Refractory hepatosplenic T-cell lymphoma was successfully treated with salvage allogeneic hematopoietic stem cell transplantation combined with enhanced myeloablative preconditioning.

This study aims to evaluate the clinical benefit of salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) in combination with enhanced myeloablative preconditioning in the treatment of refractory liver and spleen T-cell lymphomas. A retrospective analysis was performed on three patients (with refractory liver and spleen T-cell lymphomas) who have been treated with salvage allo-HSCT combined with enhanced myeloablative preconditioning. One of three patients had a liver biopsy; the other two underwent bone marrow analysis using morphology, immunology, cytogenetics, and molecular biology. All three patients were resistant to chemotherapy and with a high tumor load, so a new total body irradiation/splenic region irradiation/GEM/CLAG/ATG preconditioning regimen was conducted and followed with salvage HSCT. Two patients received haploidentical-donor hematopoietic stem cell transplants, and one received an unrelated full-donor hematopoietic stem cell transplant. The three patients survived disease-free until May 2021. Clinically, hepatosplenic T-cell lymphoma (HSTCL) is rare, with a poor prognosis and chemotherapy response. Based on the present study's encouraging clinical results, salvage allo-HSCT in conjunction with an enhanced myeloablative preconditioning regiment may be an effective and safe treatment for HSTCL.

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.

Nomogram to Predict Incomplete Cytoreduction for Pseudomyxoma Peritonei.

BACKGROUNDS: The completeness of cytoreduction is one of the most important prognostic factors for patients with pseudomyxoma peritonei (PMP). To date, no nomograms have been established to predict incomplete cytoreduction (IC) for patients with PMP. The current study therefore proposed a nomogram to predict individual IC risk for PMP patients. METHODS: Between 1 June 2013, and 22 November 2019, 144 consecutive PMP patients who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the first time in our center were included in a retrospective study. Possible predictors of cytoreducibility were analyzed using logistic regression modeling to predict IC for PMP patients. A nomogram was developed based on the multivariate analysis and further investigated for internal validation. RESULTS: After CRS, the 144 participants were divided into complete CRS (CCRS) (n = 46) and IC (n = 98) subgroups. Four independent predictors (sex, disease duration, anemia, and carbohydrate antigen 19-9 (CA 199)) were included in the prediction model. Then, a nomogram predicting IC was established based on the aforementioned variables, which demonstrated good predictive accuracy (C-index, 0.837; 95 % confidence interval [CI], 0.764-0.894). The predicted probability was close to the actual observed outcome according to the calibration plot. CONCLUSIONS: The current work led to the development of a nomogram capable of predicting IC for PMP patients who demonstrated good performance. Risk stratification by the established nomogram had ability to optimize individual IC prediction and help physicians to establish meticulous preoperative plans.

Pollution characteristics and vertical cutoff wall optimization at an industrial contaminated site in China.

Vertical cutoff walls have been widely used in the remediation of contaminated sites. However, determining the best method for evaluating the long-term barrier performance of vertical cutoff walls presents a major difficulty in actual projects. Here, a case study is presented for a typical electroplating, medical, and chemical industrial park in China. Based on the analysis of groundwater pollution characteristics at the site, pollutants included metals (Ni, Al), ammonia nitrogen, and 1,2-dichloroethane. Finite element model simulations of Ni transport at the site showed that a vertical cutoff wall with a thickness of 60 cm and a hydraulic conductivity of 1.0 × 10-8 cm/s could significantly attenuate pollutant transport in the horizontal direction. Compared with other methods such as reducing the hydraulic conductivity or increasing the adsorption retardation factor of the vertical cutoff wall, increasing the thickness was more effective in controlling pollutant transport at the study site. Doubling the thickness would cause the Ni leakage concentration to decrease by more than 98% and the breakthrough time to increase by more than 47 years. It is recommended that the thickness of cutoff walls be maximized to optimize their effects on pollutant transport.

Preoperative plasma D-Dimer level is correlated with peritoneal cancer index of patients with pseudomyxoma peritonei.

