Tongue pressure, respiratory muscle and limb strength and functional exercise capacity in oesophageal cancer.

OBJECTIVES: Preoperative management of oesophageal cancer requires effective prehabilitation. This study investigates the relationship between tongue pressure, respiratory muscle, handgrip and lower limb muscle strengths, and functional exercise capacity in patients with oesophageal cancer to develop a novel prehabilitation strategy. METHODS: This prospective, single-centre, observational study analysed data from 29 pretreatment patients with oesophageal cancer. We evaluated tongue pressure, maximal inspiratory and expiratory pressures, handgrip and lower limb muscle strengths, functional exercise capacity and dysphagia scores before treatment. The relationship between parameters was identified using Spearman's correlation analysis. RESULTS: Maximal inspiratory and expiratory pressures were significantly associated with handgrip and lower extremity muscle strengths and functional exercise capacity. However, tongue pressure was not associated with maximal inspiratory and expiratory pressures, handgrip and lower extremity muscle strengths and functional exercise capacity. Rather, tongue pressure was significantly associated with clinical T, dysphagia and nutritional status scores. CONCLUSIONS: Respiratory muscle strength was associated with conventional sarcopenia and functional exercise capacity. Tongue pressure was not associated with respiratory muscle strength, conventional sarcopenia and functional exercise capacity. Rather, tongue pressure was associated with clinical T, dysphagia and nutritional status scores. Preoperative management of oesophageal cancer requires prehabilitation consisting of exercise and nutritional therapy and an additional swallowing programme, such as tongue resistance training, for patients without progress in oral intake, based on tongue pressure evaluation.

Olprinone, a Selective Phosphodiesterase III Inhibitor, Has Protective Effects in a Septic Rat Model after Partial Hepatectomy and Primary Rat Hepatocyte.

Olprinone (OLP) is a selective inhibitor of phosphodiesterase III and is used clinically in patients with heart failure and those undergoing cardiac surgery; however, little is known about the effects of OLP on hepatoprotection. The purpose of this study aimed to determine whether OLP has protective effects in in vivo and in vitro rat models of endotoxin-induced liver injury after hepatectomy and to clarify the mechanisms of action of OLP. In the in vivo model, rats underwent 70% partial hepatectomy and lipopolysaccharide treatment (PH/LPS). OLP administration increased survival by 85.7% and decreased tumor necrosis factor-α, C-X-C motif chemokine ligand 1, and inducible nitric oxide synthase (iNOS) mRNA expression in the livers of rats treated with PH/LPS. OLP also suppressed nuclear translocation and/or DNA binding ability of nuclear factor kappa B (NF-κB). Pathological liver damage induced by PH/LPS was alleviated and neutrophil infiltration was reduced by OLP. Primary cultured rat hepatocytes treated with the pro-inflammatory cytokine interleukin-1ß (IL-1ß) were used as a model of in vitro liver injury. Co-treatment with OLP inhibited dose-dependently IL-1ß-stimulated iNOS induction and NF-κB activation. Our results demonstrate that OLP may partially inhibit the induction of several inflammatory mediators through the suppression of NF-κB and thus prevent liver injury induced by endotoxin after liver resection.

Prognostic scoring system based on indicators reflecting the tumor glandular differentiation and microenvironment for patients with colorectal cancer.

Prognostic stratification is an urgent concern for patients with colorectal cancer (CRC). The desmoplastic reaction (DR) is speculated to mirror the tumor microenvironment. DR types are considered independent prognostic indicators in CRC, but have not been incorporated in previous prognostic nomograms. We aimed to assess the prognostic significance of a novel approach incorporating histopathological indicators reflecting tumor glandular differentiation and microenvironment. We evaluated 329 consecutive patients with CRC who underwent surgical resection at Kansai Medical University. Histological glandular differentiation was scored as 2 (0 point), 3 (1 point), or 4 (2 points). Tumor buddings (TBs) were classified as TB1 (0 point), TB2 (1 point), or TB3 (2 points). pT1 or 2 was considered as 0 point, pT3 or 4 + DR non-immature type as 1 point, and pT3 or 4 + DR immature type as 2 points. Lymph node metastasis was classified as pN0 (0 point), pN1 (1 point), or pN2 (2 points). The preoperative carcinoembryonic antigen levels were categorized as < 5.0 ng/mL (0 point) and ≧5.0 (1 point). Considering these factors, the following D&M (tumor differentiation and microenvironment) scoring system was applied: I (0-2 points), II (3-4 points), III (5-6 points), and IV (7-9 points). Kaplan-Meier curves showed significant differences in disease-specific survival and recurrence-free survival among the assigned scores, highlighting their enhanced utility compared with the American Joint Committee on Cancer 8th edition staging system. The D&M scoring system was valuable as the initial prognostic nomogram, including DR.

