Pseudomyxoma peritonei (PMP), which involves both the ovaries and appendix, is usually attributed to an appendiceal primary tumor with secondary involvement. However, rare cases may present with synchronous, independent mucinous primaries. Distinguishing between these entities is important because staging, treatment, prognosis, and follow-up may differ according to the primary site. An 83-year-old woman presented with abdominal distension and ascites incidentally discovered during an evaluation for traumatic intracranial hemorrhage. Computed tomography revealed large-volume ascites, a large multilocular cystic mass arising from the left ovary, and a dilated appendix. Diagnostic laparoscopy confirmed the presence of gelatinous ascites, which was consistent with PMP. Histopathological examination revealed ovarian mucinous carcinoma and appendiceal mucinous neoplasms. Immunohistochemistry showed discordant profiles for ovarian (cytokeratin [CK]-7+/paired box 8 [PAX8]+/CK-20-/caudal-type homeobox 2 [CDX-2]-) and appendiceal (CK-20+/CDX-2+/CK-7-/PAX8-) lesions. Peritoneal tumor cells expressed CK-7 but lacked PAX8, CK-20, and CDX-2 expression, supporting an ovarian-type immunophenotype of the peritoneal disease. The patient underwent diagnostic laparoscopy with left salpingo-oophorectomy and removal of the gelatinous ascites. Two cycles of paclitaxel and carboplatin were administered before interval cytoreductive surgery because of advanced disease, arrhythmia, and poor tolerance to prolonged surgery. Complete cytoreduction was achieved through total hysterectomy, right salpingo-oophorectomy, appendectomy, total parietal peritonectomy, omentectomy, cholecystectomy, splenectomy, and the removal of visible disease, followed by carboplatin monotherapy. Complete cytoreduction was achieved, and the patient completed adjuvant carboplatin therapy without grade 3 or higher adverse effects. The patient remained disease-free for 6 months after the completion of chemotherapy.
OBJECTIVES:To analyse patient complaints from an early-stage hospital in South Korea using the Healthcare Complaints Analysis Tool, identify harm patterns across care stages and provide insights for resource allocation and risk management. DESIGN:Retrospective analysis of patient complaints (22 March 2022-28 June 2024). SETTING:A newly established general hospital with approximately 700 beds in the metropolitan area of Gyeonggi-do, South Korea, which was established during the COVID-19 pandemic. PARTICIPANTS:A total of 1113 patient complaints comprising 1952 discrete complaint issues were collected, with submissions originating from patients themselves (64%), family members or friends (21%) and individuals with unclear relationships to patients (15%). PRIMARY AND SECONDARY OUTCOME MEASURES:Primary outcome measures comprised occurrence and severity of patient harm. Secondary outcome measures included distribution of complaints across clinical, management and relationship domains, and identification of healthcare stages with concentrated harm using hotspot analysis and logistic regression. RESULTS:Of the complaints, 78% did not result in harm. Among those that did, 52%, 40% and 7% were of low, moderate and high severity, respectively. Hotspot analysis indicated that harm was concentrated during diagnosis (stage 2), ward care (stage 3) and operation/procedure (stage 4) stages, with stage 4 exhibiting the highest Pearson residual value of 9.56. Logistic regression indicated that clinical domain complaints had the strongest association with patient harm (OR=32.25, 95% CI=20.88 to 51.01, p<0.001), while the operation/procedure stage exhibited the highest stage-specific risk (OR=30.62, 95% CI=9.80 to 93.93, p<0.001). CONCLUSIONS:This study highlighted the critical care stages in which harm was concentrated, emphasising the need for proactive risk management particularly during operations and procedures. The findings provide valuable insights into resource allocation and underscore the importance of patient complaints in improving healthcare quality and safety across healthcare institutions.
Backgrounds: Capsular contracture of breast implants is a major complication of breast surgery. Clinically, covering a breast implant with acellular dermal matrix or autologous tissue is considered to be the most effective technique to prevent capsular contracture. This study was designed to clearly compare the protective effects of acellular dermal matrix and latissimus dorsi muscle flap placement on capsular contracture by increasing the rate of capsular contracture through controlled radiation exposure in a rabbit model. Methods: Twenty New Zealand white rabbits were divided into three groups. After the implant was placed beneath the pectoralis major muscle, the lateral third of the implant was left exposed in the control group (n=6). In the acellular dermal matrix group (n=7), the exposed implant was covered with AlloDerm. In the latissimus dorsi flap group (n=7), the exposed implant was covered with a pedicled latissimus dorsi muscle flap. All groups were irradiated 3 weeks after implant insertion. After 6 months, peri-implant tissues were harvested and analyzed. Results: Acellular dermal matrix showed markedly lower myofibroblast activity than the latissimus dorsi flap. However, transforming growth factor β1 levels and the activity of collagen types I and III produced in fibroblasts were significantly lower in the acellular dermal matrix group than in the latissimus dorsi flap group. Conclusions: Based on the findings of our rabbit experiments, acellular dermal matrix is expected to have a comparative advantage in reducing the risk of capsular contracture compared to the latissimus dorsi flap.
