Exosomal ROR1 in peritoneal fluid identifies peritoneal disseminated PDAC and is associated with poor survival.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters. Methods: Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed. Results: PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482). Conclusion: With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.

Clinical impact of high-quality testing for peritoneal lavage cytology in pancreatic cancer.

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.

Stercoral perforation of the cecum: A case report.

BACKGROUND: With less than 90 reported cases to date, stercoral perforation of the colon is a rare occurrence. Stercoral ulceration is thought to occur due to ischemic pressure necrosis of the bowel wall, which is caused by the presence of a stercoraceous mass. To underscore this urgent surgical situation concerning clinical presentation, surgical treatment, and results, we present the case of a 66-year-old man with a stercoral perforation. CASE SUMMARY: A 66-year-old man with a history of hypertension, hyperlipidemia, and gout presented at the emergency department with lower abdominal pain and a low-grade fever lasting for a few hours. Abdominal computed tomography indicated a suspected bezoar (approximately 7.6 cm) in the dilated cecum, accompanied by pericolic fat stranding, mild proximal dilatation of the ileum, pneumoperitoneum, and minimal ascites. Intraoperatively, feculent peritonitis with isolated cecal perforation were observed. Consequently, a right hemicolectomy with peritoneal lavage was performed. A histopathological examination supported the intraoperative findings. CONCLUSION: In stercoral perforations, a diagnosis should be diligently pursued, especially in older adults, and prompt surgical intervention should be implemented.

Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

BACKGROUND: The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. METHODS: We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. RESULTS: The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. CONCLUSIONS: The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.

Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors.

BACKGROUND: Initial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the efficacy of chemotherapy in GC. METHODS: One hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The influence of initial treatment on overall survival (OS) in each group was evaluated. RESULTS: In the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% confidence interval, 0.375-0.933: P = 0.023). CONCLUSIONS: Initial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC.

Diagnosis of small intestinal microperforation by cell morphology detection in abdominal puncture fluid: A case report.

INTRODUCTION AND IMPORTANCE: Although abdominal computed tomography angiography (CTA) may be a gold standard for early diagnosis of small intestinal microperforation, early missed and delayed diagnosis are often important factors leading to poor prognosis. The cellular morphology diagnosis of abdominal puncture fluid (DAPF) or diagnostic peritoneal lavage (DPL) may have unexpected clinical outcomes. CASE PRESENTATION: We report a case of small bowel microperforation which dues to BAT. A 39-year-old male with a chief complaint of "multiple injuries to the whole body from a car accident within 7 hours" was admitted to the trauma center. The first abdominal CTA ruled out perforation of abdominal parenchymatous organs and gastrointestinal tract. Subsequently, the patient underwent emergency surgery for traumatic shock, followed by clinical manifestations of persistent fever and septic shock. After diagnostic abdominal puncture fluid cell morphology examination, intestinal perforation was first considered. CLINICAL DISCUSSION: Routine examination of abdominal puncture fluid can usually roughly determine the condition of visceral trauma, especially quickly and conveniently determine whether there is intra-peritoneal bleeding. However specific diagnostic components which were found in the cell images of abdominal puncture fluid also showed the clinical value of cellular morphology of DAPF. CONCLUSION: The cellular morphology examination of DAPF/DPL may be the simplest, fastest, and most effective method for diagnosing small intestinal perforation due to blunt abdominal trauma(BAT). The value of DAPF /DPL in traumatic gastrointestinal injury cannot be ignored, especially for patients with BAT.

Diverticulitis, surgery, evidence-based medicine, and the Steve Jobs' dots: a narrative review.

PURPOSE: Emergency treatment of acute diverticulitis remains a hazy field. Despite a number of clinical studies, randomized controlled trials (RCTs), guidelines and surgical societies recommendations, the most critical hot topics have yet to be addressed. METHODS: Literature research from 1963 until today was performed. Data regarding the principal RCTs and observational studies were summarized in descriptive tables. In particular we aimed to focus on the following topics: the role of laparoscopy, the acute care setting, the RCTs, guidelines, observational studies and classifications proposed by literature, the problem in case of a pandemic, and the importance of adapting treatment /place/surgeon conditions. RESULTS: In the evaluation of these points we did not try to find any prospective evolution of the concepts achievements. On the contrary we simply report the individuals strands of research from a retrospective point of view, similarly to what Steve Jobes said: "you can't connect the dots looking forward; you can only connect them looking backwards. So you have to trust that the dots will somehow connect in your future". We have finally obtained what can be defined "a narrative review of the literature on diverticulitis". CONCLUSIONS: Not only evidence-based medicine but also the contextualization, as also the role of 'competent' surgeons, should guide to novel approach in acute diverticulitis management.

