Grade 2b Research Articles

Prognostic utility of the modified albumin-bilirubin score among patients undergoing curative-intent surgery for gallbladder cancer

BackgroundGallbladder cancer (GBC) has been associated with high rates of recurrence and dismal prognosis even after curative-intent resection. The prognostic utility of the modified albumin-bilirubin (mALBI) score among individuals undergoing curative-intent resection for GBC has not been determined. MethodsPatients who underwent radical resection for GBC between 2000 and 2022 were identified from an international, multi-institutional database. Preoperative albumin and bilirubin levels were used to calculate the mALBI score. The relationship among mALBI score, overall survival (OS), and recurrence-free survival (RFS) was examined. ResultsAmong 269 patients who underwent radical resection for GBC, 161 (59.9%) had mALBI grade 1, 48 (17.8%) had grade 2a, 47 (17.5%) had grade 2b, and 13 (4.8%) had mALBI grade 3. After surgery, compared with patients with a low mALBI grade (grade 1/2a), individuals with a high mALBI grade (grade 2b/3) had worse 5-year OS (54.4% vs 19.2%, respectively; P < .001) and RFS (42.0% vs 17.8%, respectively; P < .001). On multivariable analysis, after controlling for relevant clinicopathologic variables, individuals with a high mALBI score remained independently associated with higher risks of death and recurrence (OS: hazard ratio [HR], 2.38 [95% CI, 1.50–3.79]; RFS: HR, 2.12 [95% CI 1.41–3.20]) versus patients with a low mALBI score after curative-intent resection for GBC. Of note, mALBI score was associated with incrementally worse survival within T2, T3, and N+ categories, whereas classic American Joint Committee on Cancer subclassifications failed to distinguish patients with long-term survival. ConclusionThe mALBI score presents a simple, objective measure of hepatic functional reserve and may be a useful prognostic tool for patients undergoing curative-intent resection for GBC.

Conversion Surgery After Chemotherapy Plus Nivolumab as the First-Line Treatment for Unresectable Advanced or Recurrent Gastric Cancer and a Biomarker Study Using the Gustave Roussy Immune Score: A Multicenter Study.

There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers. This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases. CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p<0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b. The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS.

Factors Affecting an Increase in Spleen Volume and Association of Spleen Volume Variation with the Clinical Outcomes of Atezolizumab and Bevacizumab Treatment for Hepatocellular Carcinoma: A Retrospective Analysis

Plain Language SummaryImmunotherapy is now the standard of care for systemic therapy in hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab (Atez/Bev) is recommended for the first-line treatment, while gastrointestinal varices rupture is likely to be observed during Atez/Bev. Gastrointestinal varices rupture is a fatal event and developed due to portal hypertension. Spleen volume (SpV) plays an important role in portal hypertension based on previous studies, and we examined variation in SpV during Atez/Bev treatment and investigated predictive factors that affect the increase in SpV and the association of SpV variation and pretreatment SpV with the clinical outcome of Atez/Bev. The median pretreatment SpV was 184 (130–257) cm3 and the median SpV variation was 27 (9–60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. The present study revealed that there were no significant differences in progression-free survival and overall survival between patients with and without pretreatment spleen enlargement, as well as between patients with SpV variation ≥25 cm³ and those with SpV variation <25 cm³. In conclusion, caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or those with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy.

Prevalence of Frank's sign in healthy young individuals, morphological characteristics, and its association with family history of chronic disease.

Frank's sign (FS, earlobe crease) is known to be associated with many chronic diseases i.e. coronary, cerebrovascular, and peripheral vascular diseases. The objective of this study is to investigate the presence and grade of FS in healthy, young-adult individuals aging between 18 and 25. Furthermore, to evaluate the relationship between FS and the chronic disease history of first-degree family members. 853 healthy people with a mean age of 20.09 years were imvolved in the research on a voluntary basis. Of 853 individuals, 85.3% (n:728) had no FS, whereas 14.7% (n:125) had. Of the 125 people observed FS, 41.6% (n:52) were female and 58.4% (n:73) were male. Of the 125 people diagnosed with FS, 32.8% (n:41) had no family history of any chronic disease, and 67.2% (n:84) had at least 1 family history of chronic disease as well. It was determined that there was a statistically significant (p < 0.05) relationship between FS identified in healthy individuals and familial chronic disease history. In this study, while no FS was observed in 85.3% of the participants, grade 1 was detected in 12.4% (n:105), grade 2a in 1.9% (n:16), grade 2b in 0.2% (n:2), and grade 3 in 0.2% (n:2). To the best of our knowledge, this study investigated the relationship between the presence and grade of FS in the healthy, young, Turkish population and the presence/absence of chronic disease in the first-degree relatives of individuals for the very first time. As a result of larger studies, being aware of the presence of FS, especially in young healthy individuals, may help predict some chronic diseases, and caution may be taken to avoid these diseases at an early age in at-risk individuals.

