Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age.

Objectives: To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age. Methods: Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate-high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. Results: LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs. Conclusions: It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.

Anti-Inflammatory Effects of a Novel Nuclear Factor-κB Inhibitory Derivative Derived from Pyrazolo[3,4-d]Pyrimidine in Three Inflammation Models.

Nuclear factor-κB (NF-κB) plays a central role in inflammatory responses, and its physiologic functions are essential for cell survival and proliferation. Currently, drugs targeting NF-κB inhibition have not yet been applied in clinical practice. We investigated the physiologic effect of a novel NF-κB inhibitory compound, 1H-pyrazolo[3,4-d]pyrimidin-4-amine derivative (INH #1), on three inflammatory animal models. The pharmacokinetics were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Acute hepatitis was induced by administrating lipopolysaccharide (LPS) and D-(+)-galactosamine hydrochloride followed by the analysis of survival time and inflammatory mediators. Collagen-induced arthritis (CIA) was induced by immunization with type II collagen (CII), and serum-transfer arthritis (STA) was caused by injecting K/BxN mice serum. Clinical and histologic scores were evaluated in both arthritis models. Immune cell subset analysis, CII-induced interferon-gamma (IFN-γ) production and proliferation, and measurement of anti-CII IgG antibodies were performed in the CIA model. In the acute hepatitis model, INH #1 suppressed tumor necrosis factor-α (TNF-α) production and prevented early death in a dose-dependent manner. INH #1 significantly attenuated arthritis scores and joint inflammation in both arthritis models. Additionally, in the CIA model, dendritic cells (DCs) in the regional lymph nodes were decreased in the treated mice and antigen-induced IFN-γ production and cell proliferation in splenocytes were inhibited, whereas the titers of anti-CII IgG antibodies were comparable regardless of the treatment. Here we revealed that INH #1 exerted anti-inflammatory effects in vivo via inhibition of inflammatory mediators and suppression of cellular immune responses. This compound could be a novel candidate for inhibition of NF-κB in certain inflammatory diseases. SIGNIFICANCE STATEMENT: A novel nuclear factor-κB (NF-κB) inhibitory compound, 1H-pyrazolo[3,4-d]pyrimidin-4-amine derivative (INH #1), which retains physiologically essential NF-κB bioactivity, suppressed inflammation in three different mouse models: the acute hepatitis model, the collagen-induced arthritis model, and the K/BxN serum-transfer arthritis model. These results suggest that this compound could be a novel and potent anti-inflammatory agent.

Laparoscopic distal gastrectomy for gastric cancer in a patient with situs inversus: a case report.

BACKGROUND: Situs inversus (SI) is a rare congenital condition characterized by organ transposition from their normal positions. Careful preoperative planning is important for the safe operation of patients with SI because only a few surgeons have operated on such patients. Here, we report the case of a patient with SI who underwent laparoscopic distal gastrectomy (LDG) with D2 lymph node dissection (LND) for advanced gastric cancer (GC). CASE PRESENTATION: The patient was a 72-year-old man diagnosed with GC. Upper endoscopy revealed a type 3 tumor in the anterior wall of the stomach body. Multidetector computed tomography showed no obvious GC metastasis or inverted organs. The preoperative diagnosis was cStage IIB (i.e., cT3, cN0, and cM0) GC with SI. Although liver retracting and intracorporeal suturing required special attention, LDG with D2 LND and Billroth-I reconstruction were safely performed by reversing the usual procedure. The patient was discharged 10 days after the surgery. CONCLUSIONS: To safely perform laparoscopic surgery for GC in patients with SI, sufficient preoperative preparation is necessary. In particular, a reversible method of liver retraction should be prepared.

Chondroprotective effects of CDK4/6 inhibition via enhanced ubiquitin-dependent degradation of JUN in synovial fibroblasts.