Background: Distal bile duct cancer is an aggressive malignancy. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment are crucial for predicting prognosis in various cancers. In this study, we analyzed TIICs based on CD11b, CD163, and CD8 expression, and evaluated their association with clinicopathologic factors and prognosis in distal bile duct cancer. Methods: A total of 90 patients who underwent curative resection for distal bile duct cancer were enrolled. We analyzed CD11b+ tumor-infiltrating myeloid cells (TIMs), CD163+ tumor-infiltrating macrophages (TAMs), and CD8+ tumor-infiltrating lymphocytes (TILs) using immunohistochemistry and tissue microarrays. The correlation between TIICs and clinicopathologic characteristics was assessed. Results: Low levels of CD11b+ TIMs (p < 0.001) and high levels of CD8+ TILs (p = 0.003) were significantly associated with improved overall survival (OS). A combined low level of CD11b+ TIMs and high level of CD8+ TILs was identified as an independent favorable prognostic factor (hazard ratio, 0.159; confidence interval, 0.061–0.410; p < 0.001). Conclusions: CD11b+ TIMs play a crucial role in the tumor microenvironment and the prognosis of distal bile duct cancer. The combined analysis of CD11b+ TIMs and CD8+ TILs can predict survival in patients with distal bile duct cancer.
INTRODUCTION:Post-mastectomy radiotherapy plays a crucial role in breast cancer treatment but can lead to an inflammatory response causing soft tissue damage, particularly radiation-induced capsular contracture (RICC), impacting breast reconstruction outcomes. Adipose-derived stem cells (ADSCs), known for their regenerative potential via paracrine capacity, exhibit inherent radiotolerance. The influence of tumor necrosis factor-alpha (TNF-α) on ADSCs has been reported to enhance the paracrine effect of ADSCs, promoting wound healing by modulating inflammatory responses. OBJECTIVE:This study investigates the potential of TNF-α-treated human ADSCs (T-hASCs) on silicone implants to alleviate RICC, hypothesizing to enhance suppressive effects on RICC by modulating inflammatory responses in a radiation-exposed environment. METHODS:In vitro, T-hASCs were cultured on various surfaces to assess viability after exposure to radiation up to 20 Gy. In vivo, T-hASC and non-TNF-α-treated hASC (C-hASCs)-coated membranes were implanted in mice before radiation exposure, and an evaluation of the RICC mitigation took place 4 and 8 weeks after implantation. In addition, the growth factors released from T-hASCs were assessed. RESULTS:In vitro, hASCs displayed significant radiotolerance, maintaining consistent viability after exposure to 10 Gy. TNF-α treatment further enhanced radiation tolerance, as evidenced by significantly higher viability than C-hASCs at 20 Gy. In vivo, T-hASC-coated implants effectively suppressed RICC, reducing capsule thickness. T-hASCs exhibited remarkable modulation of the inflammatory response, suppressing M1 macrophage polarization while enhancing M2 polarization. The elevated secretion of vascular endothelial growth factor from T-hASCs is believed to induce macrophage polarization, potentially reducing RICC. CONCLUSION:This study establishes T-hASCs as a promising strategy for ameliorating the adverse effects experienced by breast reconstruction patients after mastectomy and radiation therapy. The observed radiotolerance, anti-fibrotic effects, and immune modulation suggest the possibility of enhancing patient outcomes and quality of life. Further research and clinical trials are warranted for broader clinical uses.