Outcome of non-functioning ACTH pituitary tumors: silent does not mean indolent.

Silent corticotroph tumors (siACTH) represent a rare entity of pituitary tumors (PT), usually more aggressive than other PT. Few predictor factors of recurrence in the post-operative period have been proposed until now. This study aimed (1) to evaluate the clinical outcome of siACTH after surgery according to a five-tiered clinicopathological classification (2) to compare siACTH characteristics to ACTH-secreting macroadenomas (macroCD), and silent gonadotropinomas (siLH/FSH). Between 2008 and 2022, 29 siACTH out of 865 PT cases operated in one tertiary center were included. Clinical, paraclinical, histological, and surgical data were collected and compared to 25 macroCD and 143 siLH/FSH cases, respectively. The tumor grading was established according to both invasion (no = 1; yes = 2) and proliferation (no = a; yes = b). Progression-free survival was estimated using Kaplan-Meier method and log-rank test. We identified 15 (51.7%) grade 1a, 11 (37.9%) grade 2a and 3 (10.3%) grade 2b siACTH with a trend for a 7-fold-time higher risk of progression/recurrence in grade 2b as compared to 1a (p = 0.06). The repartition of tumor grades was similar between the three subgroups, however a 5.7-fold-higher risk of progression was observed in grade 1a siACTH than in grade 1a siLH/FSH (p = 0.02). Compared to siLH/FSH, higher ACTH levels may help to preoperatively identify siACTH. The five-tiered clinicopathological classification contribute to predict the risk of recurrence of operated siACTH tumors. Noteworthy, non-invasive and non-proliferative siACTH exhibit a less favorable outcomes than their siLH/FSH counterparts, which should prompt for a personalized follow up.

The Modified Albumin–Bilirubin (ALBI) Grade Reflect the Fate of Limb Prognosis in Patients with Chronic Limb-Threatening Ischemia

ObjectiveTo examine the influence of liver function on patients with chronic limb-threatening ischemia (CLTI), we classified patients with CLTI after revascularization according to their modified ALBI grades. MethodsWe retrospectively analyzed single-center data of patients who underwent revascularization for CLTI between 2015 and 2020. Patients were classified with modified albumin–bilirubin (ALBI) grades 1, 2a, and 2b & 3 according to the ALBI score, which was calculated based on serum albumin and total bilirubin levels. The endpoints were the two-year amputation-free survival (AFS) and one-year wound healing rates. ResultsWe included 190 limbs in 148 patients, and 50, 54, and 86 cases were assigned as grade 1, 2a, and 2b & 3, respectively. The two-year AFS rates for the grade 1, 2a, and 2b & 3 groups were 79 ± 6%, 66% ± 7%, and 45 ± 6%, respectively (P < 0.01). One-year cumulative wound healing rates for grade 1, 2a, and 2b & 3 groups were 68 ± 7%, 69% ± 6%, and 48% ± 5%, respectively (P = 0.01). Multivariate Cox proportional hazard analyses identified age (≥75 years), dependent ambulatory status, and modified ALBI grades 2b & 3 compared with grades 1 and 2a as significant independent predictors of AFS. The dependent ambulatory status and WIfI stage 4 were significant negative predictors of wound healing. ConclusionsMany patients with CLTI had high modified ALBI grades and impaired liver function classified as modified ALBI grade 2b or 3 is a robust negative predictor of amputation-free survival.

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306

BackgroundIn JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis.MethodsWe obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined.ResultsypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175–0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073–0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is.ConclusionsRS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

Long-term risk of hemorrhage and mortality after treatment of high-grade intracranial dural arteriovenous fistulas

BackgroundDespite recent multi-institutional efforts, long-term data on clinical and radiological outcomes after treatment of high-grade dural arteriovenous fistulas (dAVFs) remain scarce. This study aimed to evaluate the long-term risk of...