Exfoliate cancer cell analysis in rectal cancer surgery: comparison of laparoscopic and transanal total mesorectal excision, a pilot study.

PURPOSE: Minimally invasive surgery (MIS) is currently the standard treatment for rectal cancer. However, its limitations include complications and incomplete total mesorectal resection (TME) due to anatomical features and technical difficulties. Transanal TME (TaTME) has been practiced since 2010 to improve this, but there is a risk of local recurrence and intra-abdominal contamination. We aimed to analyze samples obtained through lavage to compare laparoscopic TME (LapTME) and TaTME. METHODS: From June 2020 to January 2021, 20 patients with rectal cancer undergoing MIS were consecutively and prospectively recruited. Samples were collected at the start of surgery, immediately after TME, and after irrigation. The samples were analyzed for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) through a quantitative real-time polymerase chain reaction. The primary outcome was to compare the detected amounts of CEA and CK20 immediately after TME between the surgical methods. RESULTS: Among the 20 patients, 13 underwent LapTME and 7 underwent TaTME. Tumor location was lower in TaTME (7.3 cm vs. 4.6 cm, P=0.012), and negative mesorectal fascia (MRF) was more in LapTME (76.9% vs. 28.6%, P=0.044). CEA and CK20 levels were high in 3 patients (42.9%) only in TaTME. There was 1 case of T4 with incomplete purse-string suture and 1 case of positive MRF with dissection failure. All patients were followed up for an average of 32.5 months without local recurrence. CONCLUSION: CEA and CK20 levels were high only in TaTME and were related to tumor factors or intraoperative events. However, whether the detection amount is clinically related to local recurrence remains unclear.

Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy.

BACKGROUND: Our previous study found that the telomerase-associated protein 1 (TEP1, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (RECQL5, rs820196) single nucleotide polymorphisms (SNPs) were associated with changes in heart rate (HR) ≥ 30% during peritoneal lavage with distilled water after gastrectomy. This study established a single tube method for detecting these three SNPs using two-dimensional (2D) polymerase chain reaction (PCR), and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability (HRV). AIM: To investigate whether genotypes, genetic patterns, SNP-SNP and SNP-environment interactions were associated with HRV. METHODS: 2D PCR was used to establish a single-tube method to detect TEP1 rs938886 and rs1713449 and RECQL5 rs820196, and the results were compared with those of sanger sequencing. After adjusting for confounders such as age, sex, smoking, hypertension, and thyroid dysfunction, a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns (codominant, dominant, overdominant, recessive, and additive) of the three SNPs and a risk ≥ 15% or ≥ 30% of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer. Gene-gene and gene-environment interactions were analyzed using generalized multifactor dimensionality reduction. RESULTS: The coincidence rate between the 2D PCR and sequencing was 100%. When the HRV cutoff value was 15%, the patients with the RECQL5 (rs820196) TC genotype had a higher risk of high HRV than those who had the TT genotype (odds ratio = 1.97; 95%CI: 1.05-3.70; P = 0.045). Under the codominant and overdominant models, the TC genotype of RECQL5 (rs820196) was associated with a higher risk of HR decrease relative to the TT and TT + CC genotypes (P = 0.031 and 0.016, respectively). When the HRV cutoff value was 30%, patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG-TT genotype carriers (P = 0.01). In the three-factor model of rs938886, rs820196, and rs1713449, patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers (P = 0.01). For rs820196, nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype (P = 0.04). When the HRV cutoff value was 15%, patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers (P = 0.04 and 0.01, respectively). Patients carrying the GC-CT-TC genotypes of rs938886, rs1713449, and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers (P = 0.02). When the HRV cutoff value was 15%, the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking (P = 0.022) and rs820196-hypertension (P = 0.043) models. Consistent with the results of the previous grouping, for rs820196, the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype (P = 0.01). CONCLUSION: The polymorphism of the RECQL5 and TEP1 genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.