PURPOSE: Accurate assessment of preoperative tumor burden contribute to formulate a scientific surgical plan for patients with pseudomyxoma peritonei (PMP). Present study aimed to assess whether the preoperative plasma D-Dimer level could reflect tumor burden for PMP patients. METHODS: A total of 253 PMP patients were included between June 1, 2013 and March 1, 2022. According to the peritoneal cancer index (PCI), all participants were divided into extensive (PCI ≥ 28) and none-extensive (PCI < 28) subgroups. The D-Dimer and tumor markers were compared between the two subgroups. The correlation between the abovementioned biomarkers and PCI will be calculated, and further compared with each other. Two-sided P value less than 0.05 is considered statistically significant. RESULTS: The level of D-Dimer (ng/ml) between extensive and none-extensive subgroup were 600 (328, 1268) vs. 339 (128, 598), Z = -5.425, p < 0.001. The Spearman correlation between D-Dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), CA 19 - 9 and PCI were 0.487, 0.509, 0.469, and 0.499, respectively (all p < 0.001). The correlation coefficients were compared with each other according to Meng, Rosenthal and Rubin's method, however, there was no significant difference. CONCLUSION: Preoperative plasma D-Dimer could moderately reflect tumor burden for PMP. In the future, a multivariate prediction model will be developed to help surgeons to formulate a more precise surgical plan for the PMP patients.

Cell HE staining smears and paired cell paraffin sections in detection of epithelial growth factor receptor gene of pleural fluid specimens. / 细胞HEæŸ“è‰²æ¶‚ç‰‡ä¸Žç»†èƒžèœ¡å—æ£€æµ‹æ™šæœŸéžå°ç»†èƒžè‚ºç™Œèƒ¸è ”ç§¯æ¶²æ ‡æœ¬ä¸­è¡¨çš®ç”Ÿé•¿å› å­å—ä½“åŸºå› çªå˜.

OBJECTIVES: The advanced non-small cell lung cancer (NSCLC) patients with pleural effusion have no opportunity for surgery treatment. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line drugs for these patients with EGFR-sensitive mutation. However, the disease progression and drug update during or after treatment of EGFR-TKIs bring more challenges and puzzles to clinical diagnosis and treatment, which inevitably requires archived pleural cell samples for EGFR re-examination or comparative study. Understanding the DNA quality of archived pleural fluid samples and effectively using archival data of pleural fluid cells are of great significance for tracing the origin of cases and basic medical research. This study aims to evaluate the consistency of EGFR mutant gene expression between the 2 methods, and to explore a reliable way for preserving cytological data and making full use of cytological archival data via cell HE staining smear and cell paraffin section. METHODS: A total of 57 pleural fluid cytology cases in the Department of Pathology of China Aerospace Center Hospital from October 2014 to April 2021 were selected. Tumor cells were detected by cell HE staining smears and immunohistochemical staining for TTF-1 and Napsin A in the paired cell paraffin sections. There were more than 200 tumor cells in cell HE staining smear and the proportion of tumor cells were ≥70% in matched cell paraffin sections. Patients with 2 cell smears (one for cell data retention and the other for DNA extraction) were selected as the research subjects, and 57 pleural fluid samples were enrolled. EGFR gene mutation was detected by amplification refractory mutation system-polymerase chain reaction in 57 paired cell HE staining smears and cell paraffin sections. DNA concentration was 2 ng/µL. Cell HE smear was amplified side-by-side with DNA samples from paired cell paraffin sections. Result determination was according to the requirements of the reagent instructions. The external control cycle threshold (Ct) value of the No. 8 well of the samples to be tested was between 13 and 21, which was considered as successful and reliable samples. When the Ct value of EGFR gene mutation was <26, it was considered as positive; when the Ct value was between 26 and 29, it was critical positive; when the Ct value was equal or more than 29, it was negative. ΔCt value was the difference between mutant Ct value and externally controlled Ct value. The smaller the ΔCt value was, the better the quality of DNA of the detected sample was. RESULTS: Among the 57 pleural effusion samples, 42 patients were hospitalized with pleural effusion as the first symptom, accounting for 73.7% (42/57). EGFR mutation was detected in 37 samples [64.9% (37/57)]. The mutation rate for 19del was 37.8% (14/37) while for L858R was 48.6% (18/37). Females were 56.7% (21/37) of mutation cases. The mutation consistency rate of cell HE staining smear and matched cell paraffin sections was 100%. The ΔCt values of cell HE staining smears were less than those of matched cell paraffin sections. The mutation Ct values of 37 cytological samples were statistically analyzed according to the preservation periods of the years of 2014-2015, 2016-2017, 2018-2019, and 2020-2021. There were significant differences in cell paraffin section in the years of 2014-2015 and 2016-2017 compared with the years of 2018-2019 and 2020-2021, while no significant differences were found in cell HE staining smear. Statistical analysis of externally controlled Ct values of 57 cytological samples showed that there were significant differences between cell HE staining smears and cell paraffin section in the years of 2014-2015 and 2016-2017, compared with the years of 2018-2019 and 2020-2021. The mutational Ct values of 37 paired cell blocks and smears were all <26, and the externally controlled Ct values of 57 paired cell paraffin sections and HE staining smears were all between 13 and 21. CONCLUSIONS: The DNA quality of cell HE smears and matched cell paraffin section met the qualified requirements. Two methods possess show an excellent consistency in detecting EGFR mutation in NSCLC pleural fluid samples. The DNA quality of cell HE staining smear is better than that of cell paraffin sections, so cell HE staining smear can be used as important supplement of the gene test source. It should be noted that the limitation of cell HE staining smears is non-reproducibility, so multiple smears of pleural fluid are recommended to be prepared for multiple tests.

