Useful of proximal gastrectomy with double-tract reconstruction in preventing glucose spikes.

BACKGROUND: Volatile glucose levels after gastrectomy induce dumping syndrome, which adversely affects patient quality of life. This study aimed to evaluate the glycemic variability of proximal gastrectomy with double-tract reconstruction (PGDTR) as a function-preserving procedure. METHODS: This study used a continuous glucose monitoring (CGM) system to record glycemic profiles of patients who underwent PGDTR or total gastrectomy (TG) and compared them. Moreover, this study evaluated postgastrectomy syndrome, including dumping symptoms, between the PGDTR and TG groups using the 37-item Postgastrectomy Syndrome Assessment Scale (PGSAS-37) questionnaire. RESULTS: Of note, 44 patients underwent PGDTR, and 42 patients underwent TG, which included more advanced cases. CGM results showed that the SD, relative SD, and maximum drop in glucose level between 30 min and 2 h after a meal were smaller in the PGDTR group than in the TG group (14.81 vs 22.40 mg/dL [P < .001], 0.14 vs 0.20 mg/dL [P < .001], and 42.06 vs 117.67 mg/dL [P < .001], respectively). For nocturnal glucose levels, SD and percentage time below the range were smaller in the PGDTR group than in the TG group (11.76 vs 15.16 mg/dL [P = .005] and 11.25% vs 35.27% [P < .001]). The PGDTR group generally performed better than the TG group on all the PGSAS-37 questionnaire items. Patients in the PGDTR group without food inflow into the remnant stomach showed similar CGM results as those in the TG group but with stronger dumping symptoms. CONCLUSION: Food inflow into the remnant stomach is essential for PGDTR to be a function-preserving procedure as it leads to the control of dumping symptoms and lower glucose level spikes.

Feasibility of Robot-Assisted Cytoreductive Surgery With Upper-Abdominal Peritonectomy for Pseudomyxoma Peritonei With Low Peritoneal Carcinomatosis Index: A Pilot Study.

INTRODUCTION: Our study's objective was to provide the method for, and preliminary findings from, robot-assisted cytoreductive surgery (r-CRS) combined with upper-abdominal peritonectomy in pseudomyxoma peritonei (PMP) with limited peritoneal surface malignancy (PSM). MATERIALS AND METHODS: We conducted a retrospective pilot study on consecutive patients with PSM secondary to pseudomyxoma peritonei with a peritoneal cancer index (PCI) of under 10 who were indicated for r-CRS combined with upper-abdominal peritectomy. Perioperative and 30-day major morbidity and mortality characteristics were analyzed and compared with cases in which laparoscopic CRS (l-CRS) was performed under the same conditions. RESULTS: Six patients underwent r-CRS combined with an upper-abdominal partial peritonectomy. Their mean PCI was 4.83. Complete cytoreduction was achieved in all patients. The mean duration of the operation was 156.8 minutes. There was no major complication and no mortality. The mean length of hospital stay after surgery was 6.33 days. r-CRS resulted in less blood loss, a lower C-reactive protein level, and a shorter length of hospital stay that were significantly different compared with those of l-CRS. CONCLUSIONS: This is the initial technical report of a robotic approach for CRS combined with upper-abdominal peritonectomy. r-CRS with a combined upper-abdominal peritonectomy was shown to be safe and feasible for PMP with limited PSM.

Phase transitions and dynamics in ionic liquid crystals confined in nanopores.

We investigate the phase-transition behavior of ionic liquid crystals, namely 1-methyl-3-alkylimidazolium tetrafluoroborate, [Cnmim]BF4, confined in cylindrical nanopores using differential scanning calorimetry, x-ray scattering, and dielectric relaxation spectroscopy. Here, n is the number of carbon atoms in the alkyl part of this ionic liquid crystal. For n = 10 and 12, the isotropic liquid phase changes to the smectic phase and then to a metastable phase for the cooling process. During the subsequent heating process, the metastable phase changes to the isotropic phase via crystalline phases. The transition temperatures for this ionic liquid crystal confined in nanopores decrease linearly with the increase in the inverse pore diameter, except for the transitions between the smectic and isotropic phases. In the metastable phase, the relaxation rate of the α-process shows the Vogel-Fulcher-Tammann type of temperature dependence for some temperature ranges. The glass transition temperature evaluated from the dynamics of the α-process decreases with the decrease in the pore diameter and increases with the increase in the carbon number n. The effect of confinement on the chain dynamics can clearly be observed for this ionic liquid crystal. For n = 10, the melting temperature of the crystalline phase is slightly higher than that of the smectic phase for the bulk, while, in the nanopores, the melting temperature of the smectic phase is higher than that of the crystalline phase. This suggests that the smectic phase can be thermodynamically stable, thanks to the confinement effect.

