptable normal tissue toxicity.

Objective: This report evaluates the acceptance, results, and predictors of human immunodeficiency virus (HIV) infection in inner city women referred to a colposcopy clinic for abnormal cervical cytology., Methods: HIV testing results of 1,908 inner city women referred for abnormal cervical cytology were analyzed retrospectively with respect to acceptance, race, ethnicity, Pap smear results, sexually transmitted diseases (STDs), HIV exposures, and final histologic findings., Results: HIV testing was accepted by 50.4% of patients. Women who agreed to screening were significantly more likely to admit exposure to HIV or to be Hispanic, foreign-born, or have a history of multiple STDs. Of those screened, 3.3% were found to be HIV seropositive. Although higher grades of referral Pap smears were noted in the women found to be HIV seropositive, final histologic findings were not different. The only predictors of unknown HIV seropositivity were admitted HIV exposure and external condyloma., Conclusions: Fifty percent of inner city women of unknown HIV status referred for abnormal cervical cytology will accept HIV serotesting and 3.3% are found to be positive. Most HIV-seropositive women can be detected based on either a history of exposure to HIV or the presence of external condyloma.

Thirty-nine patients underwent pelvic exenteration for gynecologic malignancies at The Mount Sinai Medical Center between 1975 and 1992. Surgical techniques, morbidity, survival, and other variables for patients so treated in two periods, 1975-1984 and 1985-1992, were compared. The primary cancer included squamous cell carcinoma of the cervix, 27; adenocarcinoma of the cervix, 1; squamous cell carcinoma of the vagina, 4; adenocarcinoma of the endometrium, 4; squamous cell carcinoma of the vulva, 2; and adenocarcinoma of the rectum, 1. Median survival was 23.1 months, with a median follow-up of 18 months. Survival was significantly related to status of the lymph nodes (p 0.0004) and surgical margins (p 0.0038). There were two postoperative mortalities, one due to pulmonary embolus and another to myocardial infarction. The ability in the second period analyzed, 1985-1992, to integrate a continent urinary reservoir and supralevator exenteration without colostomy yet not induce increased morbidity or decreased survival, has not been previously reported.

Cefepime is a potent, broad-spectrum, fourth-generation cephalosporin with enhanced activity against most gram-positive aerobic bacterial pathogens and many gram-negative aerobic bacteria that are resistant to other cephalosporins. The drug's zwitterionic structure contributes to more rapid penetration of gram-negative bacterial cell membranes, and its low affinity for most type I beta-lactamases leads to significantly reduced enzymatic degradation compared with other cephalosporins. Cefepime has a good toxicity profile, with minor gastrointestinal and central nervous system symptoms being most prevalent. At dosages ranging from 1-2 g every 8-12 hours, it is an alternative option for infections of the lower respiratory tract, urinary tract, and skin and skin structures, as well as febrile episodes in neutropenic patients with cancer, and bacteremia or septicemia in critically ill patients.

Total cystectomy at the time of radical pelvic surgery for gynecologic malignancies is not uncommon. Many techniques have been developed for urinary diversion including the continent ileocecal urinary reservoir. Twenty-nine patients underwent construction of a continent ileocecal urinary reservoir during the reconstructive phase of an exenterative procedure or for the relief of urinary tract fistula between 1990 and 1993. All procedures were performed using the mechanical stapling devices using metal staples. The right and proximal transverse colon were mobilized to a length of 24 cm. The ileum was divided 8 cm proximal to the ileocecal valve and plicated using the stapling technique. The colonic segment was opened on its antimesenteric border and the reservoir was created by stapling in a fashion to reapproximate the distal ends to each other. The ureters were stented and implanted without tunneling. A large Malecot drain was placed in all the pouches for irrigation of the colonic mucosa in the postoperative period. The ileal stoma was fixed to the anterior abdominal wall as was the anterior surface of the pouch. Operative time ranged from 50 to 150 min for the pouch construction. All patients underwent retrograde contrast study of the pouch 7-10 days postoperatively to verify lack of anastomatic leaks. After recovery, all patients successfully self-catheterized the pouch three to five times daily without difficulty. Of the 29 patients, 17 (59%) had received prior radiation as part of therapy. All patients remained continent at the end of observation. One developed a fistula to the perineum after intraoperative placement of 125I seeds on the pelvic wall. One patient developed pouch stones; endoscopic evaluation of this pouch revealed no evidence of stones at the staple lines and metabolic workup demonstrated hypocitremia as the etiology for the stones. Mean reservoir volume was 550 ml. Mean follow-up is 15.8 months; 5 have expired due to recurrent disease and 19 (83%) remain alive. Only two patients have been admitted for urosepsis due to reflux pyelonephritis. The stapled continent ileocecal reservoir offers benefits to patients undergoing total cystectomy. Using the mechanical stapling devices decreases the operative time and has not resulted in stone formation or pouch leakage. The complications of the procedure are acceptable.