Revisiting the Use of Normal Saline for Peritoneal Washing in Ovarian Cancer.

The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing insights from clinical investigations of normal saline in fluid resuscitation and from the cytopathologic evaluation of peritoneal washings. We integrate these insights with the unique biology of the omentum and omental metastasis, highlighting the importance of considering the absorptive ability of the omentum when administering agents into the peritoneal cavity. Furthermore, we describe insights from preclinical studies regarding the mechanisms by which normal saline might render the omentum conducive for colonization by cancer cells. Importantly, we discuss the possibility that the risk of colonization of preserved omental tissues might be minimized by using balanced crystalloid solutions for peritoneal washing.

Efficacy and Safety of Extensive Intraperitoneal Lavage for Patients with Gastric Cancer - A Systematic Review and Meta-analysis.

PURPOSE: Extensive intraperitoneal lavage (EIPL) is a novel therapeutic intervention that aims to limit the chance of peritoneal metastasis during gastrectomy. Clinical trials on using EIPL after gastrectomy show controversial results. We aimed to summarize the evidence of efficacy and safety for using EIPL after gastrectomy to limit the possibility of peritoneal metastasis and improve survival. METHODS: A literature search on PubMed, Scopus, Embase, and Web of Sciences was conducted till June 2023 to identify eligible RCTs that assess the efficacy and safety of EIPL after gastrectomy. The hazard ratio with 95% CI was used to determine the survival probability, the risk ratio with 95% CI was used to assess the surgical outcomes, and ROB-2 and GRADE guidelines were used to assess the risk of bias and the certainty of evidence respectively. RESULTS: Six eligible studies with a total of 1993 patients were included in the meta-analysis. Regarding survival benefits, the survival of the EIPL group did not differ significantly from the non-EIPL group, and the pooled HR of overall survival was 0.86 (95% CI 0.58-1.26) P = 0.44, the disease-free survival was 0.81 (0.58-1.13) P = 0.21, and peritoneal recurrence-free survival was 0.97 (0.79-1.2) P = 0.25. There is no significant association between EIPL and short-term postoperative outcomes. The use of EIPL does not appear to affect postoperative mortality, infection, anastomotic leakage, bleeding, ileus, or hospital stay. CONCLUSION: Our study yielded insufficient evidence about the survival benefits and surgical outcomes of EIPL in patients with gastric cancer after gastrectomy. Therefore, it is not recommended for treating gastric cancer patients.

Failure of peritoneal lavage to prevent operative site infection and peritoneal tumor recurrence in pancreatic surgery.

BACKGROUND: Although intraoperative peritoneal lavage often is performed routinely with the aim of reducing peritoneal contamination, evidence of lavage benefit in elective pancreatic surgery is limited. METHODS: We retrospectively classified patients who had undergone pancreatic surgery to groups given or not given peritoneal lavage, then comparing clinical results. This saline lavage was performed at the end of the operation. The primary endpoint was rate of surgical site infection. Frequency of peritoneal recurrence also was evaluated. RESULTS: Among all 104 patients in the study, incidence of infectious complications in the lavage group (n = 65) was significantly higher than in the non-lavage group (n = 39; 35% vs. 15%, P = 0.041), while incidences of postoperative complications overall and surgical site infection did not differ between lavage (80% and 26%) and non-lavage groups (67% and 10%, P = 0.162 and 0.076, respectively). Among 63 patients undergoing pancratoduodenectomy, frequencies of positive bacterial cultures of drainage fluids on postoperative days 1 and 3 were greater in the non-lavage group (P < 0.001 and P = 0.012), but surgical site infection was significantly more frequent in the lavage group (P = 0.043). Among patients with pancreatic and biliary cancers, lavage did not affect frequency of peritoneal recurrence. CONCLUSION: Intraoperative lavage did not prevent surgical site infection or peritoneal recurrence of pancreatobiliary cancer.

Diagnostic Peritoneal Aspiration or Lavage in Stratified Groups of Hypotensive Blunt Trauma Patients.