OBJECTIVE: Targeting synovial fibroblasts (SF) using a cyclin-dependent kinase (CDK) 4/6 inhibitor (CDKI) could be a potent therapy for RA via inhibition of proliferation and MMP-3 production. This study was designed to elucidate the mechanism of chondroprotective effects on SFs by CDK 4/6 inhibition. METHODS: CDK4/6 activity was inhibited using CDKI treatment or enhanced by adenoviral gene transduction. Chondroprotective effects were evaluated using a collagen-induced arthritis model (CIA). Gene and protein expression were evaluated with quantitative PCR, ELISA and Western blotting. The binding of nuclear extracts to DNA was assessed with an electrophoresis mobility shift assay. RNA-Seq was performed to identify gene sets affected by CDKI treatment. RESULTS: CDKI attenuated cartilage destruction and MMP-3 production in CIA. In RASFs, CDKI impaired the binding of AP-1 components to DNA and inhibited the production of MMP-1 and MMP-3, which contain the AP-1 binding sequence in their promoter. CDK4/6 protected JUN from proteasome-dependent degradation by inhibiting ubiquitination. The RNA-Seq analysis identified CDKI-sensitive inflammatory genes, which were associated with the pathway of RA-associated genes, cytokine-cytokine receptor interaction and IL-17 signalling. Notably, the AP-1 motif was enriched in these genes. CONCLUSION: The mechanism of chondroprotective effects by CDK4/6 inhibition was achieved by the attenuation of AP-1 transcriptional activity via the impaired stability of JUN. Because the pharmacologic inhibition of CDK4/6 has been established as tolerable in cancer treatment, it could also be beneficial in patients with RA due to its chondroprotective and anti-inflammatory effects.

Effectiveness and safety of treat-to-target strategy in elderly-onset rheumatoid arthritis: a 3-year prospective observational study.

OBJECTIVES: To evaluate 3-year outcomes of following a treat-to-target (T2T) strategy targeting low disease activity for patients with elderly-onset RA (EORA) and to confirm safety profile of T2T. METHODS: Treatment was adjusted to target low disease activity with conventional synthetic DMARDs, followed by biologic DMARDs (bDMARDs) in 197 MTX-naïve EORA patients (mean age 74.9 years) with moderate-to-high disease activity. Non-implementation of T2T was evaluated at week 12, 24, 36, 52, 76, 104 and 128. To evaluate risks of using MTX, bDMARDs and glucocorticoids, 2122 periods of 3 months each were analysed using Bayesian hierarchical logistic regression models. RESULTS: Of the patients, 84.7% received methotrexate, 34.0% glucocorticoids with DMARDs and 41.6% bDMARDs during the observation period. Sixty-nine of the 197 patients failed to adhere to T2T because of comorbidities or the patient's own decision: 33 failed once, 19 twice, 10 three times and 6 four times or more. Simplified disease activity index (SDAI) remission and HAQ Disability Index (HAQ-DI) ≤0.5 at 3 years were achieved in 57.8% and 70.3% of the 128 patients adhering to T2T, and 34.8% and 43.5% of the 69 patients who did not adhere to T2T, respectively, and these were significantly different. Eighty-nine serious adverse events (SAEs) of any type were reported in 61 patients. MTX, bDMARDs and glucocorticoid were not associated with SAEs when adjusted for mean SDAI during the observation period and comorbidities at baseline. CONCLUSION: T2T strategy for EORA by using MTX and bDMARDs was effective with an acceptable safety profile. Adhering to T2T led to better outcomes.

[Laparoscopic Gastrectomy for Gastric Cancer with Adachi Type â ¥ Vascular Anomaly-A Case Report].

We report a case of laparoscopic gastrectomy for gastric cancer with an anomalous celiac trunk categorized as Type Ⅵ- Group 24 in the Adachi classification. Upper gastrointestinal endoscopy in an 81-year-old male revealed a shallow depressed lesion in the middle of the gastric body. Close examination led to diagnosis of cT1bN0M0, cStage Ⅰ gastric cancer, and laparoscopic distal gastrectomy was planned. Contrast-enhanced CT revealed no anomalous bifurcation of the hepatic artery, but the common hepatic artery ran on the dorsal side of the portal vein, branching from the superior mesenteric artery. Therefore, an Adachi Type Ⅵ-Group 24 celiac trunk anomaly was diagnosed. During surgery, the common hepatic artery could not be confirmed in guiding suprapancreatic lymph node dissection, and the portal vein was exposed. Anterior to the portal vein, nerves that are usually around the common hepatic artery continuously ran toward the hepatoduodenal ligament instead. Suprapancreatic lymph nodes were dissected, with the portal vein considered as the common hepatic artery. Adachi Type Ⅵ is a rare anomaly with an incidence of about 2%. Preoperative diagnosis enables safe and appropriate lymph node dissection.

