The tumor cell-intrinsic cGAS-STING pathway is associated with the high density of CD8+ T cells after chemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: Chemotherapy has the potential to induce CD8+ T-cell infiltration in the tumor microenvironment (TME) and activate the anti-tumor immune response in several cancers including esophageal squamous cell carcinoma (ESCC). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been known as a critical component for regulating immune cell activation in the TME. However, its effect on the infiltration of immune cells induced by chemotherapy in the ESCC TME has not been investigated. METHODS: We examined the effect of the tumor-cell intrinsic cGAS-STING pathway on the infiltration of CD8+ T cells induced by chemotherapy in ESCC using ESCC cell lines and surgically resected ESCC specimens from patients who received neoadjuvant chemotherapy (NAC). RESULTS: We found that chemotherapeutic agents, including 5-fluorouracil (5-FU) and cisplatin (CDDP), activated the cGAS-STING pathway, consequently inducing the expression of type I interferon and T-cell-attracting chemokines in ESCC cells. Moreover, the tumor cell-intrinsic expression of cGAS-STING was significantly and positively associated with the density of CD8+ T cells in ESCC after NAC. However, the tumor cell-intrinsic expression of cGAS-STING did not significantly impact clinical outcomes in patients with ESCC after NAC. CONCLUSION: Our findings suggest that the tumor cell-intrinsic cGAS-STING pathway might contribute to chemotherapy-induced immune cell activation in the ESCC TME.

M2 tumor-associated macrophages resist to oxidative stress through heme oxygenase-1 in the colorectal cancer tumor microenvironment.

M2 tumor-associated macrophages (M2-TAMs) promote cancer cell proliferation and metastasis in the TME. Our study aimed to elucidate the mechanism of increased frequency of M2-TAMs infiltration in the colorectal cancer (CRC)-TME, focusing on the resistance to oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we evaluated the correlation between M2-TAM signature and mRNA expression of antioxidant related genes using public datasets, and the expression level of antioxidants in M2-TAMs by flow cytometry and the prevalence of M2-TAMs expressing antioxidants by immunofluorescence staining using surgically resected specimens of CRC (n = 34). Moreover, we generated M0 and M2 macrophages from peripheral blood monocytes and evaluated their resistance to oxidative stress using the in vitro viability assay. Analysis of GSE33113, GSE39582, and The Cancer Genome Atlas (TCGA) datasets indicated that mRNA expression of HMOX1 (heme oxygenase-1 (HO-1)) was significantly positively correlated with M2-TAM signature (r = 0.5283, r = 0.5826, r = 0.5833, respectively). The expression level of both Nrf2 and HO-1 significantly increased in M2-TAMs compared to M1- and M1/M2-TAMs in the tumor margin, and the number of Nrf2+ or HO-1+M2-TAMs in the tumor stroma significantly increased more than those in the normal mucosa stroma. Finally, generated M2 macrophages expressing HO-1 significantly resisted to oxidative stress induced by H2O2 in comparison with generated M0 macrophages. Taken together, our results suggested that an increased frequency of M2-TAMs infiltration in the CRC-TME is related to Nrf2-HO-1 axis mediated resistance to oxidative stress.

[A Case of Perforation of the Duodenum during Chemotherapy with Ramucirumab plus Nab-Paclitaxel for Advanced Gastric Cancer].

A 70-year-old male patient was diagnosed with advanced gastric cancer with para-aortic lymph node metastasis. After diagnostic laparoscopy, the patient received 2 courses of neoadjuvant chemotherapy. Subsequently, distal gastrectomy, D2 plus para-aortic lymph node dissection, and Roux-en-Y reconstruction were performed. An enlarged lymph node(No. 16b2)was identified during surgery. The histopathological diagnosis revealed ypT4b, ypN3b, cM1(LYM; No. 16), Stage ⅣB. Chemotherapy with ramucirumab plus nab-paclitaxel was administered at 6 weeks postoperatively. However, after 2 courses of chemotherapy, the patient developed an abscess discharge from the wound, which was confirmed by an abdominal CT scan and diagnosed as an intra-abdominal abscess derived from duodenal perforation. The abscess was drained percutaneously. Subsequently, chemotherapy with nab-paclitaxel, nivolumab, and trifluridine/tipiracil hydrochloride was administered. After the appearance of brain metastases, the treatment was shifted to palliative care. The patient died 2 years and 7 months later from the primary disease.

