Clinicopathological characteristics of primary peritoneal epithelioid mesothelioma of clear cell type: A case report.

RATIONALE: Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor. PATIENTS CONCERNS: A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month. DIAGNOSIS: The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected. INTERVENTIONS: The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times. OUTCOMES: Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction. LESSONS: Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.

Physical, psychological and nutritional outcomes in a cohort of Irish patients with metastatic peritoneal malignancy scheduled for cytoreductive surgery (CRS) and heated intrapertioneal chemotherapy (HIPEC): An exploratory pilot study.

BACKGROUND: Treatment for peritoneal malignancy (PM) can include cytoreductive surgery (CRS) and heated intrapertioneal chemotherapy (HIPEC) and is associated with morbidity and mortality. Physical, psychological and nutritional outcomes are important pre-operatively. The aim of this pilot study was to investigate these outcomes in patients with PM before and after CRS-HIPEC. METHODS: Between June 2018 and November 2019, participants were recruited to a single-centre study. Primary outcome was cardiopulmonary exercise testing (CPET) variables oxygen uptake (VO2) at anaerobic threshold (AT) and at peak. Secondary outcome measures were upper and lower body strength, health related quality of life (HRQoL) and the surgical fear questionnaire. Exploratory outcomes included body mass index, nutrient intake and post-operative outcome. All participants were asked to undertake assessments pre CRS-HIPEC and 12 weeks following the procedure. RESULTS: Thirty-nine patients were screened, 38 were eligible and 16 were recruited. Ten female and 6 male, median (IQR) age 53 (42-63) years. Of the 16 patients recruited, 14 proceeded with CRS-HIPEC and 10 competed the follow up assessment at week 12. Pre-operative VO2 at AT and peak was 16.8 (13.7-18) ml.kg-1.min-1 and 22.2 (19.3-25.3) ml.kg-1.min-1, upper body strength was 25.9 (20.3-41.5) kg, lower body strength was 14 (10.4-20.3) sec, HRQoL (overall health status) was 72.5 (46.3-80) % whilst overall surgical fear was 39 (30.5-51). The VO2 at AT decreased significantly (p = 0.05) and HRQoL improved (p = 0.04) between pre and post- CRS-HIPEC. There were no significant differences for any of the other outcome measures. CONCLUSION: This pilot study showed a significant decrease in VO2 at AT and an improvement in overall HRQoL at the 12 week follow up. The findings will inform a larger study design to investigate a prehabilitation and rehabilitation cancer survivorship programme.

Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer.

PURPOSE: Presence of circulating tumor cells (CTCs) is associated with impaired clinical outcome in several solid cancers. Limited data are available on the significance of CTCs in gynaecological malignancies. The aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess their clinical relevance. METHODS: 43 patients with ovarian, fallopian tube and peritoneal cancer were included into this prospective study. Patients received chemotherapy according to national guidelines. CTC analysis was performed using the CellSearch system prior to chemotherapy, after three and six cycles. RESULTS: In 26% of the patients, ≥ 1CTC per 7.5 ml of blood was detected at baseline (17% of patients with de novo disease, compared to 35% in recurrent patients). Presence of CTCs did not correlate with other factors. After three cycles of therapy, CTC positivity rate declined to 4.8%. After six cycles, no patient showed persistent CTCs. Patients with ≥ 1 CTC at baseline had significantly shorter overall survival and progression-free survival compared to CTC-negative patients (OS: median 3.1 months vs. not reached, p = 0.006, PFS: median 3.1 vs. 23.1 months, p = 0.005). When only the subgroup with newly diagnosed cancer was considered, the association between CTC status and survival was not significant (OS: mean 17.4 vs. 29.0 months, p = 0.192, PFS: 14.3 vs. 26.9 months, p = 0.085). Presence of ≥ 1 CTC after three cycles predicted shorter OS in the entire patient cohort (p < 0.001). CONCLUSIONS: Hematogenous tumor cell dissemination is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. CTC status before start of systemic therapy correlates with clinical outcome. Chemotherapy leads to a rapid decline in CTC counts; further research is needed to evaluate the clinical value of CTC monitoring after therapy.

Tratamiento radical de la carcinomatosis peritoneal. Tiempos de cambio / Radical treatment of peritoneal carcinomatosis: Times are changing

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Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming.

Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear. Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments. Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition. Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis.

Comparative proteomic analysis of human malignant ascitic fluids for the development of gastric cancer biomarkers.

OBJECTIVES: Malignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis. Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding. DESIGN & METHODS: First, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancer patients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis. RESULTS: Comprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification, we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancer patients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA. CONCLUSIONS: This study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites.

Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases.

BACKGROUND: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. METHODS: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. RESULTS: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. CONCLUSION: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

Imaging findings of inflammatory myofibroblastic tumor from the greater omentum: One case report.

RATIONALE: Inflammatory myofibroblastic tumors (IMTs) are rare neoplastic lesions with benign tendency. Even more rare are IMTs from the greater omentum (GO-IMT). A GO-IMT is easily misdiagnosed as other malignant tumors before operation; thus, clinicians need to be familiar with its imaging findings. Here, we report the imaging findings of a GO-IMT patient presenting with a pelvic mass. PATIENT CONCERNS: Ultrasound of the IMT in the pelvic cavity showed a hypoechoic mass. A computed tomography (CT) scan showed a nearly circular soft tissue mass with a clear border and heterogeneous density, and the surrounding tissues were pushed and compressed. Contrast-enhanced CT showed severe persistent enhancement in the lesion edges and mural nodules, but not in the central necrosis. DIAGNOSES: Histopathology and immunohistochemistry confirmed that the mass was a GO-IMT. INTERVENTIONS: The tumor was resected after preoperative preparation. OUTCOMES: No recurrence or metastasis was found during a short-term follow-up. LESSONS: The GO-IMT is an inferior epigastric mass in the periphery of the bowel, and is usually well-demarcated without calcification or lymphadenopathy. Contrast-enhanced CT showed a heterogeneous hypervascular mass where the center necrosis, the edge of the tumor, and the mural nodules can be partially reinforced.

Peritoneum as the sole distant metastatic site of lung adenosquamous cell carcinoma: a case report.

BACKGROUND: Peritoneum metastasis of lung cancer is a rare event which, in addition to the peritoneum, usually involves multiple metastatic tissues. Here we report a case of a patient with lung adenosquamous cell carcinoma with the peritoneum as the sole distant metastatic site. CASE PRESENTATION: An 82-year-old Han Chinese man, in the teaching profession, was diagnosed with lung adenosquamous cell carcinoma in the upper lobe of his left lung with the involvement of ipsilateral hilar and mediastinal lymph nodes, and was initially staged as IIIa (cT2N2M0). Molecular testing identified a mutation at KRAS G12A. Due to his poor physical condition, our patient was given gamma knife radiotherapy with a total dose of 28.0 Gy. Two weeks later, our patient was diagnosed as peritoneal metastasis identified by using magnetic resonance imaging and confirmed with ascitic cytology and peritoneal histology. No other distant metastatic sites such as liver, brain, bone, paranephroi, and lungs were found. Subsequently, our patient received palliative intraperitoneal chemotherapy, and died within 2 months. CONCLUSIONS: Our patient represented a rare case of lung adenosquamous cell carcinoma harboring the KRAS G12A mutation, which metastasized distantly to the peritoneum only, and progressed rapidly.

The peritoneum: healing, immunity, and diseases.

The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Diaphragmatic Surgery and Related Complications In Primary Cytoreduction for Advanced Ovarian, Tubal, and Peritoneal Carcinoma.

BACKGROUND: To evaluate the procedures and complications of diaphragm peritonectomy (DP) and diaphragm full-thickness resection (DFTR) during primary cytoreduction for advanced stage epithelial ovarian cancer. METHODS: All the patients with epithelial ovarian carcinoma who underwent diaphragm procedures at our institution between January 2009 and August 2015 were identified. Clinicopathological data were retrospectively collected from the patients' medical records. Postoperative morbidities were assessed according to the Memorial Sloan-Kettering Cancer Center (MSKCC) grading system. RESULTS: A total of 150 patients were included in the study. The majority of the patients had ovarian cancer (96%), stage IIIC disease (76%) and serous histology (89.3%). DP and DFTR were performed in 124 (82.7%) and 26 (17.3%) patients, respectively. A total of 142 upper abdominal procedures in addition to the diaphragmatic surgery were performed in 77 (51.3%) patients. No macroscopic residual disease was observed in 35.3% of the patients, while 84% of the total patient cohort had residual disease ≤1 cm. The overall incidence of at least one major morbidity (MSKCC grades 3-5) was 18.0%, whereas pleural effusions (33.3%), pneumonia (15.3%) and pneumothorax (7.3%) were the most commonly reported morbidities. The rate of postoperative pleural drainage was 14.6% in total, while half the patients in the DFTR group received drainage intraoperatively (11.5%) and postoperatively (38.5%). The incidence of postoperative pleural effusion was associated with stage IV disease (hazard ratio [HR], 17.2; 95% confidence interval [CI]: 4.5-66.7; P < 0.001), DFTR (HR, 4.9; 95% CI: 1.2-19.9; P = 0.028) and a long surgery time (HR, 15.4; 95% CI: 4.3-55.5; P < 0.001). CONCLUSIONS: Execution of DP and DFTR as part of an extensive upper abdominal procedure resulted in an acceptable morbidity rate. Pleural effusion, pneumonia and pneumothorax were the most common pulmonary morbidities. The pleural drainage rate was not high enough to justify prophylactic chest tube placement for all the patients. However, patients who underwent DFTR merited special consideration for intraoperative prophylactic drainage.