Laparoscopic polyglycolic acid spacer placement for locally recurrent rectal cancer.

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short-term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure.

COMBINATION THERAPY WITH A SENSE OLIGONUCLEOTIDE TO INDUCIBLE NITRIC OXIDE SYNTHASE MRNA AND HUMAN SOLUBLE THROMBOMODULIN IMPROVES SURVIVAL OF SEPSIS MODEL RATS AFTER PARTIAL HEPATECTOMY.

ABSTRACT: Sepsis after a major hepatectomy is a critical problem. In septic shock, the inflammatory mediator, nitric oxide (NO), is overproduced in hepatocytes and macrophages. The natural antisense (AS) transcripts, non-coding RNAs, are transcribed from a gene that encodes inducible nitric oxide synthase (iNOS). iNOS AS transcripts interact with and stabilize iNOS mRNAs. A single-stranded "sense oligonucleotide" (designated as SO1) corresponding to the iNOS mRNA sequence inhibits mRNA-AS transcript interactions and reduces iNOS mRNA levels in rat hepatocytes. In contrast, recombinant human soluble thrombomodulin (rTM) treats disseminated intravascular coagulopathy by suppressing coagulation, inflammation, and apoptosis. In this study, the combination therapy of SO1 and a low dose of rTM was evaluated for hepatoprotection in a rat septic shock model after partial hepatectomy. Rats underwent 70% hepatectomy, followed by intravenous (i.v.) injection of lipopolysaccharide (LPS) after 48 h. SO1 was injected (i.v.) simultaneously with LPS, whereas rTM was injected (i.v.) 1 h before LPS injection. Similarly to our previous report, SO1 increased survival after LPS injection. When rTM, which has different mechanisms of action, was combined with SO1, it did not interfere with the effect of SO1 and showed a significant increase in survival compared with LPS alone treatment. In serum, the combined treatment decreased NO levels. In the liver, the combined treatment inhibited iNOS mRNA and protein expression. A decreased iNOS AS transcript expression by the combined treatment was also observed. The combined treatment decreased mRNA expression of the inflammatory and pro-apoptotic genes while increasing that of the anti-apoptotic gene. Furthermore, the combined treatment reduced the number of myeloperoxidase-positive cells. These results suggested that the combination of SO1 and rTM has therapeutic potential for sepsis.

[A Case of Unresectable Advanced Lower Esophageal Adenocarcinoma That Achieved Pathological Complete Response after Conversion Surgery following Nivolumab plus SOX Therapy].

An 80-year-old woman presented with epigastric discomfort and dysphagia, underwent upper gastrointestinal endoscopy, and was diagnosed with type 2 advanced lower esophageal adenocarcinoma. Computed tomography data revealed that there was the lower esophageal tumor is T3, but a large carina lymph node invading the left bronchus. We diagnosed this patient unresectable cT4bN1M0, cStage ⅣA advanced esophageal adenocarcinoma, and we administered nivolumab plus S-1 plus oxaliplatin(SOX)therapy. After 3 courses of the therapy, imaging showed marked reduction in the size of primary tumor and carina lymph node. We diagnosed partial response(PR)and attempted conversion surgery. Video-assisted thoracoscopic esophagectomy with 2 fields lymphadenectomy was performed. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of primary tumor was determined to be Grade 3, with a pathological complete response(pCR). Currently, the patient is alive without recurrence for 1 year after surgery.

Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model.

Levosimendan, a calcium sensitizer, has an organ protective profile through the inhibition of inflammatory mediators and cytokines in critical conditions, such as heart failure, ischemia-reperfusion injury, and sepsis. The survival effect of levosimendan for acute liver failure has not been examined yet. Male Sprague-Dawley rats were examined in the D-galactosamine hydrochloride and lipopolysaccharide (GalN/LPS) model. Levosimendan was injected intraperitoneally before GalN/LPS treatment. Survival was monitored for 7 days. For biochemical analyses, liver and blood samples were collected from the rats at 1 and 8 h after GaIN/LPS treatment. The pretreatment of levosimendan at 4 mg/kg significantly increased survival in GalN/LPS rats. In the liver specimen, levosimendan significantly inhibited the activation of nuclear factor-κB (NF-κB) at 1 h, and significantly decreased the mRNA expression of inflammatory mediators, including inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α), at 8 h. In serum, levosimendan decreased the levels of nitrite, a metabolite of nitric oxide, and TNF-α protein, as well as aspartate aminotransferase and alanine aminotransferase. These results indicated that Levosimendan ameliorated liver dysfunction and survival in acute liver failure model rats through the suppression of NF-κB activation.