Fruquintinib combined with sintilimab and SOX as conversion therapy for unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, phase 2 clinical trial.

e16021 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Fruquintinib is an oral, highly selective VEGFR 1/2/3 inhibitor that has synergistic antitumor effects when combined with ICIs/chemotherapy. This study was conducted to evaluate the efficacy and safety of fruquintinib combined with sintilimab and SOX as a conversion therapy in patients (pts) with initially unresectable locally advanced or metastatic GC/GEJC. Methods: Eligible pts received 3 to 6 cycles of fruquintinib (4mg/d, po, qd, d1-14) combined with sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m2, iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks. One more cycle of sintilimab plus SOX was given before resection. Radiographic assessments were performed every 3 cycles and MDTs were employed to determine surgical feasibility. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: From May 2022 to December 2023, 34 pts (29 males/5 females) with a median age of 62 years (range: 43–76), 71% ECOG PS1, 59% GEJC were enrolled. The unresectable factors included liver metastasis 15% (5/34), peritoneal metastasis 6% (2/34), para-aortic lymph node metastasis 3% (1/34), extensive or bulky lymph nodes 53% (18/34), and local progression 38% (13/34). Five pts had more than one unresectable factors. The ORR and DCR of 29 pts who had at least one preoperative assessment were 65.5% (19 PR) and 96.6%, respectively. Among the 18 pts who had completed surgical conversion, all of them had R0 resection (100%), 2 pts (11.1%) achieved pathological complete response (pCR), and 1 pt reached AJCC-TRG1. The pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 100% (18/18). Additionally, downstaging to pN0 was achieved in 13 pts (72.2%). During preoperative treatment, treatment-emergent adverse events (TEAEs) occurred in 85.3% (29/34) pts, and most events were grade 1–2. Grade 3 TEAEs included 2 cases of neutrophil count decreased, and 1 case of each (platelet count decreased, anemia, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX as a conversion therapy strategy shown acceptable toxicity in unresectable GC/GEJC and induced very high R0 resection, pathological response, and downstaging rate. The study is ongoing, more data will be disclosed in the future. Clinical trial information: NCT05177068 .

Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery followed by adjuvant docetaxel and S-1 for patients with large type 3 or type 4 gastric cancer: Short-term outcomes of the phase II OGSG1902 trial.

4031 Background: Patients with large type 3 (≥8 cm) or type 4 gastric cancer (GC) face a dismal prognosis, necessitating the development of multidisciplinary treatment, including neoadjuvant chemotherapy. We present the short-term results from the OGSG1902 (jRCTs051190060) trial, where resectable large type 3 or type 4 GC patients were treated with neoadjuvant docetaxel (DTX)/oxaliplatin (L-OHP)/S-1 (DOS) plus surgery and adjuvant DTX/S-1 (DS) therapy. Methods: Untreated large type 3 or type 4 GC patients without distant metastasis other than positive peritoneal lavage cytology (CY), aged 20-80 years, and with ECOG PS 0-1, were enrolled. Patients received three cycles of DTX (40 mg/m2, day1) + L-OHP (100 mg/m2, day1) + S-1 (80 mg/m2, day1-14) every 3 weeks, followed by gastrectomy with D2 lymph node dissection and 1-year DS therapy. The primary end point was the 3-year progression-free survival (PFS) rate. The secondary end points included PFS time, overall survival time, pathological response rate, response rate according to RECIST version 1.1, neoadjuvant chemotherapy completion rate, R0 resection rate, protocol completion rate, CY negative conversion rate, adverse event occurrence rate, and nutritional evaluation. Results: Forty-eight patients (pts) were enrolled from 2019 to 2022. The neoadjuvant chemotherapy completion rate was 91.7%, pathological response rate (≥Grade 1b) was 66.7%, response rate according to RECIST version1.1 for 10 pts with measurable lesions was 50.0%, CY negative conversion rate for nine CY positive pts was 88.9%, R0 resection rate was 89.6%, and the protocol completion rate was 45.8%. Adverse events (≥CTCAE Grade 3) during neoadjuvant DOS included neutropenia in 18 pts (38%), febrile neutropenia in one pt (2%), nausea in five pts (10%), diarrhea in six pts (13%), and anorexia in 18 pts (38%). Gastrectomy was performed in 47 pts [total/distal gastrectomy: 32(68%)/15(32%)]. Major postoperative complication (≥Clavien-Dindo Grade IIIa) was observed in one pt (2%), including pleural infection. Adverse events (≥CTCAE Grade 3) in 39 patients receiving adjuvant DS therapy included neutropenia in 16 pts (41%), anemia in five pts (13%), nausea in one pt (3%), diarrhea in two pts (5%), anorexia in nine pts (23%), fatigue in three pts (8%), and febrile neutropenia in four pts (10%). No treatment-related deaths were observed. Conclusions: Neoadjuvant DOS therapy for large type 3 or type 4 GC demonstrates promising efficacy with high histological response and acceptable adverse events. Future analysis of survival outcomes is planned. Clinical trial information: jRCTs051190060 .

