A Multi-institutional Analysis of Factors Influencing the Rate of Positive MRI Biopsy Among Women with Early-Stage Breast Cancer.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for early-stage breast cancer (ESBC) is increasing, but its utility in detecting additional malignancy is unclear and delays surgical management (Jatoi and Benson in Future Oncol 9:347-353, 2013. https://doi.org/10.2217/fon.12.186 , Bleicher et al. J Am Coll Surg 209:180-187, 2009. https://doi.org/10.1016/j.jamcollsurg.2009.04.010 , Borowsky et al. J Surg Res 280:114-122, 2022. https://doi.org/10.1016/j.jss.2022.06.066 ). The present study sought to identify ESBC patients most likely to benefit from preoperative MRI by assessing the positive predictive values (PPVs) of ipsilateral and contralateral biopsies. METHODS: A retrospective cohort study included patients with cTis-T2N0-N1 breast cancer from two institutions during 2016-2021. A "positive" biopsy result was defined as additional cancer (PositiveCancer) or cancer with histology often excised (PositiveSurg). The PPV of MRI biopsies was calculated with respect to age, family history, breast density, and histology. Uni- and multivariate logistic regression determined whether combinations of age younger than 50 years, dense breasts, family history, and pure ductal carcinoma in situ (DCIS) histology led to higher biopsy yield. RESULTS: Of the included patients, 447 received preoperative MRI and 131 underwent 149 MRI-guided biopsies (96 ipsilateral, 53 contralateral [18 bilateral]). PositiveCancer for ipsilateral biopsy was 54.2%, and PositiveCancer for contralateral biopsy was 17.0%. PositiveSurg for ipsilateral biopsy was 62.5%, and PositiveSurg for contralateral biopsy was 24.5%. Among the contralateral MRI biopsies, patients younger than 50 years were less likely to have PositiveSurg (odds ratio, 0.02; 95% confidence interval, 0.00-0.84; p = 0.041). The combinations of age, density, family history, and histology did not lead to a higher biopsy yield. CONCLUSION: Historically accepted factors for recommending preoperative MRI did not appear to confer a higher MRI biopsy yield. To prevent delays to surgical management, MRI should be carefully selected for individual patients most likely to benefit from additional imaging.

Our Experience in Trans Nasal Endoscopic Repair of Anterior Skull Base Defects Reinforced with Multiple Layers of Graft Materials.

Aims: To determine the best technique to repair anterior skull base defects using various grafts. Materials & Methods: This Ambi-directional cohort study was carried out at a tertiary care hospital from May 2019 to October 2021. A total of 17 patients who underwent Endoscopic Repair of Anterior Skull Base Defects using various grafts were included in the study. Detailed history and clinical evaluation followed by Diagnostic Nasal Endoscopy, Biochemical and Radiological investigations were done for all patients with postoperative follow-up for at least 6 months. Results: Most common site of anterior skull base defect in our study group was the posterior wall of the sphenoid sinus. Various graft materials used in our study were fascia lata, thigh fat, Hadad flap, Septal cartilage, nasal septal bone chip, septal mucosal free flap, surgicel and fibrin glue. The most commonly used sequence of graft materials used is the fat(underlay) - fascia lata - fat(overlay). Various complications that occurred were nasal bleeding, residual CSF leak, localized collection of pus in the Septal region, cerebral oedema and Alar trauma. Conclusions: The success of Anterior skull base defect repair depends on watertight Dural closure with multiple layers of grafts to prevent postoperative CSF leak. Although dependent on the Surgeon's preference, usually the sequence of an underlay fat - fascia lata - overlay fat followed by glue/gel foam/Hadad flap works well. Even after discharging the patient, regular follow-up and evaluation ensure that the graft is in situ and there is no CSF leak or other complication.

Opioid-Sparing Multimodal Analgesia Protocol for Lumpectomy Patients Results in Superior Postoperative Pain Control.