Role of the cGAS-STING pathway in regulating the tumor-immune microenvironment in dMMR/MSI colorectal cancer.

Deficient mismatch repair (dMMR)/microsatellite instability (MSI) colorectal cancer (CRC) has high immunogenicity and better prognosis compared with proficient MMR (pMMR)/microsatellite stable (MSS) CRC. Although the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been considered to contribute to the high number of CD8+ TILs, its role in dMMR/MSI CRC is largely unknown. In this study, to examine the role of the cGAS-STING pathway on the recruitment of CD8+ TILs in dMMR/MSI CRC, we used public datasets and clinical tissue samples in our cohorts to evaluate the expression of cGAS, STING, and CD8+ TILs in pMMR/MSS and dMMR/MSI CRCs. According to the analysis of public datasets, the expression of cGAS-STING, CD8 effector gene signature, and CXCL10-CCL5, chemoattractants for CD8+ TILs which regulated by the cGAS-STING pathway, was significantly upregulated in dMMR/MSI CRC, and the expression of cGAS-STING was significantly associated with the expression of CD8 effector gene signature. Immunohistochemistry staining of the clinical tissue samples (n = 283) revealed that cGAS-STING was highly expressed in tumor cells of dMMR CRC, and higher expression of cGAS-STING in tumor cells was significantly associated with the increased number of CD8+ TILs. Moreover, we demonstrated that the downregulation of MMR gene in human CRC cell lines enhanced the activation of the cGAS-STING pathway. Taken together, for the first time, we found that dMMR/MSI CRC has maintained a high level of cGAS-STING expression in tumor cells, which might contribute to abundant CD8+ TILs and immune-active TME.

Scattered migrating colony formation in the filamentous cyanobacterium, Pseudanabaena sp. NIES-4403.

BACKGROUND: Bacteria have been reported to exhibit complicated morphological colony patterns on solid media, depending on intracellular, and extracellular factors such as motility, cell propagation, and cell-cell interaction. We isolated the filamentous cyanobacterium, Pseudanabaena sp. NIES-4403 (Pseudanabaena, hereafter), that forms scattered (discrete) migrating colonies on solid media. While the scattered colony pattern has been observed in some bacterial species, the mechanism underlying such a pattern still remains obscure. RESULTS: We studied the morphology of Pseudanabaena migrating collectively and found that this species forms randomly scattered clusters varying in size and further consists of a mixture of comet-like wandering clusters and disk-like rotating clusters. Quantitative analysis of the formation of these wandering and rotating clusters showed that bacterial filaments tend to follow trajectories of previously migrating filaments at velocities that are dependent on filament length. Collisions between filaments occurred without crossing paths, which enhanced their nematic alignments, giving rise to bundle-like colonies. As cells increased and bundles aggregated, comet-like wandering clusters developed. The direction and velocity of the movement of cells in comet-like wandering clusters were highly coordinated. When the wandering clusters entered into a circular orbit, they turned into rotating clusters, maintaining a more stable location. Disk-like rotating clusters may rotate for days, and the speed of cells within a rotating cluster increases from the center to the outmost part of the cluster. Using a mathematical modeling with simplified assumption we reproduced some features of the scattered pattern including migrating clusters. CONCLUSION: Based on these observations, we propose that Pseudanabaena forms scattered migrating colonies that undergo a series of transitions involving several morphological patterns. A simplified model is able to reproduce some features of the observed migrating clusters.

[The Association between Intestinal Bacteria and Tumor Infiltrating Immune Cells in the Tumor Microenvironment of Colorectal Cancer].