The mutational landscape and prognostic indicators of pseudomyxoma peritonei originating from the ovary.

Pseudomyxoma peritonei (PMP) is a rare disorder with unique pathological and genetic changes. Although several studies have reported the clinical features and mutational changes of PMP that originates from the appendix, few studies on PMP originating from the ovary have been reported due to its extreme rarity. In order to characterize the somatic mutational landscape and to investigate the prognosis predicting factors of ovary-originating PMP, we examined 830 cases of PMP and identified 16 patients with PMP that originated from the ovary. Whole-exome sequencing (WES) was performed on 12 cases using formalin-fixed, paraffin-embedded (FFPE) tissue samples. We found that 25% (3/12) of the patients carried mutations in cancer driver genes, including TP53, ATM and SETD2, and 16.7% (2/12) of the patients carried mutations in cancer driver genes, including ATRX, EP300, FGFR2, KRAS, NOCR1 and RB1. The MUC16 (58.33%), BSN (41.67%), PCNT (41.67%), PPP2R5A (41.67%), PRSS36 (41.67%), PTPRK (41.67%) and SBF1 (41.67%) genes presented the highest mutational frequencies. The PI3K-Akt signaling pathway, human papillomavirus infection pathway, cell skeleton, cell adhesion, and extracellular matrix and membrane proteins were the major pathways or functions that were affected. Patients were followed up to 174 months (median: 48.26 months). The 5-year OS rate for all patients was 71.2% and the median OS was not reached. PTPRK mutations, presurgical CA199 level, completeness of cytoreduction (CCR) and peritoneal cancer index (PCI) were identified as potential predictive factors for patient survival. In conclusion, the mutational landscape for ovary-originating PMP was revealed and exhibited unique features distinct from appendix-originating PMP. PTPRK, CA199, CCR and PCI may predict patient survival.

