Peritoneal Dissemination Research Articles

Serous endometrial carcinoma metastatic to the sigmoid colon masquerading as a primary colon cancer detected by bowel obstruction

BackgroundThe majority of colorectal malignancies are primary tumors. Secondary tumors are rare, and colorectal metastasis from endometrial carcinoma is exceptionally uncommon. We report a case of serous endometrial carcinoma that metastasized to the sigmoid colon, initially presenting as a primary colon carcinoma due to bowel obstruction.Case presentationA 79-year-old woman presented with abdominal distention and constipation. Five years earlier, she had undergone an open total hysterectomy with bilateral salpingo-oophorectomy for endometrial serous carcinoma. A colonoscopy revealed stenosis encircling the entire sigmoid colon. Abdominal computed tomography demonstrated irregular wall thickening in the sigmoid colon with enhanced regional lymph node enlargement and upstream bowel dilatation. Peritoneal dissemination in the pelvis was also noted. To relieve the obstruction, two self-expanding metal stents were inserted. Subsequently, due to the presumed diagnosis of sigmoid colon carcinoma with peritoneal dissemination, an open left hemicolectomy with resection of the peritoneal dissemination was performed. Histopathological examination identified the colon tumor and peritoneal dissemination as metastatic serous endometrial carcinoma. Immunohistochemical studies showed the tumor cells were negative for CK7, CK20, and CDX2. No chemotherapy was administered, and 6 months post-operation, no recurrence was observed.ConclusionsMetastasis of endometrial carcinoma to the colon is extremely rare. Diagnosing a colon tumor as a metastasis from endometrial carcinoma is challenging during preoperative examinations. Therefore, in patients with a history of endometrial carcinoma, the possibility that the primary site might be the uterus should be considered.

Single-cell sequencing reveals PTX3 involvement in ovarian cancer metastasis

BackgroundPentraxin 3 (PTX3) has been associated with the development and progression of various malignant tumors. However, its roles and the mechanisms underlying its involvement in ovarian cancer (OC) peritoneal metastasis remain unclear.MethodsSingle-cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC) were conducted to determine the expression profiles, potential functionalities, and underlying mechanisms of PTX3 within the context of OC. To assess the proliferative response of OC cells, we utilized both EdU (5-ethynyl-2’ -deoxyuridine) and CCK8 assays. The role of PTX3 in facilitating cell migration and invasion was quantified through the use of Transwell assays. The protein expression levels were meticulously analyzed via Western blotting. Furthermore, to explore the interactions between proteins, we conducted immunofluorescence (IF) staining and co-immunoprecipitation (Co-IP) experiments. To determine the factors responsible for the upregulation of PTX3, we performed both coculture and suspension assays, providing a comprehensive approach to understanding the regulatory mechanisms involved.ResultsThis study confirmed, for the first time, that the expression of PTX3 in OC metastatic lesions is greater than that in primary lesions and that tumor cells with high PTX3 expression have greater metastatic ability. PTX3 can activate the EMT and NF-κB signaling pathways in OC cells and can interact with the TLR4 and CD44 receptors in OC cells. Additionally, PTX3’s modulation of the EMT and NF-κB pathways is partially dependent on its interaction with TLR4. Furthermore, this study revealed the intercellular regulatory network related to PTX3 in OC cells via bioinformatic analysis. High levels of PTX3 in OC cells potentially enhance the attraction of dendritic cells (DCs) and CD4 + T cells while diminishing the recruitment of B cells and CD8 + T cells. Finally, this study indicated that PTX3 upregulation was driven by multiple factors, including specific transcription factors (TFs) and modifications within the tumor microenvironment (TME).ConclusionsOur research revealed the contribution of PTX3 to the peritoneal dissemination process in OC patients, identifying a novel potential biomarker and therapeutic target for this disease.

A comparison of the clinicopathological features and genetic alterations in stage II/III gastric cancer with no recurrence, early recurrence and late recurrence after curative surgery

Background: Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery. Methods: In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared. Results: Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p<0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K/Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival. Conclusion: Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients.

