[Diffuse Hepatoid Adenocarcinoma in the Peritoneal Cavity:Report of One Case].

Hepatoid adenocarcinoma is a rare and unique type of adenocarcinoma,resembling hepatocellular carcinoma in histopathology.Most cases occur in the stomach,lacking specific clinical and imaging manifestations,which leads to high rates of missed diagnosis and misdiagnosis.Hepatoid adenocarcinoma in the peritoneal cavity is even rarer.This article reports a case of hepatoid adenocarcinoma with the manifestation of diffuse peritoneal thickening,aiming to provide reference for clinical diagnosis and treatment.

Ultrabright NIR-II Nanoprobe for Image-Guided Accurate Resection of Tiny Metastatic Lesions.

Fluorescence imaging is a vital way to delineate the tumor boundaries. Here, we achieve a NIR-II aggregation-induced emission luminogen (AIEgen) with a fluorescence quantum yield (QY) of 12.6% in water through straightforward alkyl side chain modification. After loading of NIR-II AIEgen into polystyrene (PS) nanospheres, the thermal deactivation pathway is extremely limited, thereby concentrating absorption excitation on fluorescence emission. The fluorescence intensity is further enhanced by 5.4 times, the QY increases to 21.1%, and the NIR-II imaging signal is accordingly enhanced by 8.7 times, surpassing conventional DSPE-PEG carriers. The NIR-II@PS nanoprobe showcases superior resolution and tissue penetration depth compared to indocyanine green (ICG) and short-range near-infrared AIEgens. In vivo investigations underscore its tumor-to-normal tissue ratio (3.9) at 24 h post intravenous injection, enabling complete resection of ≤1 mm metastases under NIR-II bioimaging guidance. Additionally, the PS carrier-nanoparticles exhibit low toxicity in vivo, laying a promising foundation for the future design of medical nanomaterials.

Benign Multicystic Peritoneal Mesothelioma: Two Rare Cases and Review of the Literature.

BACKGROUND: Benign multicystic peritoneal mesothelioma is a multiloculated cystic mass which originates from the peritoneum. This rare tumor is usually seen in women of childbearing age and has a high recurrence rate after surgery. CASE PRESENTATION: We present two benign multicystic peritoneal mesothelioma cases with different imaging modalities, which were also pathologically proven. CONCLUSION: The imaging features which may be diagnostic should be well known as there are very few reports regarding this entity.

[A case of malignant peritoneal mesothelioma].

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

Tumor DNA in Peritoneal Lavage as a Novel Biomarker for Predicting Peritoneal Recurrence in Patients With Gastric Cancer.

BACKGROUND: Peritoneal lavage cytology positivity (CY1) has been identified as a prognostic factor for distant metastases that is equivalent to peritoneal dissemination in Japan. Peritoneal lavage cytology is usually diagnosed by microscopic findings; a diagnostic procedure using a liquid biopsy (LB) technique has not yet been established. PATIENTS AND METHODS: We evaluated the feasibility of a LB approach using peritoneal lavage samples from 15 patients with gastric cancer. Samples were collected from both the Douglas pouch and the left subdiaphragmatic area, and cell-free DNA was extracted for analysis of TP53 mutations using droplet digital polymerase chain reaction. RESULTS: All 10 patients with CY1 had positive cytology for the left subdiaphragmatic specimen. However, only six out of the 10 patients had positive cytology for their Douglas pouch specimens, and these six patients had peritoneal tumor DNA (ptDNA) in these specimens. In all five patients with CY0, ptDNA was not detected. The overall survival was significantly shorter in the ptDNA-positive group than in the ptDNA-negative group. The survival of the group with a high amount of DNA from free intraperitoneal cells (ficDNA) was significantly worse than that of those with a low amount. In contrast, the group with a high amount of DNA from peritoneal cell-free DNA (pcfDNA) had significantly better survival than the group with a low amount. CONCLUSION: LB cytology showed equivalent utility to that of conventional microscopic examinations regarding its diagnostic ability. Therefore ptDNA, pcfDNA and ifcDNA are expected to be useful as prognostic factors.

A case of malignant peritoneal mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

Unusually large paraganglioma complicated with successive catecholamine crises: A case report and review of the literature.

