Efficacy of pancreaticojejunostomy of the pancreatic stump during distal or central pancreatectomy.

BACKGROUND: A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. METHODS: Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. RESULTS: In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. CONCLUSIONS: PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.

Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors.

BACKGROUND: Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. METHODS: Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. RESULTS: GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). CONCLUSIONS: Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.

Appropriate indications for laparoscopic repeat hepatectomy.

BACKGROUND: Laparoscopic repeat hepatectomy (LRH) has increased, but appropriate indications for LRH are unclear. This study aimed to clarify appropriate indications for LRH. METHODS: We retrospectively compared surgical outcomes between open RH (ORH) (n = 57) and LRH (n = 40) groups. To detect difficult cases of complete pure LRH, we examined patients with unplanned intraoperative hand-assisted laparoscopic surgery (HALS)/open conversion (n = 6). RESULTS: In the LRH versus ORH group, as previous hepatectomy, laparoscopic (75% vs. 12%, p < 0.001) and partial hepatectomy (Hr0) (73% vs. 37%, p = 0.002) were more frequently performed, and as RH procedure, partial hepatectomy (Hr0) (88% vs. 47%, p = 0.0002) was more frequently performed. S1 tumor cases were higher in ORH group (11% vs. 0%), but S2-6 cases were higher in LRH group (73% vs. 49%) (p = 0.02). In LRH group, compared to the pure LRH patients, HALS/open conversion patients underwent significantly more previous hepatectomy with more than lobectomy (Hr2-3) (33% vs. 2.9%, p = 0.033) and more RH procedures with segmentectomy (HrS) (33% vs. 2.9%, p = 0.03). All LRH requiring a repeat hepatic hilar approach were HALS conversions. CONCLUSION: Appropriate indications for LRH were previous hepatectomy was laparoscopic partial hepatectomy (Hr0), and RH procedure was partial hepatectomy (Hr0) for S2-6 tumor location. When RH is more than segmentectomy (HrS) requiring a repeat hepatic hilar approach, planned HALS or ORH may be a better approach than pure LRH.

Technical and oncological safety of pancreatectomy for pancreatic cancer in older adults aged over 75 years versus younger adults: A single-center retrospective cohort study.

AIM: The number of surgeries for pancreatic ductal adenocarcinoma (PDAC) in older adults has been rising. This study aimed to evaluate the technical and oncological safety of pancreatectomy for older adults aged ≥75 years with PDAC by retrospectively comparing their short- and long-term outcomes with those of younger adults aged <75 years. METHODS: Data were collected from 117 patients who underwent pancreatectomy for PDAC in our department. The indication for surgery regarding patient characteristics was considered according to each patient's American Society of Anesthesiologists physical status and Eastern Cooperative Oncology Group Performance Status Scale. Data of older adults (n = 32) were compared with those of younger adults (n = 85), and comprised patient background, surgical factors, postoperative course, histopathological factors and prognostic factors. Additionally, prognostic nutritional index values preoperatively and at 1 and 6 months postoperatively were compared between the two groups. RESULTS: Although American Society of Anesthesiologists physical status and comorbidities were worse in older adults, there were no significant differences in surgical factors, postoperative courses and histopathological factors between the two groups. The overall complication rate tended to be higher in older adults (40.6%) than in younger adults (29.4%). There were no differences in median lengths of recurrence-free survival and overall survival (older adults vs younger adults: 12 vs 13 months, P = 0.545, and 26 vs 20 months, P = 0.535, respectively) between the two groups. Furthermore, no significant differences were found in prognostic nutritional index preoperatively to 6 months after surgery. CONCLUSION: With careful determination of surgical indications, pancreatectomy for PDAC can be carried out with acceptable post-pancreatectomy morbidity in younger adults. Geriatr Gerontol Int 2023; 23: 531-536.

Impact of AI system on recognition for anatomical landmarks related to reducing bile duct injury during laparoscopic cholecystectomy.