Cholecystitis with abdominal wall biloma after percutaneous transhepatic gallbladder aspiration: A case report.

BACKGROUND: Abdominal wall biloma is an uncommon entity. We herein report an extremely rare case of cholecystitis with abdominal wall biloma after percutaneous transhepatic gallbladder aspiration (PTGBA). PRESENTATION OF CASE: A 69-year-old woman was diagnosed with acute cholecystitis, and PTGBA was performed on Day 1. PTGBA was performed a second time because of re-expansion of the gallbladder and an increased CRP level on Day 3. Computed tomography was performed on Day 9 because we suspected recurrence of cholecystitis. It revealed a well-circumscribed fluid collection between the abdominal wall or the diaphragm and the liver. Based on these intraoperative findings, we diagnosed her with cholecystitis with abdominal wall biloma. Cholecystectomy and drainage of the abdominal wall biloma were performed on Day 10. The postoperative course was uneventful, and she was discharged on Day 18. DISCUSSION: Early cholecystectomy is the gold-standard treatment for acute cholecystitis, but cholecystectomy is not performed in some cases. PTGBA is much more convenient, quicker, and less costly, but inappropriate aspiration during the second PTGBA session might have spread the infected bile to the abdominal wall through the PTGBA route. CONCLUSION: This case represents the first reported case of a biloma within the abdominal wall after PTGBA. To prevent this complication, we should aspirate gallbladder bile sufficiently during PTGBA. In addition, we should consider performing alternative therapy, such as percutaneous transhepatic gallbladder drainage or an operation, when we fail to appropriately aspirate.

Identification of Compounds With Glucocorticoid Sparing Effects on Suppression of Chemokine and Cytokine Production by Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

In recent years target based drug discovery has expanded our therapeutic armamentarium in the treatment of inflammatory and autoimmune diseases. Despite these advances and adverse effects, glucocorticoids remain reliable agents that are used in many of these diseases. The anti-inflammatory mechanisms of glucocorticoids include the suppression of transcription factor activity like nuclear factor kappa B (NF-κB). By reanalyzing data from two prior high throughput screens (HTS) that utilized a NF-κB reporter construct in THP-1 cells, we identified 1824 small molecule synthetic compounds that demonstrated NF-κB suppressive activities similar to the glucocorticoids included in the original >134,000 compound libraries. These 1824 compounds were then rescreened for attenuating NF-κB activity at 5 and 16 h after LPS stimuli in the NF-κB THP-1 reporter cells. After a "Top X" selection approach 122 hit compounds were further tested for toxicity and suppression of LPS induced CXCL8 release in THP-1 cells. Excluding cytotoxic compounds, the remaining active compounds were grouped into chemotype families using Tanimoto based clustering. Promising representatives from clustered chemotype groups were commercially purchased for further testing. Amongst these index compounds a lead chemotype: 1H-pyrazolo [3,4 d] pyrimidin-4-amine, effectively suppressed CXCL8, and TNF production by THP-1 cells when stimulated with LPS, TNF or IL-1ß. Extending these studies to primary cells, these lead compounds also reduced IL-6 and CXCL8 production by TNF stimulated fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. Importantly a lead 1H-pyrazolo [3,4 d] pyrimidin-4-amine compound demonstrated synergistic effects with dexamethasone when co-administered to TNF stimulated THP-1 cells and RA FLS in suppressing chemokine production. In summary, a cell based HTS approach identified lead compounds that reduced NF-κB activity and chemokine secretion induced by potent immunologic stimuli, and one lead compound that acted synergistically with dexamethasone as an anti-inflammatory agent showing a dose-sparing effect.

The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment.

OBJECTIVES: To test the effects of bolus supplementation of branched-chain amino acids (BCAA) on skeletal muscle mass, strength, and function in patients with rheumatic disorders taking glucocorticoid (GC). METHODS: Patients with rheumatic disorders treated with prednisolone (≥10 mg/day) were randomized to ingest additional daily 12 g of BCAA (n = 9) or not (n = 9) for 12 weeks. At baseline, and 4, 8, and 12 weeks, they underwent bioelectrical impedance analysis, muscle strength and functional tests, and computed tomography analysis for cross-sectional area of mid-thigh muscle. RESULTS: Disease activities of the patients were well controlled and daily GC dose was similarly reduced in both groups. Limb muscle mass was recovered in both groups. Whole-body muscle mass and muscle strength and functional mobility were increased only in BCAA (+) group. The effects of BCAA supplementation on recovering skeletal muscle mass were prominent in particular muscles including biceps femoris muscle. CONCLUSIONS: This trial is the first-in-man clinical trial to demonstrate that BCAA supplementation might be safe and, at least in part, improve skeletal muscle mass, strength, and function in patients with rheumatic disorders treated with GC.

