Grade-2 Patients Research Articles

Impact of grade on workup of rectal neuroendocrine tumors: a retrospective cohort study

BackgroundRectal neuroendocrine tumors (RNETs) are often discovered on screening colonoscopy. Indications for staging and definitive resection are inconsistent in current guidelines. We evaluated the role of grade in guiding staging and procedural decision-making.MethodsPatients with biopsy confirmed RNETs between 2004 and 2015 were reviewed. Baseline characteristics, staging investigations (biochemical and imaging), and endoscopic/surgical treatment were recorded. Associations between grade, preoperative staging, interventions, and survival were determined using Fisher-Freeman-Halton Exact, log-rank, and Kaplan-Meier analysis.ResultsAmongst 139 patients with RNETs, 9% were aged ≥ 75 years and 44% female. Tumor grade was: 73% grade 1 (G1), 18%, grade 2 (G2) and 9% grade 3 (G3). Staging investigations were performed in 52% of patients. All serum chromogranin A and 97% of 24-hour urine 5-hydroxyindoleacetic acid tests were normal. The large majority of staging computed tomography (CT) scans were negative (76%) with subgroup analysis showing no G1 patients with CT identified distant disease compared with 38% of G2 and 50% of G3 patients (p < 0.001). G1 patients were more likely to achieve R0/R1 resections compared to G2 (95% vs. 50%, p < 0.001) and G1 patients had significantly better 5-year overall survival (G1: 98%, G2: 67%, G3: 10%, p < 0.001).ConclusionTumor grade is important in preoperative workup and surgical decision-making. Biochemical staging may be omitted but staging CT should be considered for patients with grade ≥ 2 lesions. Anatomic resections should be considered for patients with grade 2 disease.

(256) Effect of Early Varicocelectomy Intervention on Male Hormone Levels in Adolescent Males

Abstract Introduction Varicoceles can be found in approximately 15% of the adult male population and are known to impact male fertility. Varicoceles may develop during adolescence and increase in size as these males undergo puberty. According to current guidelines, it is recommended to monitor young asymptomatic patients and consider surgical intervention if they develop testicular size discrepancies, fertility issues, abnormal semen analyses, or experience significant pain. However, the effect of varicoceles on sex hormones and management in young males is poorly understood. Objective To evaluate the impact of early surgical intervention for varicoceles with a microsurgical varicocelectomy on hormone levels and safety profiles in adolescent males. Methods A retrospective review was conducted on 67 patients between the ages of 10 and 17 years old who had a grade 2 (G2) or grade 3 (G3) varicocele, and underwent microsurgical varicocelectomy between November 2021 and May 2023. Patient demographics, varicocele laterality and grade, surgical data, and pre-and post-operative hormone levels were collected as well as post-operative complications. Hormonal panel was collected before 11AM using LCMS and included total testosterone (TT), free testosterone (FT), percent free testosterone (%FT), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (P), and sex hormone-binding globulin (SHBG). Statistical analyses were conducted using SAS System. Results A total of 67 patients had complete data (96% had G3 varicoceles). Preoperative FT was statistically significant between varicocele grades 2 and 3 (p=0.03) with G3 varicoceles having lower preop FT levels. Pre-operative hormone levels for G2 varicoceles were: TT 550ng/dL (std 177ng/dL), FT 126ng/dL (std 27), E2 33 (std 2.64), FSH 3.53 (std 1.27) and LH 5.06 (std 3.53). Pre-op levels for G3 varicoceles: TT 437ng/dL (std 199ng/dL), FT 71.3 (std 42.2), E2 25.2 (std 9.64), FSH 4.34 (std 3.3) and LH 3.73 (std 1.9). Post operatively TT levels improved in G3 varicocelectomy patients with a postop mean TT 445ng/dL (std 109ng/dL), however this did not meet statistical significance. There was no statistically significant difference between postoperative hormone panel labs between varicocele grades. There were no complications in any of the patients and no recurrence of varicoceles. Conclusions Our study evaluated the impact of early surgical intervention for G2 and G3 varicoceles on hormone levels in adolescent males. The results showed a significant difference in preoperative Free T levels between G2 and G3 varicocele patients possibly indicating the impact of varicocele grade on FT levels in adolescents. Early surgical intervention for G3 varicoceles appears to be safe with resultant improvements in TT levels with no increased risk of complications. Further investigations to explore the potential benefits of early surgical treatment in adolescent patients with varicoceles evaluating hormonal profiles in larger cohorts. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast and BK Ultrasound.

