Evaluating nutrition in advanced ovarian cancer: which biomarker works best?

BACKGROUND: Advanced epithelial ovarian cancer (OC) patients often present with malnutrition; however, the ideal nutritional evaluation tool is unclear. We aimed to evaluate the role of preoperative albumin, Prognostic Nutritional Index [PNI], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR] as independent predictors of severe postoperative complications and 90-day mortality in OC patients who underwent primary cytoreductive surgery to identify the ideal tool. METHODS: OC patients who underwent surgery at Mayo Clinic (2003-2018) were included; biomarkers were retrospectively retrieved and established cut-offs were utilized. Outcomes included severe complications (Accordion grade ≥ 3) and 90-day mortality. Univariate and multivariable logistic regression models were performed. Biomarkers were evaluated in separate models adjusted for age and American Society of Anesthesiologists (ASA) score for 90-day mortality, and adjusted for age, ASA score, stage, and surgical complexity for severe complications. RESULTS: Albumin <3.5 g/dL, PNI < 45, NLR > 6 and PLR ≥ 200 were univariately associated with 90-day mortality (all p < 0.05) in 627 patients that met inclusion criteria. Each marker remained significant in adjusted models with albumin having the highest OR: 6.04 [95% CI:2.80-13.03] and AUC (0.83). Univariately, PNI <45, NLR >6, and PLR ≥200 were significant predictors of severe complications(all p < 0.05), however failed to reach significance in adjusted models. Albumin was not associated with severe complications. CONCLUSION: All biomarkers were associated with 90-day mortality in adjusted models, with albumin being the easiest predictor to attain clinically; none with severe complications. Future research should focus less on methods of nutritional assessment and more on strategies to improve nutrition during OC tumor-directed therapy.

Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial.

BACKGROUND: After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. OBJECTIVE: This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. STUDY DESIGN: Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. RESULTS: Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). CONCLUSION: This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Dose-dense neoadjuvant chemotherapy before radical surgery in cervical cancer: a retrospective cohort study and systematic literature review.

OBJECTIVE: To evaluate the role of dose-dense neoadjuvant chemotherapy followed by radical hysterectomy in reducing adjuvant radiotherapy in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB1-IB2/IIA1 cervical cancer with disrupted stromal ring and as an alternative to concurrent chemoradiotherapy in FIGO 2018 stages IB3/IIA2. METHODS: This was a retrospective cohort study including patients with FIGO 2018 stage IB1-IIA2 cervical cancer undergoing dose-dense neoadjuvant chemotherapy at the European Institute of Oncology in Milan, Italy between July 2014 and December 2022. Weekly carboplatin (AUC2 or AUC2.7) plus paclitaxel (80 or 60 mg/m2, respectively) was administered for six to nine cycles. Radiological response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. The optimal pathological response was defined as residual tumor ≤3 mm. Kaplan-Meier curves were used to estimate survival rates. A systematic literature review on dose-dense neoadjuvant chemotherapy before surgery for cervical cancer was also performed. RESULTS: A total of 63 patients with a median age of 42.8 years (IQR 35.3-47.9) were included: 39.7% stage IB-IB2/IIA1 and 60.3% stage IB3/IIA2. The radiological response was as follows: 81% objective response rate (17.5% complete and 63.5% partial), 17.5% stable disease, and 1.6% progressive disease. The operability rate was 92.1%. The optimal pathological response rate was 27.6%. Adjuvant radiotherapy was administered in 25.8% of cases. The median follow-up for patients who underwent radical hysterectomy was 49.7 months (IQR 16.8-67.7). The 5-year progression-free survival and overall survival were 79% (95% CI 0.63 to 0.88) and 92% (95% CI 0.80 to 0.97), respectively. Fifteen studies including 697 patients met the eligibility criteria for the systematic review. The objective response rate, operability rate, and adjuvant radiotherapy rate across studies ranged between 52.6% and 100%, 64% and 100%, and 4% and 70.6%, respectively. CONCLUSIONS: Dose-dense neoadjuvant chemotherapy before radical surgery could be a valid strategy to avoid radiotherapy in stage IB1-IIA2 cervical cancer, especially in young patients desiring to preserve overall quality of life. Prospective research is warranted to provide robust, high-quality evidence.

Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

Low-Volume Metastases in Apparent Early-Stage Endometrial Cancer: Prevalence, Clinical Significance, and Future Perspectives.

Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07-1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8-98.2 versus 90.2%; CI 95% 84.9-95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.

Persistent subretinal fluid mimicking central serous retinopathy after scleral buckling surgery: possible vortex vein compression role.

PURPOSE: To describe the case of a woman who developed persistent subretinal fluid in the macular region after the placement of encircling band for retinal detachment surgery, possibly due to vortex vein compression. METHODS: Case report. RESULTS: A 66-year-old woman diagnosed with central serous retinopathy presented with poor vision and metamorphopsia in the left eye (LE). Her visual acuity had deteriorated to 20/100 in LE after retinal detachment surgery with scleral buckling 8 months before. Multimodal imaging including fundus autofluorescence and fluorescein angiography disclosed a gravitational hyperfluorescent area involving the macular region that appeared to originate from the superotemporal quadrant in correspondence with the buckling. This area corresponded to a serous retinal detachment on structural spectral-domain optical coherence tomography (SD-OCT). Interestingly, on indocyanine green angiography, the encircling band of the scleral buckling appeared located at the emergence of the superotemporal vortex vein. Based on these findings, the patient was diagnosed with gravitational serous retinal detachment secondary to vortex vein compression. Successful rapid visual recovery and decrease of retinal fluid on SD-OCT was achieved with prompt surgery of scleral buckling removal, confirming the diagnosis. CONCLUSIONS: Choroidal veins can be obliterated during retinal detachment surgery, especially when retinal breaks are posterior to the equator. Indocyanine green angiography is the gold standard to study choroidal circulation and in our case allowed us to visualize the compression of the superotemporal vortex vein at the site of scleral buckling.

DualTrack Technology Improves Optical Coherence Tomography Angiography Image Quality.

BACKGROUND AND OBJECTIVE: To evaluate the effects of DualTrack Motion Correction Technology on the performance of AngioVue optical coherence tomography angiography (Optovue, Freemont, CA). PATIENTS AND METHODS: Fifty subjects underwent two consecutive examinations with AngioVue. The operator inactivated the eye-tracking (ET) technology before the second examination. Two operators measured execution time, excluded low-quality images, and counted the number of motion artifacts per image. RESULTS: The mean execution time was lower without ET in all the groups (P < .05), regardless of retinal diseases. Percentages of available images and low-quality images were 75.0% and 25.0%, respectively, with ET and 63.0% and 37.0%, respectively, without ET. Mean number of motion artifacts was significantly lower in images obtained using ET compared to images obtained without ET in all the groups (P < .0001), regardless of retinal diseases. CONCLUSION: Although ET technology increases the mean execution time, the reduction of motion artifacts and the increase of high-quality images may represent a great advantage in clinical practice. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:918-926.].

Optical coherence tomography angiography of myopic choroidal neovascularisation.

BACKGROUND/AIMS: To describe the morphological features of choroidal neovascularisation (CNV) and to report the ability of optical coherence tomography angiography (OCT-A) to detect the presence of myopic CNV by means of this new technique. METHODS: Myopic CNV cases were individuated from a pool of patients with pathological myopia consecutively presenting between October 2015 and March 2016. OCT-A images were assessed for classification of morphological features, and to estimate sensitivity and specificity. RESULTS: Thirty-six eyes of 28 consecutive patients with myopic CNV were included. In 4 out of 36 eyes it was not possible to classify the CNV 'shape', 'core', 'margin' and 'appearance' because the vascular network was not clearly visualised due to the poor quality of the examination. CNV shape on OCT-A was rated as circular in 9 eyes and irregular in 23 eyes. CNV core was visible in 11 eyes. CNV margin was considered as well defined in 16 eyes and poorly defined in 16 eyes. CNV appearance showed an 'interlacing' aspect in 16 eyes and a 'tangled' aspect in the other 16 eyes. A total of 11 CNVs were defined as active, 9 of which (81.8%) were interlacing, while a total of 21 were inactive, 14 of which (66.7%) were tangled. OCT-A sensitivity turned out to be 90.48% and specificity was 93.75%. CONCLUSIONS: We describe the OCT-A features of myopic CNV secondary to pathological myopia and demonstrate its high sensitivity and specificity for neovascular detection. Qualitative evaluation of OCT-A characteristics may allow one to recognise different patterns, possibly corresponding to different degrees of neovascular activity.