Pancreas-sparing total duodenectomy for Spigelman stage IV duodenal polyposis associated with familial adenomatous polyposis: experience of 10 cases at a single institution.

Duodenal cancer is a leading cause of death in patients with familial adenomatous polyposis (FAP). In patients with Spigelman's classification (SC) stage IV duodenal polyposis (DP), careful endoscopic surveillance by specialists or surgical intervention is mandatory. We herein report the surgical and pathological outcomes of FAP patients with SC stage duodenal polyposis undergoing pancreas-sparing total duodenectomy (PSTD), which has been rarely reported but seems optimal in such patients. PSTD and distal gastrectomy with Billroth-I type reconstruction in ten consecutive FAP patients with SC stage IV DP are reported. The median duration of surgery was 396 min (range 314-571 min) and the median estimated blood loss was 480 mL (range 100-975 mL). Significant postoperative complications included wound infection in 1 patient, pancreatic fistula [International Study Group on Pancreatic Fistula definition (ISGPF) grade B] in 4 patients. Histopathologic examinations revealed a well-differentiated carcinoma in situ in 3 patients and others were all adenomas. Over a median follow-up period of 15 months (range 9-29 months), 1 patient developed a stomal ulcer which improved with medical treatment. There were no patients with a body weight loss of ≥10 % relative to the preoperative body weight. No recurrence were experienced during the follow up period. Patients were free from postoperative diabetes mellitus. PSTD is a feasible and acceptable procedure in FAP patients with SC stage IV DP, in terms of surgical, pathological and clinical outcome. However, accumulation of the patients and long-term follow up study is necessary.

[Two Cases of HER2-Positive Gastric Cancer with Multiple Liver Metastases Leading to Conversion Therapy with Chemotherapy].

Case 1: A 69-year-old man underwent chemotherapy with capecitabine plus cisplatin plus trastuzumab to treat advanced gastric cancer that was diagnosed as cStage IV adenocarcinoma(T3N2M1[P0, CYX, H1]). After 12 courses, liver metastases were absent on computed tomography images. The patient underwent total gastrectomy with D2 lymphadenectomy. It has been 22 months since the patient had gastrectomy without recurrence of the cancer. Case 2: A 70-year-old man underwent chemotherapy with capecitabine plus cisplatin plus trastuzumab for treatment of advanced gastric cancer that was diagnosed as cStage IV adenocarcinoma(T4aN1M1[P0, CY0, H1]). After 12 courses, regrowth of multiple liver metastases led to a treatment with weekly paclitaxel plus trastuzumab as a second-line chemotherapy. After 9 courses of second-line chemotherapy, multiple liver metastases were absent in computed tomography images. The patient underwent total gastrectomy with D2 lymphadenectomy. A small white nodule on the surface of S2 and S3 of the liver led to the patient receiving a partial liver resection. The pathological finding of the resected liver specimen was a metastasis of an adenocarcinoma. During continuous chemotherapy with weekly paclitaxel plus trastuzumab after gastrectomy, multiple liver metastases were revealed. The patient died 19 months after gastrectomy.

[A Case of Carcinoma of the Uterine Body, Right Ovary, and Duodenum in a Patient with Familial Adenomatous Polyposis].

We report a case of 4 carcinomas of the uterine body, right ovary, and duodenum in a patient with familial adenomatous polyposis (FAP). Her mother's family line carries FAP. She underwent proctocolectomy with ileoanal anastomosis for FAP when she was 20 years old. She was diagnosed with carcinoma of the uterine body and right ovary, and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy at 48 years of age. The pathological examination revealed endometrioid adenocarcinoma of the uterine body (Stage ⅠB) and endometrioid adenocarcinoma of the right ovary (Stage ⅠA). Her diagnosis was Stage Ⅳ according to the Spigelman classification of duodenal polyposis, and she underwent pancreas-preserving total duodenectomy at 50 years of age. The pathological examination was conclusive for 2 carcinomas in the adenoma, which were 20 mm and 25 mm in diameter, respectively. She has been well without any evidence of cancer recurrence 20 months after the pancreas-preserving total duodenectomy.

