Necrotic Portion Research Articles

AI-assisted Segmentation Tool for Brain Tumor MR Image Analysis.

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) ranging from 0.83 to 0.91 than 3DSlicer with a DSC ranging from 0.80 to 0.84 for the accuracy of segmented tumors. Comparative analysis with the widely used 3DSlicer software revealed TumorPrism3D to be approximately 37.4% faster in the segmentation process from initial contour drawing to final segmentation mask determination. The semi-automated nature of TumorPrism3D facilitates reproducible tumor segmentation at a rapid pace, offering the potential for quantitative analysis of tumor characteristics and artificial intelligence-assisted segmentation in brain MR imaging.

Comparison of two region-of-interest placement methods for histogram analysis of apparent diffusion coefficient maps for glioma grading.

We assessed the value of histogram analysis (HA) of apparent diffusion coefficient (ADC) maps for grading low-grade (LGG) and high-grade (HGG) gliomas. We compared the diagnostic performance of two region-of-interest (ROI) placement methods (ROI 1: the entire tumor; ROI 2: the tumor excluding cystic and necrotic portions). We retrospectively evaluated 54 patients with supratentorial gliomas (18 LGG and 36 HGG). All subjects underwent standard 3T contrast-enhanced magnetic resonance imaging. Histogram parameters of ADC maps calculated with the two segmentation methods comprised mean, median, maxi-mum, minimum, kurtosis, skewness, entropy, standard deviation (sd), mean of positive pixels (mpp), uniformity of positive pixels, and their ratios (r) between lesion and normal white matter. They were compared using the independent t-test, chi-square test, or Mann-Whitney U test. For statistically significant results, receiver operating characteristic curves were constructed, and the optimal cutoff value, sensitivity, and specificity were determined by maximizing Youden's index. The ROI 1 method resulted in significantly higher rADC mean, rADC median, and rADC mpp for LGG than for HGG; these parameters had value for predicting the histological glioma grade with a cutoff (sensitivity, specificity) of 1.88 (77.8%, 61.1%), 2.25 (44.4%, 97.2%), and 1.88 (77.8%, 63.9%), respectively. The ROI 2 method resulted in significantly higher ADC mean, ADC median, ADC mpp, ADC sd, ADC max, rADC median, rADC mpp, rADC mean, rADC sd, and rADC max for LGG than for HGG, while skewness was lower for LGG than for HGG (0.27 [0.98] vs 0.91 [0.81], p = 0.014). In ROI 2, ADC median, ADC mpp, ADC mean, rADC median, rADC mpp, and rADC mean performed well in differentiating glioma grade with cutoffs (sensitivity, specificity) of 1.28 (77.8%, 88.9%), 1.28 (77.8%, 88.9%), 1.25 (77.8%, 91.7%), 1.81 (83.3%, 91.7%), 1.74 (83.3%, 91.7%), and 1.81 (83.3%, 91.7%), respectively. HA parameters had value for grading gliomas. Ex-cluding cystic and necrotic portions of the tumor for measuring HA parameters was preferable to using the entire tumor as the ROI. In this segmentation, rADC median showed the highest performance in predicting histological glioma grade, followed by rADC mpp, rADC mean, ADC median, ADC mpp, and ADC mean.

Apparent diffusion coefficient histogram in the differentiation of benign and malignant testicular tumors.

Purpose: This retrospective study assessed the value of histogram parameters of the apparent diffusion coefficient (ADC) map (HA) in differentiating between benign and malignant testicular tumors. We compared the diagnostic performance of two different volume-of-interest (VOI) placement methods: VOI 1, the entire tumor; VOI 2, the tumor excluding its cystic, calcified, hemorrhagic, and necrotic portions. Materials and methods: We retrospectively evaluated 45 patients with testicular tumors examined with scrotal contrast-enhanced magnetic resonance imaging. These patients underwent surgery with the pathological result of seven benign and 39 malignant tumors. We calculated the HA parameters, including mean, median, maximum, minimum, kurtosis, skewness, entropy, standard deviation (SD), mean of positive pixels, and uniformity of positive pixels by the two different VOI segmentation methods. We compared these parameters using the chi-square test, Mann-Whitney U test, and area under the receiver operating characteristic curve (AUC) to determine their optimal cut-off, sensitivity (Se), and specificity (Sp). Result: This study included 45 patients with 46 testicular lesions (seven benign and 39 malignant tumors), one of which had bilateral testicular seminoma. With the VOI 1 method, benign lesions had significantly lower maximum ADC (p = 0.002), ADC skewness (p = 0.017), and ADC variance (p = 0.000) than malignant lesions. In contrast, their minimum ADC was significantly higher ADC (p = 0.000). With the VOI 2 method, the benign lesions had significantly higher ADC SD (p = 0.048) and maximum ADC (p = 0.015) than malignant lesions. In contrast, their minimum ADC was significantly lower (p = 0.000). With the VOI 1 method, maximum ADC, ADC variance, and ADC skewness performed well in differentiating benign and malignant testicular lesions with cut-offs (Se, Sp, AUC) of 1846.000 (74.4%, 100%, 0.883), 39198.387 (79.5%, 85.7%, 0.868), and 0.893 (48.7%, 100%, 0.758). Conclusion: The HA parameters showed value in differentiating benign and malignant testicular neoplasms. The entire tumor VOI placement method was preferable to the VOI placement method excluding cystic, calcified, hemorrhagic, and necrotic portions in measuring HA parameters. Using this VOI segmentation, maximum ADC performed best in discriminating benign and malignant testicular lesions, followed by ADC variance and skewness.