Characteristics of Inflammatory Markers in Diabetic Foot Patients and Their Relationship With Prognosis of Diabetic Foot Ulcers

To explore the characteristics of baseline inflammatory markers in diabetic foot patients and their relationship with the prognosis of diabetic foot ulcers. The clinical data of diabetic foot patients (n=495) admitted to West China Hospital, Sichuan University since 2016 were retrospectively collected through the hospital electronic medical record system to analyze the characteristics of inflammatory markers and their relationship with the prognosis of diabetic foot ulcers. White blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels were significantly higher in patients defined as grade 4 on the Wagner Scale than those in patients defined as grade 0-3 on the Wagner Scale. Neutrophil percentage (NE%) was higher in Wagner grade-4 patients than those in Wagner grade-0 and grade-1 patients and higher in Wagner grade-3 patients than those in Wagner grade-0 patients. NE%, CRP, PCT, and IL-6 levels were positively correlated with the severity of diabetic foot, with the respective odds ratio (OR) at 95% confidence interval (CI) being 1.038 (1.019-1.056), 1.019 (1.012-1.026), 8.225 (2.015-33.576), and 1.017 (1.008-1.025). Using Wagner grade-0 patients as the reference, patients with higher WBC were more likely to progress to Wagner grade 2, 3, and 4, with the respective OR (95% CI) values being 1.260 (1.096-1.447), 1.188 (1.041-1.356), and 1.301 (1.137-1.490); patients with higher ESR were more likely to progress to Wagner grade 3 and 4, with the respective OR (95% CI) values being 1.030 (1.006-1.054) and 1.045 (1.019-1.071). Baseline ESR (P=0.008), CRP (P=0.039), and IL-6 (P=0.033) levels were lower in patients who had received antibiotics prior to their admission than those in patients who had not received antibiotics before admission. The levels of WBC, NE%, ESR, PCT, and IL-6 were lower in the full recovery group than those in the group of patients who did not respond to treatment. The higher the levels of NE% and IL-6, the worse the prognosis of diabetic foot ulcers became, with the respective OR (95% CI) values being 1.030 (1.010-1.051) and 1.008 (1.002-1.013). The severity of diabetic foot ulcers increased with the rise in baseline levels of inflammatory markers. Elevated baseline NE% and IL-6 levels suggest a poor prognosis. Our findings suggest that early assessment of diabetic foot infection and standardized antibiotic therapy should be implemented to improve the prognosis.

P18.07.A CLINICAL OUTCOMES OF PATIENTS TREATED WITH FRACTIONATED PHOTON RADIOTHERAPY FOR INTERMEDIATE AND HIGH-RISK MENINGIOMAS AT THE CHRISTIE HOSPITAL

Abstract BACKGROUND Radiotherapy is often used as a postoperative treatment for WHO Grade 2 (G2) and Grade 3 (G3) meningioma. However, there is limited data on the long-term outcomes following radiotherapy for these patients. The present study aims to evaluate the outcomes of intermediate and high-risk meningioma patients treated with radiotherapy. MATERIAL AND METHODS A retrospective analysis was conducted on all G2 and G3 meningioma patients treated at our centre with fractionated radiotherapy from 2012 to 2021. Clinical status at follow up was updated to 20 March 2023. Those who received stereotactic radiosurgery or were re-irradiated were excluded. Univariate Cox Regression modelling was conducted to assess association of progression, progression-free survival (PFS) and overall survival (OS) with clinical variables. RESULTS Forty-three patients were included in the analysis, 25 (58.2%) female. 39 patients had G2 and 4 G3 meningioma. Median age was 60 (range 11-80) years. Median follow-up was 72 months. At the time of radiotherapy, most (n= 34) had an ECOG performance status (PS) of 0-1. The dose fractionation was 50.4Gy (n=2), 54Gy (n=20) or 59.4Gy(n=1) in 1.8Gy fractions, or 60Gy(n=20) in 2Gy fractions. The PFS was 76.7% (95%CI:64.1,89.4) at 3 years and 64.3% (95%CI:49.8,78.9) at 5 years. OS was 79.1% (95% CI:66.9,91.2) at 3 years and 74.0% (95% CI:60.8,87.3) at 5 years. For the lower dose subgroup (50.4/54Gy), 3 and 5-year PFS rates were 86.4% (95% CI: 72.0,100) and 72.7% (95% CI:54.1,91.3), while 3 and 5-year OS rates were both 86.4% (95% CI:72.0,100). For the higher dose subgroup (59.4/60Gy), 3 and 5-year PFS rates were 66.7% (95% CI:46.5,86.8) and 55.0% (95% CI: 32.8,77.2), while 3 and 5 year OS were 71.4% (95% CI: 52.1,90.8) and 59.9% (95% CI: 38.1,81.8). All survival times were calculated from radiotherapy end date. Effect of dose (low vs high), age (either continuous or categorical as &amp;lt;60 vs ≥60), gender, WHO grade and PS were examined in univariate Cox regression for relationship to each of progression free status at last assessment, PFS and OS. No factor was statistically significant for progression free status or PFS. For OS, we found a significant association of worse OS with higher doses (59.4/60Gy), Hazard ratio (HR) 3.749 (95%CI: 1.18,11.9), p=0.025, and a borderline significance for age ≥60, HR 3.056 (95%CI:0.995,9.39), p=0.051. At the end of follow-up, 18 patients were alive without progression (16 G2, 2 G3), 8 were alive with progression (all G2), 10 had died with progression (9 G2, 1 G3) and 7 had died without progression (6 G2, 1 G3). CONCLUSION The worse OS in the higher dose group likely relates to clinical risk factors beyond WHO grade. There is a need for clinical trials to improve outcomes for intermediate and high risk meningioma. This may require better risk stratification by use of molecular markers, dose escalation or dose painting of high risk sub volumes and when possible targeted agents.