Omeprazole Increases Survival Through the Inhibition of Inflammatory Mediaters in Two Rat Sepsis Models.

BACKGROUND: Omeprazole (OMZ) is a proton pump inhibitor that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of LPS-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. METHODS: In the in vivo models, the effects of OMZ were examined 1 h before treatments in both models on survival, nuclear factor (NF)-κB activation, histopathological analysis, and proinflammatory mediator expression in the liver and serum. In the in vitro model, primary cultured rat hepatocytes were treated with IL-1ß in the presence or absence of OMZ. The influence of OMZ on nitric oxide (NO) product and inducible NO synthase (iNOS) induction and on the associated signaling pathway was analyzed. RESULTS: OMZ increased survival and decreased tumor necrosis factor-alpha, iNOS, cytokine-induced neutrophil chemoattractant 1, IL-6, and IL-1ß mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes. CONCLUSIONS: OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.

Management of incidentally detected idiopathic pneumoperitoneum: A case report and literature review.

INTRODUCTION: Pneumoperitoneum usually requires emergency surgery. Asymptomatic idiopathic pneumoperitoneum is a rare subgroup of pneumoperitoneum for which a management algorithm has not been established. PRESENTATION OF CASE: In an 88-year-old female patient, pneumoperitoneum was found incidentally by chest computed tomography during a periodic follow-up for sarcoidosis. Emergency admission was ordered for conservative treatment. Upper gastrointestinal endoscopy revealed edematous mucosa in the entire gastric vestibule. After being discharged on the 7th day, her clinical course was uneventful over 2 months of follow-up. DISCUSSION: The initial clinical manifestations of pneumoperitoneum are variable and range widely from asymptomatic to septic shock. The etiology of pneumoperitoneum in our patient implied a subclinical visceral perforation that resolved without treatment. We advocate an algorithm for the initial management of pneumoperitoneum according to the extent of peritonitis and impaired conditions. CONCLUSION: Incidentally found asymptomatic pneumoperitoneum does not always require intervention. Careful and repeated physical assessment with investigation of underlying etiology is important in the management of pneumoperitoneum.

Clinicopathological characteristics of pancreatic ductal adenocarcinoma with invasive micropapillary carcinoma component with emphasis on the usefulness of PKCζ immunostaining for detection of reverse polarity.

Invasive micropapillary carcinoma (IMPC) is a rare distinct histopathological subtype, characterized by the presence of carcinoma cells displaying reverse polarity. Only limited clinicopathological information is available regarding pancreatic IMPC. The aim of the present study was to clarify the clinicopathological features of pancreatic IMPC and the usefulness of protein kinase C (PKC)ζ immunostaining for the detection of reverse polarity. We reviewed 242 consecutive surgically resected specimens of pancreatic ductal adenocarcinoma and selected samples with an IMPC component. Clinicopathological characteristics were compared between the IMPC and non-IMPC groups. Immunohistochemical staining for PKCζ was performed using an autostainer. In total, 14 cases had an IMPC component (5.8%). The extent of IMPC component ranged from 5 to 20%. There were no significant differences in tumor location, T category, lymph node metastatic status, preoperative carbohydrate antigen 19-9 level, resection status and overall survival between the IMPC and non-IMPC groups. Immunostaining for PKCζ clearly showed reverse polarity of the neoplastic cells of IMPC. Although previous reports have shown that the presence of an IMPC component (>20% of the tumor) indicated poor prognosis, the present study demonstrated that presence of IMPC <20% did not suggest a worse prognosis.

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study.

BACKGROUND: Pancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma. METHODS: A total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively. RESULTS: Sixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival. CONCLUSION: Direct invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.

[A Case of Recurrent Gastric Cancer with Durable Complete Response after Short-Term Nivolumab Therapy].