Background: Paragangliomas are rare neuroendocrine tumors that could secret catecholamines. Hypertension and heart failure caused by the catecholamine crisis are fatal cardiovascular events. However, silent paragangliomas that lack typical symptoms of catecholamine pose a significant diagnostic challenge. Case summary: A 45-year-old woman who presented with more than 1-year history of abdominal discomfort was suspected of having a gastrointestinal stromal tumor by a local hospital since a vast metastatic mass occupied her left abdomen. Thus, she was recommended to our hospital. After completing the gastroscopy, she unexpectedly developed acute heart failure and was transferred to the Intensive Care Unit (ICU) where the initial diagnosis of paraganglioma was considered through path. However, a second catecholamine crisis due to constipation led to acute heart failure again. After anti-heart failure therapy and rigorous preoperative preparation, surgery was arranged to remove the tumor. Postoperative pathology confirmed the paraganglioma, and the patient was discharged from the hospital in good condition. Conclusion: We reported a rare case of huge retro-peritoneal paraganglioma with successive catecholamine crises and acute heart failure. This was probably the largest retro-peritoneal paraganglioma since the 1980s. Besides, we were the first to use surgical drawing to illustrate its complex anatomical adjacent relationship of retro-peritoneal paraganglioma. Our case emphasizes the inclusion of extra-adrenal paraganglioma in the differential diagnosis of retroperitoneal tumors. In suspected paragangliomas, catecholamine testing is preferable to invasive procedures including gastroscopy and biopsy to avoid triggering a catecholamine crisis. Surgical resection is the primary treatment. We highlight the priority of dealing with the venous reflux branches of the tumor to prevent the release of catecholamines into the blood. In particular, preoperative preparation plays a vital role in managing paraganglioma. Moreover, it is necessary to schedule genetic testing and clinical follow-up due to the metastatic potential of paragangliomas.

Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer.

Peritoneal metastasis (PM) is the main site of gastric cancer (GC) distant metastasis and indicates an extremely poor prognosis and survival. Hypoxia is a common feature of peritoneal metastases and up-regulation of hypoxia inducible factor 1 alpha (HIF-1α) may be a potential driver in the occurrence of PM. Ferroptosis is a recently discovered form of regulated cell death and closely related to the occurrence and development of tumors. However, the underlying mechanism link HIF-1α to ferroptosis in PM of GC remains unknown. Here, lncRNA-microarrays and RNA library construction/lncRNA-seq results shown that lncRNA-PMAN was highly expressed in PM and significantly modulated by HIF-1α. Upregulation of PMAN is associated with poor prognosis and PM in patients with GC. PMAN was up-regulated by HIF-1α and improved the stability of SLC7A11 mRNA by promoting the cytoplasmic distribution of ELAVL1, which was identified in RNA-pulldown/mass spectrometry results. Accumulation of SLC7A11 increases the level of l-Glutathione (GSH) and inhibits the accumulation of reactive oxygen species (ROS) and irons in the GC cells. Finally protect GC cells against ferroptosis induced by Erastin and RSL3. Our findings have elucidated the effect of HIF-1α/PMAN/ELAVL1 in GC cells ferroptosis and provides theoretical support for the potential diagnostic biomarkers and therapeutic targets for PM in GC.

Laparoscopic cytoreductive surgery and HIPEC in LAMN with small volume of peritoneal disease: a valuable option of treatment for good patient-related experience measures (PREMs).