Cancer immunotherapy, which is attracting attention as a fourth treatment strategy for cancer therapy, eliminates cancer cells using own immune system. Therefore, the state of tumor immune responses is very important to elicit the efficacy of cancer immunotherapy. Recently, the association between the efficacy of cancer immunotherapy using immune checkpoint inhibitors and certain intestinal bacteria has been reported. It is suggested that certain intestinal bacteria may regulate tumor immune responses. We also reported that intestinal bacteria such as Bifidobacterium, Bacteroides, and Faecalibacterium (genus level)were increased in patients with high frequency of infiltrating effector regulatory T cells in the tumor microenvironment of advanced colorectal cancer. In this article, we presented the association between intestinal bacteria and tumor infiltrating immune cells, such as regulatory T cells and tumor associated macrophages, in the tumor microenvironment of advanced colorectal cancer, focusing on results of our research. Subsequently, we introduced the possibility of clinical application of intestinal bacteria based on the review of reported articles.

KRT17 as a prognostic biomarker for stage II colorectal cancer.

Adjuvant chemotherapy is considered for patients with stage II colorectal cancer (CRC) characterized by poor prognostic clinicopathological features; however, current stratification algorithms remain inadequate for identifying high-risk patients. To develop prognostic assays, we conducted a step-wise screening and validation strategy using nine cohorts of stage II patients based on multiple platforms, including microarray, RNA-sequencing (RNA-seq) and immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tissues. Four microarray datasets (total n = 458) were used as the discovery set to screen for single genes associated with postoperative recurrence. Prognostic values of candidate genes were evaluated in three independent microarray/RNA-seq validation cohorts (n = 89, n = 93 and n = 183, respectively), and then IHC for KRT17 was conducted in two independent FFPE series (n = 110 and n = 44, respectively). We found that high levels of KRT17 transcript expression were significantly associated with poor relapse-free survival (RFS) not only in the discovery set, but also in three validation cohorts, and its prognostic impact was independent of conventional factors by multivariate analyses. Positive staining of KRT17 protein was significantly associated with poor RFS in two independent FFPE cohorts. KRT17 protein expression had independent prognostic impact on RFS in a multivariate model adjusted for conventional variables, including high-risk clinicopathological features. In conclusion, using nine independent cohorts consisting of 997 stage II patients, we identified and validated the expression of KRT17 transcript and KRT17 protein as a robust prognostic biomarker that can discriminate postoperative stage II patients who are at high probability of disease recurrence, providing additional prognostic stratification beyond the currently available high-risk factors.

Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers.

BACKGROUND: Several articles have recently reported that certain colon microbiota can improve the efficacy of cancer immunotherapy. To develop new treatment strategies, including immunotherapy for colorectal cancer (CRC), we evaluated the correlations between subpopulations of tumor-infiltrating immune cells (TIICs) and intestinal microbiota in CRC. METHODS: Fresh surgically resected specimens, formalin-fixed paraffin-embedded whole tissue samples, and stool samples were collected. TIICs including Tregs, Th17 cells and tumor-associated macrophages (TAMs) in the surgically resected specimens were analyzed using flow cytometry. FOXp3, CD8, CD163, and phosphorylated-STAT1-positive TIICs in the whole tissue samples were analyzed using IHC, and intestinal microbiota in the stool samples was analyzed using 16S metagenome sequencing. TIICs subpopulations in the normal mucosa and tumor samples were evaluated, and the correlations between the TIIC subpopulations and intestinal microbiota were analyzed. RESULTS: FOXp3lowCD45RA+ Tregs were significantly reduced (p = 0.02), FOXp3lowCD45RA- Tregs were significantly increased (p = 0.006), and M1 TAMs were significantly reduced in the tumor samples (p = 0.03). Bacteroides (phylum Bacteroidetes) and Faecalibacterium (phylum Firmicutes) were increased in the patients with high numbers of Tregs and clearly high distribution of FOXp3highCD45RA- Tregs, which are the effector Tregs. Faecalibacterium, Ruminococcaceae, Eubacterium (phylum Firmicutes), and Bacteroides were increased in patients with a high distribution of M1 TAMs. CONCLUSIONS: The findings of the present study indicate that immune responses to tumors are suppressed in the tumor microenvironment of CRC depending on the increment of Tregs and the reduction of M1 TAMs and that intestinal microbiota might be involved in immunosuppression.