BACKGROUND: We sought to determine if lumpectomy patients who received perioperative opioid-sparing multimodal analgesia reported less pain when compared with those who received traditional opioid-based care. STUDY DESIGN: A prospective cohort of patients undergoing lumpectomy who received an opioid-sparing multimodal analgesia protocol [no opioids group (NOP)] was compared with a large cohort of patients who received traditional care [opioids group (OG)]. In-hospital and discharge opioids were compared using oral morphine equivalents (OMEs). Postoperative day one and week one pain scores were compared using the Kruskal-Wallis test. RESULTS: Overall, 1153 patients underwent lumpectomy: 634 patients received the protocol (NOP), and 519 patients did not (OG). Median pain scores were significantly lower in the NOP cohort when compared with the OG cohort the day after surgery (2 vs. 0, p < 0.001) and the week after surgery (1 vs. 0, p < 0.001). NOP patients were significantly less likely to report severe pain (7-10 on a 10-point scale) the day after surgery compared with OG patients (15.7% vs. 6.9%, p = 0.004). Patients in the NOP cohort were discharged with a median of zero OMEs (range 0-150), while patients in the OG were discharged with a median of 90 OMEs (range 0-360; p < 0.001). CONCLUSION: Implementation of an opioid-sparing multimodal analgesia protocol for lumpectomy patients resulted in superior pain control without a routine opioid prescription. Surgeons can improve their own patients' outcomes while addressing the larger societal issue of the opioid crisis by adopting similar protocols that decrease the quantity of opioids available for diversion.

PET-CT scan-based maximum standardized uptake value as a prognostic predictor in oropharynx squamous cell cancer.

INTRODUCTION: Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is clinically useful and extensively used in initial staging and follow-up of patients with head and neck squamous cell carcinoma (HNSCC). We studied the potential prognostic significance of primary tumor maximum standard uptake value (SUVmax) by 18F-FDG PET-CT in oropharyngeal cancer. METHODS: Sixty patients with early and locally advanced histopathologically proven oropharyngeal squamous cell cancer were staged using FDG PET-CT at diagnosis. All patient received radiation therapy and concurrent chemotherapy (in stage III and IVA disease) and were assessed prospectively for treatment outcome. Groups were created based on stage and cut off for SUVmax. The association of SUVmax of primary tumour and stage with disease-free survival and overall survival was analyzed by univariate and multivariate statistics. RESULTS: In univariate analysis, a primary tumour SUVmax of greater than 13.0 and advanced stage (IVA) predicted inferior disease-free survival (P=0.0241 and 0.0005, respectively) and overall survival (P=0.0510, toward significance and 0.0003, respectively). In proportional hazards analysis, stage was significant only when adjusted for primary SUVmax. CONCLUSION: SUVmax failed to demonstrate predictive significance in oropharyngeal cancer, and an increase in primary tumor uptake is possibly a direct effect of advanced disease and consequently increased metabolic activity and aggressiveness.

Obese Patients Who Receive an Opioid-Sparing Enhanced Recovery After Surgery (ERAS) Protocol are at Increased Risk of Persistent Pain After Breast Surgery.

BACKGROUND: Obese patients are at increased risk of persistent pain and chronic opioid dependence after surgery. We sought to evaluate the impact of an Enhanced Recovery After Surgery (ERAS) protocol in breast surgery patients to determine whether multimodal analgesia was effective for both obese and non-obese patients. METHODS: A prospective cohort of patients undergoing breast surgery who received an opioid-sparing ERAS protocol was compared with patients who did not receive ERAS, including a historical cohort. Pain scores were compared with respect to body mass index (BMI). Obesity was defined as BMI ≥ 30, and moderate to severe pain was defined as 4-10 of a 10-point scale. Postoperative day one and week one pain scores were compared using the Kruskal-Wallis test. RESULTS: A combined contemporary and historical cohort of 1353 patients underwent lumpectomy and mastectomy without reconstruction. The present analysis comprises 622 patients with pain scores who did and did not receive ERAS between 2015 and 2018. The two groups were demographically similar. The day after surgery, those who received ERAS reported lower rates of moderate to severe pain, regardless of BMI (obese: 46.3% vs. 21.8%, p < 0.001; non-obese: 36.3% vs. 19.4%, p = 0.002). One week after surgery, obese patients who received ERAS had higher rates of persistent pain compared with non-obese patients (18.6% vs. 11.1%, p = 0.042). CONCLUSIONS: An opioid-sparing ERAS protocol utilizing multimodal analgesia significantly improved postoperative pain control for obese and non-obese patients. However, it appears that obese patients are still at relatively greater risk for persistent pain after surgery.