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the best effective treatment for pseudomyxoma peritonei (PMP). In the last years, the advances in histopathology have stratified PMP lesions in different degrees of aggressivity suggesting the possibility of a tailored treatment. In a subset of patients with small volume peritoneal disease, laparoscopic CRS and HIPEC is feasible. The aim of this study is to analyze the results of laparoscopic CRS + HIPEC in a monocentric series of patients under patient-related experience measures (PREMs). METHODS: All consecutive patients who underwent laparoscopic CRS-HIPEC with curative intent at Cancer Institute of Montpellier were retrieved from a prospectively maintained database and analyzed. Selection criteria for laparoscopic approach were low-grade PMP with pathological confirmation prior to CRS-HIPEC, age < 75 years, no extra-peritoneal disease, peritoneal cancer index (PCI) < 10, and a limited history of abdominal surgery. A PREMS interview was conducted before analysis with all the included patients. Outcomes of interest included postoperative morbidity, medium-term survival, and PREMs. RESULTS: Fourteen patients were operated on for low-grade PMP with a laparoscopic approach at our institution. Conversions to laparotomy were necessary in three patients, and postoperative complications were observed in three patients (Clavien 3b in one patient). In-hospital postoperative median stay was 9.5 days. No death or recurrence was observed during the study period. CONCLUSIONS: Laparoscopic CRS-HIPEC for LAMN in presence of small peritoneal disease is feasible in terms of postoperative morbidity and mortality. According to our PREMs questionnaire, patients' expectations were satisfied.

Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases.

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.

Deuterium Depletion Inhibits Cell Proliferation, RNA and Nuclear Membrane Turnover to Enhance Survival in Pancreatic Cancer.

The effects of deuterium-depleted water (DDW) containing deuterium (D) at a concentration of 25 parts per million (ppm), 50 ppm, 105 ppm and the control at 150 ppm were monitored in MIA-PaCa-2 pancreatic cancer cells by the real-time cell impedance detection xCELLigence method. The data revealed that lower deuterium concentrations corresponded to lower MiA PaCa-2 growth rate. Nuclear membrane turnover and nucleic acid synthesis rate at different D-concentrations were determined by targeted [1,2-13C2]-D-glucose fate associations. The data showed severely decreased oxidative pentose cycling, RNA ribose 13C labeling from [1,2-13C2]-D-glucose and nuclear membrane lignoceric (C24:0) acid turnover. Here, we treated advanced pancreatic cancer patients with DDW as an extra-mitochondrial deuterium-depleting strategy and evaluated overall patient survival. Eighty-six (36 male and 50 female) pancreatic adenocarcinoma patients were treated with conventional chemotherapy and natural water (control, 30 patients) or 85 ppm DDW (56 patients), which was gradually decreased to preparations with 65 ppm and 45 ppm deuterium content for each 1 to 3 months treatment period. Patient survival curves were calculated by the Kaplan-Meier method and Pearson correlation was taken between medial survival time (MST) and DDW treatment in pancreatic cancer patients. The MST for patients consuming DDW treatment (n = 56) was 19.6 months in comparison with the 6.36 months' MST achieved with chemotherapy alone (n = 30). There was a strong, statistically significant Pearson correlation (r = 0.504, p < 0.001) between survival time and length and frequency of DDW treatment.

Diffuse peritoneal leiomyomatosis: An exceptional entity in a male patient.

Diffuse peritoneal leiomyomatosis is a benign peritoneal tumor which develops from smoother muscular fibers. It is a rare entity in females undergoing hormonal effects. This pathological entity is exceptional in male patients. Hence, we report a unique case of diffuse peritoneal leiomyomatosis that occurred in a male patient without hormonal stimulations. The etiopathology and genesis are not completely elucidated. Besides, the clinical symptoms are not specific. The positive diagnosis is based on sets of imaging argument. The anatomicopathological studies allow confirming the diagnosis and reject any tumoral origin. The evolution of the pathology is often favorable. The malignant transformation is exceptional. The treatment is based on abolishing any of the hormonal stimulations. The surgical exeresis is indicated in case of higher peritoneal mass. In case of recurrence or progression, luteinizing hormone-releasing hormone analogs or surgical castrations are indicated.

Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic. Proposals for prioritization from the RENAPE and BIG-RENAPE groups.

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.

Peritoneal spillage is not an issue in patients undergoing minimally invasive surgery for colorectal cancer.