Adjuvant chemotherapy does not improve outcome in children with ovarian immature teratoma: A comparative analysis of clinical trial data from the Malignant Germ Cell International Consortium.

Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom. From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS). Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p=.05), stage II-IV EFS: 67% versus 79% (p=.32), stage II-IV OS: 93% versus 97% (p=.44); amongst grade-3 patients, there was no difference in EFS or OS. Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone.

Is There a Role for Surgical Resection of Grade 3 Neuroendocrine Neoplasms?

Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are aggressive tumors with poor survival outcomes for which medical management is generally recommended. This study sought to evaluate outcomes of surgically treated G3 GEP-NEN patients. A single-institutional prospective NEN database was reviewed. Patients with G3 GEP-NENs based on World Health Organization (WHO) 2019 definitions included well-differentiated neuroendocrine tumors (G3NET) and poorly differentiated neuroendocrine carcinomas (G3NEC). Clinicopathologic factors were compared between groups. Overall survival from G3 diagnosis was assessed by the Kaplan-Meier method. Surgical resection was performed for 463 patients (211 G1, 208 G2, 44 G3). Most had metastatic disease at presentation (54% G1, 69% G2, 91% G3; p < 0.001). The G3 cohort included 39 G3NETs and 5 G3NECs, 22 of pancreatic and 22 of midgut origin. Median overall survival (mOS; in months) was 268.1 for G1NETs, 129.9 for G2NETs, 50.5 for G3NETs, and 28.5 for G3NECs (p < 0.001). Over the same period, 31 G3 patients (12 G3NETs, 19 G3NECs) were treated non-surgically, with mOS of 19.0 for G3NETs and 12.4 for G3NECs. Surgical resection of G3 GEP-NENs remains controversial due to poor prognosis, and surgical series are rare. This large, single-institutional study found significantly lower mOS in patients with resected G3NENs than those with G1/G2 tumors, reflecting more aggressive tumor biology and a higher proportion with metastatic disease. The mOS for resected G3NETs and G3NECs exceeded historical non-surgical G3NEN series (mOS 11-19 months), suggesting surgery should be considered in carefully selected patients with G3NENs, especially those with well-differentiated tumors.

Initial Experience With a Novel Sheathless Guiding Catheter (Hyperion SheathLess) for Transradial Coronary Intervention.

The Hyperion SheathLess guiding catheter (Asahi Intecc) is a novel guiding system for transradial percutaneous coronary intervention (PCI). Compared with the previous model (SheathLess Eaucath; Asahi Intecc), improvements achieved with the Hyperion SheathLess catheter are a more flexible tip and a smaller outer diameter of the catheter while maintaining the diameter of the inner lumen. The aim of this study was to report our initial experience with this guiding catheter. A total of 127 consecutive patients undergoing transradial PCI using a 6-Fr Hyperion SheathLess guiding catheter (n = 78) or a 7-Fr catheter (n = 49) were analyzed. Procedural success was 99.2%, with 1 patient (0.8%) requiring conversion to femoral access. No patients were noted to have coronary ostial dissection. Doppler ultrasound examination of the radial artery at 30-day follow-up was available in 111 of 127 patients, with 3 patients (2.7%; all 3 patients in the 7-Fr catheter group) found to have radial artery occlusion. Radial spasm occurred in 3 patients (2.4%; all 3 patients in the 7-Fr catheter group). Forearm hematoma occurred in 10 patients (7.9% total; 4 grade-1 patients [3.2%], 5 grade-2 patients [3.9%], and 1 grade-3 patient [0.8%]). The use of the Hyperion SheathLess guiding catheter for transradial PCI was feasible and associated with a low rate of procedure-related complications, including coronary ostial dissection. This sheathless guiding catheter could be a valuable option to further decrease the risk of procedure-related complications.