Ten-Year Outcome of a Randomized Trial: Cytoreduction and HIPEC with Mitomycin C Versus Oxaliplatin for Appendiceal Neoplasm with Peritoneal Dissemination.

Appendiceal cancer is a rare disease that has proven difficult to study in prospectively. Our initial reportof this trial showed minor hematologic toxicity with both mitomycin C and oxaliplatin and similar 3-year survival. We now report an update of the first prospective randomized trial for appendiceal cancer with 10-year follow up. Patients with mucinous appendiceal neoplasms and evidence of peritoneal dissemination were enrolled in the Multicenter Randomized Trial to evaluating HIPEC for 120min with oxaliplatin (200mg/M2) or mitomycin C (40mg). Overall survival and disease-free survival were calculated at 10 years and compared between the groups. A total of 121 patients were included in the study. The patients were 57% female, with a mean age of 55.3 years (range 22-82 years). The disease was low grade in 71% and high grade in 29%. The average peritoneal cancer index (PCI) score was 18 (SD 10) in the mitomycin C group and 17.9 (SD 9.4) in the oxaliplatin group (p = 0.94). The 10-year survival rate was 56.2% (SE 7.2) with mitomycin C and 47.5% (SE 8.4) with oxaliplatin, p = 0.83. The 10-year progression-free survival rate in the mitomycin C group was 45.2% (SE 8.4) compared with 50.4% (SE 6.7) in the oxaliplatin group, p = 0.95. Median survival was 9.1 years after HIPEC with oxaliplatin, and median not reached for the mitomycin C group (> 5.6years). Oxaliplatin and mitomycin C have similar long-term efficacy for hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal neoplasms and peritoneal dissemination. Long-term survival is experienced by most patients after cytoreduction surgery (CRS) and HIPEC for appendiceal neoplasms.

Surgical resection following chemoradiotherapy for thoracic SMARCA4-deficient undifferentiated tumor: a report of two cases

BackgroundThoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a high-grade malignant neoplasm with a poor prognosis. Most cases of SMARCA4-UT have extensive chest wall and mediastinum involvement. The efficacy of surgical resection has not been clearly established. Here, we report two surgical cases of SMARCA4-UT with chest wall invasion after chemoradiotherapy.Case presentationThe first patient was a 40-year-old man with back pain. Computed tomography revealed a 6.8 cm mass in contact with the thoracic vertebrae near the intervertebral foramen, which was suspected to involve the third to fifth ribs. The patient was diagnosed with SMARCA4-UT with clinical T3N0M0 stage IIB. The tumor shrank after chemoradiotherapy, and conversion surgery combined with partial vertebrectomy was performed. Histopathological findings revealed 30% residual tumor in the tumor bed. Thirty-six days after surgery, the patient developed multiple liver metastases and peritoneal dissemination. Chemotherapy combined with immune checkpoint inhibitor treatment was performed, resulting in tumor shrinkage. However, peritoneal dissemination recurred within a short interval. The patient died 5 months postoperatively. The second patient was a 74-year-old man with chest pain. Computed tomography revealed a 7.4-cm mass in the left upper lobe with invasion of the third and fourth ribs. The patient was initially diagnosed with non-small cell lung cancer with clinical T4N1M0 stage IIIA. The tumor shrank after induction chemoradiotherapy, and a left upper lobectomy combined with the chest wall resection was performed. Based on histopathological findings, the patient was diagnosed with SMARCA4-UT. The residual tumor percentage was 3%. The patient was followed up for 12 months postoperatively without recurrence.ConclusionsWe performed the complete resection of SMARCA4-UT following chemoradiotherapy. The two surgical cases had different postoperative courses. Radical surgery after chemoradiotherapy is effective for local control. However, its long-term prognostic efficacy remains unclear. Multidisciplinary approaches and further investigations of novel therapeutic options are required.

YAP signaling orchestrates the endothelin-1-guided invadopodia formation in high-grade serous ovarian cancer.