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.

In spite of diagnostic and therapeutic improvements the Surveillance Epidemiology and End Results Program data suggest that the overall cure rate for patients with ovarian cancer is 39%. Because of the dramatic difference in cure between patients with local disease (80% to 90%) and those with distant disease (15% to 25%), screening to find early ovarian cancer or its precursors is desirable. Transvaginal ultrasonography is the most efficient, accurate, and least expensive of the imaging modalities (transabdominal ultrasonography, computed tomography, magnetic resonance imaging, radioimmunoscintigraphy) for this purpose. To date, 10,000 women have been screened in three large programs; 11 cancers were detected (10 stage I, one occult stage IIIB) and all have apparently been cured. Doppler flow imaging and morphology index values improve the accuracy of transvaginal ultrasonography. A cost analysis suggests that screening costs are not yet less than treatment costs if there is to be universal screening of 27 million women at risk in the United States. However, for a population with a lifetime risk for ovarian cancer of 1%, screening will save five lives per 2000 patients screened.

The application of operative laparoscopy to patients with gynecologic malignancy is in its infancy, but promising findings have been demonstrated for surgical end staging after cytotoxic therapy for ovarian cancer, laparoscopic lymph node sampling for cervical cancer, and laparoscopic staging, vaginal hysterectomy and adnexectomy for corpus cancer. The most significant difficulty in integrating operative laparoscopy with gynecologic oncology, at this time, is the lack of controlled studies to demonstrate the ability of endoscopy to improve the contemporary management of these diseases. Further study will be necessary by subspecialists in gynecologic oncology to demonstrate the proper application of these new techniques.

Objective: To review the role of itraconazole as oral therapy for the major infections caused by Aspergillus spp.: allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis., Data Sources: A MEDLINE search of articles published in the English language between 1986 and 1993 was used to identify relevant citations, including review articles. In addition, a search of the published abstracts of the past two Interscience Conferences on Antimicrobial Agents and Chemotherapy (ICAAC) was performed., Study Selection: Clinical trials that evaluated itraconazole therapy in either allergic bronchopulmonary aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed. Trials were evaluated based upon entry criteria for the diagnosis of each type of aspergillosis, risk factors for the development of aspergillosis (neutropenia, transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and dose and duration of itraconazole therapy., Data Synthesis: Overall, the clinical trials of itraconazole therapy for aspergillosis are limited and of variable quality. In the treatment of allergic bronchopulmonary aspergillosis, itraconazole has been reported to prompt a reduction in corticosteroid dosage in selected patients. There have been no controlled trials of itraconazole as treatment for aspergilloma, but data from several open-label trials suggest that this agent may be of clinical benefit in aspergilloma, primarily as an alternative to surgery. The use of itraconazole for invasive aspergillosis has been evaluated in several trials, most often in patients who were intolerant to amphotericin B treatment. Response to oral itraconazole has generally been promising., Conclusions: Although itraconazole offers promise for oral therapy against infections caused by Aspergillus spp., it should not presently be regarded as primary therapy for any of these diseases. Amphotericin B, in doses ranging from 1 to 1.5 mg/kg to a total dose of 1.5-4.0 g, should remain the treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole use should be restricted to patients who experience severe toxicity with amphotericin B therapy. Corticosteroids continue to be first-line therapy for allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved for those patients who would benefit from a reduction in corticosteroid dose.