Postoperative Early Body Weight Loss Is a Risk Factor for Recurrence in Patients with pStage III Gastric Cancer.

INTRODUCTION: The goal of this study was to determine whether postoperative early body weight loss (EWL) after radical gastrectomy is a risk factor for recurrence in patients with pathological stage III (pStage III) gastric cancer who received postoperative adjuvant chemotherapy, which included tegafur/gimeracil/oteracil (S-1). METHODS: Patients who underwent gastrectomy for gastric cancer were identified from a prospectively managed gastric cancer database. We analyzed 58 consecutive patients who underwent radical gastrectomy with D2 lymph node dissection for confirmed pStage III gastric cancer treated postoperatively with adjuvant chemotherapy including S-1 between 2010 and 2019. Clinical and pathologic characteristics, baseline body mass index (BMI), and postoperative weights were extracted. Weight changes were evaluated from the preoperative period to the start of adjuvant chemotherapy. EWL was defined as % BMI change = (preoperative BMI - postoperative BMI at the start of adjuvant chemotherapy) × 100/preoperative BMI. RESULTS: Of the 58 consecutive patients who underwent radical resection for gastric cancer, 72.4% were male, with a mean age of 65.5 years, and a mean preoperative BMI of 21.2 (range: 15.4-29.1) kg/m2. The degree of EWL was found to be closely correlated to compliance with adjuvant chemotherapy. Multivariate analysis by Cox proportional hazard analysis revealed that EWL was an independent factor for relapse-free survival (RFS), and patients with an EWL of 15.9% or more severe had poorer RFS. CONCLUSION: EWL above a certain rate at the start of adjuvant chemotherapy was a predictor of poor compliance with adjuvant chemotherapy and a high risk of disease recurrence in patients with pStage III gastric cancer.

Indocyanine Green Tracer-Guided Radical Robotic Distal Gastrectomy Using the Firefly™ System Improves the Quality of Lymph Node Dissection in Patients with Gastric Cancer.

BACKGROUND: This study investigated indocyanine green (ICG) as an intraoperative tool for improving lymph node dissection quality in radical robotic distal gastrectomy (RDG) for gastric cancer by comparing the rate of lymph node (LN) noncompliance with or without use of the Firefly™ system. METHODS: Patients with potentially resectable gastric cancer including cT1-T4a, N0/ + , M0 were registered in a prospective nonrandomized cohort study at our institution between March 2019 and December 2022. Patients were assigned to the da Vinci surgical system with Firefly system (F group) or that without Firefly system (non-F group). F group patients received endoscopic peritumoral injection of ICG to the submucosa one day before surgery. Rate of LN noncompliance, number of harvested LNs, and short-term outcomes were compared. RESULTS: Of the 94 patients in this study, 55 underwent Firefly system-guided RDG and 39 underwent conventional RDG. The mean [SD] total number of harvested lymph nodes in F group, 31.2 [10.2], was significantly higher than that harvested in non-F group (25.6 [12.6]; p = 0.026). The LN noncompliance rate in F group was lower than that in non-F group (32.7% vs. 61.5%, p = 0.006). The mean number of LNs harvested in F group was significantly higher than that harvested in non-F group (31.2 [10.2] vs. 25.7 [12.6], p = 0.02). Significant differences were found between the F vs. non-F groups in blood loss and postoperative hospital stay (83.9 [75.1] vs. 301.9 [766.7] mL; p = 0.003 and 13.4 vs. 17.4 days, p = 0.049). CONCLUSION: The Firefly system-assisted ICG tracer improved LN dissection quality without compromising safety.

