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1.
J Med Case Rep ; 18(1): 222, 2024 May 05.
Article En | MEDLINE | ID: mdl-38704583

BACKGROUND: The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient. CASE PRESENTATION: A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up. DISCUSSION AND CONCLUSION: We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research.


Leiomyoma , Omentum , Peritoneal Neoplasms , Smooth Muscle Tumor , Tomography, X-Ray Computed , Humans , Male , Omentum/pathology , Middle Aged , Leiomyoma/pathology , Leiomyoma/surgery , Leiomyoma/diagnostic imaging , Leiomyoma/diagnosis , Smooth Muscle Tumor/pathology , Smooth Muscle Tumor/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/secondary , Diagnosis, Differential
2.
Asian J Endosc Surg ; 17(3): e13319, 2024 Jul.
Article En | MEDLINE | ID: mdl-38716506

Benign multicystic peritoneal mesothelioma (BMPM) is a rare condition, particularly in men, and the preoperative diagnosis poses a challenge. Here, we present a case involving single-incision laparoscopic surgery (SILS) for BMPM in a 24-year-old man with a pelvic mass and a history of ulcerative colitis. Pelvic imaging revealed multifocal cysts, prompting the performance of SILS. The tumor was successfully resected with no residual lesions, and pathology confirmed the diagnosis of BMPM. This case represents the first documented instance of SILS being employed for BMPM in a man. BMPM, characterized by pelvic multifocal cysts, is a differential diagnosis, and SILS emerges as a viable option for both diagnosis and treatment.


Laparoscopy , Mesothelioma, Cystic , Peritoneal Neoplasms , Humans , Male , Laparoscopy/methods , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/diagnostic imaging , Mesothelioma, Cystic/surgery , Mesothelioma, Cystic/pathology , Mesothelioma, Cystic/diagnosis , Mesothelioma, Cystic/diagnostic imaging , Young Adult
3.
Sci Rep ; 14(1): 10199, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702437

In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.


Carcinoma, Pancreatic Ductal , Pancreatectomy , Pancreatic Neoplasms , Peritoneal Lavage , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgery , Male , Female , Aged , Middle Aged , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/diagnosis , Cytodiagnosis/methods , Aged, 80 and over , Neoplasm Recurrence, Local/pathology , Liquid Biopsy/methods , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/diagnosis , Adult , Cytology
4.
Cancer Rep (Hoboken) ; 7(5): e2086, 2024 May.
Article En | MEDLINE | ID: mdl-38767517

BACKGROUND: Malignant extrarenal rhabdoid tumor (MERT) is a rare and highly metastatic tumor, which is more than 75% of patients dying within 6 months of initial diagnosis, and it often leads to misdiagnosis and delayed treatment. CASE: This paper reports a 16-year-old girl who presented with the chief complaint of acute abdominal pain. She underwent laparoscopic exploration and excisional biopsy, then pathological examination and immunohistochemistry revealed "extrarenal malignant rhabdomyoma." One month after operation, she died of intra-abdominal hemorrhage and multiple organ dysfunction. CONCLUSION: MERT were often misdiagnosed and had a poor prognosis. The surgery and chemotherapy are usually beneficial to prolong the survival time of patients with MERT.


Omentum , Rhabdoid Tumor , Humans , Female , Rhabdoid Tumor/pathology , Rhabdoid Tumor/diagnosis , Rhabdoid Tumor/surgery , Adolescent , Omentum/pathology , Omentum/surgery , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/secondary , Fatal Outcome
5.
World J Surg Oncol ; 22(1): 134, 2024 May 21.
Article En | MEDLINE | ID: mdl-38769546

BACKGROUND: Appendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications. METHODS: From October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments. RESULTS: Tubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion. CONCLUSION: Tubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.


Appendiceal Neoplasms , Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms , Postoperative Complications , Pseudomyxoma Peritonei , Humans , Pseudomyxoma Peritonei/therapy , Pseudomyxoma Peritonei/pathology , Female , Male , Middle Aged , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/pathology , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/therapy , Appendiceal Neoplasms/mortality , Prognosis , Hyperthermic Intraperitoneal Chemotherapy/methods , Hyperthermic Intraperitoneal Chemotherapy/adverse effects , Cytoreduction Surgical Procedures/adverse effects , Follow-Up Studies , Postoperative Complications/etiology , Adult , Retrospective Studies , Combined Modality Therapy , Survival Rate , Aged , Risk Factors , Hyperthermia, Induced/adverse effects , Hyperthermia, Induced/methods
6.
J Transl Med ; 22(1): 463, 2024 May 15.
Article En | MEDLINE | ID: mdl-38750559

