Peritoneal Dissemination Research Articles

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.

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.

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.

The Significance of the Morphological Appearance of Peritoneal Lesions on Imaging in Patients With Peritoneal Malignancies-A Report From Phase 1 of the PRECINCT Study.

This is a report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, in which we studied the incidence of disease at pathological evaluation in different morphological appearances of peritoneal malignancies (PM) on imaging. Radiological findings were captured in a specific format that included a description of the morphological appearance of PM and a correlation performed with pathological findings. In 630 patients enroled at seven centres (September 2022-December 2023), 24 morphological terms were used. Among prespecified terms (N = 8 used in 6350 [92.2%] regions), scalloping was pathologically positive in 93.5%, confluent disease in 78.8%, tumour nodules in 69.6%, thickening in 66.1%, infiltration in 56.3%. Among unspecified appearances (N = 16) for 540 (7.8%) regions, 'enhancement' was positive in 41.5%, micronodules in 65.3% and nodularity in 60.2%. Hierarchal clustering placed gastric cancer and rare tumours together and colorectal cancer, ovarian cancer and peritoneal mesothelioma in one cluster. The incidence of disease at pathological evaluation for most morphological appearances was high (> 50%). Morphological description should be provided in routine radiology reports. A set of standardized terms with their description should be developed by a consensus among experienced radiologists.

Molecular diagnosis for detecting KRAS mutation in peritoneal washing fluid of pancreatic ductal adenocarcinoma

Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P < 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (P < 0.01). The optimal Ct cut-off to predict KRAS mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%, P = 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF.

A Case Study of a High-Grade Serous Carcinoma of the Fallopian Tube Transformed into Carcinosarcoma at the Site of Peritoneal Dissemination With Immunohistological Evidence of an Epithelial-Mesenchymal Transition.

We report a patient in whom a primary high-grade serous carcinoma (HGSC) of the fallopian tube transformed into a carcinosarcoma at the site of peritoneal dissemination, and immunohistological analysis suggested the involvement of an epithelial-mesenchymal transition (EMT). The patient, a 70-year-old woman, had an abdominal mass palpated on admission, and a laparotomy was performed after a close examination. The resected right fallopian tube was cystically dilated, and a solid mass was observed in its lumen. The histological diagnosis was HGSC of the right fallopian tube with a papillary or complex tubular structure composed of tumor cells with marked nuclear irregularities. p53 was overexpressed, and no mesenchymal tumor component was observed. The resected left-sided abdominal mass of the omentum was a solid with a long diameter of 100 mm. Microscopically, the tumor exhibited a mixture of HGSC and high-grade sarcoma with nonspecific differentiation. Furthermore, a heterologous chondrosarcoma was subsequently observed from the high-grade sarcoma. The HGSC component was E-cadherin positive. The high-grade sarcoma component was positive for EMT-related proteins such as zinc finger E-box-binding homeobox 1 (ZEB1) and twist family bHLH transcription factor 1 (TWIST1). The chondrosarcoma component was ZEB1 positive and TWIST1 negative. p53 overexpression was found in all 3 components. The tumor of the omentum suggested that an EMT phenomenon was involved in the tumorigenesis. In this scenario, the primary HGSC of the fallopian tube with obvious invasion demonstrated that the conversion from carcinoma to sarcoma by EMT occurs only with peritoneal dissemination.

Impact of Previous Abdominal Surgery and Timing of Peritoneal Metastases on Accuracy of Imaging in Predicting the Surgical PCI: A Report From the PRECINCT Study.

In this report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, a correlation was performed between the radiological PCI (peritoneal cancer index; rPCI) and surgical PCI (sPCI). The impact of timing of peritoneal malignancy (PM) and previous abdominal surgery was also studied. The rPCI and sPCI were considered the 'same' if they differed by ≤ 3 points. The agreement was assessed using Bland-Altman analysis and the strength of the agreement was assessed using the concordance correlation coefficient (CCC). The extent of prior surgery was classified according to prior surgical score (PSS). In 707 (79.4%) patients, rPCI and sPCI concurred in 280 (39.6%). In the Bland-Altman analysis, < 40% patients were in the ±3 PCI points limit of acceptable difference. The average difference between the two scores was 4.5 points (95% CI- -5.16 to -3.92). The CCC- was 0.59 for the whole cohort ('moderate' concordance) and was not influenced by imaging modality, timing of PM or PSS. The rPCI underestimated sPCI by an average of 4.5 points. The role of peritoneal MRI in patients undergoing iterative procedures and the performance of imaging according to sites of recurrence need further evaluation.