The high-grade serous ovarian cancer (HG-SOC) is a notoriously challenging disease, characterized by a rapid peritoneal dissemination. HG-SOC cells leverage actin-rich membrane protrusions, known as invadopodia, to degrade the surrounding extracellular matrix (ECM) and invade, initiating the metastatic cascade. In HG-SOC, the endothelin-1 (ET-1)/endothelin A receptor (ETAR)-driven signaling coordinates invadopodia activity, however how this axis integrates pro-oncogenic signaling routes, as YAP-driven one, impacting on the invadopodia-mediated ECM degradation and metastatic progression, deserves a deeper investigation. Herein, we observed that downstream of the ET-1/ET-1R axis, the RhoC and Rac1 GTPases, acting as signaling intermediaries, promote the de-phosphorylation and nuclear accumulation of YAP. Conversely, the treatment with the dual ETA/ETB receptor antagonist, macitentan, inhibits the ET-1-driven YAP activity. Similarly, RhoC silencing, or cell transfection with a dominant inactive form of Rac1, restore the YAP phosphorylated and inhibited state. Mechanistically, the ET-1R/YAP signal alliance coordinates invadopodia maturation into ECM-degrading structures, indicating how such ET-1R-guided protein network represents a route able to enhance the HG-SOC invasive potential. At functional level, we found that the interconnection between the ET-1R/RhoC and YAP signals is required for MMP-2 and MMP-9 proteolytic functions, cell invasion, and cytoskeleton architecture changes, supporting the HG-SOC metastatic strength. In HG-SOC patient-derived xenografts (PDX) macitentan, turning-off the invadopodia regulators RhoC/YAP, halt the metastatic colonization. ET-1R targeting, hindering the YAP activity, weakens the invadopodia machinery, embodying a promising therapeutic avenue to prevent peritoneal dissemination in HG-SOC.

PAR1 Is a Candidate Target for the Treatment of Peritoneal Dissemination in Gastric Cancer.

Peritoneal dissemination (PD) is a frequent cause of death in gastric cancer (GC), and there is evidence of an association between protease-activated receptor-1 (PAR1) and the development of PD. This study hypothesized that PD in GC might be influenced by PAR1. The cytotoxic effect of paclitaxel (PTX) on PAR1-transfected MKN45 (MKN45/PAR1) cells was analyzed using the MTT assay, and IC50 values were determined. In female athymic nude mice, MKN45/PAR1 cells were suspended in 0.05 ml phosphate-buffered saline (PBS) medium and inoculated into the stomach mid-wall. In each group, intraperitoneal injections of PBS, PTX, SCH79797 (PAR1-antagonist), or PTX plus SCH79797 were administered on days 8, 15, and 22 following tumor inoculation. At 56 days after tumor inoculation, mice were examined for both abdominal tumor nodule status and size and weight of the tumors. The IC50 of PTX for MKN45/PAR1 cells was 0.0697 μM and that of SCH79797 was 0.0145 μM. Mean survival of the MKN45/PAR1 mice in the PBS group was 28.75 days, whereas survival times for the mice treated with SCH79797, PTX, or a combination of PTX and SCH79797 were 31.2, 49.2, and 48.5 days, respectively. Tumor weight was smaller in the group receiving PTX and SCH79797 intraperitoneally compared with that in the PBS group (1,086±127.2 mg vs. 33.2±19.9 mg; p<0.001). The PAR1 antagonist was found to inhibit PD in a PAR1-expressing GC cell line. PAR1 may serve as a promising therapeutic target for managing PD in gastric cancer, as it plays a crucial role in its progression.

Clinical Outcomes and Prognostic Factors for R0 Resected Colorectal Cancer with Synchronous Peritoneal Metastasis: A Retrospective Study.