Pattern of Presentation of Iatrogenic Biliary Injury Following Laparoscopic Cholecystectomy

Background: Cholecystectomy is one of the most now common abdominal surgeries performed every day. The incidence of bile duct injury (BDI) following open cholecystectomy is only 0.1% - 0.2%. After the introduction of laparoscopic cholecystectomy, the incidence has gone up to 0.4% - 0.7%. The present study is a prospective analysis of all patients with bile duct injury who were admitted to Dhaka Medical College Hospital during or at a variable period following cholecystectomy. Methods: To determine the pattern of presentation of iatrogenic biliary injury following cholecystectomy in the department of surgery of Dhaka Medical College Hospital, a total of 30 patients were purposively selected from May 2018 to November 2018. Patient particulars, records of physical and clinical evaluation, and operative details were collected by individual researchers. Data analysis was done by SPSS for windows version 21. Results: BDI was found very common among the age group 21 - 30 yrs (36%) and female dominant (60%). Majority of the patients presented with abdominal pain (96%), intra-abdominal collection (88%), biliary peritonitis (68%), cholangitis (60%), and obstructive jaundice (40%), and biliary fistula (40%). Laparoscopic cholecystectomy (84%) was the principal cause of biliary injury in our study. 48% of patients experienced clinical features within 7 days post-cholecystectomy. Per-operative diagnosis was done in only 12% of cases. 44% of patients in this study were recognized as Bismuth grade-3, followed by 36%, grade-2 patients. Management outcomes included wound infection (41.66%), minor bile leak (25%), peritonitis (8.33%), and renal impairment (8.33%). Conclusion: The effect of BDI is an extremely distressful clinical condition for the patients and their family members, hence proper care and management protocol should be followed.

A Retrospective Analysis of the Correlation between Functional Imaging and Clinical Outcomes in Grade 3 Neuroendocrine Tumors (NETs G3).

Grade 3 (G3) neuroendocrine tumors (NETs) are a novel category among digestive neuroendocrine neoplasms, characterized by Ki-67 >20% and a well-differentiated morphology, presenting high intra-tumor heterogeneity. We aimed to explore the role of dual-tracer PET imaging (68Gallium (Ga)-DOTATOC and 18Fluorodeoxyglucose (FDG)) as overall survival (OS) predictor in NET G3 patients. We performed a retrospective analysis in NET G3 patients treated at our institution between 2003 and 2021. Accordingly, 30 NET G3 patients were analyzed. 68Ga-DOTA-TOC and 18F-FDG uptake were assessed by tumor/non-tumor (T-nonT) ratio. We reported a slightly better OS for patients with ≥75% concordance between 68Ga-DOTA-TOC and 18F-FDG PET/CT (p = 0.42). Among patients with discordant functional imaging, we reported a better 5-y OS rate for patients with a prevalent 68Ga-DOTATOC vs. 18F-FDG PET/CT (p = 0.016). In positive 18F-FDG PET/CT cases, we reported a better OS for <4 vs. ≥4 T/non-T ratio (p = 0.021). Among upfront-NET G3 patients with concordant exams, 5-y OS rate was 83.3% (95% CI: 27.3–97.5). Among patients with discordant exams, 5-y OS rate was 81.3% (52.5–93.5), 100% for those with prevalent receptor expression, and 50% (11.1–80.4) for those with prevalent 18F-FDG uptake. Our findings suggest that dual-tracer PET/CT can be considered as a predictor of patient outcome, able to stratify NET G3 patients with poorer prognosis.

Arthroscopic surgery for femoroacetabular impingement has limited effect in patients with Tönnis grade-2 at 4-year follow-up.