Nomogram to predict overall survival of patients with pseudomyxoma peritonei of appendiceal origin: A retrospective cohort study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease, with the rate of overall survival (OS) influenced by many factors. The present study aimed to define independent predictors and establish a nomogram for individual risk prediction in PMP patients. METHODS: One hundred forty-seven PMP patients were consecutively included between June 1, 2013, and November 22, 2019. The log-rank test was used to compare the OS rate between groups; subsequently, variables with p < .10 were subjected to multivariate Cox modeling for defining independent prediction indicators. Finally, a nomogram was established based on independent prognosticators and assessed for internal validation. RESULTS: Multivariate Cox analysis showed that D-dimer level, carbohydrate antigen (CA) 125 level, CA 19-9 level, degree of radical surgery, and histological grade were all independently associated with OS in PMP patients. A nomogram was plotted and underwent internal validation. The discrimination ability of the nomogram revealed a good predictive ability as indicated by the C-index value (0.825), and calibration plots confirmed good consistency between the predicted and observed survival probabilities. CONCLUSIONS: Five independent prognostic factors for predicting the survival of PMP patients were identified, and the nomogram based on these independent indicators showed a reasonable discrimination ability for individual risk prediction.

Management and prognostic prediction of appendiceal mucinous adenocarcinoma with peritoneal metastasis: a single center study in China.

BACKGROUND: To investigate the clinical and pathological characteristics of appendiceal mucinous adenocarcinoma with peritoneal metastasis and analyze the prognostic factors. METHODS: A retrospective analyses of clinicopathological features of 50 patients with appendiceal mucinous adenocarcinoma with peritoneal metastasis from January, 2013 to December, 2017 in Aerospace Central Hospital, Beijing, China. Survival data calculation and comparison were respectively performed with the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression method was used for multivariate survival analyses. RESULTS: Cytoreduction for appendiceal mucinous adenocarcinoma was conducted on 50 patients (24 males and 26 females), with a median age of 52.5 years at the time of surgery (range 31-71 years). The median overall survival (OS) time was 24 months, with 2-,3- and 5-year survival rates of 53, 24 and 8%, respectively. At the last follow-up in December 2018, 13 patients were still alive. Multivariate analysis revealed that patients who had low Ki-67 expression (less than 50%) and CCR (completeness of cytoreduction) 0/1/2 score had significantly better OS rate than their respective counterparts. CONCLUSIONS: Ki-67 expression statue and CCR score could be employed as the prognosis prediction in patients with appendiceal mucinous adenocarcinoma.

Value of preoperative ultrasound in evaluating the peritoneal cancer index of pseudomyxoma peritonei.

PURPOSE: This study aimed to explore the value of preoperative ultrasonography (US) in evaluating the peritoneal cancer index (PCI) of pseudomyxoma peritonei (PMP). METHODS: An ultrasound examination was performed on 59 patients with PMP before surgery, and the ultrasound PCI was evaluated. The accuracy of ultrasound PCI score was evaluated with the surgical PCI score as the gold standard. RESULTS: The preoperative ultrasound PCI was compared with the surgical PCI. The Spearman correlation coefficient of the total PCI score was 0.608 (P < 0.05). The difference in the Spearman correlation coefficient between the preoperative ultrasound PCI and the surgical PCI in areas 0-7 was statistically significant. (1) Among them, the total score and the correlation between 0-3 and 6 were higher. (2) Compared with the surgical PCI, overestimation (> 20%) was concentrated mainly in areas 2 and 4-8 for 2 points, and underestimation (< 20%) was concentrated mainly in areas 1, 3, 4, and 8 for 3 points. (3) The sensitivity and specificity of preoperative ultrasound for predicting the presence or absence of lesions were 85.7% and 50.0%, respectively. The sensitivity of LS 1, LS 2, and LS 3 was 31.7%, 48.2%, and 71.0%, respectively, and the specificity was 44.8%, 55.3%, and 58.8%, respectively. CONCLUSION: The ultrasound examination can be used to score the preoperative PCI, judge the severity, and predict the prognosis in patients with PMP.

[Prognostic value of clinical and pathological characteristics in 48 women with pseudomyxoma peritonei].