Does the Necrotic Portion of Metastatic Lymphadenopathy from Squamous Cell Carcinoma Still Have Tumoral Oncologic Information? Differential Diagnosis of Benign Necrotic Lymphadenopathy Using microRNA.

Neck necrotic lymph nodes commonly correspond to metastasis or benign inflammatory conditions such as Kikuchi disease and tuberculosis. Ultrasound-guided biopsy can be used for differential diagnosis, but results may be unclear. Therefore, this study aimed to identify target microRNAs (miRNAs) and genes for the differential diagnosis of inflammatory and malignant necrotic lymph nodes. We selected six inflammatory lymphadenitis formalin-fixed paraffin-embedded (FFPE) samples that showed internal necrosis and five cancer necrotic FFPE samples. Tissue microarray (TMA) was performed to separate the necrotic and cancerous portions. Total RNA was extracted from six pairs of separated inflammatory necrosis, five pairs of cancer necrosis, and cancer portions. Differentially expressed miRNAs were analyzed by comparing inflammatory necrosis, cancer, and cancer necrosis. Seventeen miRNAs were upregulated in cancer necrosis compared to inflammatory necrosis, and two miRNAs (hsa-miR-155-5p and hsa-miR-146b-5p) showed lower expression in cancer necrotic cells. Nineteen miRNAs that were differentially expressed between inflammatory and cancer necrosis were analyzed for target gene expression; these transcripts demonstrated a clear relationship with cancer. The differentially expressed miRNAs in inflammatory and tumor necrosis were associated with cancer-related pathways. These preliminary results might help in the differential diagnosis of cervical metastatic necrotic lymphadenopathy and avoiding unnecessary excisional biopsies.

Locally advanced thymoma; does neoadjuvant chemotherapy make a difference?

BackgroundRegardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the region. Surgical resection, via thymectomy, remains the mainstay treatment modality. In locally advanced and borderline resectable tumors, neoadjuvant chemotherapy (NACT) may be utilized to increase the chance of R0 resection, raising the question of its efficacy and safety.MethodsDemographic and clinical data from patients who presented to a tertiary cancer center between January 2015–October 2021 with a diagnosis of thymoma and underwent curative surgical resection was collected. Computed tomography scan was used to delineate clinical staging, tumor size and to detect post-therapeutic variations in tumor burden. The response evaluation criteria in solid tumors (RECIST) was used to classify the effect of NACT on tumor burden. The pathological response was determined by measuring the percentage of necrotic tissue.ResultsA total of 23 patients were diagnosed with thymoma. Most patients were male with a mean age 46 (± 15) years at diagnosis. The most common clinical stage was stage II with 5 patients (22%). A total of 12 patients had NACT as compared to 11 patients who had upfront surgery. The mean change in tumor volume was 165 cm3 (p = 0.079) and the change in and maximum diameter was 1.53 ± 1.49 cm (p < 0.01). The effect of NACT on tumor burden based on RECIST criteria was minimal as 8 patients had stable disease. Based on pathological findings, the average necrotic portion of the tumor was 39.5% (p = 0.152). The overall survival rate is 95.65%, mean survival was 115 months (4–125). Recurrence occurred in 5 patients. The NACT group had a higher risk for recurrence (4; 33.3%) with a mean survival of 43.8 months compared to 59.6 months in those who did not receive induction therapy.ConclusionsThe exact role of induction chemotherapy in locally advanced thymoma patients remains controversial. NACT effect after utilizing radiological and pathological assessment tools was not found to significantly improve oncological outcomes compared to upfront surgery in locally advanced disease, with minimal radiologic and pathologic effect. To further demonstrate the impact of induction chemotherapy, we recommend multicentric collaborative studies.