This study evaluated intraoperative findings and outcomes in Tönnis grade-2 patients after hip arthroscopy and compared these results with patients with Tönnis grade-0 and grade-1. Retrospective cohort study of patients undergoing hip arthroscopy between January 2013 and December 2017. Patients were divided into either Tönnis grade-2, grade-1, and grade-0 osteoarthritis groups. Labral and chondral status were evaluated. Radiographic analysis, modified Harris hip score (mHHS), a self-administered Hip Outcome Score (HOS) questionnaire, with activity of daily living (ADL) and sports subscale (SSS), and a self-administered short version of the International Hip Outcome Tool (IHOT-12) were assessed at 6, 12months, and then yearly. Clinical meaningful outcomes were measured with the minimal clinical important difference (MCID), patient acceptable symptom state (PASS), and substantial clinical benefit (SCB) for mHHS, HOS-ADL and HOS-SSS, and IHOT-12. A total of 264 hip arthroscopic procedures met the inclusion criteria. There were 38 patients Tönnis grade-2, 91 patients Tönnis grade-1, and 135 patients Tönnis grade-0. Mean follow-up was 48.7months in Tönnis grade-2 group, 48.6months in Tönnis grade-0 group, and 48.1months in Tönnis grade-1 group. Tönnis grade-2 patients had more extensive rim chondral damage, and a higher rate of labral debridement was performed in this group. There were no statistically significant differences in preoperative PROs among the groups. Tönnis grade-2 group had statistically significant improvement in mHHS, but not in HOS-AVD, HOS-SSS and IHOT-12. Between T1 and T2 groups there were no statistically significant differences in outcomes. Lower significant percentage values of Tönnis grade-2 patients achieved MCID, PASS, and SCB threshold. Improvements in PROs and rates of achieving clinical meaningful outcomes were limited for patients with Tönnis grade-2 after HA at 4-year follow-up. The outcomes of the Tönnis grade-2 cohort deteriorate over mid-term follow-up. Our results could be used in orthopedic practice to inform patients about the limited role of hip arthroscopy as a joint preservation procedure in these selected patients. Cohort study, level 3.

Characteristics, Treatment, Outcomes, and Survival in Neuroendocrine G1 and G2 Pancreatic Tumors: Experiences From a Single Tertiary Referral Center.

PurposeNeuroendocrine tumors of the pancreas (Pan-NETs) are usually hormonally inactive with a capacity to metastasize. Since Pan-NETs are rare, more knowledge is needed.MethodsWe reviewed all patients’ medical files with Pan-NET treated at a tertiary center (2006-2019). Grade 1 (G1) and grade 2 (G2) tumors were compared. The latter group was subdivided arbitrarily based on proliferation index into G2a (3-9.9%) and G2b (10-19.9%).ResultsWe found 137 patients (76 females, 61 males; G1 n=66, G2 n=42), the median age at diagnosis 61 years (interquartile range (IQR) 50–71), and tumor size 2 cm (1.3–5 cm). The initial surgery was performed in 101 patients. The remaining (n=36) were followed conservatively. Metastatic disease was evident in 22 patients (16%) at diagnosis while new lesions developed in 13 out of 22 patients (59%). In patients without previous metastatic disease, progressive disease was discovered in 29% of G1 vs. 55% of G2 patients (P=0.009), 47% of G2a vs. 75% of G2b patients (NS). Survival was poorer in patients with metastasis at diagnosis vs. those with local disease (P<0.001). During follow-up of 74 months, Pan-NET related death was found in 10 patients. Survival was not different between G1 vs. G2 or G2a vs. G2b, or if tumors were functional. Size ≤2 cm was associated with a better outcome (P=0.004). During the follow-up of small tumors (≤2 cm, n=36) two were resected.ConclusionIn small non-functional Pan-NETs, active surveillance is reasonable. Progressive disease was more common in G2, but survival was similar in G1, G2 and between G2 subgroups. Survival was poorer in patients with metastasis at diagnosis.

Efficacy and Safety of Inhaled Indacaterol and Tiotropium in Patients of Chronic Obstructive Pulmonary Disease

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide. Indacaterol is a new once daily inhaled bronchodilator, recently approved for the treatment of COPD. Once daily dosing is an important step to improve the adherence and compliance of the patients. Methods: Efficacy and Safety of Indacaterol and Tiotropium in Patients of COPD with Stage-2 and Stage-3 GOLD criteria were compared. Total 119 patients were divided into Indacaterol group and Tiotropium group receiving 150 mcg daily of Indacaterol and 18 mcg daily of Tiotropium in each group respectively. Efficacy treatment was determined by assessment of Pulmonary function test (PFT), Symptom score and SGRQ (St. George’s Respiratory Questionnaires) score at day zero (before therapeutic intervention) and at two weeks of interval till 24 weeks. Results: The treatment with inhaled indacaterol 150 mcg once daily and inhaled tiotropium 18 mcg once daily improved spirometric variable, FEV1, decrease in mean Symptoms score and in mean SGRQ in Grade-2 and Grade-3 COPD patients. Conclusion: Indacaterol (150 mcg/day) is non-inferior to tiotropium (18 mcg /day) in efficacy and safety profile of Grade-2 and Grade-3 patients with COPD.