Hybrid esophagogastric tube anastomosis after minimally invasive McKeown esophagectomy to prevent stenosis in patients with esophageal cancer.

PURPOSE: The use of a small circular stapler has been reported to increase the incidence of benign anastomotic stenosis in reconstruction. In circular stapling anastomosis after esophagectomy, the anastomotic lumen is dependent on the size of the esophagus and the replacement organ. We developed a new and foolproof method to prevent stenosis in esophagogastric tube anastomosis for patients with esophageal cancer that is not dependent on operator skill. METHODS: Seven patients with esophageal squamous cell carcinoma underwent minimally invasive McKeown esophagectomy in our hospital. Esophagogastric tube anastomosis was tried for all patients using the novel "hybrid esophagogastric tube anastomosis" technique. A 21-mm circular stapler was applied to perform an end-to-side anastomosis between the cervical esophagus and the posterior wall of the gastric tube. Then, a 30-mm linear stapler was positioned in the esophagogastric anastomosis formed by the 21-mm circular stapler with the anvil fork inserted into the esophagus and the cartridge fork inserted into the gastric tube. A supplementary side-to-side anastomosis of appropriately 15 mm was created. Afterward, the entry hole was closed with a linear stapler. RESULTS: The hybrid esophagogastric tube anastomosis was successful in all seven patients receiving it between June 2020 and March 2022. No postoperative complications related to this anastomosis were observed in any of the patients. Five patients underwent follow-up gastrointestinal endoscopy at 6 months after esophagectomy. No patient had an anastomotic stenosis. CONCLUSIONS: Hybrid esophagogastric tube anastomosis can be performed easily and safely and can reduce the complications associated with anastomosis.

Development of an artificial portal vein using bioabsorbable polymers.

PURPOSE: During surgical resection of malignant tumors in the hepatobiliary pancreatic region, portal vein resection and reconstruction may be needed. However, there is no alternative to the portal vein. We therefore developed an artificial portal vein that could be used in the abdominal cavity. METHODS: In the experiments, hybrid pigs (n = 8) were included. An artificial portal vein was created using a bioabsorbable polymer sheet (BAPS). Subsequently, the portal vein's anterior wall was excised into an elliptical shape. A BAPS in the form of a patch was implanted at the same site. At 2 weeks (n = 3) and 3 months (n = 5) after the implantation, the BAPS implantation site was resected and evaluated macroscopically and histopathologically. RESULTS: Immediately after the implantation, blood leakage was not detected. Two weeks after implantation, the BAPS remained, and endothelial cells were observed. Thrombus formation was not observed. Three months after implantation, the BAPS had been completely absorbed and was indistinguishable from the surrounding portal vein. Stenosis and aneurysms were not observed. CONCLUSIONS: BAPS can replace a defective portal vein from the early stage of implantation to BAPS absorption. These results suggest that it can be an alternative material to the portal vein in surgical reconstruction.

[A Case of pagetoid Carcinoma of the Breast with Pathological Complete Response by Neoadjuvant Chemotherapy].

We herein report a 63-year-old woman who presented with about 20 mm-sized mass in the right breast and the right nipple with erosion. Preoperative examinations revealed a diagnosis of HER2-type pagetoid carcinoma with axillary lymph node metastasis. After neoadjuvant chemotherapy(pertuzumab, trastuzumab, and docetaxel, followed by adriamycin and cyclophosphamide), a pathological complete response was achieved. The patient was treated with anti-HER2 therapy without recurrence.

[A Case of Robotic Abdominoperineal Resection for Rectal Cancer with Leriche Syndrome].

We report a case of robotic abdominoperineal resection for rectal cancer with Leriche syndrome. Case: A 75-year-old male. Colonoscopy, which was performed due to persistent diarrhea, revealed type 2 lower rectal circumferential tumor. Pathological examination revealed adenocarcinoma. Computed tomography revealed no distant metastasis, and incidentally complete occlusion from the abdominal aorta to both common iliac arteries. He was diagnosed to rectal cancer(RbRaP, cT3N0M0, cStage Ⅱa)with Leriche syndrome. Therefore, robotic abdominoperineal resection(D3 dissection)was performed. There was no complication, and he was discharged 15 days after surgery. Postoperative pathological examination revealed pT3N1asM0, pStage Ⅲb.