Peritoneal metastasis indicates a poor prognosis in patients with colorectal cancer (CRC). Studies have shown improved prognosis in patients after removal of peritoneal dissemination, and this surgery is recommended if not excessively invasive. The aim of this study was to examine clinical outcomes and prognostic factors for R0 resected CRC with synchronous peritoneal metastasis. We analyzed data retrospectively from 250 patients with stage IV CRC who underwent R0 resection at our hospital. The patients were divided into three groups according to the type of surgery: non-resected (N), palliative primary tumor resection (P), and R0 resection (R0) groups. Overall survival (OS) and recurrence-free survival (RFS) were investigated and clinicopathological parameters were analyzed for prognostic significance. The 3-year OS was 57.2% in the R0 group. The R0 group had a significantly higher 3-year OS than that in the other groups (p < 0.0001). Multivariate analysis revealed that histological type, lymphatic and venous invasion, liver metastasis, R0 resection, and perioperative chemotherapy were independent prognostic factors. The 5-year RFS in the R0 group was 26.5%. Multivariate analysis revealed that the number of peritoneal metastases and surgical procedure were independent prognostic factors. Laparoscopic surgery had better 5-year RFS in the R0 group compared with that in the open surgery group (p = 0.0044). R0 resection of colorectal cancer with synchronous peritoneal metastasis should be considered for improving long-term survival. The laparoscopic approach for this disease is another promising method to prolong survival in patients with R0 resection.

Epithelial splicing regulatory protein 1 promotes peritoneal dissemination of ovarian cancer by inducing the formation of circular RNAs modulating epithelial plasticity

Peritoneal metastases prevalently occur in ovarian cancer, deteriorating patient prognosis. During the metastatic cascade, tumor plasticity enables cells to adapt to environmental changes, thereby facilitating dissemination. We previously found that epithelial splicing regulatory protein 1 (ESRP1) is linked to peritoneal metastasis and epithelial-mesenchymal plasticity in ovarian cancer. This study delves into the underlying mechanism. We found that ESRP1 preserves epithelial plasticity in ovarian cancer cells in vitro and in vivo. Functionally, ESRP1 enhances ovarian cancer cell growth and peritoneal dissemination. High-throughput sequencing revealed several ESRP1-related epithelial RNAs, encompassing both linear and circular forms. Specifically, ESRP1 triggers the cyclization of circPAFAH1B2 and circUBAP2 through binding to the GGU sequences in adjacent introns. The two ESRP1-induced circular RNAs stabilize DKK3 and AHR mRNAs, which are critical for epithelial plasticity, through interaction with IGF2BP2. Collectively, ESRP1 triggers the formation of circPAFAH1B2 and circUBAP2, which in turn stabilizes DKK3 and AHR through IGF2BP2 binding, thereby modulating the epithelial plasticity and aiding the peritoneal spread of ovarian cancer cells. The findings unveiled a biological network, orchestrated by ESRP1, that governs the epithelial-mesenchymal plasticity of ovarian cancer cells, emphasizing the therapeutic potential of ESRP1 and its induced circular RNAs for ovarian cancer treatment.

Tissue factor pathway inhibitor-2 inhibits integrin β1 activation and focal adhesion formation and suppresses peritoneal ovarian cancer dissemination in mice

Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells.

NEU4-mediated desialylation enhances the activation of the oncogenic receptors for the dissemination of ovarian carcinoma.

Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Our results provide new insights into how the OC glycome is dysregulated during OC progression and reveal a functionally important glycosite on EGFR for its abnormal activation in cancer.

Aging affects regrowth of stealthperitoneal dissemination of advanced ovarian cancer: a multicenter retrospective cohort study

Ovarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology.

Perioperative systemic and prophylactic intraperitoneal chemotherapy for type 4/large type 3 gastric cancer: DRAGON-10.

Large type 3 and type 4 gastric cancers (GC) have a significantly poor prognosis, primarily due to their high predisposition for peritoneal dissemination. The application of intraperitoneal chemotherapy has emerged as a viable therapeutic strategy for managing GC patients with peritoneal metastasis. This study is planned to enroll 37 resectable large type 3 or type 4 GC patients. These patients are scheduled to undergo a treatment comprising preoperative chemotherapy with paclitaxel, oxaliplatin and S-1, followed by D2 gastrectomy, and concluding with postoperative treatments that include prophylactic intraperitoneal chemotherapy. The study's primary objective is to evaluate the 3-year peritoneal recurrence rate. Secondary objectives are to assess the 3-year disease-free survival, 3-year overall survival and to monitor the adverse events.Clinical trial registration number: ChiCTR2400083253 (https://www.chictr.org.cn).

