Combined ultrasonography and CT for prognosis and predicting clinical outcomes of patients with pseudomyxoma peritonei.

OBJECTIVES: This study aimed to identify the diagnostic accuracy of combined ultrasonography (US) and computed tomography (CT) in evaluating the tumor burden of pseudomyxoma peritonei (PMP). Besides, we assessed the ability of this combination to predict the likelihood of complete resection. METHODS: This retrospective study involved 504 patients diagnosed with PMP and scheduled for cytoreduction surgery. We compared tumor burden-quantified as peritoneal cancer index (PCI) by preoperative US and CT (US-CT-PCI)-with surgical findings. Next, we assessed the prognostic value of US-CT PCI and imaging features in determining the completeness of cytoreduction (CCR) score using multivariate analysis. RESULTS: US-CT PCI demonstrated a high PCI evaluation accuracy under moderate tumor burden. Higher US-CT PCI could predict incomplete resection. In addition, we identified imaging features such as mesenteric involvement as an independent predictor of incomplete resection (hazard ratio (HR) = 2.006; p = 0.007). CONCLUSIONS: US-CT PCI allowed us to predict the completeness of cytoreductive surgery in patients with PMP. Moreover, the combined US and CT imaging detected several features indicating incomplete cytoreduction. KEY POINTS: • Ultrasonography (US) can act as a complementary diagnostic modality in peritoneal cancer index (PCI) evaluation by combining CT in the small bowel area and US in the abdominal area. • A modified peritoneal cancer index (US-CT PCI) helps preoperatively evaluate tumor burden with high accuracy and allows to predict incomplete resection. • US-CT PCI of 20 or above and the involvement of particular structures such as mesentery, independently indicate incomplete resection.

Identification and validation of prognostic autophagy-related genes associated with immune microenvironment in human gastric cancer.

Autophagy-related genes (ATGs) play critical roles in tumorigenesis and progression in gastric cancer (GC). The present study aimed to identify immune-based prognostic ATGs and verify their functions in tumor immune microenvironment (TIME) in GC. Macrophage infiltration was found to negatively correlate with prognosis in GC patients. After stratifying by infiltration levels of macrophages, we screened The Cancer Genome Atlas and Human Autophagy Database to identify the differentially expressed ATGs (DE-ATGs). Of 1,433 differentially expressed genes between the two groups, seven genes qualified as DE-ATGs. Of these, CXCR4, DLC1, and MAP1LC3C, exhibited strong prognostic prediction ability in Kaplan-Meier survival-log-rank test. High expression of these genes correlated with increased occurrence of advanced grade 3 tumors and poor prognoses. Furthermore, GSEA indicated that they were significantly associated with oncogenic and immune-related pathways. The comprehensive evaluation of TIME via GEPIA, ESTIMATE, CIBERSORT, and TIMER suggested that the three DE-ATGs were closely associated with immune condition, both in terms of immune cells and immune scores. Thus, the outcome of this study may aid in better understanding of the ATGs and their interaction with the immune microenvironment, which would allow the development of novel inhibitors, personalized treatment, and immunotherapy in gastric cancer.

Prognostic Value of CEA, CA19-9, CA125, CA724, and CA242 in Serum and Ascites in Pseudomyxoma Peritonei.

PURPOSE: To investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA19-9, CA724, and CA242 in serum and ascites of pseudomyxoma peritonei (PMP) patients and evaluate the predictive value of these elevated biomarkers in pathological grade, completeness of cytoreduction (CC), and survival. METHODS: From May 2009 to October 2019, a total of 512 patients diagnosed with PMP through pathology in Aerospace Center Hospital were enrolled. The serum and ascites tumor biomarkers were obtained. The diagnostic values between serum and ascites biomarkers in pathology and CC were compared by the receiver operating characteristic (ROC) curves. The correlation between pathology, cytoreduction, and biomarkers was calculated by univariate and multivariate logistic regression. The associations between different numbers of elevated biomarkers and survival status were examined using univariate and multivariate backward Cox proportional hazard regression models. RESULTS: The results showed that the areas under the ROC curves (AUROC) in the diagnosis of CC were 0.798 (95% CI: 0.760-0.836) and 0.632 (95% CI: 0.588-0.676) in serum and ascites biomarkers, respectively. The elevated serum and ascites biomarkers were independent risk factors for both pathology and CC. The 1-year, 3-year, and 5-year survival rates were 89.07%, 73.22%, and 66.94%, respectively. Longer survival was observed in patients who had less than two elevated serum biomarkers compared with those with 2-3 and 4-5 elevated serum biomarkers (p < 0.001). CONCLUSION: CEA, CA125, CA19-9, CA724, and CA242 in serum and ascites can be used to judge the severity and predict the resectability. Furthermore, different numbers of elevated biomarkers can help determine the prognosis of PMP.