Haemodynamic changes during hyperthermic intra-thoracic chemotherapy for pseudomyxoma peritonei.

PURPOSE: Hyperthermic intra-thoracic chemotherapy (HITOC) combined with cytoreductive surgery (CRS) is a novel approach in the management of pseuodmyxoma peritonei with thoracic extension. The haemodynamic effects of hyperthermic chemotherapy present an anaesthetic challenge. Here, we describe the haemodynamic changes seen during HITOC. MATERIALS AND METHODS: A retrospective case note review of adult patients undergoing CRS with HITOC from 2009 to 2016. Intra-operative haemodynamics were measured using the LIDCOrapidTM brand of invasive cardiac output (CO) monitor. Intravenous fluids, vasopressor requirements and urine output (UO) were recorded. RESULTS: Four patients were included in the study. Mean heart rate (HR) peaked at 20 min following commencement of HITOC. The difference between HR at time 0 and at peak was minimal. There was minimal change in CO, and stroke volume variation (SVV) remained stable. Vasopressor dose was minimally changed throughout surgery. Average UO during HITOC was 142.5 ± 109.6 mls at 60 min. Mean fluid requirements during HITOC was 586.2 ± 441.2 mls. No significant change occurred in pH or base excess (BE). CONCLUSIONS: Significant haemodynamic instability including cardiac asystole has been reported during HITOC. The application of hyperthermic agents to the thorax results in vasodilatation, cardiac warming and compression of mediastinal vessels. Measurement of haemodynamic variables allowed careful titration of intravenous fluid therapy to CO and stroke volume, allowing for haemodynamic stability. This has not been described elsewhere.

Hyperthermic chemotherapy intra-abdominal laparoscopic approach: development of a laparoscopic model using CO2 recirculation system and clinical translation in peritoneal carcinomatosis.

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal carcinomatosis (PC). Laparoscopic surgery is performed in the treatment of colorectal and appendiceal cancer, and PC from diverse origin in selected patients. HIPEC management by laparoscopic approach after cytoreductive surgery (CRS) completed locoregional treatment of PC, and may be feasible and safe after appropriate patient selection. OBJECTIVE: Development of an experimental model of HIPEC by laparoscopic approach, with CO2 recirculation. Clinical translation in two patients with PC and low peritoneal cancer index. MATERIAL AND METHODS: We performed CRS in a porcine model of 5 pigs (35-38 kg) by laparoscopic approach. Laparoscopic HIPEC by CO2 recirculation system was performed; laparoscopic access was used for catheter input and output placement (Paclitaxel 175 mg/m2 for 60 min at 42 °C). The experimental variables were: blood gases, haemodynamic and intra-abdominal and central temperature. Clinical model application was performed in three cases with PC from colorectal origin. RESULTS: No statistically significant differences was found in blood gases, haemodynamic or temperature in the experimental study. In clinical study, there were no technical complications during laparoscopic-HIPEC approach, and we observed no changes in haemodynamic variables during the procedure. CONCLUSIONS: CRS and HIPEC laparoscopic model by CO2 recirculation system is safe and feasible technique in selected patients, that include low PC index, local and accessible tumour recurrences or high-risk of PC tumours.

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum.

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Besides the lymphatic and haematogenous routes of dissemination, CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity, which ultimately leads to peritoneal carcinomatosis (PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However, this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements, involving several well-defined steps, together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor, gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum, subsequently invade the subperitoneal space, where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript, we review current data regarding the molecular mechanisms underlying the development of colorectal PC, with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread.

Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.

Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.

Gastrointestinal Infantile Hemangioma: Presentation and Management.