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant interest for their tumor-tropic property, making them potential therapeutic delivery vehicles for cancer treatment. We have previously shown the significant anti-tumour activity in mice preclinical models and companion animals with naturally occurring cancers using non-virally engineered MSCs with a therapeutic transgene encoding cytosine deaminase and uracil phosphoribosyl transferase (CDUPRT) and green fluorescent protein (GFP). Clinical studies have shown improved response rate with combinatorial treatment of 5-fluorouracil and Interferon-beta (IFNb) in peritoneal carcinomatosis (PC). However, high systemic toxicities have limited the clinical use of such a regime. METHODS: In this study, we evaluated the feasibility of intraperitoneal administration of non-virally engineered MSCs to co-deliver CDUPRT/5-Flucytosine prodrug system and IFNb to potentially enhance the cGAS-STING signalling axis. Here, MSCs were engineered to express CDUPRT or CDUPRT-IFNb. Expression of CDUPRT and IFNb was confirmed by flow cytometry and ELISA, respectively. The anti-cancer efficacy of the engineered MSCs was evaluated in both in vitro and in vivo model. ES2, HT-29 and Colo-205 were cocultured with engineered MSCs at various ratio. The cell viability with or without 5-flucytosine was measured with MTS assay. To further compare the anti-cancer efficacy of the engineered MSCs, peritoneal carcinomatosis mouse model was established by intraperitoneal injection of luciferase expressing ES2 stable cells. The tumour burden was measured through bioluminescence tracking. RESULTS: Firstly, there was no changes in phenotypes of MSCs despite high expression of the transgene encoding CDUPRT and IFNb (CDUPRT-IFNb). Transwell migration assays and in-vivo tracking suggested the co-expression of multiple transgenes did not impact migratory capability of the MSCs. The superiority of CDUPRT-IFNb over CDUPRT expressing MSCs was demonstrated in ES2, HT-29 and Colo-205 in-vitro. Similar observations were observed in an intraperitoneal ES2 ovarian cancer xenograft model. The growth of tumor mass was inhibited by ~ 90% and 46% in the mice treated with MSCs expressing CDUPRT-IFNb or CDUPRT, respectively. CONCLUSIONS: Taken together, these results established the effectiveness of MSCs co-expressing CDUPRT and IFNb in controlling and targeting PC growth. This study lay the foundation for the development of clinical trial using multigene-armed MSCs for PC.


Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Pentosyltransferases , Peritoneal Neoplasms , Transgenes , Animals , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/pathology , Humans , Pentosyltransferases/genetics , Pentosyltransferases/metabolism , Cell Line, Tumor , Interferon-beta/metabolism , Interferon-beta/genetics , Xenograft Model Antitumor Assays , Cytosine Deaminase/genetics , Cytosine Deaminase/metabolism , Mice , Female
7.
J Pak Med Assoc ; 74(5): 1007-1008, 2024 May.
Article En | MEDLINE | ID: mdl-38783460

Psuedomyxoma peritonei is an infrequent clinical entity characterised by intraperitoneal mucinous/gelatinous ascites produced by the cancerous cells. It has been associated with gastrointestinal, gynaecological, lung and breast tumours. It is commonly asymptomatic and is most often detected incidentally on abdominopelvic imaging or laparoscopy. Higher histological grade of the tumour shows increased metabolic activity on 18F-Fluorodeoxyglucose (FDG) positron-emission tomography (PET) computed tomography (CT). It has been rarely reported in patients with sarcoma. We hereby present an interesting case of incidentally diagnosed pseudomyxoma peritonei on 18FDG PET-CT scan of a patient with soft tissue sarcoma of peripheral nerve sheath.


Fluorodeoxyglucose F18 , Incidental Findings , Peritoneal Neoplasms , Positron Emission Tomography Computed Tomography , Pseudomyxoma Peritonei , Humans , Pseudomyxoma Peritonei/diagnosis , Pseudomyxoma Peritonei/pathology , Pseudomyxoma Peritonei/diagnostic imaging , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/diagnosis , Nerve Sheath Neoplasms/diagnostic imaging , Nerve Sheath Neoplasms/pathology , Nerve Sheath Neoplasms/diagnosis , Nerve Sheath Neoplasms/surgery , Female , Middle Aged , Male , Radiopharmaceuticals
8.
Langenbecks Arch Surg ; 409(1): 113, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38589714

PURPOSE: Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS: A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS: Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION: Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.


Hyperthermia, Induced , Percutaneous Coronary Intervention , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/pathology , Peritoneum , Hyperthermic Intraperitoneal Chemotherapy , Cytoreduction Surgical Procedures , Retrospective Studies , Tertiary Care Centers , Quality of Life , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate
9.
World J Surg Oncol ; 22(1): 103, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38637820

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.


Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/pathology , Cytoreduction Surgical Procedures , Colorectal Neoplasms/pathology , Neoadjuvant Therapy , Peritoneum/pathology , Retrospective Studies , Survival Rate , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
10.
Medicine (Baltimore) ; 103(17): e37985, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38669368

RATIONALE: Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and intestine, retroperitoneal mesothelioma is, to our knowledge, very rare and rarely reported. In recent years, our best clinical protocols for the treatment and diagnosis of retroperitoneal mesothelioma have not been proven and the diagnosis and treatment are challenging. PATIENT CONCERNS: A 37-year-old Chinese woman complained of bilateral low back pain for a month, with obvious symptoms of low back pain on the left side. To treat low back pain, retroperitoneal masses were found during physical examination. The patient consulted a urological specialist for further treatment. DIAGNOSIS: After the operation, pathological biopsy confirmed retroperitoneal epithelioid diffuse mesothelioma. INTERVENTIONS: After exclusion of surgical contraindications, the patient underwent laparoscopic retroperitoneal lesion resection under tracheal intubation and general anesthesia, and the operation was successful. OUTCOMES: On the tenth day after surgery, the patient vital signs were stable, and he was discharged. LESSONS: Patients with malignant peritoneal mesothelioma may have no typical clinical symptoms, and the diagnosis is based on pathological and immunohistochemical examination. In selected patients, surgical cell reduction and intraoperative intraperitoneal heat chemotherapy have become the first choice of treatment, which can achieve ideal therapeutic effects and prolong survival.


Mesothelioma, Malignant , Retroperitoneal Neoplasms , Humans , Adult , Female , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/surgery , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/therapy , Mesothelioma, Malignant/diagnosis , Mesothelioma, Malignant/pathology , Mesothelioma, Malignant/therapy , Mesothelioma/diagnosis , Mesothelioma/pathology , Mesothelioma/therapy , Mesothelioma/surgery , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/surgery , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Laparoscopy/methods
11.
Anticancer Res ; 44(5): 2239-2241, 2024 May.
Article En | MEDLINE | ID: mdl-38677761

BACKGROUND/AIM: Pseudomyxoma peritonei (PMP) is a rare condition characterized by diffuse spread of mucinous tumors within the peritoneal cavity. Traditional treatment modalities, such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are challenging in cases of recurrent disease, owing to anatomical complexities and increasing morbidity and mortality risk. BromAc® has emerged as a novel, targeted therapy for PMP with evidence for intra-tumoral administration to break down mucin deposits. CASE REPORT: We present a 70-year-old female with confirmed diagnosis of symptomatic appendiceal PMP situated behind the stomach, refractory to prior CRS and HIPEC. Transhepatic intra-tumor injection of BromAc® was performed, guided by imaging, with catheter placement into the posterior gastric mucinous tumor. The procedure was well-tolerated, and post-treatment imaging revealed a significant 40% reduction in tumor burden. The patient had fever on cycle days two and three, which self-resolved and septic screen performed was negative. Following BromAc® administration, the patient demonstrated improvement in symptoms and quality of life. CONCLUSION: This case highlights the potential efficacy and safety of transhepatic administration of BromAc® for the treatment of recurrent PMP behind the stomach. The targeted delivery of BromAc® directly into a mucinous tumor via the transhepatic route offers a minimally invasive alternative for cases where traditional surgical interventions pose challenges. However, further research and clinical trials are warranted to validate the broader applicability of this novel approach, assess long-term outcomes, and optimize procedural parameters for enhanced therapeutic outcomes in PMP treatment.


Peritoneal Neoplasms , Pseudomyxoma Peritonei , Humans , Female , Aged , Pseudomyxoma Peritonei/drug therapy , Pseudomyxoma Peritonei/pathology , Pseudomyxoma Peritonei/therapy , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology
12.
Cancer Lett ; 591: 216901, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38641311