[A Case of Rectal Colon Cancer with Paraneoplastic Cerebellar Degeneration].

A case complicated with colorectal and prostate cancers in paraneoplastic(subacute)cerebellar degeneration(PCD)is extremely rare. We report a retrospective case of rectal carcinoma with paraneoplastic cerebellar degeneration. A 79-year-old man with Parkinson's disease was unable to walk because of paralysis. Brain MRI showed cerebellar atrophy. He was admitted to our hospital for anal bleeding and was diagnosed with colon cancer. An associated diagnosis of PCD was made. After resection, his paralysis and dysarthria were resolved to the extent of beingable to walk and speak fluently. Brain MP-RAGE showed no findings suggestive of metastasis or atrophy. He was treated surgically, which resulted in a transient improvement in PCD symptoms. Per blood testing, cytokines IL-6 and IL-10 were lower postoperatively. Immunosuppressive levels of myeloid- derived suppressor cells(MDSCs)were lower compared with the preoperative values. Thus, innate immunocompetence and resolution of paralysis followed the surgical intervention.

[A Case of Esophageal Cancer with Cervical Lymph Node Recurrence Six Years after Complete Response to Definitive Chemoradiotherapy].

Neoadjuvant chemotherapy plus surgery is recommended for clinical StageⅡ and Ⅲ esophageal cancer treatment by the JCOG9906. In contrast, definitive chemoradiotherapy(dCRT)is also a curative treatment. We encountered a case of recurrence in the cervical lymph nodes that was confirmed 6 years later, although thoracic esophageal cancer had completely disappeared following dCRT. Since there was no recurrence or metastasis in the primary lesion or other organs, we performed bilateral cervical lymph node dissection. There were 3 lymph node metastases among the dissected cervical lymph nodes pathologically. After the surgery, no relapses have occurred without the adjuvant chemotherapy.

[A Case of AFP and PIVKA- II Producing Gastric Cancer Presenting with Metachronous Multiple Liver Metastases].

A 55-year old man underwent distal gastrectomy with lymphadenectomy for gastric cancer(T1N0M0, Stage I A). Six months after the radical operation, he presented with multiple liver metastases. Based on immunohistochemical examination, he was diagnosed with AFP-producing gastric cancer and metachronous liver metastases. He underwent a surgery to remove the liver metastases. Two months after the surgery, recurrent tumors were found in the lung and remnant liver. He received chemotherapy(S-1/CDDP and CPT-11/CDDP)for the recurrent tumor and lived for 15 months after the surgical intervention.

Stereo-controlled synthesis of polyheterocycles via the diene-transmissive hetero-Diels-Alder reaction of ß,γ-unsaturated α-keto esters.

We describe the stereoselective synthesis of polyring-fused heterocyclic compounds based on diene-transmissive hetero-Diels-Alder reactions utilizing ß,γ-unsaturated α-keto esters. This protocol involves the initial endo- or exo-selective Diels-Alder (DA) reactions with electron-rich dienophiles, methylenation of the ester carbonyl groups with the Tebbe reagent, and a stereoselective second DA reaction with electron-deficient dienophiles. The use of enantioselective DA reactions in the initial reaction enables access to chiral polyring-fused heterocyclic compounds with multiple chiral centres.

[Surgical Resection for a Metachronous Liver Metastasis of an Esophagogastric Junction Adenocarcinoma].

The patient was a 56-year-old man with advanced esophagogastric junction cancer. He received neoadjuvant chemotherapy with 5-FU plus CDDP followed by lower esophagectomy and total gastrectomy via the left thoracoabdominal approach in October 2011. Pathological examination revealed EGJ adenocarcinoma (ypT4aN1M0, Stage ⅢA, Japanese Classification of Gastric Carcinoma ver.14), and histological analysis indicated Grade 0 (no change). Adjuvant chemotherapy with S-1 was administered. Nevertheless, 6 months after the operation, a solitary hepatic metastasis (f: 32 mm) was detected in S7 of the liver. The patient underwent proton beam irradiation of the liver metastasis, resulting in a complete response, and he was followed up without any chemotherapy. However, 21 months after the irradiation, regrowth of the previous lesion with FDG re-accumulation was noted. Given the absence of any neoplasms other than the liver metastasis, right hepatic lobectomy was performed. Pathological examination revealed a small cluster of viable tumor cells surrounded by extensive fibrotic tissue (Grade 2). At 45 months after the initial operation (10 months after the liver lobectomy), the patient is living without any signs of recurrence. Surgical resection for liver metastasis of EGJ cancer may be feasible after careful selection.