[A Case of Perforated Rectal Cancer with Laparoscopic Low Anterior Resection].

We report a case of perforated rectal cancer with laparoscopic low anterior resection. Case: A 60-year-old man was transported to the hospital with a chief complaint of sudden lower abdominal pain. Computed tomography revealed wall thickening of the upper rectum and free air localized around the rectum and fecal mass in the mesorectum. He was diagnosed with perforated rectal cancer. Because of the early onset, young age, and ascites confined to the pelvic floor, we decided to perform laparoscopic low anterior resection(D3 dissection). Intraabdominal observation revealed tumor in the upper rectum with a large rectal perforation 3 cm proximal to the tumor. By using gauze and suction, we were able to complete the surgery with ingenuity laparoscopically. The postoperative course was good, and he was discharged 9 days after surgery. Postoperative pathological examination revealed pT4apN0sM0, pStage Ⅱb. Adjuvant chemotherapy of 8 courses of capecitabine was performed. There has been no recurrence 3 years after surgery.

[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

[A Case of Long-Term Survival Achieved by Multimodal Treatments for Postoperative Lung Metastasis and Mediastinal Lymph Node Metastasis after Surgery for Ascending Colon Cancer].

A 52-year-old male patient with Stage Ⅲc ascending colon cancer underwent laparoscopic right hemicolectomy with D3 lymph node dissection. Adjuvant chemotherapy was administered for 6 months, and no recurrence was observed during the follow-up period. Left lung metastasis was detected and surgically removed 7 years after the initial surgery. He underwent open partial small bowel resection with lymph node dissection when mesenteric lymph node metastasis was identified 2 years later. Although chemotherapy was conducted on the identification of mediastinal lymph node metastasis 2 years later, the mediastinal lymph nodes increased. Although attempted, lymph node dissection was impossible because of the strong adhesion to the trachea. Subsequently, chemotherapy and radiation therapy were administered. However, an infiltration of the mediastinal lymph nodes into the trachea was observed. The patient underwent bronchoscopic laser tumor ablation. The patient died 4 months after the resumption of chemotherapy(18 years after the initial surgery). Mediastinal lymph node recurrence after curative resection for colon cancer is a rare clinical condition. Nevertheless, long-term survival could be achieved by multimodal treatments in such patients.

Ruptured ileocolic artery pseudoaneurysm after laparoscopic appendectomy for acute appendicitis.

BACKGROUND: A pseudoaneurysm of the splanchnic vessels is considered to be rare, and in particular, very few cases of pseudoaneurysm in the ileocolic artery are reported. Here, we report a case of rupture of a pseudoaneurysm of the appendicular branch of the ileocolic artery after laparoscopic appendectomy. CASE PRESENTATION: A 52-year-old man was diagnosed as having phlegmonous appendicitis, and an emergency laparoscopic appendectomy was performed. Bleeding from the inter-appendicular ligament during detachment of adhesions was stopped by white coagulation and Z-suture, and the inter-appendicular ligament was treated. The postoperative course was uneventful, and there were no adverse events or findings suggestive of abscess formation. On postoperative day 30, he presented with a ruptured pseudoaneurysm of the appendicular branch of the ileocolic artery. A definitive diagnosis was made by computed tomography, and emergency interventional radiology was performed with hemostasis achieved by coiling. The patient's postprocedure course was favorable, and he was discharged with no adverse events, such as intestinal ischemia. CONCLUSIONS: We experienced a case of delayed pseudoaneurysm rupture after laparoscopic appendectomy. Care must be taken when handling the appendicular artery during the procedure, and the potential for pseudoaneurysm formation should be considered at postoperative follow-up.

Validity and safety of laparoscopic gastrectomy with D1+ lymphadenectomy for very elderly advanced gastric cancer patients; retrospective cohort study.