Surgery with Radical Intent: Is There an Indication for G3 Neuroendocrine Neoplasms?

While platinum-based chemotherapy represents the standard treatment for advanced grade 3 (G3) neuroendocrine neoplasms (NENs) according to the European Neuroendocrine Tumor Society guidelines, the role of radical-intended surgery in these patients, as well as the use of adjuvant chemotherapy, are still controversial. The aim of the present work is to describe, in a retrospective series of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) G3, the overall survival (OS) rate and risk factors for death after radical surgery. Secondary aims are the description of median recurrence-free survival (RFS) and of the role of adjuvant chemotherapy. Multicenter analysis of a series of stage I-III GEP-NEN G3 patients receiving radical surgery (R0/R1) with/without adjuvant chemotherapy was performed. Sixty patients from eight neuroendocrine tumor (NET) referral centers, with median follow-up of 23months (5-187months) were evaluated. While 28.6% of cases had NET G3, 71.4% had neuroendocrine carcinoma G3 (NEC G3). The 2-year OS rate after radical surgery was 64.5%, with a statistically significant difference in terms of Ki67 threshold (cut-off 55%, P = 0.03) and tumor differentiation (NEC G3 vs. NET G3, P = 0.03). Median RFS after radical surgery was 14months, and 2-year RFS rate was 44.9%. Use of adjuvant chemotherapy provided no benefit in terms of either OS or RFS in this series. Surgery with radical intent might represent a valid option for GEP-NEN G3 patients with locoregional disease, especially with Ki67 value ≤ 55%.

Pancreatic neuroendocrine tumor: prediction of the tumor grade using magnetic resonance imaging findings and texture analysis with 3-T magnetic resonance.

PurposeThe purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) findings and texture parameters for prediction of the histopathologic grade of pancreatic neuroendocrine tumors (PNETs) with 3-T magnetic resonance.Patients and methodsPNETs are classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity. A total of 77 patients with pathologically confirmed PNETs met the inclusion criteria. Texture analysis (TA) was applied to T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) maps. Patient demographics, MRI findings, and texture parameters were compared among three different histopathologic subtypes by using Fisher’s exact tests or Kruskal–Wallis test. Then, logistic regression analysis was adopted to predict tumor grades. ROC curves and AUCs were calculated to assess the diagnostic performance of MRI findings and texture parameters in prediction of tumor grades.ResultsThere were 31 G1, 29 G2, and 17 G3 patients. Compared with G1, G2/G3 tumors showed higher frequencies of an ill-defined margin, a predominantly solid tumor type, local invasion or metastases, hypo-enhancement at the arterial phase, and restriction diffusion. Four T2-based (inverse difference moment, energy, correlation, and differenceEntropy) and five DWI-based (correlation, contrast, inverse difference moment, maxintensity, and entropy) TA parameters exhibited statistical significance among PNETs (P<0.001). The AUCs of six predicting models on T2WI and DWI ranged from 0.703–0.989.ConclusionOur data indicate that MRI findings, including tumor margin, texture, local invasion or metastases, tumor enhancement, and diffusion restriction, as well as texture parameters can aid the prediction of PNETs grading.

Predictors of Pelvic Recurrence in Stage IB Grade 2-3 Endometrioid Endometrial Adenocarcinoma Treated with Post-Operative Vaginal Brachytherapy