Fourth consecutive emergency thrombectomy followed by femoral distal popliteal bypass in a patient with type VI popliteal artery entrapment syndrome: a case report

The article describes a case of the fourth consecutive emergency thrombectomy for popliteal and tibial artery thrombosis, followed by femoral distal popliteal bypass with a reversed vein in a patient with I. I. Zatevakhin grade 2B acute limb ischemia. The cause of repeated thrombosis type VI popliteal artery entrapment syndrome.

NAVIGATING THE UNCHARTED WATERS: MANAGING CONCURRENT CYTOMEGALOVIRUS MYOCARDITIS AND ALLOGRAFT REJECTION IN A PATIENT WITH HEART TRANSPLANTATION

Abstract A 49–year–old female with hypertrophic cardiomyopathy underwent orthotopic heart transplantation. She was cytomegalovirus(CMV)–positive and received a heart from a CMV–negative donor, so prophylaptic therapy was not administered. Initial immunosuppression included cyclosporine and induction with Basiliximab in a steroid–free regimen. The first routine biopsy (EMB) showed mild focal cellular rejection (grade 1A) and C4d positivity with granular aspect. Mycophenolate mofetil (MMF) was added. The second EMB, 7 days later, showed mild diffuse cellular rejection (grade 1B) and diffuse C4d positivity. Anti–HLA donor–specific antibodies (DSA) had increased anti–B13 levels (MFI=21298) compared to pre–transplantation tests. Echocardiography showed a normal ejection fraction (LVEF) and mild concentric hypertrophy (LVH). Treatment included pulse methylprednisolone therapy (1 g/day for three days) followed by oral prednisone with a slow tapering regimen, and increased MMF. CMV count weekly monitored was negative. The next two EMBs performed one week apart from each other described a grade 1A mild focal pattern while the 5th EMB (1 month and 2 weeks post–transplant) showed a grade 1A rejection together with focal mild fibrosis and eosinophils, so we replaced cyclosporine with tacrolimus, increased MMF and prednisone. At this time, the patient had no overt clinical signs of CMV infection but a CMV–PCR of 100847 IU/mL so ganciclovir 5 mg/Kg bid was started and CMV–PCR decreased to 42308 IU/mL after 1 week. Subsequently, she developed sinus tachycardia, mildly reduced LVEF, moderate LVH and diastolic dysfunction. Troponin was elevated. A new EMB revealed interstitial edema, diffuse ischemic injury, and eosinophilic inclusions suggesting CMV myocarditis. Treatment involved down–titrating MMF and Prednisone, administering standard intravenous immunoglobulin (IVIG), and high–dose Ganciclovir (7.5 mg/Kg bid). Leukopenia subsequently led to Ganciclovir down–titration. In the next days, the patient improved, CMV cleared, and leukocyte count normalized. She was discharged on Tacrolimus, MMF, Prednisone and Valganciclovir. Subsequent tests showed no cellular or antibody–mediated rejection (AMR), no CMV inclusions, recovered cardiac function, and markedly reduced anti–B13 DSA (MFI 3000). This case raises some concerns: in this context, the use of IVIG in the treatment of CMV infection and AMR appears reasonable, in support of antiviral and immunosuppressive therapy.

Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.

Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group). Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

Differences in branched-chain amino acid to tyrosine ratio (BTR) among etiologies of chronic liver disease progression compared to healthy adults.