A phase I study of bintrafusp alfa and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic genitourinary (GU) malignancies.

4571 Background: Bintrafusp alfa is a novel bifunctional fusion protein targeting PD-L1 and TGF-β which has demonstrated clinical efficacy in some tumor types and a manageable safety profile. M9241 is an immunocytokine that allows targeting of the pro-inflammatory IL-12 cytokine to exposed DNA in necrotic portions of tumors. SBRT can help promote anti-tumor responses and may potentially synergize with immunotherapy by inducing DNA damage. Methods: This is an open label, non-randomized, three arm phase I trial of bintrafusp alfa and M9241 combination therapy administered alone (Arm 1), or with either sequential (Arm 2), or concurrent (Arm 3) SBRT. Eligible patients must have metastatic non-prostate GU cancers with measurable disease. Bintrafusp alfa was used at a flat dose of 1200mg (q2w) for arms 1-3 and a fixed dose of SBRT (24Gy in 3 fractions) was used for arms 2-3. M9241 was administered at 16.8mcg/kg (q4w) for Arm 1 and decreased if side effects occur. Arm 1 used bintrafusp alfa and M9241 alone, with the maximum tolerated dose (MTD) of M9241 being dose level 1 (DL1) for Arm 2. Arm 2 used SBRT followed by bintrafusp alfa and M9241, with the MTD of M9241 being DL1 for Arm 3. Arm 3 used concurrent SBRT with bintrafusp alfa and M9241. The primary objective was to determine the safety and highest tolerable doses of each arm. Secondary objectives include objective response rate (ORR), progression free survival (PFS), and overall survival (OS). Results: Study enrollment began in 12/2019, with interim safety analyses performed quarterly. A total of 16 patients have enrolled, 12 in Arm 1, three in Arm 2, and one in Arm 3 at data cutoff 1/2/23. The first six patients enrolled in Arm 1 had no DLTs allowing Arm 2 to open, Arm 2 had no DLTs after 3 patients enrolled allowing Arm 3 to open. At data cut off four of 16 patients remained on treatment. The median age was 63 and 19% were female. The most frequent TRAEs were fatigue (grade 2, 38%), lipase increase (grade 2+3, 31%), and anemia (grade 2+3, 31%). Grade 3 hematuria occurred in 2 patients (13%); a grade 4 creatinine increase occurred in one (8%). There were no grade 5 TRAEs. Two (13%) patients had treatment discontinued and 5 (31%) had dose reductions due to AEs. Of the 16 patients enrolled on study, 11 were evaluable at data cutoff. Currently three patients (38%) on Arm 1 and one patient (50%) in Arm 2 had objective responses, corresponding to an ORR of 36.4% (4/11). All responses have been partial responses. On Arm 1 the responding patients included one with small cell carcinoma of the renal pelvis, one with Leydig cell tumor, and one with urothelial carcinoma. On Arm 2 the responding patient had a Sertoli cell tumor. Conclusions: The use of bintrafusp alfa and M9241 either alone or in combination with sequential or concurrent SBRT has shown clinical activity in pts with GU tumors and has not been associated with any DLTs. Clinical trial information: NCT04235777 .

What Is New in Stage 3 of the 2019 Revised Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head: A Relationship to Bone Resorption.

The aim of the study is to evaluate the stage 3 findings of the 2019 revision of the Association Research Circulation Osseous (ARCO) staging system for osteonecrosis of the femoral head between 3A and 3B and the relationship with bone resorption area. We retrospectively enrolled 87 patients with ARCO stage 3 osteonecrosis of the femoral head, divided into stage 3A (n = 73) and 3B (n = 14). The revised stage 3 findings included subchondral fracture, fracture in necrotic portion, and flattening of the femoral head and were compared between stage 3A and 3B. The association between these findings and the causative features of bone resorption area was also evaluated. All stage 3 cases had subchondral fractures. In stage 3A, these fractures were generated by crescent sign (41.1%) and by fibrovascular reparative zone in 58.9%; however, in stage 3B, fibrovascular reparative zone generated 92.9% of these fractures and crescent sign only 7.1% with statistical significance (P = 0.034). Necrotic portion fracture was noted in 36.7% and femoral head flattening was observed in 14.9% of all stage 3. Necrotic portion fracture (92.9% vs 26.0%) and femoral head flattening (71.4% vs 4.1%) were observed more frequently in stage 3B than 3A (P < 0.001). Almost all subchondral fractures by fibrovascular reparative zone (96.4%) and necrotic portion fracture (96.9%), and all femoral head flattening was presented with bone resorption area with expanding areas. The ARCO stage 3 descriptions reflect severity in this order: subchondral fracture, necrotic portion fracture, and femoral head flattening. More severe findings are usually associated with expanding bone resorption areas.