The group of hypermethylated long noncoding RNA genes is associated with different types of metastasis in ovarian cancer

Background: Ovarian tumors are characterized by asymptomatic progression until their late stages, when at the time of diagnosis the patient already has extensive metastatic disease. In addition to lymphogenous and hematogenous metastasis in ovarian cancer, there are peritoneal dissemination and metastasis to the greater omentum with ascites; moreover, peritoneal carcinomatosis is the predominant route of metastasizing of ovarian cancer. Epigenetic factors, such as gene methylation, regulatory microRNAs and long non-coding RNAs (lncRNAs), contribute to progression of this cancer. Our previous bioinformatic and experimental studies have identified 13 genes of lncRNAs (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) hypermethylated in the ovarian neoplasms. Aim: To evaluate the clinical significance of methylation levels of 13 lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) associated with various types of ovarian cancer metastasis, including lymphogenous, peritoneal, omental, and distant metastases. Methods: The methylation levels of lncRNA genes GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1 were analyzed by quantitative real-time methylation-specific polymerase chain reaction. We tested 122 duplicate samples of ovarian neoplasms, including 104 malignancies and 18 borderline tumors, as well as 45 peritoneal macro metastases, collected in the N.N. Blokhin National Medical Research Center of Oncology in 2020 to 2023. The study included 21 samples of primary tumor from patients with lymphogenous metastases, 45 samples from patients with peritoneal dissemination, 61 from those with omental metastases, 49 from patients with ascites, and 9 with distant metastases. Results: The tumor samples from the patients with lymphatic nodes metastases showed a significant increase in the methylation level of two lncRNA genes: SNHG6 (p = 0.044) and SNHG12 (p = 0.006). Peritoneal dissemination was associated with hypermethylation of four lncRNA genes: GAS5, HOTAIR, LINC00472 (p 0.05), and most significantly TINCR (p = 0.001). GAS5, HOTAIR, LINC00886 (p 0.05) and most significantly LINC00472 (p 0.001) hypermethylation was typical for omental metastasis, and that of LINC00472 and LINC00886, with ascites (p 0.05). Peritoneal macroscopic metastases demonstrated increased methylation of MAFG-DT (p 0.001) and TP53TG1 (p 0.001) and desmethylation of LINC00886 (p = 0.003) and SNHG12 (p = 0.002), compared to their primary tumors. Conclusion: We performed the analysis of clinical significance of 13 hypermethylated lncRNA genes in ovarian cancer and were the first to show that 10 genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, SNHG6, SNHG12, TINCR, TP53TG1, TUG1) were associated with various types of ovarian tumor metastasis. Also, we were able to determine certain panels of lncRNA, which, if demonstrate abnormal methylation, were specific for lymphogenous and peritoneal metastasis of ovarian tumors.

Real-world outcomes of stage II and III colorectal cancers treated by postoperative adjuvant chemotherapy based on the mismatch repair status.

In Japan, immunohistochemistry for mismatch repair (MMR) proteins targeted at stage II and III colorectal cancers (CRCs) has been covered by national insurance since October, 2022. This study aimed to clarify the long-term outcomes of patients with stage II and III CRCs receiving postoperative adjuvant chemotherapy based on their MMR status. The outcomes of 640 patients who underwent radical surgery for stage II and III CRCs were analyzed retrospectively. Deficient MMR (dMMR) was diagnosed in 41 (13.3%) patients with stage II and 28 (9.1%) patients with stage III CRC. The overall survival and recurrence rates were not significantly different between the patients with stage II and those with stage III CRC. The risk factors for recurrence among those with stage II CRC were tumors on the left side, T4 disease, and the presence of BRAF wild type. The recurrence rates were lower in the stage II CRC patients with sporadic dMMR than in those with suspected Lynch syndrome (LS). The first site of recurrence was more frequently the peritoneum or distant lymph node in patients with dMMR. Stage IICRC patients with sporadic dMMR were found to have a very good prognosis. On the other hand, peritoneal dissemination or distant lymph node metastasis tended to develop in patients with dMMR.