OBJECTIVE: To investigate the clinic-pathological characteristics and prognosis of 48 female cases with peritoneal pseudomyxoma(PMP). METHODS: The clinicopathologic features and follow-up data of 48 female patients with PMP diagnosed in the General Hospital of People's Liberation Army from Jan.1982 to Dec.2011 were retrospectively reviewed. The relationship between clinic-pathological characteristics and prognosis were analyzed using log-rank test and Cox proportional hazards model. RESULTS: (1) Clinicopathologic features: the mean age of the 48 cases was 58.8 years (range from 24 to 79 years). SYMPTOMS: abdominal distention and abdominal discomfort were the main symptoms. Imaging examinations showed nonspecific abdominal and pelvic lesions in most cases. TREATMENT: all the 48 patients underwent laparotomy and cytoreductive surgery (CRS), in which 15(31%) patients with completeness of the cancer resection (CCR) -1, 24(50%) cases with CCR-2, and CCR-3 in 9(19%) cases. Six (12%) cases were treated by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, 20(42%) patients were treated with different options postoperative adjuvant chemotherapy. Pathological types:the cases were histologically classified into 3 subcategories:disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D), which were 22(46%) cases, 9 (19%)cases and 17 (35%)cases, respectively. Appendiceal tumors: 44(92%) cases underwent appendectomy, in which 38 cases presented appendiceal tumors (including 20 cases of low-grade appendiceal mucinous adenoma and 18 cases of appendiceal mucinous adenocarcinoma), 2 cases were diagnosed as appendicitis, 4 cases with unknown pathologic diagnosis. And the other 4(8%) cases, who didn't undergo appendectomy at the first operation, presented peritoneal tumor recurrence and appendiceal mucinous tumors 1, 11, 32 and 85 months after surgery, respectively. Parenchymal organs involved: ovarian involving was happened in 34 (71%) patients including 15 cases with the right ovary involving, 13 cases in both sides, and 6 cases involving the left side. The other parenchymal organs in 10(21%) cases. (2) Prognostic factors: 11 patients died, 31 survived and 6 cases were lost to follow-up. The mean survival time was 99 months(ranged from 1 to 312 months). The 3-year, 5-year and 10-year survival rates were 73.3%, 68.0% and 46.6%, respectively. Univariate statistical analysis showed that age, pathological type and parenchymal involvement were significantly relationship with the survival time (all P < 0.05). But the operation times, appendiceal tumor type, ovarian involvement, CCR, intraperitoneal HIPEC and post-operative adjuvant chemotherapy were not significantly correlate with survival time (all P > 0.05). Multivariate analysis showed that age and pathologic type were independent prognostic factors(P < 0.05). CONCLUSIONS: No specific clinical features presented in PMP. CRS with HIPEC should the recommended treatment. Both ovaries exploration and appendectomy should be carried out routinely in CRS. The 10-year overall survival of PMP is low. Age, pathological type and parenchymal organs involvement other than ovarian are correlated with the prognosis. And the pathological type and age are independent prognostic factors of PMP.

Differential diagnosis of appendiceal serrated lesions and polyps and low-grade appendiceal mucinous neoplasm: analysis of 88 cases.

PURPOSE: To identify clinicopathological features for the differential diagnosis of appendiceal serrated lesions and polyps (SPs) and low-grade appendiceal mucinous neoplasm (LAMN) for the purpose of avoiding over-diagnosis. METHODS: Clinical data and pathological features of 66 patients with SPs diagnosed at the Aerospace Center Hospital between January 2013 and January 2021 were collected and compared to 22 cases of LAMN. RESULTS: SPs, compared with LAMN, are likely to be associated with acute inflammation (SPs 53.0% vs. LAMN 18.2%), and may be located in the appendix partly, although with smaller diameter (average 9.6 vs. 27.2 mm); epithelial structures of serrated (100% vs. 22.7%) and filiform villous (47.0% vs. 18.2%) were often found in SPs. SPs occasionally show attenuated or flattened morphology (16.7% vs. 100%) and undulating or scalloped (7.6% vs. 40.9%) structures, and can also be accompanied by diverticulum (18.2% vs. 18.2%) and acellular mucin in the appendiceal wall (16.7% vs. 54.5%), which causes confusion with LAMN. The key point of the differential diagnosis is to observe whether the muscularis mucosa exists (loss, 0% vs. 100%) and fibrosis of the appendiceal wall (0% vs. 100%). SMA immunohistochemistry can assist in the diagnosis. Calcification is also indicative of LAMN. CONCLUSIONS: The epithelial structure of SPs can appear flattened and focally scalloped, and can be accompanied by mucin in the appendiceal wall, which may appear as complex lesions, easily over-diagnosed as LAMN. Key differential diagnostic features are identifying the structure of lamina propria, determining whether the muscularis mucosa exists, and whether the appendiceal wall is fibrotic.