A Novel Study Using Accelerated Mass Spectrometry to Evaluate the Pharmacokinetics of Total (14)C AL-8309 (Tandospirone) Following Topical Ocular Administration in Healthy Male Subjects.

The primary objective of this study is to characterize the pharmacokinetics of total (14)C concentrations following bilateral, topical ocular drops of (14)C-AL-8309B labeled either at the pyrimidyl ring (cohort A) position or at the imido-carbonyl ring (cohort B) position twice daily from day 1 through day 6 and once in the morning of day 7 in 16 healthy male subjects (8 per cohort). Each drop (approximately 24 µL) of (14)C-AL-8309B 1.75% ophthalmic solution (equivalent to 420 µg-equiv AL-8309) contained approximately 500 nCi of (14)C-AL-8309. AL-8309 systemic absorption was relatively slow; the time of maximum observed plasma concentrations ranged from 0.25 to 3 hours. Moderate accumulation (1.48- to 1.86-fold) was observed in the mean systemic total (14)C plasma concentrations at steady state (day 7) compared with single dose (day 1). The mean total (14)C eliminated was 3.5-fold and 3.7-fold greater in the urine than the feces for cohort A and cohort B, indicating that (14)C-AL-8309 is primarily excreted through renal elimination. Single and multiple topical doses of AL-8309B were found to be safe and well-tolerated in healthy subjects. This is the first reported use of accelerator mass spectrometry technology with a topically applied ophthalmic product.

Agonists at the serotonin receptor (5-HT(1A)) protect the retina from severe photo-oxidative stress.

PURPOSE: 5-HT(1A) agonists are neuroprotective in CNS injury models. The authors evaluated the efficacy of 5-HT(1A) agonists to protect the retina from severe blue light-induced photo-oxidative damage. METHODS: Albino rats were dosed (subcutaneously) with AL-8309A, 8-OH DPAT, or buspirone once or three times before 6-hour exposure to blue light. Electroretinograms (ERGs) were measured to assess retinal function, and retinal damage was evaluated by light microscopy. Topical ocular dosing with 1.75% AL-8309B was also evaluated. Rats were dosed with WAY-100635, a 5-HT(1A) antagonist, to determine whether protection required activation of the 5-HT(1A) receptor. RESULTS: ERG response amplitudes were significantly (P < 0.05) depressed more than 66% in vehicle-dosed rats after light exposure. ERGs were significantly higher in rats treated with AL-8309A (0.1-30 mg/kg), 8-OH DPAT (0.1-1 mg/kg), buspirone (5-20 mg/kg) or topical ocular with 1.75% AL-8309B. Retinas from AL-8309A and 8-OH DPAT-treated rats were devoid of histologic lesions. Significant protection was measured in rats dosed once 0, 24, or 48 hours before light exposure. Protection provided by dosing with AL-8309B or 8-OH DPAT was inhibited in rats predosed with WAY-100635. CONCLUSIONS: 5-HT(1A) agonists provided potent and complete functional and structural protection. Protection was inhibited by treatment with WAY-100635, confirming the requirement for activating the 5-HT(1A) receptor in initiating this survival pathway. Single-dose experiments with AL-8309A suggest that the mechanism of protection is rapidly activated and protection persists for 48 hours. AL-8309B (1.75%) was effective after topical ocular dosing. AL-8309B is under evaluation in the clinic and may be useful in treating age-related macular degeneration.