An actinomycosis infection resembling peritoneal dissemination of rectal cancer: a case report

BackgroundActinomycosis is a suppurative and granulomatous inflammation commonly caused by Actinomyces israelii. Due to its rarity and the paucity of characteristic clinical features, diagnosis of intra-abdominal actinomycosis is challenging, especially when the patient has a treatment history of abdominal cancer.Case presentationThe patient is a 72-year-old man who has a history of multiple abdominal surgeries for rectal cancer, including low anterior resection for primary rectal cancer, partial hepatic resection for metachronous liver metastasis, and Hartmann surgery for local recurrence. The patient has also undergone parastomal hernia repair using the Sugarbaker method. One year after hernia repair, computed tomography (CT) identified a mass lesion between the abdominal wall and the mesh, suggesting the possibility of peritoneal recurrence of rectal cancer. The accumulation of fluorodeoxyglucose (FDG) was evident via positron emission tomography-CT (PET-CT), while tumor marker levels were within the normal range. On laparotomy, the small intestine, abdominal wall, mesh, colon, and stoma were observed to be associated with the mass lesion, and en bloc resection was carried out. However, postoperative histopathological examination revealed an actinomyces infection without any cancerous cells.ConclusionsThis case highlights the challenges faced by surgeons regarding preoperative diagnosis of actinomycosis, especially when it occurs after the resection of abdominal cancer. Also, this case reminds us of the importance of a histopathological examination for abdominal masses or nodules before starting chemotherapy.

Telotristat ethyl, a tryptophan hydroxylase inhibitor, enhances antitumor efficacy of standard chemotherapy in preclinical cholangiocarcinoma models.

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer, carries a grim prognosis with a 5-year survival rate of 5%-15%. Standard chemotherapy regimens for CCA, gemcitabine plus cisplatin (GemCis) or its recently approved combination with durvalumab demonstrate dismal clinical activity, yielding a median survival of 12-14 months. Increased serotonin accumulation and secretion have been implicated in the oncogenic activity of CCA. This study investigated the therapeutic efficacy of telotristat ethyl (TE), a tryptophan hydroxylase inhibitor blocking serotonin biosynthesis, in combination with standard chemotherapies in preclinical CCA models. Nab-paclitaxel (NPT) significantly enhanced animal survival (60%), surpassing the marginal effects of TE (11%) or GemCis (9%) in peritoneal dissemination xenografts. Combining TE with GemCis (26%) or NPT (68%) further increased survival rates. In intrahepatic (iCCA), distal (dCCA) and perihilar (pCCA) subcutaneous xenografts, TE exhibited substantial tumour growth inhibition (41%-53%) compared to NPT (56%-69%) or GemCis (37%-58%). The combination of TE with chemotherapy demonstrated enhanced tumour growth inhibition in all three cell-derived xenografts (67%-90%). PDX studies revealed TE's marked inhibition of tumour growth (40%-73%) compared to GemCis (80%-86%) or NPT (57%-76%). Again, combining TE with chemotherapy exhibited an additive effect. Tumour cell proliferation reduction aligned with tumour growth inhibition in all CDX and PDX tumours. Furthermore, TE treatment consistently decreased serotonin levels in all tumours under all therapeutic conditions. This investigation decisively demonstrated the antitumor efficacy of TE across a spectrum of CCA preclinical models, suggesting that combination therapies involving TE, particularly for patients exhibiting serotonin overexpression, hold the promise of improving clinical CCA therapy.

A Case of Advanced Hepatocellular Carcinoma with Multiple Intrahepatic Metastases and Peritoneal Dissemination Treated using Atezolizumab plus Bevacizumab Combination Therapy, Resulted in Pathological Complete Response, with Concomitant Endoscopic Therapies for Early Gastric and Colorectal Cancers

A Case of Advanced Hepatocellular Carcinoma with Multiple Intrahepatic Metastases and Peritoneal Dissemination Treated using Atezolizumab plus Bevacizumab Combination Therapy, Resulted in Pathological Complete Response, with Concomitant Endoscopic Therapies for Early Gastric and Colorectal Cancers

Recent Progress in the Application of Exosome Analysis in Ovarian Cancer Management.

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosomemediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.