BACKGROUND: According to the National Clinical Database of Japan, the incidence of bile duct injury (BDI) during laparoscopic cholecystectomy has hovered around 0.4% for the last 10 years and has not declined. On the other hand, it has been found that about 60% of BDI occurrences are due to misidentifying anatomical landmarks. However, the authors developed an artificial intelligence (AI) system that gave intraoperative data to recognize the extrahepatic bile duct (EHBD), cystic duct (CD), inferior border of liver S4 (S4), and Rouviere sulcus (RS). The purpose of this research was to evaluate how the AI system affects landmark identification. METHODS: We prepared a 20-s intraoperative video before the serosal incision of Calot's triangle dissection and created a short video with landmarks overwritten by AI. The landmarks were defined as landmark (LM)-EHBD, LM-CD, LM-RS, and LM-S4. Four beginners and four experts were recruited as subjects. After viewing a 20-s intraoperative video, subjects annotated the LM-EHBD and LM-CD. Then, a short video is shown with the AI overwriting landmark instructions; if there is a change in each perspective, the annotation is changed. The subjects answered a three-point scale questionnaire to clarify whether the AI teaching data advanced their confidence in verifying the LM-RS and LM-S4. Four external evaluation committee members investigated the clinical importance. RESULTS: In 43 of 160 (26.9%) images, the subjects transformed their annotations. Annotation changes were primarily observed in the gallbladder line of the LM-EHBD and LM-CD, and 70% of these shifts were considered safer changes. The AI-based teaching data encouraged both beginners and experts to affirm the LM-RS and LM-S4. CONCLUSION: The AI system provided significant awareness to beginners and experts and prompted them to identify anatomical landmarks linked to reducing BDI.

Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma.

BACKGROUND: The prognosis of distal cholangiocarcinoma (dCCA) remains poor; thus, the identification of new therapeutic targets is warranted. Phosphorylated S6 ribosomal protein indicates a mammalian target of rapamycin complex 1 (mTORC1) activity, and mTORC1 plays a central role in controlling cell growth and regulating glucose metabolism. We aimed to clarify the effect of S6 phosphorylation on tumor progression and the glucose metabolic pathway in dCCA. METHODS: Thirty-nine patients with dCCA who underwent curative resection were enrolled in this study. S6 phosphorylation and the expression of GLUT1 were evaluated by immunohistochemistry, and their relationship with clinical factors was investigated. The effect of S6 phosphorylation on glucose metabolism with PF-04691502 treatment, an inhibitor of S6 phosphorylation, was examined in cancer cell lines by Western blotting and metabolomics analysis. Cell proliferation assays were performed with PF-04691502. RESULTS: S6 phosphorylation and the expression of GLUT1 were significantly higher in patients with an advanced pathological stage. Significant correlations between GLUT1 expression, S6 phosphorylation, and SUV-max of FDG-PET were shown. In addition, cell lines with high S6 phosphorylation levels showed high GLUT1 levels, and the inhibition of S6 phosphorylation reduced the expression of GLUT1 on Western blotting. Metabolic analysis revealed that inhibition of S6 phosphorylation suppressed pathways of glycolysis and the TCA cycle in cell lines, and then, cell proliferation was effectively reduced by PF-04691502. CONCLUSION: Upregulation of glucose metabolism via phosphorylation of S6 ribosomal protein appeared to play a role in tumor progression in dCCA. mTORC1 may be a therapeutic target for dCCA.

Development of a cross-artificial intelligence system for identifying intraoperative anatomical landmarks and surgical phases during laparoscopic cholecystectomy.

BACKGROUND: Attention to anatomical landmarks in the appropriate surgical phase is important to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC). Therefore, we created a cross-AI system that works with two different AI algorithms simultaneously, landmark detection and phase recognition. We assessed whether landmark detection was activated in the appropriate phase by phase recognition during LC and the potential contribution of the cross-AI system in preventing BDI through a clinical feasibility study (J-SUMMIT-C-02). METHODS: A prototype was designed to display landmarks during the preparation phase and Calot's triangle dissection. A prospective clinical feasibility study using the cross-AI system was performed in 20 LC cases. The primary endpoint of this study was the appropriateness of the detection timing of landmarks, which was assessed by an external evaluation committee (EEC). The secondary endpoint was the correctness of landmark detection and the contribution of cross-AI in preventing BDI, which were assessed based on the annotation and 4-point rubric questionnaire. RESULTS: Cross-AI-detected landmarks in 92% of the phases where the EEC considered landmarks necessary. In the questionnaire, each landmark detected by AI had high accuracy, especially the landmarks of the common bile duct and cystic duct, which were assessed at 3.78 and 3.67, respectively. In addition, the contribution to preventing BDI was relatively high at 3.65. CONCLUSIONS: The cross-AI system provided landmark detection at appropriate situations. The surgeons who previewed the model suggested that the landmark information provided by the cross-AI system may be effective in preventing BDI. Therefore, it is suggested that our system could help prevent BDI in practice. Trial registration University Hospital Medical Information Network Research Center Clinical Trial Registration System (UMIN000045731).