BACKGROUND: Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared to ultrasonography. However, whether both moderately hypotensive (systolic blood pressure [SBP] < 90 mmHg) and severely hypotensive (SBP < 70 mmHg) patients benefit from DPA/DPL is unclear. We hypothesized DPA/DPL used within the first hour increases risk of death for severely vs moderately hypotensive BTPs. METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for BTPs ≥ 18 years old with hypotension upon arrival. We compared moderately and severely hypotensive groups. A multivariable logistic regression analysis was performed controlling for age, comorbidities, emergent operation, blood transfusions, and injury profile. RESULTS: From 134 hypotensive patients undergoing DPA/DPL, 66 (49.3%) had severe hypotension. Patients in both groups underwent an emergent operation (43.9% vs 58.8%, P = .09) in a similar amount of time (median, 42-min vs 54-min, P = .11). Compared to the moderately hypotensive group, severely hypotensive patients had a higher rate and associated risk of death (84.8% vs 50.0%, P < .001) (OR 5.40, CI 2.07-14.11, P < .001). The strongest independent risk factor for death was age ≥ 65 (OR 24.81, CI 4.06-151.62, P < .001). DISCUSSION: Among all BTPs undergoing DPA/DPL within the first hour of arrival, an over 5-fold increased risk of death for patients with severe hypotension was demonstrated. As such, DPA/DPL within this group should be used with caution, particularly for older patients, as they may be better served by immediate surgeries. Future prospective research is needed to confirm these findings and elucidate the ideal DPA/DPL population in the modern era of ultrasonography.

Prognostic Value of Peritoneal Lavage Cytology in Potentially Resectable Pancreatic Cancer Stratified by Cytologic Status.

BACKGROUND/AIM: Patients with pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal lavage cytology (CY) reportedly have poor prognoses. However, the value of diagnosis of suspicious for malignancy on CY is unknown. This study aimed to elucidate the prognostic impact of CY by focusing on CY subgroups. PATIENTS AND METHODS: Data were collected from 231 resectable PDAC patients who underwent curative-intent resection. Patients were divided into three CY-based groups: negative (CY0), suspicious for malignancy (CY-S), and positive (CY1). Clinicopathological characteristics and prognostic factors were analyzed. RESULTS: CY1 and CY-S were diagnosed in 7.8% and 3.9% of the patients, respectively. The CY1 group had significantly larger tumors and higher frequencies of distal tumors, anterior pancreatic tissue invasion, retropancreatic tissue invasion, and R1 resection than the CY0 group. Patient characteristics did not differ between the CY0 and CY-S groups. The CY1 group exhibited worse survival than the CY0 and CY-S groups (median survival time: 18.8 vs. 39.6 months, p=0.0021 and vs. 62.2 months, p=0.018). Multivariate analysis for survival indicated that a tumor size >2 cm, preoperative CA19-9 value >100 U/ml, CY1, lymph node metastasis, R1 resection, and lack of adjuvant chemotherapy were associated with poor prognosis. Both the CY1 and CY-S groups had higher frequencies of peritoneal recurrence than the CY0 group (50% vs. 11.8%, p<0.001 and 44.4% vs. 11.8%, p=0.019). CONCLUSION: The prognosis of the CY1 group was poor. Although CY-S was associated with a higher frequency of peritoneal recurrence than CY0, the long-term outcomes of patients with surgical treatment were acceptable.

Effect of mitoTEMPO on Redox Reactions in Different Body Compartments upon Endotoxemia in Rats.