Prognosis for Young Females with Pseudomyxoma Peritonei of Appendiceal Origin and Unilateral or Bilateral Ovaries Preserved During Cytoreductive Surgery.

Objective: To determine prognosis for young female patients with peritoneal pseudomyxoma (PMP) of appendiceal origin and unilateral or bilateral ovaries preserved during cytoreductive surgery (CRS). Methods: Clinical data of female patients treated with CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) at the Aerospace Center Hospital, Beijing between January, 2009 and December, 2019 were retrospectively reviewed. Patients had no changes in the bilateral ovaries on gross pathological observations or biopsy during CRS, and normal ovarian function. The demographic and clinical characteristics and prognosis of women with ovaries preserved (ovarian preservation group) or resected (ovarian resection group) during CRS were compared. Independent prognostic factors for survival were identified using univariate and multivariate analysis. Results: 40 patients were included in the final analysis. 19 patients chose ovarian preservation while 21 patients underwent ovarian resection. Completeness of cytoreduction (CCR) scores were CCR-0/1. There were significant differences in age (<40 vs. ≥40), symptoms, intraoperative HIPEC (Y vs. N), and histopathologic subtype of PMP (low-grade vs. high-grade) (p < 0.001) between patients in the ovarian preservation and ovarian resection groups. In the ovarian preservation group, median overall survival (OS) was 59 months (range, 53-65 months), and the 5-year survival rate was 37.9%. Median disease-free survival (DFS) was 13 months (range, 9-17 months), and the 5-year recurrence rate was 87.4%. In the ovarian resection group, the 5-year survival rate was 87.7%, and the 5-year recurrence rate was 18.3%. Median OS and median DFS were not reached. In patients with low-grade PMP, median DFS was significantly longer in patients with ovarian resection compared to ovarian preservation (p < 0.001). Univariate analysis showed histopathologic subtype of PMP (low-grade vs. high-grade, p < 0.001) was significantly associated with OS and DFS. On multivariate analysis, high-grade histopathologic subtype of PMP was an independent predictor of poor prognosis (OS and DFS). Conclusion: Histopathologic subtype of PMP represents an independent predictor of prognosis in female patients with PMP of appendiceal origin and unilateral or bilateral ovaries preserved during CRS. These findings imply that ovarian preservation is a more suitable option for young females with low-grade PMP compared to high-grade PMP. Further prospective studies should be done investigating the role of resection of uninvolved ovaries in PMP.

Kaempferol acts on bile acid signaling and gut microbiota to attenuate the tumor burden in ApcMin/+ mice.

Emerging evidence points to a strong association between the bile acid (BA)-gut microbiota (GM) axis, and the risk of colorectal cancer (CRC). Kaempferol, a common polyphenol in the daily diet, shows various pharmacological activities. However, it remains unclear about the effect of kaempferol on the CRC development and the BA-GM homeostasis. Here, we found kaempferol effectively reduced tumor burden, restored the damaged intestinal barrier and downregulated antigen Ki67 and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expressions in ApcMin/+ mice. For BA metabolism, kaempferol reversed the decreasing trend in chenodesoxycholic acid (CDCA) and 12α-hydroxylated BAs by increasing the sterol 27-hydroxylase (CYP27A1) and sterol 12α-hydroxylase (CYP8B1) expressions, and upregulated FXR expression. Importantly, molecular docking analysis revealed a direct interaction between kaempferol and farnesoid X receptor (FXR), the mater regulator of BA signaling. For GM analysis, we found higher abundances of species with anticancer properties and lower abundances of species associated with inflammation, obesity, and metabolic disorders in kaempferol-treated groups. Moreover, the gut of kaempferol-treated mice was predominantly colonized by short-chain fatty acid (SCFA) and lactic acid producing bacteria. Based on the PICRUSt-predicted pathways of our GM dataset, we demonstrated that kaempferol downregulated secondary BA synthesis pathways, increased G protein-coupled receptor activity and decreased NOD-like receptor activity, affecting cell differentiation, proliferation, survival, and apoptosis. Collectively, these results reveal that kaempferol effectively attenuates the tumor burden in ApcMin/+ mice by modulating the BA signaling and GM homeostasis.