A comparative in vivo study of hyperthermic intraperitoneal chemotherapy with cisplatin versus doxorubicin versus cisplatin plus doxorubicin for the treatment of intra-abdominally disseminated alveolar rhabdomyosarcoma in mice.

Treatment options for advanced intra-abdominal pediatric rhabdomyosarcoma (RMS) with peritoneal sarcomatosis (PS) include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, optimal dosages and combination regimens of drugs used for HIPEC are underexplored. We aimed to evaluate the efficacy of HIPEC with cisplatin, doxorubicin, and their combination in vivo. We established PS/RMS mouse model by intraperitoneally injecting RH30 cells into NOD/LtSz-scid IL2Rγ-null mice. Two weeks post xenotransplantation, mice underwent a single HIPEC procedure at 42°C for 60minutes. Treatment groups received cisplatin (50, 100, and 150mg/m2) and doxorubicin (30, 45, and 60mg/m2), administered alone or combined. The control group underwent an intraperitoneal lavage with isotonic saline. Peritoneal cancer index (PCI) was used to quantify the extent of peritoneal tumor spread. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (caspase 3). Mice treated with cisplatin at 100mg/m2 (PCI of 3.875, p=.007) and 150mg/m2 (PCI of 4.556, p=.026), and doxorubicin at 30mg/m2 (PCI of 2.875, p<.001) and 45mg/m2 (PCI of 4.143, p=.021) showed reduced PCI, with the combination of cisplatin 50mg/m2 and doxorubicin 30mg/m2 showing the most prominent effect (PCI of 3.333, p<.001) compared to the control group (PCI of 8.615). Histologically, there was no difference in Ki-67 or caspase 3 expression among the groups. The cisplatin- and doxorubicin-based HIPEC significantly reduces peritoneal tumor dissemination in vivo. Further investigations are needed to explore the underlying molecular responses to optimize therapeutic strategies.

Cell-cell contact-dependent secretion of large-extracellular vesicles from EFNBhigh cancer cells accelerates peritoneal dissemination.

Large non-apoptotic vesicles released from the plasma membrane protrusions are classified as large-EVs (LEVs). However, the triggers of LEV secretion and their functions in tumors remain unknown. Coculture system of cancer cells, peritoneal mesothelial cells (PMCs), and macrophages (MΦs) was conducted to observe cell-cell contact-mediated LEV secretion. Lineage tracing of PMCs was performed using Wt1CreERT2-tdTnu mice to explore the effects of LEVs on PMCs in vivo, and lymphangiogenesis was assessed by qRT-PCR and flow-cytometry. In peritoneal dissemination, cancer cells expressing Ephrin-B (EFNB) secreted LEVs upon the contact with PMCs expressing ephrin type-B (EphB) receptors, which degraded mesothelial barrier by augmenting mesothelial-mesenchymal transition. LEVs were incorporated in subpleural MΦs, and these MΦs transdifferentiated into lymphatic endothelial cells (LEC) and integrated into the lymphatic vessels. LEC differentiation was also induced in PMCs by interacting with LEV-treated MΦs, which promoted lymphangiogenesis. Mechanistically, activation of RhoA-ROCK pathway through EFNB reverse signaling induced LEV secretion. EFNBs on LEVs activated EphB forward signaling in PMC and MΦs, activating Akt, ERK and TGF-β1 pathway, which were indispensable for causing MMT and LEC differentiation. LEVs accelerated peritoneal dissemination and lymphatic invasions by cancer cells. Blocking of EFNBs on LEVs using EphB-Fc-fusion protein attenuated these events. EFNBhigh cancer cells scattered LEVs when they attached to PMCs, which augmented the local reactions of PMC and MΦ (MMT and lymphangiogenesis) and exaggerated peritoneal dissemination.

Krukenberg tumours: which patients should be considered for surgery?-a narrative literature review.