Mitochondrial ROS (mitoROS) control many reactions in cells. Biological effects of mitoROS in vivo can be investigated by modulation via mitochondria-targeted antioxidants (mtAOX, mitoTEMPO). The aim of this study was to determine how mitoROS influence redox reactions in different body compartments in a rat model of endotoxemia. We induced inflammatory response by lipopolysaccharide (LPS) injection and analyzed effects of mitoTEMPO in blood, abdominal cavity, bronchoalveolar space, and liver tissue. MitoTEMPO decreased the liver damage marker aspartate aminotransferase; however, it neither influenced the release of cytokines (e.g., tumor necrosis factor, IL-4) nor decreased ROS generation by immune cells in the compartments examined. In contrast, ex vivo mitoTEMPO treatment substantially reduced ROS generation. Examination of liver tissue revealed several redox paramagnetic centers sensitive to in vivo LPS and mitoTEMPO treatment and high levels of nitric oxide (NO) in response to LPS. NO levels in blood were lower than in liver, and were decreased by in vivo mitoTEMPO treatment. Our data suggest that (i) inflammatory mediators are not likely to directly contribute to ROS-mediated liver damage and (ii) mitoTEMPO is more likely to affect the redox status of liver cells reflected in a redox change of paramagnetic molecules. Further studies are necessary to understand these mechanisms.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy. AIM: To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL. METHODS: According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. RESULTS: The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group (P < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group (P < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group (P = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group (P < 0.05). CONCLUSION: EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.

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.

Long-term adjuvant chemotherapy after resection for pancreatic cancer patients with positive peritoneal lavage cytology.

PURPOSE: The significance of resection for pancreatic cancer with positive peritoneal lavage cytology (CY +) remains controversial, and the lack of evidence concerning adjuvant chemotherapy (AC) in these patients remains an issue. The aim of the present study was to investigate the prognostic impacts of AC and its duration on the survival outcome in patients with CY + pancreatic cancer. METHODS: A total of 482 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2017 were retrospectively analyzed. The overall survival (OS) was compared among the patients with CY + tumors according to the duration of AC. RESULTS: Among the resected patients, 37 (7.7%) had CY + tumors: 13 received AC for > 6 months, 15 received AC for ≤ 6 months and 9 did not receive AC. The OS of 13 patients with resected CY + tumors who received AC for > 6 months was comparable to that of 445 patients with resected CY- tumors (median survival time 43.0 vs. 33.6 months, P = 0.791), and was significantly better than that of 15 patients with resected CY + tumors who received AC for ≤ 6 months (vs. 16.6 months, P = 0.017). The duration of AC (> 6 months) was an independent prognostic factor in patients with resected CY + tumors (hazard ratio 3.29, P = 0.005). CONCLUSION: Long-term AC (> 6 months) may improve postoperative survival in pancreatic cancer patients with CY + tumors.

Effectiveness of intraoperative peritoneal lavage with saline in patient with intra-abdominal infections: a systematic review and meta-analysis.

BACKGROUND: Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with intra-abdominal infections (IAIs) remains controversial. This study aims to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of IOPL in patients with IAIs. METHODS: The databases of PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, and CBM databases were searched from inception to December 31, 2022. Random-effects models were used to calculate the risk ratio (RR), mean difference, and standardized mean difference. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence. RESULTS: Ten RCTs with 1318 participants were included, of which eight studies on appendicitis and two studies on peritonitis. Moderate-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (0% vs. 1.1%; RR, 0.31 [95% CI, 0.02-6.39]), intra-abdominal abscess (12.3% vs. 11.8%; RR, 1.02 [95% CI, 0.70-1.48]; I2 = 24%), incisional surgical site infections (3.3% vs. 3.8%; RR, 0.72 [95% CI, 0.18-2.86]; I2 = 50%), postoperative complication (11.0% vs. 13.2%; RR, 0.74 [95% CI, 0.39-1.41]; I2 = 64%), reoperation (2.9% vs. 1.7%; RR,1.71 [95% CI, 0.74-3.93]; I2 = 0%) and readmission (5.2% vs. 6.6%; RR, 0.95 [95% CI, 0.48-1.87]; I2 = 7%) in patients with appendicitis when compared to non-IOPL. Low-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (22.7% vs. 23.3%; RR, 0.97 [95% CI, 0.45-2.09], I2 = 0%) and intra-abdominal abscess (5.1% vs. 5.0%; RR, 1.05 [95% CI, 0.16-6.98], I2 = 0%) in patients with peritonitis when compared to non-IOPL. CONCLUSION: IOPL with saline use in patients with appendicitis was not associated with significantly decreased risk of mortality, intra-abdominal abscess, incisional surgical site infection, postoperative complication, reoperation, and readmission compared with non-IOPL. These findings do not support the routine use of IOPL with saline in patients with appendicitis. The benefits of IOPL for IAI caused by other types of abdominal infections need to be investigated.