This investigation examined whether or not a gender-related effect on theophylline pharmacokinetics and metabolism exists in smoking and nonsmoking subjects with and without the concurrent administration of cimetidine. With a crossover design, 28 healthy men and premenopausal women (14 in each group) were administered intravenous aminophylline before (phase 1) and during (phase 2) a 10-day course of cimetidine, 300 mg four times a day. Statistically significant gender- and smoking-related effects were seen for theophylline half-life and clearance in phase 1, but only the smoking effect was statistically significant for these pharmacokinetic parameters in phase 2. Urinary metabolite excretion patterns demonstrated a greater percentage of excretion of 3-methylxanthine in female smokers than in male smokers in phase 1. Time-averaged urinary clearance of 1,3-dimethyluric acid was greater in female smokers than in male smokers. In phase 2, a significant reduction in the clearance of 1,3-dimethyluric acid was noted in female smokers but not in any other group. The results of our investigation suggest that a significant difference in the pharmacokinetics of theophylline exists that is related to gender and smoking status. Theophylline metabolism also seems to vary according to these factors. Administration of cimetidine results in a significant reduction in clearance of theophylline and abolishes the gender differences but not the smoking differences.

In order to assess the acute effects of the intraoperative administration of intraperitoneal (IP) carboplatin with and without intravenous (IV) doxorubicin in patients with gynecologic malignancies, 25 patients were treated at the conclusion of their surgical procedure. Twenty-three had epithelial ovarian cancer and 2 had advanced endometrial cancer. Twelve patients received IP carboplatin and IV doxorubicin at the conclusion of their primary cytoreduction. The remaining 13 received IP carboplatin alone and consisted of 4 reassessment laparotomies for ovarian cancer, 7 secondary cytoreductions, 1 minilaparotomy for the placement of an IP catheter, and 1 second-look laparoscopy. The median age of the 25 patients was 59 years. Eight patients underwent bowel resections with anastomoses; 2 had ureteral resections and ureteroneocystostomies, 1 required a splenectomy, and 1 underwent a partial hepatic resection. There were no mortalities. Three of the 13 patients who received the IP carboplatin alone had postoperative fevers with no infectious source, which did not delay discharge. No other morbidity was noted in this group. However, 7 patients who received IV doxorubicin along with the IP carboplatin developed severe leukopenia requiring antimicrobial and colony-stimulating factor support. One patient required reexploration for postoperative hemorrhage and also developed a pulmonary embolus. One woman developed postoperative pneumonia. The median hospital stay for the 25 patients was 9 days. Intraoperative chemotherapy can be administered with tolerable immediate adverse effects.

Objective: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms., Methods: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors., Results: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types., Conclusion: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with advanced epithelial ovarian cancer who undergo incomplete surgery followed by six cycles of chemotherapy could benefit from second-look or consolidation cytoreductive surgery (CCRS). The primary goal of this study was to evaluate the overall survival (OS) in patients undergoing complete CCRS and the factors affecting survival. The secondary goal was to study the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients., Methods: This was a retrospective analysis of 173 patients with CCRS with (n = 118) or without (n = 55) HIPEC treated at 12 French centers. Only patients having a completeness of cytoreduction (CC) 0/1 resection and a minimum of 5 years of follow-up were included. HIPEC was performed systematically for all patients except those treated at the four centers that did not perform HIPEC., Results: The median Peritoneal Cancer Index was 6 (range 0-33). Closed HIPEC was performed in 59 (34.1%) patients and open HIPEC was performed in 56 (32.3%) patients. Grade 3-4 complications occurred in 64 (36.9%) patients. The median OS was 35.67 months (95% confidence interval [CI] 29.8-46.1) and was significantly longer for CCRS + HIPEC (31.4 months without HIPEC and 42.5 months with HIPEC; p = 0.022). On multivariate analysis, closed HIPEC (hazard ratio [HR] 0.46, 95% CI 0.29-0.73; p < 0.001) resulted in a longer OS, and age > 65 years (HR 2.17, 95% CI 1.14-4.11; p = 0.018) and bowel resection (HR 1.98, 95% CI 1.27-3.08; p = 0.020) led to a shorter OS. On multivariate logistic regression analysis, closed HIPEC (odds ratio 0.18; p = 0.001) was associated with a lower risk of dying at 5 years., Conclusions: CCRS was performed with an acceptable morbidity and resulted in good overall survival. The role of HIPEC in addition to CCRS should be evaluated in prospective, randomized studies and the closed technique prospectively compared with the open technique., (© 2023. Society of Surgical Oncology.)