Tactics of surgical treatment in necrotising enterocolitis stage II-B in newborn

An analysis was made of the results of surgical treatment of 18 newborns with a diagnosis of stage II-B NEC, admitted in the period from 2018 to 2022. The aim of the work: to analyze the results of surgical treatment for stage II-B necrotizing enterocolitis in newborns using modern technologies. A total of 18 diagnostic laparoscopies (DL) were performed, of which 4 cases were converted - laparotomy. In 14 patients cases, DL was completed by therapeutic laparoscopy using minilaparotomy with video-assessment, including 8 patients, resection of the necrotic portion of the intestine was performed with end-to-end anastomosis. In 6 cases, an intestinal stoma was applied through a minilaparotomy.In comparison, after laparoscopic operations with video assessment, mortality was observed of cases 1 patient out of 14, after traditional surgical interventions, mortality was in 25% of cases 1 patient out of 4. Based on the results of DL at the surgical stage of NEC, it is possible to build further tactics of radical surgical treatment, the possibility of transforming it into a therapeutic one minimizes intraoperative trauma, which positively affects the postoperative survival of patients.

Temporal radiographic and histological study of necrosis development in a mouse glioblastoma model.

Tumor necrosis is a poor prognostic marker in glioblastoma (GBM) and a variety of other solid cancers. Accumulating evidence supports that necrosis could facilitate tumor progression and resistance to therapeutics. GBM necrosis is typically first detected by magnetic resonance imaging (MRI), after prominent necrosis has already formed. Therefore, radiological appearances of early necrosis formation and the temporal-spatial development of necrosis alongside tumor progression remain poorly understood. This knowledge gap leads to a lack of reliable radiographic diagnostic/prognostic markers in early GBM progression to detect necrosis. Recently, we reported an orthotopic xenograft GBM murine model driven by hyperactivation of the Hippo pathway transcriptional coactivator with PDZ-binding motif (TAZ) which recapitulates the extent of GBM necrosis seen among patients. In this study, we utilized this model to perform a temporal radiographic and histological study of necrosis development. We observed tumor tissue actively undergoing necrosis first appears more brightly enhancing in the early stages of progression in comparison to the rest of the tumor tissue. Later stages of tumor progression lead to loss of enhancement and unenhancing signals in the necrotic central portion of tumors on T1-weighted post-contrast MRI. This central unenhancing portion coincides with the radiographic and clinical definition of necrosis among GBM patients. Moreover, as necrosis evolves, two relatively more contrast-enhancing rims are observed in relationship to the solid enhancing tumor surrounding the central necrosis in the later stages. The outer more prominently enhancing rim at the tumor border probably represents the infiltrating tumor edge, and the inner enhancing rim at the peri-necrotic region may represent locally infiltrating immune cells. The associated inflammation at the peri-necrotic region was further confirmed by immunohistochemical study of the temporal development of tumor necrosis. Neutrophils appear to be the predominant immune cell population in this region as necrosis evolves. This study shows central, brightly enhancing areas associated with inflammation in the tumor microenvironment may represent an early indication of necrosis development in GBM.

A Case Study on Anaesthesia of a Patient with Pancreatic Necrosis in Bangladesh

Acute pancreatitis causes devastating changes in body involves organ dysfunction, metabolic imbalance, electrolyte disturbance as well as acid base disorder. Pancreatic necrosis complicates the condition. Patient may develops systemic inflammatory response syndrome (SIRS) followed by sepsis. Laparotomy and removal of necrotic part along with peritoneal toileting is the surgical management. We present a case of a 45 years old male admitted with a diagnosis of pancreatic necrosis is scheduled for exploratory laparotomy followed by peritoneal toileting along with excision of necrotic portion. Maintaining a smooth anesthesia is a challenge during surgery. Disease and its complications along with surgery produce extreme condition for anesthesiologist. Patient sometimes response badly therefore may need postoperative intensive care support. Meticulous fluid administration, inotrope support, choice of proper intraoperative drugs, monitoring vital signs including urine output, blood gas analysis- these should be focused during anaesthesia