OBJECTIVES: The aim of the present study was to document the clinical presentation, diagnostic studies, and therapy of gastrointestinal infantile hemangiomas. METHODS: This is a retrospective analysis of children with gastrointestinal hemangiomas culled from our Vascular Anomalies Center database. We detailed the location of visceral and cutaneous tumors, as well as radiologic and procedural methods used for diagnosis and treatment. RESULTS: A total of 9 of the 16 children (14 girls and 2 boys) with hollow visceral hemangiomas also had cutaneous lesions. The most common extravisceral sites were regional facial lesions (n = 6), multifocal lesions (n = 2), and a solitary chest lesion (n = 1). Presenting symptoms were melena and hematochezia in the first 4 months of life (n = 14); several infants required multiple blood transfusions. The most frequent locations were small bowel and mesentery. One-half of the patients (n = 8) were diagnosed by laparotomy; the majority (n = 12) had suspicious radiologic findings. Corticosteroid and/or propranolol were the most common therapies. CONCLUSIONS: Melena and hematochezia, sometimes with profound anemia, in the first 4 months of life, suggest the possibility of intestinal infantile hemangioma even in the absence of cutaneous tumor. Intestinal bleeding, particularly in association with a regional facial lesion, should initiate workup: ultrasonography, computed tomography, and magnetic resonance imaging display diagnostic features. First-line treatment is medical management; bowel resection may be necessary, particularly for perforation.

Alterations in hemostasis during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently associated with coagulation impairment and perioperative blood transfusion. Our aim was to investigate the impact of each procedure step on hemostasis, as measured by rotational thromboelastometry™ (ROTEM), fibrinogen level and platelet count as a primary outcome, along with its relationship with transfusion needs. METHODS: A prospective longitudinal study was performed. Hemoglobin level, fibrinogen level, platelet count and ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), α-angle (EXTEM, INTEM, FIBTEM) were measured before the procedure, at the end of cytoreductive surgery and after HIPEC. Appropriate statistical tests were used for comparison. A P<.05 was considered as significant. RESULTS: Forty-one women, with median age 54 (range 34-76) were recruited. Cytoreductive surgery was followed by a reduction of hemoglobin level from 11,4±1,5g/dl to 10,6±1,6g/dl, a reduction of serum fibrinogen level from 269±69mg/dl to 230±48mg/dl (P<.01) and MCF decline from 20±10 to 16±8mm (P<.01), in the FIBTEM test. HIPEC was followed by no hemostatic impairment. The number of packed red blood cells administered during patients stay kept a mild significant relationship with both fibrinogen level (ρ = -0.5, P=.002), and MCF EXTEM values (ρ= -0.43, P=0.006), recorded after HIPEC. CONCLUSIONS: The mild observed hemostatic impairment appeared after cytoreductive surgery instead of HIPEC, involving surgical hemorrhage as the most likely responsible factor. Further studies are required to confirm a correlation between transfusion needs and postoperative hemostatic tests.

Peritoneal Tumorigenesis and Inflammation are Ameliorated by Humidified-Warm Carbon Dioxide Insufflation in the Mouse.

BACKGROUND: Conventional laparoscopic surgery uses CO2 that is dry and cold, which can damage peritoneal surfaces. It is speculated that disseminated cancer cells may adhere to such damaged peritoneum and metastasize. We hypothesized that insufflation using humidified-warm CO2, which has been shown to reduce mesothelial damage, will also ameliorate peritoneal inflammation and tumor cell implantation compared to conventional dry-cold CO2. METHODS: Laparoscopic insufflation was modeled in mice along with anesthesia and ventilation. Entry and exit ports were introduced to maintain insufflation using dry-cold or humidified-warm CO2 with a constant flow and pressure for 1 h; then 1000 or 1 million fluorescent-tagged murine colorectal cancer cells (CT26) were delivered into the peritoneal cavity. The peritoneum was collected at intervals up to 10 days after the procedure to measure inflammation, mesothelial damage, and tumor burden using fluorescent detection, immunohistochemistry, and scanning electron microscopy. RESULTS: Rapid temperature control was achieved only in the humidified-warm group. Port-site tumors were present in all mice. At 10 days, significantly fewer tumors on the peritoneum were counted in mice insufflated with humidified-warm compared to dry-cold CO2 (p < 0.03). The inflammatory marker COX-2 was significantly increased in the dry-cold compared to the humidified-warm cohort (p < 0.01), while VEGFA expression was suppressed only in the humidified-warm cohort. Significantly less mesothelial damage and tumor cell implantation was evident from 2 h after the procedure in the humidified-warm cohort. CONCLUSIONS: Mesothelial cell damage and inflammation are reduced by using humidified-warm CO2 for laparoscopic oncologic surgery and may translate to reduce patients' risk of developing peritoneal metastasis.