[A case of two re-resections for peritoneal recurrence of pancreatic cancer].

A 63-year-old man underwent subtotal stomach-preserving pancreaticoduodenectomy and intraoperative radiation therapy for pancreatic head cancer (Stage IVa, JPS). Subsequently, he received adjuvant chemotherapy including gemcitabine (GEM). A peritoneal recurrence appeared adjacent to the right colon and the lower pole of the right kidney. He received chemotherapy including S-1 and GEM+S-1. Since the recurrent lesions were localized, he underwent resection for the recurrence lesions 2 years and 9 months after surgery. The resection was R1, and re-recurrence appeared in the lower pole of the right kidney. After chemotherapy and chemoradiotherapy, he underwent re-resection for the recurrence 4 years and 3 months after the first surgery. Three months after re-resection, multiple liver metastases appeared in the bilateral lobes. Reoperation can be one of the multidisciplinary management options for local recurrence of pancreatic cancer under specific conditions.

Towards Improved Radiological Diagnostics: Investigating the Utility and Limitations of GPT-3.5 Turbo and GPT-4 with Quiz Cases.

BACKGROUND AND PURPOSE: The rise of large language models such as generative pre-trained transformers (GPTs) has sparked significant interest in radiology, especially in interpreting radiological reports and image findings. While existing research has focused on GPTs estimating diagnoses from radiological descriptions, exploring alternative diagnostic information sources is also crucial. This study introduces the use of GPTs (GPT-3.5 Turbo and GPT-4) for information retrieval and summarization, searching relevant case reports via PubMed, and investigates their potential to aid diagnosis. MATERIALS AND METHODS: From October 2021 to December 2023, we selected 115 cases from the "Case of the Week" series on the American Journal of Neuroradiology website. Their Description and Legend sections were presented to the GPTs for the two tasks. For the Direct Diagnosis task, the models provided three differential diagnoses that were considered correct if they matched the diagnosis in the diagnosis section. For the Case Report Search task, the models generated two keywords per case, creating PubMed search queries to extract up to three relevant reports. A response was considered correct if reports containing the disease name stated in the diagnosis section were extracted. McNemar's test was employed to evaluate whether adding a Case Report Search to Direct Diagnosis improved overall accuracy. RESULTS: In the Direct Diagnosis task, GPT-3.5 Turbo achieved a correct response rate of 26% (30/115 cases), whereas GPT-4 achieved 41% (47/115). For the Case Report Search task, GPT-3.5 Turbo scored 10% (11/115), and GPT-4 scored 7% (8/115). Correct responses totaled 32% (37/115) with three overlapping cases for GPT-3.5 Turbo, whereas GPT-4 had 43% (50/115) of correct responses with five overlapping cases. Adding Case Report Search improved GPT-3.5 Turbo's performance (p = 0.023) but not that of GPT-4 (p = 0.248). CONCLUSIONS: The effectiveness of adding Case Report Search to GPT-3.5 Turbo was particularly pronounced, suggesting its potential as an alternative diagnostic approach to GPTs, particularly in scenarios where direct diagnoses from GPTs are not obtainable. Nevertheless, the overall performance of GPT models in both direct diagnosis and case report retrieval tasks remains not optimal, and users should be aware of their limitations.ABBREVIATIONS: AI = Artificial Intelligence, GPT = generative pretrained transformer, LLM = large language model.

Impact of CT-determined low kidney volume on renal function decline: a propensity score-matched analysis.