Ultrasound for Preoperatively Predicting Pathology Grade, Complete Cytoreduction Possibility, and Survival Outcomes of Pseudomyxoma Peritonei.

OBJECTIVES: This study aimed to investigate the value of using ultrasound (US) preoperatively for predicting pathological classification, complete cytoreduction possibility, and survival rate of patients with pseudomyxoma peritonei (PMP). METHODS: We retrospectively studied PMP patients who were scheduled for cytoreductive surgery between May 2009 and October 2019. US examination was performed before surgery. Factors related to high-grade pathology and poor completeness of cytoreduction (CC) score were identified. Associations between ultrasound characteristics and the survival status were also examined to identify independent predictive factors. RESULTS: PMP patients with clear ascites, abdominal lymph nodes, omental cake, abdominal mass, portal infiltration, and mesenteric involvement visible on US were considered to have high-grade pathology. Various US features were shown to be independent prognostic markers for inadequate cytoreduction in PMP patients. Portal infiltration and mesenteric involvement were significant prognostic factors for lower survival rates (hazard ratio = 3.092, 3.932, respectively). A visual nomogram including these factors was constructed to predict survival rates. The consistency index was 0.777, which reflected relatively high accuracy. CONCLUSIONS: Preoperative US has the potential to predict pathological grade and resectability of PMP. Portal infiltration and mesenteric involvement were independent predictors of poor clinical outcomes in PMP patients. Furthermore, a simple-to-use nomogram derived from our study data may be a helpful visual tool in clinical practice to predict 1-, 2-, and 3-year survival rates for PMP patients.

Pseudomyxoma peritonei originating from intestinal duplication: A case report and review of the literature.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare mucinous neoplasm with a relatively low incidence of 1 to 2 per million individuals. It is typically characterized by a type of gelatinous ascites named "jelly belly". Most cases of PMP occur in association with ruptured primary mucinous tumors of the appendix (90%). Periodically, PMP can originate from mucinous carcinomas at other sites, including the colorectum, gallbladder, and pancreas. However, unusual origin can occur, as noted in this case report. CASE SUMMARY: A 52-year-old woman had an unusual derivation of PMP from intestinal duplication. The patient complained of abdominal distension and increasing abdominal girth. Abdominal contrast-enhanced computed tomography showed a mass in the greater omentum located on the left side of the abdomen, likely to be a cystic mass of peritoneal origin. A PMP diagnosis was presumed based on the specific signs of the mass with flocculent and stripe-like echoes in ultrasound images. Ultrasound-guided percutaneous aspiration suggested a high likelihood of PMP. Once the PMP diagnosis was recognized, identification of the origin of the primary tumor was indicated. Thus, an exploratory laparoscopy was performed. In the absence of a primary tumor of appendix origin, the diagnosis of a low-grade mucinous neoplasm of intestinal duplication origin was finally confirmed by histopathology. CONCLUSION: PMP is secondary to mucinous carcinomas of the appendix mostly. This case resulted from an unusual derivation from intestinal duplication.

64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model.

Here, we report that it's feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64Cu. 64Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/µmol. It showed good stability in vitro. The specificity of 64Cu-PSMA-617 was confirmed by cell uptake experiments in PSMA (+) LNCaP cell and PSMA (-) PC-3 and gastric adenocarcinoma BGC-823 cells. Micro-PET imaging in BGC-823 and PC-3 xenografts nude mice was evaluated (n = 4). And the tumors were visualized and better tumor-to-background achieved till 24 h. Co-administration of N- [[[(1S)-1-Carboxy-3-methylbutyl]amino]-carbonyl]-L-glutamic acid (ZJ-43) can substantially block the uptake in those tumors. Dissected tumor tissues were analyzed by auto-radiography and immunohistochemistry, and these results confirmed the PSMA expression in neo-vasculature which explained the target molecular imaging of 64Cu-PSMA-617. All those results suggested 64Cu-PSMA-617 may serve as a novel radio-tracer for tumor imaging more than prostate cancer.

68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68Ga/177Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68Ga/177Lu for 68Ga/177Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68Ga-DOTA-TATE or 177Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68Ga-DOTA-TATE and 177Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.

PURPOSE: We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. METHODS: 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. RESULTS: The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. CONCLUSION: 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.