Diffuse-type gastric cancer (DGC) is a subtype of gastric cancer that is prone to peritoneal dissemination, with poor patient prognosis. Although intercellular adhesion loss between cancer cells is a major characteristic of DGCs, the mechanism underlying the alteration in cell-to-extracellular matrix (ECM) adhesion is unclear. We investigated how DGCs progress and cause peritoneal dissemination through interactions between DGC cells and the tumour microenvironment (TME). P53 knockout and KRASG12V-expressing (GAN-KP) cells and Cdh1-deleted GAN-KP (GAN-KPC) cells were orthotopically transplanted into the gastric wall to mimic peritoneal dissemination. The GAN-KPC tumour morphology was similar to that of human DGCs containing abundant stroma. RNA sequencing revealed that pathways related to Rho GTPases and integrin-ECM interactions were specifically increased in GAN-KPC cells compared with GAN-KP cells. Notably, we found that Rac Family Small GTPase 1 (RAC1) induces Integrin Subunit Alpha 6 (ITGA6) trafficking, leading to its enrichment on the GC cell membrane. Fibroblasts activate the FAK/AKT pathway in GC cells by mediating extracellular matrix (ECM)-Itga6 interactions, exacerbating the malignant phenotype. In turn, GC cells induce abnormal expression of fibroblast collagen and its transformation into cancer-associated fibroblasts (CAFs), resulting in DGC-like subtypes. These findings indicate that Cdh1 gene loss leads to abnormal expression and changes in the subcellular localization of ITGA6 through RAC1 signalling. The latter, through interactions with CAFs, allows for peritoneal dissemination.


Cadherins , Peritoneal Neoplasms , Stomach Neoplasms , Tumor Microenvironment , rac1 GTP-Binding Protein , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Cadherins/metabolism , Cadherins/genetics , rac1 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/genetics , Cell Line, Tumor , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/pathology , Animals , Antigens, CD/metabolism , Antigens, CD/genetics , Mice , Signal Transduction , Stromal Cells/metabolism , Stromal Cells/pathology , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Cell Adhesion , Gene Expression Regulation, Neoplastic
13.
Anticancer Res ; 44(4): 1553-1557, 2024 Apr.
Article En | MEDLINE | ID: mdl-38537963

BACKGROUND/AIM: Among postoperative complications, fascial dehiscence (FD) is registered in up to 10% of patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aimed to evaluate the risk factors related to FD after CRS-HIPEC. PATIENTS AND METHODS: A retrospective analysis of a prospectively maintained database of consecutive patients who underwent CRS-HIPEC between 2015 and 2023 was performed. For each patient, risk factors for postoperative fascial dehiscence were identified using multivariate analysis. RESULTS: During the study period (2018-2023), 217 patients were treated with CRS-HIPEC. The incidence of FD was observed in seven cases (3.2%), which were reoperated with direct fascial closure. In three cases, FD was associated with other grade III-IV complications. Body mass index, (BMI; p=0.024), doxorubicin-based HIPEC (p=0.005), and open technique (p=0.004) were identified as risk factors for FD in univariate analysis. Systemic chemotherapy, prior surgical score, and peritoneal cancer index (PCI) were not associated with an increased risk of FD. In multivariable regression analysis, doxorubicin-based HIPEC and open technique were confirmed as risk factors for FD. CONCLUSION: Although FD is a relatively rare event after CRS-HIPEC, open technique and doxorubicin-based HIPEC were significant predictors of this complication. Specific fascial closure techniques and proper wound care should be considered in high-risk patients.


Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/pathology , Hyperthermic Intraperitoneal Chemotherapy , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Staging , Retrospective Studies , Hyperthermia, Induced/adverse effects , Doxorubicin/adverse effects , Risk Factors , Cytoreduction Surgical Procedures/adverse effects , Survival Rate
16.
BMC Med ; 22(1): 119, 2024 Mar 13.
Article En | MEDLINE | ID: mdl-38481209

BACKGROUND: Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. METHODS: This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. RESULTS: A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6-54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1-45.2%), and the disease control rate was 86.7% (95% CI, 62.1-96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29-36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. CONCLUSIONS: Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.


Leiomyomatosis , Peritoneal Neoplasms , Humans , Disease Progression , Leiomyomatosis/drug therapy , Leiomyomatosis/complications , Leiomyomatosis/pathology , Peritoneal Neoplasms/complications , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Pilot Projects , Sirolimus/adverse effects
17.
Biomed Pharmacother ; 174: 116474, 2024 May.
Article En | MEDLINE | ID: mdl-38518604