OBJECTIVES: To investigate the relationship between low kidney volume and subsequent estimated glomerular filtration rate (eGFR) decline in eGFR category G2 (60-89 mL/min/1.73 m2) population. METHODS: In this retrospective study, we evaluated 5531 individuals with eGFR category G2 who underwent medical checkups at our institution between November 2006 and October 2017. Exclusion criteria were absent for follow-up visit, missing data, prior renal surgery, current renal disease under treatment, large renal masses, and horseshoe kidney. We developed a 3D U-net-based automated system for renal volumetry on CT images. Participants were grouped by sex-specific kidney volume deviations set at mean minus one standard deviation. After 1:1 propensity score matching, we obtained 397 pairs of individuals in the low kidney volume (LKV) and control groups. The primary endpoint was progression of eGFR categories within 5 years, assessed using Cox regression analysis. RESULTS: This study included 3220 individuals (mean age, 60.0 ± 9.7 years; men, n = 2209). The kidney volume was 404.6 ± 67.1 and 376.8 ± 68.0 cm3 in men and women, respectively. The low kidney volume (LKV) cutoff was 337.5 and 308.8 cm3 for men and women, respectively. LKV was a significant risk factor for the endpoint with an adjusted hazard ratio of 1.64 (95% confidence interval: 1.09-2.45; p = 0.02). CONCLUSION: Low kidney volume may adversely affect subsequent eGFR maintenance; hence, the use of imaging metrics may help predict eGFR decline. CRITICAL RELEVANCE STATEMENT: Low kidney volume is a significant predictor of reduced kidney function over time; thus, kidney volume measurements could aid in early identification of individuals at risk for declining kidney health. KEY POINTS: • This study explores how kidney volume affects subsequent kidney function maintenance. • Low kidney volume was associated with estimated glomerular filtration rate decreases. • Low kidney volume is a prognostic indicator of estimated glomerular filtration rate decline.

Synthesis of Hybrid Data Consisting of Chest Radiographs and Tabular Clinical Records Using Dual Generative Models for COVID-19 Positive Cases.

To generate synthetic medical data incorporating image-tabular hybrid data by merging an image encoding/decoding model with a table-compatible generative model and assess their utility. We used 1342 cases from the Stony Brook University Covid-19-positive cases, comprising chest X-ray radiographs (CXRs) and tabular clinical data as a private dataset (pDS). We generated a synthetic dataset (sDS) through the following steps: (I) dimensionally reducing CXRs in the pDS using a pretrained encoder of the auto-encoding generative adversarial networks (αGAN) and integrating them with the correspondent tabular clinical data; (II) training the conditional tabular GAN (CTGAN) on this combined data to generate synthetic records, encompassing encoded image features and clinical data; and (III) reconstructing synthetic images from these encoded image features in the sDS using a pretrained decoder of the αGAN. The utility of sDS was assessed by the performance of the prediction models for patient outcomes (deceased or discharged). For the pDS test set, the area under the receiver operating characteristic (AUC) curve was calculated to compare the performance of prediction models trained separately with pDS, sDS, or a combination of both. We created an sDS comprising CXRs with a resolution of 256 × 256 pixels and tabular data containing 13 variables. The AUC for the outcome was 0.83 when the model was trained with the pDS, 0.74 with the sDS, and 0.87 when combining pDS and sDS for training. Our method is effective for generating synthetic records consisting of both images and tabular clinical data.

Capability of GPT-4V(ision) in the Japanese National Medical Licensing Examination: Evaluation Study.

BACKGROUND: Previous research applying large language models (LLMs) to medicine was focused on text-based information. Recently, multimodal variants of LLMs acquired the capability of recognizing images. OBJECTIVE: We aim to evaluate the image recognition capability of generative pretrained transformer (GPT)-4V, a recent multimodal LLM developed by OpenAI, in the medical field by testing how visual information affects its performance to answer questions in the 117th Japanese National Medical Licensing Examination. METHODS: We focused on 108 questions that had 1 or more images as part of a question and presented GPT-4V with the same questions under two conditions: (1) with both the question text and associated images and (2) with the question text only. We then compared the difference in accuracy between the 2 conditions using the exact McNemar test. RESULTS: Among the 108 questions with images, GPT-4V's accuracy was 68% (73/108) when presented with images and 72% (78/108) when presented without images (P=.36). For the 2 question categories, clinical and general, the accuracies with and those without images were 71% (70/98) versus 78% (76/98; P=.21) and 30% (3/10) versus 20% (2/10; P≥.99), respectively. CONCLUSIONS: The additional information from the images did not significantly improve the performance of GPT-4V in the Japanese National Medical Licensing Examination.