Optic pathway glioma (OPG) is a rare brain tumor affecting children, with no standard treatment strategy. This study described the sporadic OPG survival outcomes after surgical treatment and analyzed the role of imaging features and resection status in children receiving different adjuvant treatments. This retrospective study included 165 OPG patients whose clinical information were obtained from the hospital record system. Tumor volume and residual tumor volume were calculated by delineating the lesion area. Kaplan-Meier method and Cox proportional hazards model were conducted to analyze the independent prognosis factor. A total of 165 patients were included in this study. Respectively, the 5-year overall survival (OS) and progression-free survival (PFS) were 87.58% and 77.87%. Residual tumor size and first adjuvant treatment (AT) after surgery were both associated with PFS. In patients with small-size residual tumors, there was no significant difference in PFS between the AT treatment groups. Moreover, age, exophytic cystic components, leptomeningeal metastases, and AT were associated with OS. In patients with exophytic cystic components and those with leptomeningeal metastases, there was no significant difference in OS. Our results revealed that OPG patients could avoid or defer AT by maximized resection. Age ≤ 2 years was a disadvantageous factor for OS. Patients with exophytic cystic components were more likely to benefit from primary surgery, and CT or RT was not beneficial for these patients. Patients with leptomeningeal metastases had a poor prognosis regardless of the treatment they received. Future prospective clinical studies are needed to develop more effective treatment regimens., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The efficacy, safety, and tolerability of drugs are dependent on numerous factors that influence their disposition. A dose that is efficacious and safe for one individual may result in sub-therapeutic or toxic blood concentrations in others. A significant source of this variability in drug response is drug metabolism, where differences in presystemic and systemic biotransformation efficiency result in variable degrees of systemic exposure (e.g., AUC, C max , and/or C min ) following administration of a fixed dose.Interindividual differences in drug biotransformation have been studied extensively. It is recognized that both intrinsic factors (e.g., genetics, age, sex, and disease states) and extrinsic factors (e.g., diet , chemical exposures from the environment, and the microbiome) play a significant role. For drug-metabolizing enzymes, genetic variation can result in the complete absence or enhanced expression of a functional enzyme. In addition, upregulation and downregulation of gene expression, in response to an altered cellular environment, can achieve the same range of metabolic function (phenotype), but often in a less predictable and time-dependent manner. Understanding the mechanistic basis for variability in drug disposition and response is essential if we are to move beyond the era of empirical, trial-and-error dose selection and into an age of personalized medicine that will improve outcomes in maintaining health and treating disease., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 patients (NF1). They are found along the optic pathway and may involve the optic nerves, chiasm, retro-chiasmatic structures, and the optic radiations. NF1 associate OPG (NF1-OPG) have variable presentation, disease course and response to treatment. The optimal management is patient-specific and should be tailored by a multidisciplinary team. Age, sex, histology, and molecular markers may be important factors in the individualized decision-making process. Chemotherapy is the first-line treatment in cases of progressive tumors, and visual preservation is the main goal of treatment., Purpose: In this paper we will review the disease, practical management, and recent advances of NF1-OPG.