Kaempferol suppression of acute colitis is regulated by the efflux transporters BCRP and MRP2.

The bioavailability of most flavonoids is low but effective in vivo; however, the mechanism of the efficacy of flavonoids has not been elucidated. Kaempferol is typical flavonoids., preliminary research indicates that kaempferol has a significant anti-colon cancer and anti-inflammatory effect. We reported previously that the triple recycling pathways significantly increase the local bioavailability of flavonoids and prolong the residence time of flavonoids in the liver and intestines, which is likely the mode by which flavonoids exert local efficacy. Notably, Efflux transporters (ETs), such as Breast cancer resistance protein (BCRP) and Multi drug resistance-associated protein 2 (MRP2), are the main regulatory molecules of the enterohepatic triple recycling pathways. Thus, our current study explored the regulation of kaempferol by BCRP and MRP2 and the role of BCRP and MRP2 in the suppression of Dextran sulfate sodium (DSS)-induced colitis by kaempferol. Herein, four mouse model was constructed, and the Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established to simultaneously quantify kaempferol and its 3 metabolites and investigate the oral pharmacokinetic characteristics and tissue distribution of these compounds. In Bcrp-/--Mrp2-/- mice, the movement of kaempferol via the enterohepatic triple recycling was blocked, and the preventative and therapeutic effects of this compound on acute colitis were inhibited. BCRP and MRP2 defects hindered the efflux of kaempferol and its phase II metabolites and increased the plasma levels. Our study revealed that the disposal of kaempferol was regulated by the ETs BCRP and MRP2, and most importantly, the results will help elucidate the mechanism by which kaempferol suppresses the transformation of colitis into colon cancer.

Case Report: Stage IIIc primary malignant mixed Müllerian tumor of the fallopian tube: A case of 5-year disease-free survival after cytoreductive surgery combined with peritoneal resection and adjuvant chemotherapy with paclitaxel plus carboplatin.

Malignant mixed Müllerian tumor (MMMT) of the fallopian tube is rare and has a poor prognosis. For the patient with fallopian tube MMMT, complete resection of the tumor invading the viscera and the peritoneum is a prerequisite for long-term survival. We report a case of stage IIIc MMMT of the fallopian tube treated by cytoreductive surgery (CRS), peritoneal resection, and adjuvant chemotherapy (paclitaxel plus carboplatin), with 5-year tumor-free survival. Postoperative chemotherapy combining platinum and paclitaxel is the most potent adjuvant therapy.

Clinicopathological Features of Low-Grade Appendiceal Mucinous Neoplasms Confined to the Appendix.