Krukenberg tumours (KTs) are metastatic signet ring cell (SRC) adenocarcinomas of the ovary, arising from the stomach in most cases (70%). Other common primary sites are the colon, appendix and breast. The use of the term "Krukenberg tumour" is inconsistent in the literature which makes data interpretation difficult. Prognosis of KTs is dismal and, in the absence of randomised controlled trials, the best treatment strategies remain controversial. Evidence from retrospective studies suggests that metastectomy is associated with improved survival. Our narrative literature review set out to determine which patients gain maximal survival benefit from surgical management. A comprehensive literature search was performed using PubMed and Google Scholar databases, from 1 January 2000 to 15 July 2024, with the terms 'Krukenberg', 'metastatic mucinous adenocarcinoma of ovary'. This search identified 20 full-text manuscripts, including data on 1,815 patients. We found that the overall prognosis of these patients remains poor, with a median overall survival (mOS) ranging between 9 and 50 months. Metastectomy is associated with survival benefit only when all visible disease is removed (R0): mOS in patients with microscopic residual disease (R1) or gross residual disease (R2) is similar to mOS in unresected patients (11 vs. 10 months). The following other factors have been identified as independent prognostic factors for survival in multivariate analyses: heated intraperitoneal chemotherapy (HIPEC), adjuvant chemotherapy, curative surgery for the primary tumour, i.e., gastrectomy, no ascites, non-gastric origin, a good performance status, less extensive metastatic disease, i.e., no extra-ovarian disease or no extra-pelvic disease, no peritoneal carcinomatosis or a low Peritoneal Cancer Index (PCI), smaller size of lesion, no SRC features, expression of oestrogen receptor-β (ER-β) and progesterone receptors (PR), metachronous tumours, linitis plastica, tumour grade. Multiple retrospective analyses have demonstrated that metastectomy is associated with a survival benefit in patients with metastatic mucinous ovarian adenocarcinomas. However, patients with poor prognostic factors are less likely to benefit from surgery and should be counselled accordingly. Diagnostic laparoscopy could be considered before debulking surgery, to assess resectability of disease and to avoid a futile exploratory laparotomy. HIPEC after cytoreductive surgery (CRS) remains controversial, with possible survival benefit for KTs of gastric origin, particularly when peritoneal dissemination is present but the PCI is low.

Sugar-binding Profiles of the Mesothelial Glycocalyx in Frozen Tissues of Mice Revealed by Lectin Staining

The mesothelium is a non-adhesive protective surface that lines the serosal cavities and organs within the body. The glycocalyx is a complex structure that coats the outer layer of the mesothelium. However, due to the limitations of conventional fixation techniques, studies on glycans are limited. In this study, lectin staining of frozen tissues was performed to investigate the diversity of glycans in the glycocalyx of mesothelial cells in mice. Datura stramonium lectin (DSL), which recognizes lactosamine and binds to Galectin-3 and -1, was broadly bound to the mesothelial cells of the visceral and parietal peritoneum but not to the pancreas, liver, intestine, or heart. Furthermore, human mesothelial cells in the omentum and parietal peritoneum were positive for DSL. Erythrina cristagalli lectin binding was specific to mesothelial cells in the parietal peritoneum, that is, the pleura, diaphragm, and peritoneum. Intriguingly, surface sialylation, the key element in reducing peritoneal dissemination and implantation, and promoting ascites formation by ovarian carcinoma cells, was much higher in the parietal peritoneum than in the omentum. These findings revealed slight differences in the glycans of mesothelial cells of different organs, which may be related to clinical diseases. These results also suggest that there may be differences in the functions of parietal and visceral mesothelial cells.

Effects of Hyperbaric Oxygen Therapy for Malignant Bowel Obstruction Caused by Peritoneal Dissemination.

This study aimed to investigate the efficacy of hyperbaric oxygen therapy (HBOT) in patients presenting with malignant bowel obstruction (MBO) and peritoneal dissemination. We retrospectively examined whether HBOT affects prognosis following MBO with peritoneal dissemination. This study included 44 patients diagnosed with MBO secondary to peritoneal dissemination at our hospital between January 2013 and December 2022. Among these patients, 30 underwent HBOT. The treatment protocol involved daily HBOT administration, comprising 100% oxygen at 2.5 atmospheres absolute for 60 min. In a univariate analysis of HBOT and non-HBOT groups, the proportion of patients able to resume eating was significantly higher in the HBOT group. Therefore, the percentage of patients in the non-HBOT group whose MBO did not improve was significantly higher than that in the HBOT group. The percentage of patients undergoing surgery or receiving anticancer treatment did not differ significantly between the groups, whereas overall survival was significantly longer in the HBOT group. Furthermore, when examining inoperable patients, significantly more individuals in the HBOT group could resume eating, and their overall survival was significantly prolonged. HBOT may increase the spontaneous resolution rate and improve long-term prognoses of patients with MBO secondary to peritoneal dissemination.