Chemotherapy and targeted drugs-induced senescent ovarian cancer cells that accumulate in peritoneal adipose tissue contribute significantly to chronic inflammation, disrupt homeostasis, and may fuel various aspects of cancer progression. However, the pro-senescence effects of chemotherapy and targeted drugs on adipose derived stem cells (ADSCs) within peritoneal adipose tissue remain poorly understood. In this study, we show that the first-line chemotherapy and targeted drugs can induce the cellular senescence of ADSCs in vitro and increase the aging of peritoneal adipose tissue in vivo. These treatments significantly promoted the dysregulation of glucose and lipid metabolism, including insulin resistance and liver lipid accumulation. Our study shows that dasatinib and quercetin, as senolytics, effectively restore glucose homeostasis in mice with ovarian cancer and significantly reduce adipose tissue aging. Importantly, combining these drugs with Carboplatin or Olaparib results in a marked decrease in both peritoneal and adipose tissue metastasis of ovarian cancer cells. Mechanistically, we revealed that there is crosstalk between ovarian cancer cells and senescent ADSCs. The crosstalk increases inflammatory cytokines and chemokines production in ADSCs and notably upregulates chemokine receptors on cancer cells. Collectively, these data indicate that senescent ADSCs induced by chemotherapy and targeted therapy drugs impair adipose tissue function. However, the senolytic drugs dasatinib and quercetin, can significantly ameliorate organ aging and damage induced by these treatments. Notably, dasatinib and quercetin combined with Carboplatin or Olaparib reduced the peritoneal and adipose tissue metastasis of ovarian cancer, ultimately benefiting the mice undergoing chemotherapy and targeted therapy.


Adipose Tissue , Carboplatin , Cellular Senescence , Dasatinib , Ovarian Neoplasms , Peritoneal Neoplasms , Phthalazines , Piperazines , Quercetin , Dasatinib/pharmacology , Dasatinib/administration & dosage , Female , Animals , Quercetin/pharmacology , Quercetin/administration & dosage , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Phthalazines/pharmacology , Phthalazines/administration & dosage , Carboplatin/pharmacology , Carboplatin/administration & dosage , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/pathology , Piperazines/pharmacology , Piperazines/administration & dosage , Cellular Senescence/drug effects , Mice , Humans , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/pathology , Senotherapeutics/pharmacology , Cell Line, Tumor , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Mice, Inbred C57BL
18.
Int J Gynecol Cancer ; 34(5): 730-737, 2024 May 06.
Article En | MEDLINE | ID: mdl-38485223

OBJECTIVE: The aim of this study was to investigate the relation between the peritoneal cancer index, overall survival, and recurrence free survival, in patients with epithelial ovarian cancer. METHODS: Patients treated at the Gustave-Roussy Institute between December 2004 and November 2017 for advanced epithelial ovarian cancer in complete resection were included. The correlation between the peritoneal cancer index and survival was studied using statistical modeling. Multivariate analysis was performed with a logistic regression model. RESULTS: Of the 351 patients included, 94 (27%) had initial surgery and 257 (73%) had interval surgery. Median follow-up was 52.7 months (range 47.6-63.9). Median peritoneal cancer index was 10 (range 0-32). The linear model best represented the relationship between peritoneal cancer index and overall survival. Patients with neoadjuvant chemotherapy had a greater instantaneous risk of baseline death than those with initial surgery, as well as a more rapid increase in this risk as the peritoneal cancer index increased. Overall survival and recurrence free survival were better in the initial surgery group (103.4 months (79.1-not reached (NR)) vs 66.5 months (59.1-95.3) and 31.8 months (23.7-48.7) vs 25.9 months (23.2-29), respectively). Risk factors for death were body mass index, peritoneal cancer index, and need for neoadjuvant chemotherapy. CONCLUSION: The peritoneal cancer index is a prognostic indicator, but its linear relationship with survival precluded setting a unique peritoneal cancer index cut-off. Moreover, the prognostic impact of peritoneal cancer index was stronger in the setting of neoadjuvant chemotherapy.


Carcinoma, Ovarian Epithelial , Ovarian Neoplasms , Peritoneal Neoplasms , Humans , Female , Middle Aged , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/surgery , Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Aged , Adult , Retrospective Studies , Aged, 80 and over , Cytoreduction Surgical Procedures/methods , Neoadjuvant Therapy , Prognosis
19.
ANZ J Surg ; 94(4): 628-633, 2024 Apr.
Article En | MEDLINE | ID: mdl-38450829

BACKGROUND: This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves. RESULTS: 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed. CONCLUSIONS: The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding.


Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/pathology , Hyperthermic Intraperitoneal Chemotherapy , Combined Modality Therapy , Quality of Life , Chemotherapy, Cancer, Regional Perfusion , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytoreduction Surgical Procedures , Survival Rate , Retrospective Studies
20.
Medicina (Kaunas) ; 60(3)2024 Mar 10.
Article En | MEDLINE | ID: mdl-38541186

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis.


Carcinoma , Ovarian Neoplasms , Peritoneal Neoplasms , Teratoma , Female , Humans , Middle Aged , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/pathology , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Carcinoma/diagnosis , Carcinoma/surgery , Teratoma/diagnosis , Teratoma/surgery , Teratoma/pathology
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