An intraoperative artificial intelligence system identifying anatomical landmarks for laparoscopic cholecystectomy: a prospective clinical feasibility trial (J-SUMMIT-C-01).

BACKGROUND: We have implemented Smart Endoscopic Surgery (SES), a surgical system that uses artificial intelligence (AI) to detect the anatomical landmarks that expert surgeons base on to perform certain surgical maneuvers. No report has verified the use of AI-based support systems for surgery in clinical practice, and no evaluation method has been established. To evaluate the detection performance of SES, we have developed and established a new evaluation method by conducting a clinical feasibility trial. METHODS: A single-center prospective clinical feasibility trial was conducted on 10 cases of LC performed at Oita University hospital. Subsequently, an external evaluation committee (EEC) evaluated the AI detection accuracy for each landmark using five-grade rubric evaluation and DICE coefficient. We defined LM-CBD as the expert surgeon's "judge" of the cystic bile duct in endoscopic images. RESULTS: The average detection accuracy on the rubric by the EEC was 4.2 ± 0.8 for the LM-CBD. The DICE coefficient between the AI detection area of the LM-CBD and the EEC members' evaluation was similar to the mean value of the DICE coefficient between the EEC members. The DICE coefficient was high score for the case that was highly evaluated by the EEC on a five-grade scale. CONCLUSION: This is the first feasible clinical trial of an AI system designed for intraoperative use and to evaluate the AI system using an EEC. In the future, this concept of evaluation for the AI system would contribute to the development of new AI navigation systems for surgery.

Pancreas-preserving partial duodenectomy for non-ampullary duodenal neoplasms: three case reports.

BACKGROUND: There are multiple surgical procedures for resecting non-ampullary duodenal neoplasms (NADNs), and the appropriate method is selected depending on the tumor location and diagnosis. We herein report 3 cases of NADNs that were resected using pancreas-preserving partial duodenectomy (PPD). CASE REPORTS: The first patient, a 73-year-old woman with a circumferential duodenal adenoma in the supra-ampullary duodenum, underwent surgery. After laparotomy, the duodenum proximal to the tumor was confirmed using intraoperative endoscopy and dissected. The duodenum distal to the tumor was dissected under direct visualization, and the specimen was removed. The distal stump of the duodenum was closed, and duodenojejunostomy was performed as described by Billroth II. The tumor was diagnosed as an adenoma 75 mm in size. She was discharged 12 days after surgery without any complications. The second patient, a 48-year-old man, was diagnosed with a neuroendocrine neoplasm (NEN) with a diameter of 14 mm in the supra-ampullary duodenum. Laparoscopic PPD was performed. He was diagnosed with NEN G1 and discharged the 11th day after surgery. The third patient, a 71-year-old man with a 0-Is + IIa lesion in the horizontal duodenum, underwent surgery. After laparotomy, the horizontal duodenum and proximal jejunum were resected, and duodenojejunostomy was performed. The patient was diagnosed with stage I adenocarcinoma and discharged on the 15th day after surgery. CONCLUSION: PPD is useful for avoiding the morbidity of pancreatoduodenectomy in the management of NADNs without invasion to the ampulla of Vater or pancreas.

Changes of Short-Chain Fatty Acids and Their Receptors in an Obese Rat Model After Sleeve Gastrectomy.

BACKGROUND: Short-chain fatty acids (SCFAs) and gut microbiota have health-related effects and are associated with a wide range of disorders. However, the changes of SCFAs and their receptors after sleeve gastrectomy (SG) remain unclear. This study aimed to examine changes of SCFAs and their receptors after SG in an obese rat model. METHODS: Thirty obese Sprague-Dawley rats eating a high-energy diet for 6 weeks were divided into three groups: sham-operated (SO) control, pair-fed (PF) control, and SG group. Six weeks after the surgery, metabolic parameters, SCFA levels in the blood and stool, mRNA and protein expression of SCFA receptors in the ileum and epididymal fat, and gut microbiota were examined. RESULTS: Metabolic parameters in the SG group were significantly improved compared with the SO group. Acetic acid levels in the blood and stool were significantly higher in the SG group than the PF group. The butyric acid level in the stool was also significantly higher in the SG group than in the PF group. In the ileum and epididymal fat, mRNA and protein expression of GPR41 was significantly higher in the SG group than in the other two groups, and mRNA and protein expression of GPR43 was significantly higher in the SG group than in the PF group. Increases in the genera Enterococcus, Lactobacillus, Lactococcus, and Clostridium were observed in the stool after SG. CONCLUSIONS: SG may activate SCFA pathways through a change in gut microbiota.