An unusual presentation of intestinal duplication mimicking torsion of Meckel\u2019s diverticulum: a rare report of a pediatric case

BackgroundEnteric duplication is a congenital disease that occurs throughout the entire gastrointestinal tract. Although it may sometimes cause intestinal volvulus, a few reports have described cases of enteric duplication twisted on itself. We experienced a rare pediatric case of long-segment tubular ileal duplication showing torsion. Torsion of enteric duplication is extremely rare. We herein report a pediatric case showing unusual torsion of ileal duplication requiring emergency surgery.Case presentationA 3-year-old boy presented with abdominal pain and vomiting. Contrast-enhanced computed tomography (CT) revealed a cystic luminal structure with a blind end and fluid collection in the pelvic cavity. CT also showed no findings of ileus or intestinal dilatation except for a cystic luminal structure. The preoperative diagnosis was torsion of Meckel’s diverticulum. The patient underwent emergent explorative diagnostic laparoscopy. As a result, a necrotic luminal structure and bloody ascites were recognized, and small-scale laparotomy was performed. Long-segment ileal duplication was recognized. The long-segment tubular ileal duplication shared the anti-mesenteric side of the intestinal wall along one-third of its length. The residual two-thirds of its length was free from the ileum and its blind end was twisted in a manner that looked similar to Meckel’s diverticulum. Normal ileum and the duplication, including the twisted necrotic portion, were resected, and ileal anastomosis was performed. The postoperative course was uneventful. A pathological examination confirmed the definitive diagnosis of enteric duplication.ConclusionsWe reported the unusual presentation of intestinal duplication mimicking torsion of Meckel’s diverticulum. Enteric duplication shows various clinical symptoms and presentations. We must understand that the classification of digestive enteric duplication is diverse with a variety of associated clinical symptoms.

Acute Small Bowel Obstruction Caused By Transmesenteric Hernia Strangulation In A Young Man: A Case Report.

We report a rare case of a 20 year old patient with a transmesenteric hernia leading to small bowel obstruction and intestinal necrosis. An intestinal resection removed the necrotic portion and the mesenteric defect. Then, an immediate end-to-end anastomosis was realized. Transmesenteric hernia is a rare but serious entity. The surgical management must be rapid because of the increased risk of intestinal necrosis. Keywords: Transmesenteric hernia, small bowel obstruction, intestinal necrosis

Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction.

ObjectivesThe proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.Materials and MethodsA total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.ResultsAmong 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume (β = -0.348, P = 0.009), hemorrhagic portion volume (β = -0.327, P = 0.014), tumor ADC (β = 0.530, P <.001), and ALPS index (β = -0.750, P <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC (β = 0.303; P = 0.004) and ALPS index (β = -0.624; P < 0.001) were the two independent factors associated with PTBE volume.ConclusionMetastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.

A phase I study of bintrafusp alfa (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies.

TPS4599 Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.

NHS-IL12, a Tumor-Targeting Immunocytokine.

NHS-IL12 is a novel immunocytokine designed for delivery of IL-12 to the tumor microenvironment (TME). NHS-IL12 consists of two molecules of IL-12 fused to a human IgG1 (NHS76) recognizing DNA/histone complexes, which are often exposed in the necrotic portions of tumors. Preclinical studies demonstrated the tumor-targeting ability and longer plasma half-life for NHS-IL12 when compared with recombinant IL-12 (rIL-12). NHS-IL12 outperformed rIL-12 in enhancing the proliferation and activation of immune as well as antigen-presenting cells, resulting in a more robust primary immune response. NHS-IL12 also reduced the number and function of suppressive myeloid cells (myeloid derived suppressor cells/macrophages) within the TME. In a murine bladder tumor model, NHS-IL12 administration led to a coordinated increase in host immunity with a reduction of immunosuppressive myeloid cells in the TME resulting in substantial reduction in tumor growth. Several preclinical studies have demonstrated increased overall anti-tumor efficacy when NHS-IL12 was combined with either immune-based therapeutics or chemotherapeutic approaches.

Gastrointestinal Bleeding and Acute Liver Failure

Question: A 73-year-old man was referred to emergency after falling at home in a context of fever (38.5°C), abdominal pain, and several episodes of melena. He had undergone emergency surgery 10 days earlier for an acute bowel occlusion requiring resection and anastomosis of a necrotic portion of the small intestine. The patient’s notable history included nonmetastatic basal tongue cancer treated with radiotherapy/chemotherapy (cisplatin then currently cetuximab).