We report the case of a patient with recurrent gastric cancer that showed a complete response(CR)after short-term nivolumab administration. A 76-year-old woman was diagnosed with unresectable advanced gastric cancer(T4b, N+, M0, cStage ⅣA). The patient was administered 7 courses of SOX. Since the primary lesion was reduced significantly after the chemotherapy, radical gastrectomy was performed. Although postoperative adjuvant chemotherapy with weekly nab-PTX was performed, cancer recurrence occurred in the abdominal cavity, and another surgery was performed. However, complete resection was difficult to achieve. Postoperatively, chemotherapy was continued; however, CEA levels increased, and thus RAM+PTX was administered as second-line treatment. Stable disease was maintained for a while; however, disease progression occurred eventually. Thus, RAM+PTX was discontinued after 8 courses, and nivolumab was administered as the third-line treatment. However, due to the rapid deterioration of renal function, nivolumab could not be continued after 3 courses. After nivolumab discontinuation, CEA levels normalized and the image showed CR. Approximately 1.5 years have passed since then, with no report of recurrence without any treatment. Although nivolumab has been shown to be useful as a third-line treatment for unresectable advanced/recurrent gastric cancer, there are few reports demonstrating CR and none showing maintenance of CR after short-term nivolumab administration. Moreover, the rationale of continuing nivolumab is unclear once clinical CR is achieved. Our experience shows the feasibility of discontinuation of short-term nivolumab if CR is achieved.

Benefits of Conversion Surgery after Multimodal Treatment for Unresectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC. METHODS: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months). RESULTS: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, p < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, p = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS. CONCLUSION: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.

Bile Duct Stones Predict a Requirement for Cholecystectomy in Older Patients.

BACKGROUND: The requirement for elective cholecystectomy in older patients is unclear. To determine predictors for requiring elective cholecystectomy in older patients, a prospective cohort study was performed. METHODS: All patients with gallstone disease who presented to our department from 2006 to 2018 were included if they met the following criteria: (1) age 75 years or older, (2) presentation for elective cholecystectomy, and (3) preoperative diagnosis of cholecystolithiasis. Two therapeutic options, elective surgery and a wait-and-see approach, were offered at their initial visit. Enrolled patients were assigned to one arm of the study according to their choice of the therapeutic options. The primary endpoint was the incidence of gallstone-related complications. The endpoint was compared between patients who underwent cholecystectomy (CH group) and those who chose a wait-and-see approach (No-CH group). RESULTS: During the study period, there were 344 patients in the CH group and 161 in the No-CH group. Among patients with a history of bile duct stones, the incidence of gallstone-related complications in the No-CH group was significantly higher (45% within 3 years, including two gallstone-related deaths) than that in the CH group (RR 2.66, 95% confidence interval 1.50-4.77, p = 0.0009). Among patients with no history of bile duct stones, the incidence of gallstone-related complications in the No-CH group reached only 10% over the 12 years. CONCLUSION: Cholecystectomy is recommended for older patients with both histories of cholecystolithiasis and bile duct stones, whereas a wait-and-see approach is preferable for patients with no bile duct stone history. A history of bile duct stones is a good predictor for cholecystectomy in older patients.

Prognosis in Patients With Gallbladder Edema Misdiagnosed as Cholecystitis.

BACKGROUND AND OBJECTIVES: Edema of the gallbladder may pose a diagnostic challenge because it also occurs in patients without an indication for cholecystectomy. METHODS: We evaluated all consecutive patients with gallstone disease who presented for cholecystectomy at the Department of Surgery of Kansai Medical University from January 2006 to April 2019. Using the prospectively collected database in our department, we obtained information on patients whose final diagnoses were gallbladder edema. We identified 12 patients with gallbladder edema who were misdiagnosed with acute cholecystitis among 2661 patients and who presented for cholecystectomy for benign gallbladder diseases. The outcome of these patients was assessed to prevent unnecessary cholecystectomy. RESULTS: In all 12 patients, computed tomography and ultrasonographic imaging showed gallbladder wall thickening. Acute cholecystitis was suspected, and emergent cholecystectomy was performed for the first 5 patients. Of these 5 patients, 2 patients died of liver failure postoperatively. Based on the misdiagnosis in the first 5 patients, the latter 7 patients did not undergo cholecystectomy; instead, they were treated specifically for their systemic disease. To date, no cholecystitis has occurred in these 7 patients. In all misdiagnosed cases in the present report, mesh-like wall thickening was a distinctive feature of gallbladder edema on ultrasonography. We consider this feature important for distinguishing simple gallbladder edema from cholecystitis. CONCLUSION: Careful evaluation of clinical symptoms and imaging findings, especially mesh-like wall thickening on ultrasonography, is necessary in this setting to prevent misdiagnosis and unnecessary cholecystectomy.