The branched-chain amino acids (BCAAs) to tyrosine (Tyr) ratio (BTR) test is used to evaluate the progression of chronic liver disease (CLD). However, the differences across sex, age, body mass index (BMI) and etiologies are still unclear. We retrospectively reviewed data from 2,529 CLD cases with free amino acids (FAAs) in peripheral blood from four hospitals and 16,421 general adults with FAAs data from a biobank database. In total, 1,326 patients with CLD (covering seven etiologies) and 8,086 healthy controls (HCs) were analyzed after exclusion criteria. We investigated the change of BTR in HCs by sex, age and BMI and then compared these to patients divided by modified ALBI (mALBI) grade after propensity score matching. BTR is significantly higher in males than females regardless of age or BMI and decreases with aging in HCs. In 20 types of FAAs, 7 FAAs including BCAAs were significantly decreased, and 11 FAAs including Tyr were significantly increased by mALBI grade in total CLD. The decreasing timings of BTR were at mALBI grade 2b in all CLD etiologies compared to HCs, however in chronic hepatitis C (CHC), chronic hepatitis B (CHB) and alcoholic liver disease (ALD), BTR started to decrease at 2a. There was a positive correlation between BCAAs and albumin among parameters in BTR and mALBI. The correlation coefficients in PBC, ALD and MASLD were higher than those of other etiologies. BTR varies by sex and age even among healthy adults, and decreasing process and timing of BTR during disease progression is different among CLD etiologies.

Limb salvage surgery for primary bone tumors: retrospective study in a tertiary care centre

Background: Limb salvage surgery is the standard of care for patients with primary bone tumors. The study retrospectively analyses a single center experience of use of endo-prosthesis for limb conservation in cases of primary bone tumors over a five-year period (2015-2020). Methods: Total of 34 histologically proven primary bone tumor were retrospectively studied which included 25 males and 9 females who received limb salvage surgery for bone tumors at department of surgical oncology, Rajiv Gandhi Government general hospital, Madras medical college, Chennai. Results: Median age at diagnosis was 23 years. Tumor localized to lower limb in 23 patients, and upper limb in 9 patients, pelvic bones in 3 cases. Tumors were malignant in 24 patients (70.4%) and benign in 10 patients (29.4%). The most common diagnosis was osteosarcoma17 patients (50%). The median resection length was 10 cm. High grade tumors (grade 2a and 2b and grade 3) was found in 14 cases (41.1%). 6 patients had prosthesis related complications. The mean follow-up was 5 years (range: 3-7). 27 (79.4%) patients of 34 were alive with the endo-prosthesis at the last follow-up. Conclusions: The custom mega prosthesis favored by us in most of the cases in limb sparing surgery for bone tumors results in satisfactory results in terms of local tumor control and limb function.

Abstract TP282: Impact of Interhospital Transfer on Patients Undergoing Endovascular Thrombectomy for Acute Ischemic Stroke From a Comprehensive Stroke Center

Objective: This study aims to evaluate how interhospital transfers impact the correlation between functional outcomes, mortality, reperfusion rates, and workflow time metrics in patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion (LVO). Background: This analysis is based on a prospective database encompassing consecutive patients who underwent EVT for LVO between January 2021 and June 2023 at a comprehensive stroke center (CSC). Main Outcome Measures: The primary outcome measures assessed include the rate of favorable 90-day functional outcomes (modified Rankin Scale 0-2), successful reperfusion (Thrombolysis in Cerebral Infarction scale grade 2b or 3), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. Additionally, essential workflow time metric milestones were analyzed. Results: Out of 363 patients, 172 (47.4%) were transferred from other hospitals. The transferred patients were relatively younger than those who presented directly (66.5 ± 15.6 vs. 70.6 ± 14.5). No significant differences were observed in baseline characteristics, including gender, National Institutes of Health Stroke Scale score, and the rate of intravenous thrombolysis, between the transferred and direct presentation groups (all p &gt; 0.05). The time of symptom onset to groin puncture time was significantly higher for the transfer group (703.6 min vs. 394.5 min, p &lt; 0.0001), while comparable figures were noted for groin puncture to reperfusion time (43.9 min vs. 45.1 min, p = 0.7071) and ICU length of stay (70.8 hours vs. 59.3 hours, p = 0.7071) between the two cohorts. Similar rates were also seen for successful reperfusion (p = 0.2348), sICH (p = 0.4933), favorable 90-day functional outcomes (p = 0.9457), mortality (p = 0.8534), and composite complications during hospitalization (p = 0.5779). Conclusion: Although we observed significantly longer time intervals from symptom onset to initiation of mechanical thrombectomy in patients transferred from outside facilities, there were no adverse consequences on patient outcomes.