[Minilaparotomy in Pancreas-Preserving Total Duodenectomy for Familial Adenomatous Polyposis Associated with Spigelman Stage â £ Duodenal Polyposis].

INTRODUCTION: Reports on pancreas-preserving total duodenectomy (PPTD) for duodenal polyposis (DP) in familial adenomatous polyposis (FAP) patients are rare. We herein report a case of PPTD performed by minilaparotomy for DP in an FAP patient. CASE: A 27-year-old female FAP patient was diagnosed with Spigelman classification (SC) stage Ⅳ DP on gastroduodenoscopy. She underwent PPTD through a 7 cm upper abdominal incision. All polyps were confirmed as adenomas histopathologically. After 6 months of follow-up, complications related to total duodenectomy, such as weight loss, diabetes mellitus, and fatty liver have not been observed. DISCUSSION: SC stage Ⅳ refers to non-advanced cancers, and PPTD is basically prophylactic surgery. Therefore, pancreatoduodenectomy seems too aggressive for SC stage Ⅳ patients. PPTD by minilaparotomy is suitable for young female patients for its curability, esthetic outcome, and safety.

[A Case of NET G1 of Vater's Papilla in Familial Adenomatous Polyposis-Associated Duodenal Adenomatous Polyposis].

INTRODUCTION: Familial adenomatous polyposis (FAP) is characterized by the development of duodenal polyposis (DP), which later develops into colonic adenomatous polyps and, eventually, colorectal cancer. Neuroendocrine tumors (NET) are rare in FAP and reports of pancreas-preserving total duodenectomy (PPTD) to treat NET are limited. CASE: A 62-year-old. woman was previously diagnosed with FAP and she underwent a total colectomy and ileorectal anastomosis. Surveillance by upper gastrointestinal endoscopy revealed duodenal polyposis and a 35 mm flat, elevated tumor near the ampulla of Vater. She was diagnosed as having Spigelman stage Ⅳ DP and she underwent PPTD. Histopathology revealed a 7 mm NET G1 in the ampulla of Vater and multiple adenomas. DISCUSSION: Little is known about duodenal NET G1in FAP patients who undergo PPTD. Close follow-up is necessary.

[A Case of Pelvic Schwannoma, Mimicking Metastasis of Rectal Carcinoma].

INTRODUCTION: Schwannoma in the lateral lymph node region is extremely rare; however, this tumor has been reported to have relatively high SUV on PET-CT, suggestive of malignancy. CASE: A 67-year-old man with advanced lower rectal cancer had a small nodule with FDG accumulation (SUVmax 2.6) near the left internal iliac artery. His preoperative diagnosis was rectal cancer with lateral lymph node metastasis. He underwent super-low anterior resection with lateral lymph node dissection. Histopathological examination was conclusive for pT3 (A), with an Rt263D lymph node metastasis. Interestingly, a schwannoma was detected among the harvested lymph nodes. CONCLUSION: Although rectal cancer is known to involve pelvic lymph nodes, the role of preoperative diagnosis with FDG-PET is unclear. We should consider that schwannoma is associated with slight elevation of SUVmax and it may mimic lymph node metastasis.

Prognostic role of gastrectomy in patients with gastric cancer with positive peritoneal cytology.

This retrospective study identified the optimal treatment strategy for patients with gastric cancer with positive peritoneal cytology. We analyzed clinicopathologic and survival data for 54 patients who had undergone gastrectomy and/or chemotherapy for treatment of gastric cancer with positive peritoneal cytology with (n = 40) or without (n = 14) metastatic disease. The median overall survival did not differ significantly between patients with gastric cancer with positive peritoneal cytology with and without metastatic disease (19 versus 13 months, respectively). Among 14 clinicopathologic variables, the lack of gastrectomy was the only significant independent unfavorable factor for survival (odds ratio, 1.64; 95% confidence interval, 1.04-2.57; P = 0.03). The median overall survival significantly differed among patients who had undergone gastrectomy plus chemotherapy, chemotherapy alone, and gastrectomy alone (25, 10, and 17 months, respectively; P < 0.01). Gastrectomy may be optimal for patients with (gastric cancer with positive peritoneal cytology), considering its favorable prognostic effect with respect to perioperative chemotherapy.