Comparison of postoperative prognoses for resectable colorectal cancer with vs. without oncologic emergency using propensity score‑matched analyses: A single-center retrospective observational study.

While oncological emergencies in colorectal cancer present distinct challenges, existing literature offers conflicting evidence regarding long-term outcomes. Therefore, the present study compared the postoperative prognoses between patients with and without oncological emergencies. A retrospective evaluation was conducted on patients who had undergone radical surgery for pathological stages II and III colorectal cancer at a single center between January 2012 and December 2020. Patients were classified into the non-emergency and oncological emergency groups. The status of oncologic emergency was divided into obstruction and perforation. The outcomes were compared using propensity score matching. The primary objective was to compare the postoperative prognoses between non-emergency and oncological emergency situations. The secondary objectives included comparing prognoses between obstruction and perforation, identifying the type of recurrence depending on the status of oncologic emergency, and assessing the effect of adjuvant chemotherapy for oncologic emergencies. This study included 524 patients. After propensity score matching, the prognoses of oncological emergencies were worse compared with those without any emergency, whereas those of obstruction and perforation did not significantly differ. Regarding the type of recurrence, peritoneal dissemination in obstruction and local recurrence in perforation was more common compared with that in non-emergency cases. Adjuvant chemotherapy improved the recurrence-free survival for cases with oncological emergencies. The prognoses in cases with oncological emergencies could be worse compared with those without any emergency, whereas obstruction and perforation outcomes can be comparable. The administration of adjuvant chemotherapy should be strongly considered for oncological emergencies.

Stage IV gastric cancer with microsatellite instability–high achieving long-term survival by gastrectomy after nivolumab as third-line therapy: a case report and literature review

BackgroundThe prognosis for stage IV gastric cancer remains poor; however, the advent of immune checkpoint inhibitors (ICIs) such as nivolumab has increased the number of patients with long-term survival. Patients with microsatellite instability (MSI)–high gastric cancer have been recognized as a highly effective population for ICIs. Herein, we report a patient with MSI–high advanced gastric cancer treated with gastrectomy after the administration of nivolumab as third-line therapy.Case presentationA 73-year-old woman presented with a type 3 tumor in the lower part of the gastric body, which was diagnosed as gastric cancer through biopsy. Staging laparoscopy revealed that the tumor had invaded the pancreas and the posterior lobe of the transverse mesocolon, and disseminated nodules were found near the ligament of Treitz. After 4 courses of S-1 plus cisplatin therapy, laparoscopic gastrojejunal bypass was performed because of difficulty in oral intake. She received S-1 plus oxaliplatin therapy after a gastrojejunal bypass; however, her regional lymph nodes were enlarged. After six courses of paclitaxel plus ramucirumab as second-line chemotherapy, computed tomography (CT) showed exacerbation of peritoneal dissemination; thus, nivolumab was selected as the third-line therapy. The tumor was characterized by MSI–high. At 24 courses, CT and gastroscopy revealed a complete clinical response of the tumor; however, re-growth of the primary tumor was observed at 36 courses. The patient underwent distal gastrectomy with D1 + lymph node dissection, and received S-1 monotherapy as adjuvant therapy for 1 year. No recurrence was noted at 39 months after the surgery.ConclusionsWe report a patient with highly advanced gastric cancer with peritoneal dissemination, which worsened during second-line therapy and was successfully treated with gastrectomy after nivolumab administration as a third-line therapy. MSI–high gastric cancer is a target that should be actively considered for the administration of ICIs, such as nivolumab, and multidisciplinary treatment combined with chemotherapy and gastrectomy, including conversion surgery, can lead to patients’ long-term survival.