Clinical Impact of Cytokine Release Syndrome on Prolonged Hematotoxicity after Chimeric Antigen Receptor T Cell Therapy: KyoTox A-Score, a Novel Prediction Model

Prolonged hematotoxicity is the most common long-term adverse event in chimeric antigen receptor T cell therapy (CAR-T). To evaluate the impact on prolonged cytopenia of inflammatory status after CAR T infusion, we performed a single-center retrospective study and analyzed patients with B cell lymphomas after CAR-T. Among 90 patients analyzed at 90 days after infusion, the cumulative incidence was 57.5% for prolonged neutropenia, 36.7% for anemia, and 49.8% for thrombocytopenia. Patients who experienced cytokine release syndrome (CRS) had significantly higher incidence and longer duration of prolonged cytopenia. In addition, we found that among patients with grade 1 CRS, those with a longer duration of CRS-related symptoms (>5 days; grade 1b in modified CRS grading [m-CRS]) had a significantly higher incidence and longer duration of prolonged cytopenia than those whose CRS-related symptoms resolved within 5 days (grade 1a m-CRS). Multivariate analysis revealed that a higher m-CRS grade (grade 1b or 2; hazard ratio [HR], 2.42), higher peak CRP (≥10 mg/dL; HR, 1.66), longer duration of elevated CRP (≥10 days; HR, 1.83), and a decrease in serum inorganic phosphorus concentration (≥30% from baseline; HR, 1.95) were associated with significantly higher cumulative incidence of prolonged neutropenia, as well as anemia and thrombocytopenia. Using these factors, we developed a new predictive scoring model for prolonged hematotoxicity, the KyoTox a-score, which can successfully stratify the incidence and duration of cytopenia independent of the existing model, CAR-HEMATOTOX, which is based on laboratory data at lymphodepletion. Thus, this newly developed post-CAR-T inflammation-dependent score is accurate and useful for predicting prolonged hematotoxicity.

Randomized phase II study comparing neoadjuvant FLOT versus DOS for patients with type 4 or large type 3 gastric cancer (JCOG2204).

TPS418 Background: A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin (SP) for patients with resectable macroscopic type 4 and large type 3 gastric cancer (GC). Currently, initial resection followed by adjuvant chemotherapy is performed as the standard treatment for this population as well as general type GC in Japan. However, macroscopic type 4 and large type 3, mostly overlapping with scirrhous or linitis plastica type, have distinctive natures in age, dominant histology and metastatic site, exhibiting unfavorable prognosis after surgery with curative intent. Further therapeutic development using peri-operative chemotherapy is urgently desired for the improvement of this hard-to-treat subset of GC. Based on the successful results of the FLOT4 trial and PRODIGY trial, FLOT (5-fluorouracil/leucovorin/oxaliplatin/docetaxel) and DOS (docetaxel/oxaliplatin/S-1) will be anticipated to offer more potent efficacy compared to platinum doublet. However, it remains unclear which of these two regimens should be selected as a test arm of future phase III confirming efficacy of neoadjuvant chemotherapy in Japan. Methods: JCOG2204 is a multi-center, randomized phase II trial comparing neoadjuvant chemotherapy with FLOT (5-fluorouracil/levofolinate/oxaliplatin/docetaxel) versus DOS for resectable type 4 and large type 3 GC. This trial adopted the selection design to determine the most promising regimen for the subsequent phase III trial. Patients with histologically confirmed adenocarcinoma of the stomach, presenting with macroscopic type 4 or larger lesions (≥8 cm) of type 3, are eligible for this trial. Prior to registration, it is required to confirm the absence of non-curable factors other than positive lavage cytology (CY1) or peritoneal dissemination localized around the stomach (P1a) in a staging laparoscopy. Neoadjuvant FLOT arm consist of 4 courses of oxaliplatin (85 mg/m2) and docetaxel (50 mg/m²) with levofolinate (200 mg/m2) IV infusion for 1-2 hours, then 5-FU (2600 mg/m2, civ) for 24 hours on day 1, biweekly. Neoadjuvant DOS arm consists of 3 courses of oxaliplatin (100 mg/m2) and docetaxel (40 mg/m2) IV infusion for 1-2 hours on day 1, followed by oral S-1 80–120 mg/m2/day for 2 weeks (days 1–14), in a 3-week cycle. Adjuvant chemotherapy is performed according to the pathological TNM stage. A sample size was calculated based on Simon’s selection design assuming that a proportion of patients achieving pathological response Grade 1b or higher will be 65% in the superior regimen, 10% higher than 55% in the other. A total of 76 patients, which are required to ensure at least an 80% probability of correct selection, are planned to be enrolled over 2 years. Enrollment in JCOG2204 begun on 14th July, 2023 and clinical trial information is available in Japan Registry of Clinical Trials (jRCTs031230231). Clinical trial information: jRCTs031230231 .