PAP-FcK and PSA-FcK prostate cancer antigenic proteins transiently co-expressed in plant induce their specific humoral immune responses in mice. Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been considered as immunotherapeutic antigens for prostate cancer. The use of a single antigenic agent is unlikely to be effective in eliciting immunotherapeutic responses due to the heterogeneous and multifocal nature of prostate cancer. Thus, multiple antigens have been combined to enhance their anti-cancer effects. In the current study, PSA and PAP were fused to the crystallizable region (Fc region) of immunoglobulin G1 and tagged with KDEL, the endoplasmic reticulum (ER) retention signal motif, to generate PSA-FcK and PAP-FcK, respectively, and were transiently co-expressed in Nicotiana benthamiana. Western blot analysis confirmed the co-expression of PSA-FcK and PAP-FcK (PSA-FcK + PAP-FcK) with a 1:3 ratios in the co-infiltrated plants. PSA-FcK, PAP-FcK, and PSA-FcK + PAP-FcK proteins were successfully purified from N. benthamiana by protein A affinity chromatography. ELISA showed that anti-PAP and anti-PSA antibodies successfully detected PAP-FcK and PSA-FcK, respectively, and both detected PSA-FcK + PAP-FcK. Surface plasmon resonance (SPR) analysis confirmed the binding affinity of the plant-derived Fc fusion proteins to FcγRI/CD64. Furthermore, we also confirmed that mice injected with PSA-FcK + PAP-FcK produced both PSA- and PAP-specific IgGs, demonstrating their immunogenicity. This study suggested that the transient plant expression system can be applied to produce the dual-antigen Fc fusion protein (PSA-FcK + PAP-FcK) for prostate cancer immunotherapy.
Multiple myeloma (MM) is an incurable disease characterized by malignant plasma cells within the bone marrow, and its increasing occurrence has highlighted the need for innovative strategies to address relapse and treatment resistance. Given the substantial expression of programmed death ligand 1 (PD-L1) in the human multiple myeloma cell line RPMI8226, we propose PD-L1 as a promising target for multiple myeloma therapy. Here, we successfully engineered an anti-PD-L1 monoclonal antibody (mAb) within a plant-based system. Building upon our previous findings, we germinated seeds derived from transgenic plants under in vitro conditions. Afterward, we screened the resulting seedlings for expression of the anti-PD-L1 mAb using polymerase chain reaction (PCR) and western blot analyses. Anti-PD-L1 mAbs were successfully purified from plant leaves and characterized through SDS-PAGE analysis. Our findings, which were confirmed via indirect enzyme-linked immunosorbent assay (ELISA), validate the binding affinity of the anti-PD-L1 mAb to recombinant PD-L1 protein. Furthermore, we investigated the interaction between the plant-derived anti-PD-L1 mAb and Fc gamma receptor I (FcγRI) as well as Fc gamma receptor IIIa (FcγRIIIa) molecules, confirming robust affinity. Additionally, the antibody’s binding affinity to the human multiple myeloma cancer cell line RPMI8226 was confirmed via cell ELISA. Our findings demonstrated that, unlike existing therapeutics, the plant-derived anti-PD-L1 antibody not only effectively binds to human recombinant PD-L1 protein but also to FcγRI and FcγRIIIa. These findings suggest the potential of plant-derived anti-PD-L1 mAb for the development of innovative therapies against multiple myeloma, emphasizing the need for further research and preclinical evaluation.
Background Benign lesions cause ovarian torsion more commonly than malignant ovarian tumors. Further, Krukenberg tumors have rarely been reported to cause ovarian torsion. Case Presentation Herein, we present the case of a patient with an incidentally discovered ovarian mass, which was finally diagnosed as a Krukenberg tumor accompanying ovarian torsion with primary stomach cancer. We further review the clinical, imaging, and histological features of Krukenberg tumors. Conclusion Radiologists should be aware of Krukenberg tumors that may present with ovarian torsion.
This study demonstrated that the fermentation of oak tree sawdust increases peanut (Arachis hypogaea L.) seed germination, sprout biomass, and the total vigor index (TVI). The seed germination rate (0, 3.9, 30.8, and 65.4%) varied significantly among the different fermentation treatments (0, 30, 45, and 60 days, respectively). Seedlings grown in the sawdust with the 60-day fermentation period showed the highest weight (2.8 g) with the longest epicotyl with true leaves (2.5 cm), hypocotyls (2.4 cm), and roots (6.6 cm), consequently having the highest TVI (629.23). Seedlings grown for 0 and 30 days in fermented sawdust had the lowest TVIs (32.7 and 0, respectively). In a microbiome analysis, the fungal community varied among the different fermentation treatments, suggesting that the fungal community affects the seed germination physiology.