An additional port in difficult laparoscopic cholecystectomy for surgical safety.

BACKGROUND: Tokyo Guidelines 2018, clinical practice guidelines for acute cholangitis and cholecystitis, recommend bailout procedures to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC) for difficult gallbladder. We first insert an additional port (AP) for difficult gallbladder that may require bailout procedures. Because the usefulness of an AP during LC is unclear, we therefore examined the efficacy of the AP during LC in this study. METHODS: Data were collected from 115 patients who underwent LC for acute cholecystitis in our department. The indications for AP were excessive bleeding, scarring, and poor visual field around Calot's triangle. AP was inserted into the right middle abdomen so as not to interfere with other trocars and was used by the assistant. Surgical outcomes were evaluated based on AP use during LC. RESULTS: AP was inserted in 19 patients during LC (AP group). The indications for AP were excessive bleeding in nine patients, scarring around Calot's triangle in seven patients, and poor visual field around Calot's triangle in three patients. Open conversion was performed in two patients in the non-AP group. BDI occurred in one patient in the non-AP group. In patients with Difficulty Score 3, operation time was significantly shorter (P = .038) and Critical View of Safety (CVS) score was significantly higher in the AP group (P = .046). CONCLUSION: AP is useful in patients with excessive bleeding to shorten operation time and increase the CVS score. AP may be one useful option for difficult gallbladder.

Risk factors of unplanned intraoperative conversion to hand-assisted laparoscopic surgery or open surgery in laparoscopic liver resection.

BACKGROUND: Laparoscopic liver resection (LLR) is possible in many patients, but pure LLR is sometimes difficult to complete, and unplanned intraoperative hand-assisted laparoscopic surgery (HALS) or open conversion is sometimes necessary. However, appropriate indications and timing for conversion are unclear. This study aimed to clarify the indications for HALS and open conversion from pure LLR. METHODS: We collected data from 208 patients who underwent LLR from January 2010 to February 2021 in our department. We retrospectively examined these data between cases of unplanned intraoperative HALS conversion, open conversion, and pure LLR, and clarified risk factors and indications for HALS or open conversion. RESULTS: There were 191 pure LLRs, nine HALS conversions, and eight open conversions. In the HALS conversion group versus pure LLR group, body mass index (BMI) (27.0 vs. 23.7 kg/m2, p = 0.047), proportions of patients with history of upper abdominal surgery (78% vs. 33%; p = 0.006), repeat hepatectomy (56% vs. 15%; p = 0.002), S7 or S8 tumor location (67% vs. 35%; p = 0.049), and difficulty score (DS) ≥ 7 (56% vs. 19%; p = 0.008) were significantly higher, and surgical time (339 vs. 239 min; p = 0.031) was significantly longer. However, postoperative states were not significantly different between the two groups. The BMI cutoff value for risk of unplanned intraoperative conversion determined by receiver operating characteristic curve analysis was 25 kg/m2, and the proportion of patients with BMI ≥ 25 kg/m2 (89% vs. 31%, p < 0.001) was significantly higher in the HALS conversion versus pure LLR group. In the open conversion group, although there were no significant differences compared to the HALS group in clinicopathological factors except for sex, blood loss was greater (1425 vs. 367 mL; p < 0.001). CONCLUSION: Risk factors for considering HALS during LLR were patients with a history of upper abdominal surgery including repeat hepatectomy, BMI ≥ 25 kg/m2, S7 or S8 tumor location, DS ≥ 7, and prolonged surgical time. Furthermore, uncontrollable intraoperative bleeding was an indication for open conversion.

Predictors of early withdrawal from follow-up visits after laparoscopic sleeve gastrectomy in a Japanese institution.