Choroidal neovascularization and coincident perforating scleral vessels in pathologic myopia.

PURPOSE: To describe the coincidence of perforating scleral vessels and choroidal neovascularization (CNV) in pathologic myopia. METHODS: Medical records and multimodal imaging were reviewed from patients with CNV secondary to pathologic myopia who presented to the Medical Retina and Imaging Unit of San Raffaele Hospital in Milan between October 2015 and March 2016. Main outcomes were the prevalence of coincident perforating scleral vessels and overlying CNV and association between perforating scleral vessels and CNV position within the macula and neovascular activity. RESULTS: Forty-one eyes of 39 patients (6 male, 33 female, mean age 63.7 ± 14.1 years) with CNV secondary to pathologic myopia were included in the study. Scleral perforating vessels (average number of perforating vessels per eye 2.1 ± 1.0) were found in 29 out of 41 eyes (70.7%) at the site of CNV. There was no association between presence of perforating vessels and neovascular activity or CNV position. CONCLUSIONS: Perforating scleral vessels are often coincident with myopic CNV. We hypothesize that scleral vessels located beneath myopic CNV can play a role in neovascular development.

Optical coherence tomography angiography findings in laser maculopathy.

PURPOSE: Handheld laser pointer thermal injury affects primarily the retinal pigment epithelium (RPE). However, so far no study has reported on the possible effects of laser pointers in the deeper layers, beneath the RPE. Here, we describe the spectral-domain optical coherence tomography angiography findings in the choriocapillaris of a patient with laser maculopathy. METHODS: A 13-year-old boy presented to our department with decreased vision in the left eye 12 hours after having stared at the beam of a laser pointer. RESULTS: Structural optical coherence tomography (OCT) showed 2 focal hyperreflective columns at the fovea extending from the RPE, involving all outer retinal layers, and terminating at the outer plexiform layer. The patient also underwent OCT angiography (OCT-A), which in the choriocapillary segmentation revealed 2 hypointense lesions in correspondence of the focal hyperreflectivities detected on structural OCT. We hypothesize that the OCT-A findings could represent a rarefaction of the choriocapillaris. However, the choriocapillary OCT-A findings could also represent artifacts due to the overlaying hyperreflective lesions. CONCLUSIONS: It is known that the RPE is primarily damaged by the laser injury. Our findings suggest that the thermal injury could involve also the choriocapillaris, and thus not limited to the RPE. Multimodal imaging in laser maculopathy including OCT-A may lead to a better comprehension of the pathogenesis of laser retinal damages.

Sudden visual loss after cardiac resynchronization therapy device implantation.

PURPOSE: To report a case of sudden decrease in visual acuity possibly due to a cardiogenic embolism in a patient who underwent cardiac resynchronization therapy (CRT) device implantation. METHODS: A 62-year-old man with severe left ventricular systolic dysfunction and a left bundle branch block was referred to our department because of a sudden decrease in visual acuity. Nine days earlier, he had undergone cardiac transapical implantation of a CRT device, which was followed, 2 days later, by an inflammatory reaction. The patient underwent several general and ophthalmologic examinations, including multimodal imaging. RESULTS: At presentation, right eye (RE) best-corrected visual acuity (BCVA) was counting fingers and RE pupil was hyporeactive. Fundus examination revealed white-centered hemorrhagic dots suggestive of Roth spots. Fluorescein angiography showed delay in vascular perfusion during early stage, late hyperfluorescence of the macula and optic disk, and peripheral perivascular leakage. The first visual field test showed complete loss of vision RE and a normal left eye. Due to suspected giant cell arteritis, temporal artery biopsy was performed. Thirty minutes after the procedure, an ischemic stroke with right hemisyndrome and aphasia occurred. The RE BCVA worsened to hands motion. Four months later, RE BCVA did not improve, despite improvement in fluorescein angiography inflammatory sign. CONCLUSIONS: We report a possible cardiogenic embolism secondary to undiagnosed infective endocarditis causing monocular visual loss after CRT device implantation. It remains unclear how the embolus caused severe functional damage without altering the retinal anatomical structure.