Image Guidance in Ablation for Hepatocellular Carcinoma: Contrast-Enhanced Ultrasound and Fusion Imaging.

The ultrasound (US) imaging technology, including contrast-enhanced US (CEUS) and fusion imaging, has experienced radical improvement, and advancement in technology thus overcoming the problem of poor conspicuous hepatocellular carcinoma (HCC). On CEUS, the presence or absence of enhancement distinguishes the viable portion from the ablative necrotic portion. Using volume data of computed tomography (CT) or magnetic resonance imaging (MRI), fusion imaging enhances the three-dimensional relationship between the liver vasculature and HCC. Therefore, CT/MR-US fusion imaging provides synchronous images of CT/MRI with real-time US, and US-US fusion imaging provides synchronous US images before and after ablation. Moreover, US-US overlay fusion can visualize the ablative margin because it focuses the tumor image onto the ablation zone. Consequently, CEUS and fusion imaging are helpful to identify HCC with little conspicuity, and with more confidence, we can perform ablation therapy. CEUS/fusion imaging guidance has improved the clinical effectiveness of ablation therapy in patients with poor conspicuous HCCs. Therefore; this manuscript reviews the status of CEUS/fusion imaging guidance in ablation therapy of poor conspicuous HCC.

計画的二期手術にて救命し得た，高浸透圧高血糖症候群を契機に発症した非閉塞性腸管虚血症の1例(Succesful treatment of non–occlusive mesenteric ischemia induced by hyperosmolar hyperglycemic state, requiring planned two–stage surgery: a case report)

要旨症例は67歳の男性で，喉頭癌（cT3N1M0 stage III）に対し喉頭亜全摘術および気管切開術を施行された。術後の経管栄養開始後に血糖上昇傾向となり，その後，高浸透圧高血糖症候群（hyperosmolar hyperglycemic syndrome: HHS）を発症した。さらに浸透圧利尿による脱水にて腸管低灌流を合併したことによると思われる非閉塞性腸管虚血症（non–occlusive mesenteric ischemia: NOMI）が疑われたため，緊急で診断的腹腔鏡検査を施行した。その結果，明らかに壊死した腸管を認めたため開腹手術に移行し，初回手術では壊死腸管の切除のみを行った。集中治療後に二期的に腸管再建術を施行し，その際にインドシアニングリーン蛍光法にて残存腸管に血流障害がないことを確認した。今回我々は，HHSを契機に発症したと考えられるNOMIの1例を経験した。NOMIは非常に致死率の高い予後不良な疾患であるが，計画的な二期手術および集中治療にて救命し得た。自験例について，文献的考察を交えて報告する。

Osteotomies for avascular necrosis of the femoral head.

In osteonecrosis of the femoral head (ONFH), blood supply is insufficient for the metabolic requirements of the bone. The initial management is conservative, and, in case of failure, surgery is indicated. Osteotomies aim to change the spatial position of the necrotic portion of the femoral head. This systematic review evaluates the effectiveness and safety of osteotomies for ONFH. The systematic review, organized, conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, was performed on PubMed and Google Scholar. We analysed outcomes in term of Harris Hip Score, leg shortening, secondary collapse and blood loss. We also verified the percentage of patients who required total hip replacement (THR) after osteotomy for ONFH. A total of 16 articles were selected, including 775 patients and 852 osteotomies [curved varus osteotomy in 369 (43.3%) patients; transtrochanteric rotational osteotomy in 435 (51.05%) patients; half wedge osteotomy in 48 (5.6%) patients]. There was an overall THR conversion rate of 31.5% (268 hips on 852 osteotomies). There were no prospective randomized trials, and the outcome measures employed were often heterogeneous. Approximately one-third of the osteotomies performed in cases of ONFH are converted to THR over a period of ~7years. In older patients, primary THR should be considered, especially as the conversion to THR after osteotomy is technically demanding. Randomized clinical studies should be conducted in order to define the parameters of the patient that can direct towards the most suitable osteotomic technique.

Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis

ObjectivesThis study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA). BackgroundCoronary CTA can noninvasively assess coronary plaques quantitatively. MethodsPatients who underwent 2 coronary CTAs at a minimum of 24 months’ interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome. ResultsThree distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm3 [interquartile range (IQR): 0.0 to 39.6 mm3]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm3 [IQR: 0.0 to 127.4 mm3]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm3 [IQR: 96.7 to 306.4 mm3]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features. ConclusionsThe TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)