Optimal adjuvant management of surgically staged FIGO stage IB grade 2 (G2) and grade 3 (G3) endometrial endometrioid adenocarcinoma (EAC) is controversial. The objective of this study is to report outcomes utilizing adjuvant vaginal brachytherapy (VB) without pelvic radiotherapy (RT) for patients with surgically staged IB G2 and G3 EAC and to analyze rates and predictors of pelvic recurrence. Retrospective review of an institutional database identified patients diagnosed between 2005-2015 with 2009 FIGO stage IB G2 and G3 EAC. All patients underwent comprehensive surgical staging and VB as the sole adjuvant RT as per institutional guidelines during the study period. Disease free survival (DFS) was calculated from the date of primary surgery to date of last follow up or recurrence, and a minimum of 6 months follow-up was required for inclusion. Kaplan-Meier methods were used to estimate DFS. Pearson chi-squared test was used to determine association of pathologic variables and pelvic recurrence. A total of 78 patients were identified for inclusion. The median age at diagnosis was 67 (range, 42-93). Surgical staging included hysterectomy, bilateral salpingo-oopherectomy, pelvic washings, pelvic lymph node dissection (98.7%), and paraaortic node sampling (78.2%). Fifty-five patients (71%) had G2 EAC and 23 (29%) had G3 EAC. Lymphovascular invasion (LVI) was observed in 37 (47%), lower uterine segment involvement (LUSI) in 38 (49%), and outer 1/3rd myometrial invasion (MMI) (defined as ≥ 67% MMI) in 39 (50%). Median number of pelvic lymph nodes removed was 18. The majority (88.5%) received VB alone and 11.5% received VB in combination with chemotherapy. Median follow up was 45.5 months (range 6.3-151.8) and 3-year estimated DFS was 84.7% for the entire cohort. There were a total of 11 recurrences, of which 3 (27.3%) were distant only. The remainder (72.3%) had a pelvic component including 5 which were pelvic and distant and 3 which were isolated to the pelvis. Median time to recurrence was 27.8 months (range, 11.5 - 46.9). On univariate analysis, G3 versus G2 (p = 0.600), LVI present versus absent (p = 0.388), and ≥20 versus <20 pelvic nodes dissected (p = 0.051) were not associated with higher pelvic recurrence risk. Presence of LUSI (p = 0.03) and outer 1/3rd MMI (p = 0.03) were associated with increased risk of pelvic failure. Stage IB G2 and G3 patients treated with adjuvant VB following surgical staging overall fared well, and isolated pelvic recurrences were few in number. While grade and LVI were not associated with increased pelvic failure in this cohort, the association of LUSI and outer 1/3rd MMI is intriguing. Further investigation into risk factors for pelvic recurrence in stage I EAC would be valuable to identify subgroups which benefit the most from pelvic RT.

Quantitation of 99mTc-DPD uptake in patients with transthyretin-related cardiac amyloidosis

Purpose: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), initially developed as a bone-seeking radiotracer, is remarkably sensitive for imaging cardiac ATTR amyloid deposits. Our aim was to investigate the feasibility and utility of estimating 99mTc-DPD uptake in myocardial tissue; this has the potential to yield reliable quantitative information on cardiac amyloid burden, which is urgently required to monitor disease progression and response to novel treatments.Methods: Three methods of quantitation were developed and tested on 74 patients with proven cardiac ATTR amyloidosis who had recently undergone 99mTc-DPD planar whole-body imaging and SPECT-CT. Quantitative results were compared to measurements of extracellular volume fraction (ECV) by cardiac magnetic resonance imaging, a validated technique for measuring amyloid burden.Results: An experienced clinician graded uptake using a widely-used visual scoring system as 1 (n = 15), 2 (n = 39) or 3 (n = 20). Linear correlations between the SPECT and ECV data (p < .001) were demonstrated. None of the methods showed that 99mTc-DPD uptake in the heart was significantly greater in patients with grade-3 uptake than in those with grade-2 uptake.Conclusions: Quantitation of 99mTc-DPD uptake in cardiac transthyretin amyloid deposits is complex and is hindered by competition for radiotracer with amyloid in skeletal muscle. The latter underlies differences in uptake between grade-2 and grade-3 patients, not cardiac uptake.

Is quantitative sensory testing helpful in the management of oxaliplatin neuropathy? a two-year clinical study

PurposeTo better understand how quantitative sensory testing could help the clinician in the management of oxaliplatin-induced peripheral neuropathy in terms of earlier and more reliable detection, we conducted a two-year prospective study. MethodsThermal sensory assessment, tactile sensory assessment, neuropathic pain assessment and adverse events gradation (NCI-CTC) were performed during treatment and 6 months after treatment completion. Results35 patients were enrolled and followed-up during one year. Cold and Warm Detection Thresholds were higher 6 months after treatment completion than at enrollment. Mechanical detection thresholds didn't change significantly. Neurotoxicity was mostly grade-1, only 18% grade-2 and no grade-3. Grade-2 patients received lower oxaliplatin cumulative dose than grade-1, which reveals effective dose adaptation and grade-2 patients were more likely to develop painful neuropathy. ConclusionThermal thresholds impairment emerges too late to help the clinician in the prophylaxis of neuropathy. Management of OXA-treatment based on NCI-CTC, as currently recommended, remains the best way to detect neuropathy and ensure treatment adaptation.