BACKGROUND: It remains unclear whether laparoscopic gastrectomy with optimal lymphadenectomy is appropriate for very elderly patients with advanced gastric cancer. This study aimed to assess the validity of laparoscopic gastrectomy with D1+ lymphadenectomy performed for advanced gastric cancer in patients aged 80 years or more. METHODS: Included in this retrospective study were 122 patients who underwent curative laparoscopic gastrectomy for advanced gastric cancer between 2013 and 2018. All patients over 80 years old underwent laparoscopic gastrectomy with D1+ lymphadenectomy. We divided patients by age between those who were very elderly (age ≥ 80 years; very elderly group [n = 57]) and those who were non-very elderly (age < 80 years; control group [n = 65]), and we compared patient and clinicopathological characteristics, intraoperative outcomes, and short- and long-term outcomes between the two groups. We also performed multivariate analyses to identify predictors of postoperative prognosis. RESULTS: Eastern Cooperative Oncology Group Performance Status of grade 2 or higher and mean Charlson comorbidity index score and body mass index were significantly different between the very elderly group and the control group. Adjuvant chemotherapy was used in relatively few very elderly group patients. Operation time, blood loss volume, and postoperative morbidity and mortality did not differ between the two groups. The overall survival and disease-specific survival rate of very elderly group patients with the Charlson comorbidity index score of <3 was not significantly different from that of the control group patients. CONCLUSION: The treatment of advanced gastric cancer by laparoscopic gastrectomy with D1+ lymphadenectomy to be both safe and effective in the very elderly group patients with the Charlson comorbidity index score of <3.

Evaluating the burden of the COVID-19 pandemic on patients with colorectal cancer.

After the emergence of the coronavirus disease 2019 (COVID-19) pandemic, individuals needing medical help preferred to not go to the hospital to avoid the risk of severe acute respiratory syndrome coronavirus 2 infection. The present study investigated the influence of the COVID-19 pandemic on patients with colorectal cancer. Patients with colorectal cancer treated between January and December 2019 were classified as the pre-pandemic group (pre-group) and those treated between April 2020 and March 2021 as the post-pandemic group (pandemic group). The clinicopathologic features of patients who underwent surgery for colorectal cancer in the two groups were retrospectively compared. A total of 161 patients were enrolled: 79 In the pre-group and 82 in the pandemic group. Although no significant differences were observed in tumor location and surgical procedure between the two groups, circumferential lesions (P<0.001), colorectal stenting (P=0.016) and Stage IV classification (P=0.019) had a higher frequency in the pandemic group compared with the pre-group; additionally, surgical curability was significantly lower (P=0.036) in the pandemic group. The spread of COVID-19 has increased the incidence of patients with advanced colorectal cancer. To reduce this incidence, healthcare professionals should inform the general public not only about the risk of COVID-19, but also about the increased incidence of advanced colorectal cancer after the pandemic.

A novel VCP modulator KUS121 exerts renoprotective effects in ischemia-reperfusion injury with retaining ATP and restoring ERAD-processing capacity.

Acute kidney injury (AKI) is a life-threatening condition and often progresses to chronic kidney disease or the development of other organ dysfunction even after recovery. Despite the increased recognition and high prevalence of AKI worldwide, there has been no established treatment so far. The aim of this study was to investigate the renoprotective effect of Kyoto University substance 121 (KUS121), a novel valosin-containing protein modulator, on AKI. In in vitro experiments, we evaluated cell viability and ATP levels of proximal tubular cells with or without KUS121 under endoplasmic reticulum (ER) stress conditions. In in vivo experiments, the effects of KUS121 were examined in mice with AKI caused by ischemia-reperfusion injury. ER-associated degradation (ERAD)-processing capacity was evaluated by quantification of the ERAD substrate CD3delta-YFP. KUS121 protected proximal tubular cells from cell death under ER stress. The apoptotic response was mitigated as indicated by the suppression of C/EBP homologous protein expression and caspase-3 cleavage, with maintained intracellular ATP levels by KUS121 administration. KUS121 treatment suppressed the elevation of serum creatinine and neutrophil gelatinase-associated lipocalin levels and attenuated renal tubular damage after ischemia-reperfusion. The expression of inflammatory cytokines in the kidney was also suppressed in the KUS121-treated group. Valosin-containing protein expression levels were not altered by KUS121 both in vitro and in vivo. KUS121 treatment restored ERAD-processing capacity associated with potentiation of its upstream pathway, phosphorylated inositol-requiring enzyme-1α, and spliced X box-binding protein-1. In conclusion, these findings indicate that KUS121 can protect renal tubular cells from ER stress-induced injury, suggesting that KUS121 could be a novel and promising therapeutic compound for ischemia-associated AKI.NEW & NOTEWORTHY Novel findings of this study are as follows: 1) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.