Unveiling the mille-feuille sign: a key to diagnosing ovarian carcinosarcoma in addition to ovarian metastasis from colorectal carcinoma on MRI.

PURPOSE: To clarify the diagnostic utility and formation of the Mille-feuille sign for ovarian carcinosarcoma (OCS) on MRI, and to evaluate the other MRI findings and serum markers compared to ovarian metastases from colorectal carcinoma (OMCRC). METHOD: Three blinded radiologists retrospectively reviewed MR images of 12 patients with OCS, 18 with OMCRC, and 40 with primary ovarian carcinoma (POC) identified by the electronic database of radiology reports. The interobserver agreement was analyzed using Fleiss' kappa test. Their MRI characteristics and tumor markers were compared using Fisher's exact test and Mann-Whitney's U test. Receiver operating characteristic curve analyses were used to determine the cutoff points for the ADC value. This study was approved by the institutional ethics committee. RESULTS: Interobserver agreement analysis was moderate or higher for all MRI characteristics. The frequency of Mille-feuille sign was comparable for both OCS and OMCRC groups, and predominantly higher than that of the POC group (p < 0.001, p < 0.001), respectively. Pathologically, the Mille-feuille sign in OCS reflected alternating layers of tumor cells with stroma and necrosis or intraluminal necrotic debris. Compared to OMCRC, intratumoral hemorrhage (p = 0.02), margin irregularity (p = 0.048), unilateral adnexal mass (p = 0.02), and low ADC values (p < 0.01) were more frequently observed and serum CEA levels was significantly lower (p = 0.007) in the OCS group. Under setting of the cutoff value of ADC at 0.871 × 10-3mm2/s, the discriminative ability for OCS showed 66.7% sensitivity, 94.4% specificity, and 81.0% accuracy, respectively. CONCLUSIONS: The Mille-feuille sign was seen in both OCS and OMCRC. MR findings of intratumoral hemorrhage, margin irregularity, unilateral adnexal mass, low ADC values, and low serum CEA levels can be useful in differentiating OCS from OMCRC.

Factors affecting the use of a three-dimensional model during robot-assisted partial nephrectomy.

INTRODUCTION: This study aimed to identify cases that require a three-dimensional-printed kidney model in robot-assisted partial nephrectomy. METHODS: We enrolled 93 patients undergoing robot-assisted partial nephrectomy for renal tumors at a single institution between November 2018 and May 2021. The endpoints were how often and how long the surgeon consulted the three-dimensional-printed model, determined using intraoperative video. Multivariate analyses of the endpoints were adjusted by preoperative patient and kidney characteristics, including renal vascular complexity that was defined as the number of vascular branches penetrating the surface tangential to the ventral side of the kidney. RESULTS: Of the 93 cases, the median frequency and duration of intraoperative three-dimensional-printed model consultation were four times and 39 s, respectively. The multivariate linear regression analyses showed that the frequency of intraoperative three-dimensional-printed model consultation by the surgeon was significantly related to the complexity of the arterial structure (≥4 branches), presence of hilar tumor, and high Mayo Adhesive Probability score; the regression coefficients were 1.81, 2.79, and 1.34, respectively. All p-values were ≤.03. The duration of the three-dimensional-printed model consultation was significantly related to the complexity of the arterial structure (≥4 branches) and the presence of hilar tumor; the regression coefficients were 21.6, and 29.0 s, respectively. All p-values were <.01. CONCLUSION: During robot-assisted partial nephrectomy, a three-dimensional-printed model would be helpful in cases with a complex arterial structure or hilar tumor.