Production of intraperitoneal interleukin-6 following open or laparoscopic assisted distal gastrectomy.

The interleukin (IL)-6 concentration in plasma or serum has been considered to represent the degree of stress resulting from surgery. However, IL-6 in peritoneal fluid has rarely been considered. The aim of this study was to assess the concentration and amount of IL-6 in peritoneal fluid as indicators of surgical stress. To obtain basic data on peritoneal release of IL-6 during gastric cancer surgery, we measured IL-6 in peritoneal drainage samples, stored for up to 72 hours postoperatively, from patients who had undergone conventional open (ODG group, n = 20) and laparoscopic-assisted (LADG group, n = 19) distal gastrectomy. Within 24 hours, 61 and 77% of the IL-6 was released into the peritoneal cavity in the LADG and ODG groups, respectively. In both groups, the concentration and amount of peritoneal fluid IL-6 were significantly correlated with each other (LADG group: Spearman's rank correlation test [rS] = 0.48, P = 0.04; ODG group: rS = 0.58, P = 0.01). The concentration and amount of IL-6 in peritoneal fluid was 2.8- and 3.6-fold higher in the ODG than in the LADG group, respectively (P < 0.01). With regard to the relationship between the serum C-reactive protein (CRP) peak and the concentration or amount of peritoneal fluid IL-6 released within 24 hours, only the concentration of peritoneal fluid IL-6 in the LADG group was significantly correlated (rS = 0.60, P = 0.01) with the serum CRP peak. Our findings suggest that the amount and concentration of IL-6 released into the peritoneal cavity for up to 24 hours after surgery can each be a reliable parameter for assessment of surgical stress.

Predicting the amount of intraperitoneal fluid accumulation by computed tomography and its clinical use in patients with perforated peptic ulcer.

The correlation between the amount of peritoneal fluid and clinical parameters in patients with perforated peptic ulcer (PPU) has not been investigated. The authors' objective was to derive a reliable formula for determining the amount of peritoneal fluid in patients with PPU before surgery, and to evaluate the correlation between the estimated amount of peritoneal fluid and clinical parameters. We investigated 62 consecutive patients who underwent emergency surgery for PPU, and in whom prediction of the amount of accumulated intraperitoneal fluid was possible by computed tomography (CT) using the methods described by Oriuchi et al. We examined the relationship between the predicted amount of accumulated intraperitoneal fluid and that measured during surgery, and the relationship between the amount of fluid predicted preoperatively or measured during surgery and several clinical parameters. There was a significant positive correlation between the amount of fluid predicted by CT scan and that measured during surgery. When patients with gastric ulcer and duodenal ulcer were analyzed collectively, the predicted amount of intraperitoneal fluid and the amount measured during surgery were each associated with the period from onset until CT scan, perforation size, the Mannheim peritoneal index, and the severity of postoperative complications according to the Clavien-Dindo classification. Our present results suggest that the method of Oriuchi et al is useful for predicting the amount of accumulated intraperitoneal fluid in patients with PPU, and that this would be potentially helpful for treatment decision-making and estimating the severity of postoperative complications.

[Evaluation of immunity in elderly patients with unresectable gastric cancer receiving S-1/Lentinan combination chemotherapy].

PURPOSE: This retrospective study evaluated immunity in elderly patients with unresectable gastric cancer receiving S-1/ Lentinan combination chemotherapy. PATIENTS AND METHODS: This study included 10 patients aged≥70 years with unresectable gastric cancer who received S-1/Lentinan combination chemotherapy between October 2008 and December 2012. All patients gave written informed consent. Immune parameters for regulatory T cell(Treg)ratio, prostaglandin E2(PGE2), C3, CH50, and granulocyte/lymphocyte ratio were measured before chemotherapy initiation and at 7 weeks after it. Clinicopathological or immune parameters affecting overall survival(OS)were consequently evaluated. RESULTS: A high Treg ratio(p=0.02) and low PGE2(p=0.05)levels at 7 weeks after chemotherapy and a decrease in the Treg ratio(p=0.02)were found to be significant favorable factors affecting OS. CONCLUSION: The outcome of elderly patients with unresectable gastric cancer receiving S-1/Lentinan combination chemotherapy seemed to be correlated with the change in immunity.