Prostate-specific antigen (PSA) is a protein highly expressed in cancer cells of the prostate gland. In this study, the PSA recombinant protein was fused to the human immunoglobulin G crystallizable fragment (Fc) with the endoplasmic reticulum (ER) Lys-Asp-Glu-Leu (KDEL) retention signal tag for the plant expression system. Agrobacterium -mediated plant transformation was applied to generate transgenic tobacco plants expressing PSA tagged to KDEL (PSAK), PSA-Fc, and PSA-Fc fused to KDEL (PSA-FcK). Western blot analysis showed that the PSA-FcK protein was the most highly expressed among the three different proteins in the transgenic plant leaf. The PSAK, PSA-Fc, and PSA- FcK proteins were successfully purified from plant leaves. Reduced and non-reduced sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed that the PSA proteins fused to Fc and FcK were dimerized, whereas the PSA itself was not dimerized. N -glycan analysis demonstrated that the N -glycan profile of the PSA-Fc was mainly the structure with α (1,3)-fucose (Fuc) or β (1,2)-xylose (Xyl) glycan residues, whereas the PSA-Fc tagged with the KDEL ER retention signal had mainly an oligomannose-type structure. ELISA and SPR showed that PSA-FcK had a higher binding activity to Fc gamma receptor I than PSA-Fc and human Fc. In addition, PSA-FcK induced anti-PSA, and thus has the potential to be utilized as a prostate cancer vaccine.
Silicone is the primary implant material used in plastic surgery; however, it exhibits some inherent disadvantages. For instance, it can cause delayed seroma, breast implant-associated anaplastic large cell lymphoma, and capsular contracture, which are closely related to the type of implant surface. Biomaterial surface modification techniques are continuously being improved for application in many fields. Herein, conditions for oxygen (O-2) plasma treatment on various surface types of peri-silicone implants were optimized. Following optimal treatment, surface hydrophilicity, protein adsorption, bacterial adhesion, cell viability and proliferation, changes in implant shell mechanical properties, and in vivo tissue response were examined. Hydrophobicity decreased following O-2 plasma treatment. Bacterial adhesion and protein adsorption were significantly inhibited, and mechanical properties were improved. There was no topographic change on the implant surface. In vitro cells were evenly distributed on the O-2 plasma treated surface, and in vivo analysis confirmed a decrease in capsule thickness, collagen fiber composition, number of inflammatory cells, and TGF-beta 1 and alpha-SMA expression. Additionally, reduced activation of cytokines related to macrophage and T-cell responses was observed. O-2 plasma surface treatment, under optimal conditions, is a simple and effective method with potential clinical applications for attenuating excessive capsule formation and the immune response. (C) 2021 Published by Elsevier B.V. on behalf of The Korean Society of Industrial and Engineering Chemistry.
Transgenic Arabidopsis thaliana expressing an anti-rabies monoclonal antibody (mAb), SO57, was obtained using Agrobacterium-mediated floral dip transformation. The endoplasmic reticulum (ER) retention signal Lys-Asp-Glu-Leu (KDEL) was tagged to the C-terminus of the anti-rabies mAb heavy chain to localize the mAb to the ER and enhance its accumulation. When the inaccurately folded proteins accumulated in the ER exceed its storage capacity, it results in stress that can affect plant development and growth. We generated T1 transformants and obtained homozygous T3 seeds from transgenic Arabidopsis to investigate the effect of KDEL on plant growth. The germination rate did not significantly differ between plants expressing mAb SO57 without KDEL (SO plant) and mAb SO57 with KDEL (SOK plant). The primary roots of SOK agar media grown plants were slightly shorter than those of SO plants. Transcriptomic analysis showed that expression of all 11 ER stress-related genes were not significantly changed in SOK plants relative to SO plants. SOK plants showed approximately three-fold higher mAb expression levels than those of SO plants. Consequently, the purified mAb amount per unit of SOK plant biomass was approximately three times higher than that of SO plants. A neutralization assay revealed that both plants exhibited efficient rapid fluorescent focus inhibition test values against the rabies virus relative to commercially available human rabies immunoglobulins. KDEL did not upregulate ER stress-related genes; therefore, the enhanced production of the mAb did not affect plant growth. Thus, KDEL fusion is recommended for enhancing mAb production in plant systems.
Background Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far. Case presentation The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2 . They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1 . They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years. Conclusion This report indicates a novel germline c.1367delC variant in MLH1 , and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.
Primary pulmonary choriocarcinoma (PPC) is frequently fatal due to difficulties in diagnosis. Few cases of PPC are bilateral and involve exceptionally large nodules. Here, we report an unusual case of PPC involving disseminated bilateral nodules, which was misdiagnosed as tuberculosis, but successfully treated using chemotherapy. A review of 65 cases revealed six cases of bilateral disease, including the present one. Patients treated with surgery, chemotherapy, or a combination of both showed similar treatment outcomes; however, chemotherapy may be the preferred option. Despite its rarity, PPC should be included in the differential diagnosis for all lung nodules to enable early detection.