BACKGROUND: Surgery for colorectal cancer (CRC) is increasingly being performed via the minimally invasive route. However, reports of postoperative wound and port site seeding as well as peritoneal spillage have been worrisome. We investigated the risk of peritoneal spillage in patients undergoing laparoscopic surgery for CRC. METHODS: Cytology specimens were gained from the retrieval bag following intracorporeal resection and specimen retrieval using an endoscopic retrieval bag. Histopathologic examination of the cytology specimens was performed for the presence of malignant cells. RESULTS: Cytology specimens of 73 (34 female and 39 male) consecutive patients with a median age of 71 years were included for analysis. Advanced CRC in stages III and IV was present in 41% of the study population. Malignant cells were not found in any specimen. CONCLUSION: Laparoscopic oncologic resection of colorectal cancer is not a risk factor for peritoneal spillage. Minimally invasive oncologic colorectal resection is safe without the increased risk of peritoneal carcinomatosis.

[Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic. Proposals for prioritization from the RENAPE and BIG-RENAPE groups]. / Prise en charge des tumeurs primitives et métastatiques du péritoine en période de pandémie CoViD-19. Pistes de réflexion et de priorisation du groupe RENAPE et BIG-RENAPE.

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.

The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy.

Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23-0.69 and HR 0.49; 95%CI 0.29-0.83) and OS (HR 0.33; 95%CI 0.18-0.62 and HR 0.36; 95%CI 0.20-0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.

Interobserver, intraobserver, and interlaboratory variability in reporting pT4a colon cancer.

Clinical significance of the pT4 category in colon cancer is increasing with several therapeutic implications. The aim of this study was to evaluate variability in diagnosing pT4a colon cancer. Twelve pathologists classified 66 preselected scanned Hematoxylin/Eosin-stained slides with tumor cells at a distance of 25-1500 µm (n = 22), 0-25 µm (n = 22), or on (n = 22) the peritoneal surface. Inter- and intraobserver variability were calculated using Kappa statistics. For interlaboratory variability, pathology reports of pT3 and pT4a colon cancer were extracted from the Dutch Pathology Registry between 2012 and 2015. The proportion of pT4a (pT4a/(pT3+pT4a)) was compared between 33 laboratories. Potential risk of understaging was assessed by determining the average number of blocks taken from pT3 and pT4a N0-2M0 tumors with metachronous peritoneal metastasis. Interobserver variability among 12 pathologists was 0.50 (95%CI 0.41-0.60; moderate agreement). Intraobserver variability (8 pathologists) was 0.71 (substantial agreement). A total of 7745 reports with pT3 or pT4aN0-2M0 colon cancer from 33 laboratories were included for interlaboratory analysis. Median percentage of pT4a was 15.5% (range 3.2-24.6%). After adjustment for case mix, 8 labs diagnosed pT4a significantly less or more frequently than the median lab. Metachronous peritoneal metastases were histologically verified in 170 of 6629 pT3 and in 129 of 1116 pT4a tumors, with a mean number of blocks of 4.03(SD 1.51) and 4.78 (SD 1.76) taken from the primary tumors, respectively (p < 0.001). A substantial variability in diagnosing pT4a colon cancer exists, both at pathologist and laboratory level. Diagnosis of pT4a stage appears to be challenging and there is a need for standardizing assessment of this pathological entity.

Imaging for Peritoneal Metastases.

MRI provides considerable advantages for imaging of patients with peritoneal tumor. Its inherently superior contrast resolution compared with computed tomography allows MRI to more accurately depict small peritoneal tumors that are often missed on other imaging tests. Combining different contrast mechanisms, including diffusion-weighted MRI and gadolinium-enhanced MRI, provides a powerful tool for preoperative and surveillance imaging in patients being considered for cytoreductive surgery and heated intraperitoneal chemotherapy.

Exploiting Uptake of Nanoparticles by Phagocytes for Cancer Treatment.

Many cancers including ovarian, pancreatic, colon, liver, and stomach cancers are largely confined to the peritoneal cavity. Peritoneal tumors are directly accessible by intraperitoneal injections. Previously we demonstrated that intraperitoneal injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes can be used to either directly impact tumors or stimulate antitumor immune responses. Here we outline methods to specifically utilize iron oxide nanoparticles with the ID8-Defb29/Vegf-A murine ovarian cancer model and discuss the tendency of phagocytes to ingest nanoparticles and the potential of phagocytes to carry nanoparticles to tumors resulting in direct killing of tumor cells or stimulate antitumor immune responses in peritoneal cancers. This basic approach can be modified as needed for different types of tumors and nanoparticles.