OBJECTIVE: To investigate the clinicopathological features and follow-up of low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix. METHODS: The clinicopathological features, pathological primary tumor (pT) staging and follow-up of 22 patients with LAMNs confined to the appendix were analyzed retrospectively. RESULTS: Of 22 patients with LAMNs, 14 were pTis (eight pTism and six pTisf), six were pT3, and two were pT4a. The appendiceal diameter was significantly larger for pTisf than for pTism. The interval between first symptoms and surgery was longer for pTisf than for pTism, but not significantly different. No significant differences were found between the pT stages and appendiceal diameter or in the interval between the first symptoms and surgery. Pathomorphologically, the epithelial structures were mainly flat (100%), undulating or scalloped (82%); a few showed filiform villous hyperplasia (46%), and seven (32%) had serrated lesions in the background. Diverticula may be associated with LAMNs, and the location of acellular mucin caused by diverticula affected the pT stage of the LAMNs. The immunohistochemistry information showed the same pattern with cytokeratin 7 (CK7) negative, cytokeratin 20 (CK20) positive and caudal type homeobox 2 (CDX-2) positive. No lymph node metastasis was found. The lack of treatment guidelines for LAMNs confined to the appendix and different acceptances of patients of preventive intervention led to varied clinical treatments. However, we found no short-term benefits of prophylactic extended resection or hyperthermic intraperitoneal chemotherapy. CONCLUSION: LAMNs confined to the appendix are rare and must be differentiated from serrated lesions and diverticula. LAMNs with different pT stages have inert biological behavior. Determining the long-term effects of preventive treatment on survival and recurrence requires more data and a longer follow-up.

Clinicopathological Characteristics and Prognostic Prediction in Pseudomyxoma Peritonei Originating From Mucinous Ovarian Cancer.

OBJECTIVE: To describe the clinicopathological characteristics of mucinous ovarian cancer (MOC)-derived pseudomyxoma peritonei (PMP) and identify prognostic factors for survival. METHODS: Medical records from patients with MOC-derived PMP who attended the Aerospace Center Hospital, Beijing, China between January 2009, and December 2019 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model. RESULTS: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP originating from MOC were performed on 22 patients, who had a median age of 52 years at the time of surgery. At the last follow-up in June 2020, 9 (41%) patients were still alive. Median OS was 12 months (range, 1 to 102 months), and the 2-, 3-, and 5-year survival rates were 23, 9, and 5%, respectively. CONCLUSION: Histopathologic subtype and PCI may be applied as predictors of prognosis in patients with MOC-derived PMP. Patients with high-grade disease could benefit from completeness of cytoreduction (CCR) 0/1.

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.

Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease.

OBJECTIVE: This study was conducted in order to investigate the significance of the entire appendiceal evaluation in the pathological diagnosis of appendiceal serrated lesions, low-grade appendiceal mucinous neoplasm (LAMN), and appendiceal diverticulosis disease (ADD). METHODS: A total of 702 appendectomy specimens diagnosed from 2017 to 2020 were reviewed retrospectively. The specimens were divided into two groups according to the different sampling procedures. In group 1, the vast majority of 337 specimens were partially submitted by routine sampling within 18 months from October 2017 to March 2019. In group 2, 365 of specimens were entirely submitted and examined within 18 months from April 2019 to October 2020. The incidence and pathological features of serrated lesions, LAMN, and ADD in the two groups were compared and analyzed. The clinicopathological characteristics between different entities were also studied. RESULTS: Forty appendiceal serrated lesions, 8 LAMNs, and 21 diverticula were accidentally detected in 702 appendectomy specimens. As compared with group 1, the incidence of appendiceal serrated lesions in group 2 was significantly increased (9.3% vs. 1.8%, P < 0.01), especially for the serrated lesions without dysplasia (7.4% vs. 1.2%, P < 0.01). The entire sampling revealed that loss of lamina propria and replacement with dysplastic mucinous epithelium were statistically significantly associated with LAMN rather than serrated lesions and ADD (P < 0.01 and P < 0.01, respectively). Mural mucin deposition and fibrosis were useful features to distinguish LAMN from simple serrated lesions (P < 0.01 and P < 0.05, respectively), but mucin deposition was useless for the distinction between LAMN and ADD (P > 0.05) or serrated lesions combined with ADD. CONCLUSION: Our study highlights the importance and necessity of careful gross assessment and histologic examination of the entire appendectomy specimen, since the association with unexpected appendiceal lesions is significant and cannot be ignored. The entirely submitted appendix is more sensitive for the detection of appendiceal serrated lesions. In addition, thorough examination and evaluation are essential to distinguish the key pathological features between appendiceal serrated lesions, LAMN, and ADD.