Comparison of Different Methods of Semiquantitative Assessment and Subjective Scores for Retropatellar Articular Cartilage Evaluation in Advancing Osteoarthritis.

cartilage layer thickness, composition of the extracellular matrix (ECM), geometry and configuration of retropatellar cartilage partially differ significantly from those found at other locations and are essential for patellofemoral biomechanics. 119 serial medial and lateral patella facet samples of patients undergoing implantation of a total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS Grade 1b) respectively advanced (Group B, macroscopically ICRS Grade 3a/3b) (38 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 22 healthy biopsies by means of immunohistochemistry and histology investigations. We quantified our results on the gene expression of collagen type I and II and aggrecan with real-time (RT)-PCR rsp using colourimetry for proteoglycan content. The digitized images of histology and immunohistochemistry staining with Safranin O, Alcian blue, PAS, Masson Goldner, immunostaining, e.g. for collagen I and II were also analyzed with Photoshop software. The most significant decrease in staining intensity was revealed for Safranin-O staining in Group B at the lateral patellar facet, and the most relevant increase was for Col I staining at the same site. The lateral patella site in Group B also showed the highest increase in the ratio of expression indices for the genes Col1A1 and the reference gene following the equation 2-ΔCt with a quotient of 29.6. 1. Comparisons of our retropatellar cartilage analysis with femoral and tibial studies utilizing similar techniques show significant differences. 2. Cartilage layer thickness, ECM composition, geometry and configuration are essential for patellofemoral biomechanics. 3. Consequently, there is a need for diversified approaches towards retropatellar surface during TKA as well as for advanced cartilage restoration techniques.

An analysis of the recommendations of the 2022 Society for Vascular Surgery clinical practice guidelines for patients with asymptomatic carotid stenosis

ObjectivePatients with asymptomatic carotid artery stenosis currently account for the majority of carotid interventions performed in the United States; therefore, the following article will review the 2022 Society for Vascular Surgery (SVS) clinical practice guidelines perspective in treating patient with asymptomatic carotid stenosis. MethodsA systemic review and meta-analysis were conducted by the evidence practice center of the Mayo Clinic using a specified population, intervention, comparison, outcome (PICO) framework. ResultsBased on published randomized trials and related supporting evidence, the following were noted: the SVS recommends that patients with asymptomatic ≥70% stenosis can be considered for carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), or transfemoral carotid artery stenting (TFCAS) for the reduction of long-term risk of stroke, provided the patient has a life expectancy of 3 to 5 years with risk of perioperative stroke and death not exceeding 3%. The type of carotid intervention should be based on the presence or absence of high-risk criteria for each specified intervention. Data from CREST, ACT, and the Vascular Quality Initiative suggest that certain properly selected asymptomatic patients can be treated with carotid stenting with equivalent outcome to CEA in the hands of experienced interventionalists. The institutions and operator performing carotid stenting must exhibit expertise sufficient to meet the established American Heart Association guidelines for treatment of patient with asymptomatic carotid stenosis (ie, combined stroke/death rate of less than 3%). ConclusionsSVS recommends that low surgical risk patients with asymptomatic carotid stenosis of ≥70% to be treated with CEA with best medical therapy over medical therapy alone for the long-term prevention of stroke/death (GRADE 1B). Carotid intervention should also be based on the presence or absence of high-risk criteria for each specified intervention (ie, CEA, TCAR, and TFCAS).