"Metastatic malignant pheochromocytomas mimicking pelvic leiomyosarcomas: a case report." Journal of Obstetrics and Gynaecology, 41(5), pp. 838–839
Purpose Capsular contracture (CC) is a troublesome complication after breast surgery with breast implants, and the risk increases in breast cancer patients after radiotherapy. Studies investigating leukotriene antagonists (eg, montelukast, zafirlukast) found that the acellular dermal matrix (ADM) can help prevent CC. We aimed to compare the effects of ADM and montelukast on CC after irradiation. Methods Eighteen New Zealand white rabbits were randomly divided into 3 groups of 6 each. Miniature cohesive gel implants were inserted into the pocket under the latissimus dorsi muscle. The lateral part was uncovered by the latissimus dorsi muscle. Six animals were included in the control group. In experimental group A (EG-A) (n = 6), the site was partially wrapped with ADM but not covered with muscle. Montelukast (Singulair, 0.2 mg/kg) was administered in experimental group B (EG-B) (n = 6) daily. Groups were irradiated at postoperative day 21 with Co-60 γ rays (25 Gy, single fraction) at the peri-implant area. Rabbits were sacrificed 12 weeks after surgery; implants with peri-implant capsule were harvested. Capsule thickness, collagen pattern, myofibroblast, and transforming growth factor (TGF) β1/2 levels in the peri-implant capsule were evaluated. Results On histological evaluation, the capsule was thinner on the lateral aspect (covered with ADM) in EG-A (P = 0.004) and the entire capsule in EG-B (P = 0.004) than in the control group. However, there was no significant difference between EG-A and EG-B (P = 0.073). The collagen distribution pattern was more parallel with low density in the lateral capsular aspect in EG-A, but in the entire capsule in EG-B. The myofibroblast amount (EG-A, P = 0.031; EG-B, P = 0.016) and levels of TGF-β1 and TGF-β2 were reduced in the experimental groups (TGF-β1, EG-A, P = 0.019; TGF-β1, EG-B, P = 0.045; TGF-β2, EG-A, P = 0.018; TGF-β2, EG-B, P = 0.022). There was no significant difference between EG-A and EG-B (myofibroblast, P = 0.201; TGF-β1, P = 0.665; TGF-β2, P = 0.665). Conclusions Acellular dermal matrix and montelukast have a prophylactic effect for CC even when the breast is irradiated. There was no significant difference between ADM and montelukast in preventing capsular formation. The difference is that ADM will only have the effect of covering the capsular formation with ADM and montelukast can cause systemic effects or complications.
The anti-colorectal cancer monoclonal antibody CO17-1A (mAb CO), which recognizes the tumor-associated antigen EpCAM, was expressed in transgenic Arabidopsis plants. PCR and western blot analyses showed the insertion and expression of heavy chain (HC)/HC fused to the KDEL ER retention modif (HCK) and light chain (LC) of mAb CO and mAb CO with HCK (mAb COK) in Arabidopsis transformants. Both plant-derived mAbP CO and mAbP COK were purified from a biomass of approximately 1,000 seedlings grown in a greenhouse. In sandwich ELISA, both mAbP CO showed a slightly higher binding affinity for the target, EpCAM, compared to mAbM CO. In cell ELISA, both mAbsP COs showed binding affinity to the human colorectal cancer cell line SW480. Furthermore, mAbM CO, mAbP CO, and mAbP COK exhibited dose and time-dependent regression effects on SW480 cells in vitro. In summation, both mAbP CO and mAbP COK, expressed in Arabidopsis, recognized the target antigen EpCAM and showed anti-proliferative activity against human colorectal cancer cells.
The monoclonal antibody (mAb) CO17-1A specifically binds to the tumor-associated cell surface glycoprotein GA733 in colorectal cancer cells. Thus, mAb CO17-1A has the potential to act as an immune therapeutic protein against colorectal cancer. Recently, it was shown that the baculovirus insect cell expression system produces anti-colorectal cancer mAb CO17-1A. In this study, the colorectal cancer antibody mAb CO17-1A fused to the endoplasmic reticulum (ER) retention signal sequence (KDEL), and the (mAb CO17-1AK) was expressed in Spodoptera frugiperda Sf9 insect cells. The yield, cell cytotoxicity, and in vitro anti-tumor activity of mAb CO17-1AK were verified. Western blotting was performed to confirm that both heavy and light chains of mAb CO17-1A were expressed in Sf9 insect cells. The insect-derived mAb (mAb(I)) CO17-1A was purified using a protein G affinity column. An in vitro wound healing assay was conducted to determine the inhibition activity of mAb CO17-1A during tumor cell migration, showing that mAb(I) CO17-1AK was effective as mammalian-derived mAb CO17-1A (mAb(M) CO17-1A). These results suggest that the insect cell expression system can produce and properly assemble mAbs that inhibit tumor cell migration.