Double tract-like gastric tube reconstruction decreases the incidences of delayed gastric emptying and bile reflux after esophagectomy: results of a pilot study of an experimental technique.

PURPOSE: Esophagectomy with gastric tube reconstruction is often complicated postoperatively by duodenogastric reflux and/or delayed gastric emptying and the accompanying symptoms, leading to patients being dissatisfied with their quality of life (QOL). Medical interventions to relieve patients of their symptoms are rarely effective. We began, in 2018, performing double tract-like gastric tube reconstruction, and, in a pilot study, we compared postoperative QOL between patients in whom this experimental reconstruction was performed and those in whom conventional reconstruction was performed. METHODS: Included in the study were 33 patients who underwent thoracoscopic McKeown esophagectomy with two- or three-field lymph node dissection for thoracic esophageal cancer between April 2015 and March 2020. A gastric tube about 4 cm in width was created in all patients, and in 14 of the patients (DT group), a double tract was appended by anastomosing the elevated jejunum to the anterior wall of the gastric tube, QOL was assessed 10-14 months later by means of the DAUGS-32 questionnaire, and bile reflux and the presence or absence of food residue were assessed by upper gastrointestinal endoscopy. RESULTS: DAUGS-32 food passage dysfunction, nausea and vomiting, and reflux symptoms scores were significantly lower in the DT group than in the conventional reconstruction group. There was no significant between-group difference in the incidence of postoperative complications. No food residue was seen in DT patients' gastric tube, and no reflux esophagitis was observed. CONCLUSION: Double tract-like gastric tube reconstruction shows promise as an effective means of improving patients' post-esophagectomy QOL.

The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5'-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice.

BACKGROUND: Osteocrin (OSTN), a bone-derived humoral factor, was reported to act on heart and bone by potentiating the natriuretic peptide (NP) system. Ostn gene polymorphisms have been associated with renal function decline, but its pathophysiological role in the kidney remains unclear. METHODS: The role of endogenous OSTN was investigated using systemic Ostn-knockout (KO) mice. As a model for OSTN administration, liver-specific Ostn-overexpressing mice crossed with KO (KO-Tg) were generated. These mice were subjected to unilateral ischemia-reperfusion injury (IRI) and renal lesions after 21 days of insult were evaluated. A comprehensive analysis of the Wnt/ß-catenin pathway was performed using a polymerase chain reaction (PCR) array. Reporter plasmid-transfected proximal tubular cells (NRK52E) were used to investigate the mechanism by which OSTN affects the pathway. RESULTS: After injury, KO mice showed marginal worsening of renal fibrosis compared with wild-type mice, with comparable renal atrophy. KO-Tg mice showed significantly ameliorated renal atrophy, fibrosis and tubular injury, together with reduced expressions of fibrosis- and inflammation-related genes. The PCR array showed that the activation of the Wnt/ß-catenin pathway was attenuated in KO-Tg mice. The downstream targets Mmp7, Myc and Axin2 showed similar results. MMP7 and Wnt2 were induced in corticomedullary proximal tubules after injury, but not in KO-Tg. In NRK52E, OSTN significantly potentiated the inhibitory effects of NP on transforming growth factor ß1-induced activation of the Wnt/ß-catenin pathway, which was reproduced by a cyclic guanosine monophosphate analog. CONCLUSIONS: Ectopic Ostn overexpression ameliorated subsequent renal injury following ischemia-reperfusion. OSTN could represent possible renoprotection in acute to chronic kidney disease transition, thus serving as a potential therapeutic strategy.