Muscle ultrasound

Our study aimed to evaluate the utility of muscle ultrasound in newborn screening of infantile-onset Pompe disease (IOPD) and to establish a system of severity grading. We retrospectively selected 35 patients with initial low acid alpha-glucosidase (GAA) activity and collected data including muscle ultrasound features, GAA gene mutation, activity/performance, and pathological and laboratory findings. The echogenicity of 6 muscles (the bilateral vastus intermedius, rectus femoris, and sartorius muscles) was compared to that of epimysium on ultrasound and rated either 1 (normal), 2 (mildly increased), or 3 (obviously increased). These grades were used to divide patients into 3 groups. IOPD was present in none of the grade-1 patients, 5 of 9 grade-2 patients, and 5 of 5 grade-3 patients (P < .001). Comparing grade-2 plus grade-3 patients to grade-1 patients, muscle ultrasound detected IOPD with a sensitivity and specificity of 100.0% (95% confidence interval [CI]: 69.2%–100%) and 84.0% (95% CI: 63.9%–95.5%), respectively. The mean number of affected muscles was larger in grade-3 patients than in grade-2 patients (4.2 vs. 2.0, P = .005). Mean alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) levels were differed significantly different between grade-3 and grade-1 patients (P < .001). Because it permits direct visualization of injured muscles, muscle ultrasound can be used to screen for IOPD. Our echogenicity grades of muscle injury also correlate well with serum levels of muscle-injury biochemical markers.

Prevalence of pterygium and outcome of pterygium surgery in hilly western Nepal

Introduction: Surgical removal is the treatment of choice for pterygium; however, prevention of recurrence is a challenge. Several techniques have been tried to reduce the fibro-vascular activity aiming to reduce rate of recurrence such as B-irradiation, conjunctival and limbal auto-grafting, anti-mitotic drugs, and amniotic membrane transplantation. This study reports the magnitude of the disease in a hilly region of western Nepal and outcome of excision and conjunctival autografting for pterygium surgery.&#x0D; Methods: A prospective study was done from 1st July 2015 to 31st December 2016 in which all patients with primary pterygium presented to Palpa Lions Lacoul Eye Hospital from 1st July 2015 to 30th June 2016 were treated and followed up for next six months. Patients were treated medically or surgically as indicated. Data on age, sex, visual acuity, extent of disease, treatment modality, complications, and outcome were collected and analyzed by descriptive statistics, Chi-square test, t-test, and Anova tests. P value less than 0.05 was considered significant.&#x0D; Results: There were 18,960 patients in total attending hospital for various conditions among which 290 (1.5%) had pterygium. There were 186 (64.1%) female and 104 (35.9%) male and this difference was significant (p&lt;0.001). The mean age was 47.42 yrs (SD=14.23) with age ranging from 20 to 80 years. Right eye was affected more (43.1%) than left eye (33.1%); remaining 23.8% had bilateral disease. Grade-1 disease occurred in younger age compared to Grade-2 and Grade-3 disease. All grade-1 patients were managed medically; grade-2 and grade-3 patients were equally likely to be managed medically or surgically. There were no major intra or post-operative complications. Minor post-operative complications noted were subconjunctival hemorrhage, corneal scarring, suture gaping, and conjunctival cyst among others.&#x0D; Conclusion: Despite much advanced techniques in pterygium surgery, pterygium excision combined with conjunctival autograft is found to be a safe and effective method for treating pterygium in developing world.

Lateral Approach for Anterior and Anterolateral Placed Cervical Meningioma or Schwannoma

Introduction Cervical meningioma and schwannoma are benign tumors that may present with a wide variety of clinical features. Surgical treatment of those tumors carries a risk of neurological complications and spinal deformities. Surgical approaches include posterior, anterior, or anterolateral options. This is a Descriptive retrospective clinical case series to evaluate the lateral surgical approach in these tumors. Patients and Methods We reviewed patients who underwent lateral surgery for anterior and anterolateral placed cervical meningioma or schwannoma through the past 7 years. A total of 23 patients including 15 females and 8 males were reported. Mean age was 46 years. The average duration of history was 14.9 months. Fourteen patients had meningioma and 9 had schwannoma. According to the JOA-score 15 were normal, 5 were grade-1 and 3 was grade-2. The following factors were evaluated; age, sex, duration, pathology, levels, topographical locations, neurological status, operative time, blood loss, hospital stay, morbidity, and clinical outcome. Results All patients were operated through the lateral cervical approach. All patients but three had total tumor removal where small fragment were lift due to technical reasons. According to the JOA-score the 15 normal patients remain the same, the 5 grade-1 improved to normal, and the 3 grade-2 patients improved to normal in one and to grade-1 in another. There was no reported major morbidity or mortality. CSF leak into the closed drainage system was reported in 5 patients without serious effects. Conclusions The lateral approach allows for safe and effective removal of anterior and anterolateral placed cervical meningioma or schwannoma. It gives a direct access to tumor without risk of cord manipulation or destabilizing the spine. In addition it gives the same clinical results.as the standard posterior approach.