Clinical impact of the sequentially-checked drain removal criteria on postoperative outcomes after pancreatectomy: a retrospective study.

BACKGROUND: Strict criteria for impeccably safe drain management following pancreatectomy have not yet been developed. We evaluated the utility of the sequentially-checked drain removal criteria by comparison with conventional criteria. METHODS: Postoperative outcomes of 801 patients who underwent pancreatectomy, including 395 patients for whom drain fluid amylase (DFA) < 375U/l on postoperative day (POD) 3 (control group), were used and 406 patients for whom the sequentially-checked criteria of DFA <5,000 U/l on POD 1 and DFA <3,000 U/l on POD 3 (sequentially-checked group) were used and were retrospectively evaluated. RESULTS: DFA on POD 3 and fistula risk score did not differ between groups. Significantly more patients in the sequentially-checked group met the criteria (control, 63.8% vs. sequentially-checked, 76.1%, P < 0.001). The incidences of clinically relevant postoperative pancreatic fistula (CR-POPF) (17.0% vs. 11.1%), intra-abdominal abscess (21.0% vs. 9.1%) were significantly lower in the sequentially-checked group (all P < 0.05). Multivariate analysis revealed that use of the sequentially-checked criteria was significantly associated with CR-POPF (odds ratio 0.601, 95% confidence interval [CI] 0.389-0.929; P = 0.022). C-reactive protein <15 mg/dl at POD 3 was identified as an independent predictive factor for false positive CR-POPF results in the sequentially-checked group (odds ratio 0.872, 95% CI 0.811-0.939; P < 0.001); thus, this criterion was added to create the new triple-checked criteria. CONCLUSIONS: The sequentially-checked criteria can provide safe drain management and improve postoperative outcomes.

The Proton Pump Inhibitor Lansoprazole Has Hepatoprotective Effects in In Vitro and In Vivo Rat Models of Acute Liver Injury.

BACKGROUND/AIMS: The proton pump inhibitor lansoprazole (LPZ) is clinically used to reduce gastric acid secretion, but little is known about its possible hepatoprotective effects. This study aimed to investigate the hepatoprotective effects of LPZ and its potential mechanisms using in vitro and in vivo rat models of liver injury. METHODS: For the in vitro model of liver injury, primary cultured rat hepatocytes were treated with interleukin-1ß in the presence or absence of LPZ. The influence of LPZ on inducible nitric oxide synthase (iNOS) induction and nitric oxide (NO) production and on the associated signaling pathways was analyzed. For the in vivo model, rats were treated with D-galactosamine (GalN) and lipopolysaccharide (LPS). The effects of LPZ on survival and proinflammatory mediator expression (including iNOS and tumor necrosis factor-α) in these rats were examined. RESULTS: LPZ inhibited iNOS induction partially through suppression of the nuclear factor-kappa B signaling pathway in hepatocytes, thereby reducing potential liver injury from excessive NO levels. Additionally, LPZ increased survival by 50% and decreased iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 mRNA expression in the livers of GalN/LPS-treated rats. LPZ also inhibited nuclear factor-kappa B activation by GalN/LPS. CONCLUSIONS: LPZ inhibits the induction of several inflammatory mediators (including cytokines, chemokines, and NO) partially through suppression of nuclear factor-kappa B, resulting in the prevention of fulminant liver failure. The therapeutic potential of LPZ for liver injuries warrants further investigation.

Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis.

OBJECTIVE: Adipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC. METHODS: By immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed. RESULTS: Of the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses. CONCLUSIONS: Adipophilin is a potential independent prognostic marker for PDAC.

Assessment of clinical outcome of cholecystectomy according to age in preparation for the "Silver Tsunami".

BACKGROUND: Recent rapid increases in the aging population have created an impending "Silver Tsunami" in advanced countries. The overall prevalence of gallstone disease and its related complications will soon increase, and there will be a larger demand for gallbladder surgery. METHODS: We examined the outcomes of cholecystectomy according to age among patients with cholelithiasis to determine how a patient's age influences the outcome of cholecystectomy. All patients with gallstone disease who presented for cholecystectomy at our institute from January 2006 to December 2018 were analyzed. RESULTS: All perioperative outcomes (operation length, length of hospital stay, rate of open surgery, urgent surgery, postoperative complications, incidental gallbladder cancer, postoperative hospital death, concomitant bile duct stones, and total medical costs per patient) increased as patients aged. CONCLUSIONS: To prevent the progression of biliary disease, elective laparoscopic cholecystectomy is recommended before patients with cholelithiasis advance in age.