PURPOSE: Postoperative weight loss is related to postoperative adherence to follow-up after bariatric/metabolic surgery, but many patients stop attending follow-up visits early. The aim of this study was to clarify predictors of early withdrawal from follow-up after laparoscopic sleeve gastrectomy (LSG) in a Japanese institution. METHODS: One hundred and fifty-three patients who underwent LSG were retrospectively included in this study. Multivariate analysis was performed to evaluate independent predictors of withdrawal from follow-up visits within 12 months after LSG among significant or nearly significant factors in the univariate analyses. The discrimination power of significant factors was estimated using area under the receiver operating characteristic curve (AUC). RESULTS: Within 12 months after LSG, 25 of the 153 patients withdrew from follow-up visits. The multivariate analysis showed that age was the only significant predictor of withdrawal. The AUC for age was 0.685, and the cut-off value was < 40 years. The younger patients (< 40 years old) had a significantly higher rate of withdrawal compared with the older patients (≥ 40 years) (27.0% vs. 8.9%). CONCLUSION: Older Japanese patients (≥ 40 years old) may be better candidates for LSG. We consider it significant to continue to emphasize the importance of follow-up visits in younger patients after LSG.

Gastric Wall Thickness and Linear Staple Height in Sleeve Gastrectomy in Japanese Patients with Obesity.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a standard procedure due to its low complication rates and favorable outcomes. However, limited data are available regarding the optimal size of linear staplers in relation to gastric wall thickness (GWT). METHODS: Between August 2016 and December 2020, we performed LSG in 70 patients with an average age, body weight, and body mass index of 42 years, 107 kg, and 40 kg/m2, respectively. We measured the GWT at the antrum, body, and fundus using resected specimens. We used an endo-linear stapler, and the closed staple height (CSH) was 1.75 mm. RESULTS: We found that the average GWT at the antrum was significantly thicker than the GWT at the body and fundus. There was a statistically significant relationship between body weight and the GWT at the antrum and body and obstructive sleep apnea and the GWT at the body. The average CSH/GWT ratios were 0.55, 0.62, and 0.90 at the antrum, body, and fundus, respectively. However, in 20 patients (29%), the CSH/GWT ratio at the fundus area was ≥ 1.0, and only preoperative body weight was a significant predictor for a CSH/GWT ratio of ≥ 1.0. CONCLUSION: A light body weight may be related to a CSH/GWT ratio of ≥ 1.0 at the fundus.

[Long‒Term Survival after Lung Resection for Lung Metastasis of Pancreatic Cancer-A Report of Two Cases].

Some reports have shown that the prognosis of recurrent lung metastases after resection of pancreatic cancer is better than that for other organs. We report on 2 cases of long‒term survival after lung resection for lung metastases from pancreatic cancer. Case 1: A 73‒year‒old man underwent distal pancreatectomy for pancreatic body cancer. Adjuvant chemotherapy of S‒1 was administered for 6 months. At 3 years after surgery, 2 small metastatic nodules were detected in the right lung, and the patient underwent thoracoscopic right upper lobectomy. At 5 years and 9 months after the initial surgery, he is alive without recurrence. Case 2: An 81‒year‒old woman underwent pylorus‒preserving pancreatoduodenectomy for pancreatic head cancer. Adjuvant chemotherapy of S‒1 was administered for 4 months. At 1 year and 9 months after surgery, a metastatic nodule was detected in the left upper lung, and the patient underwent thoracoscopic left upper lobectomy. At 4 years and 6 months after initial surgery, radiation therapy was performed for localized bone metastasis. At 5 years and 1 month after the initial surgery, she is alive without other recurrences. In conclusion, recurrent lung metastases of pancreatic cancer with a small number of metastases may result in long‒term survival following resection.

Port-sharing techniques for laparoscopic cholecystectomy and sleeve gastrectomy.

In Japan, the number of bariatric surgeries performed has remained low. Thus, concomitant laparoscopic cholecystectomy (LC) with laparoscopic sleeve gastrectomy (LSG) is still relatively uncommon, but is increasing. We developed new port-sharing techniques for LC and LSG, which we performed on 26 obese Japanese patients with gall bladder (GB) diseases, using the LSG trocar arrangement and one additional trocar. We performed LC first, and after exchanging a port for a liver retractor in the epigastrium, we then completed LSG. One patient with an anomalous extrahepatic bile duct required one additional port. The mean LC time was 55 min, and the transition to LSG just after LC was smooth in all the patients. One patient suffered postoperative intraperitoneal hemorrhage, which was managed conservatively. Concomitant LC with LSG using port-sharing techniques is feasible and safe for obese Japanese patients with GB diseases.

Clinical Significance of Splenic Vessels and Anatomical Features in Laparoscopic Splenectomy.

Introduction: Laparoscopic splenectomy (LS) has become the standard treatment for benign hematological disorders and hypersplenism. However, serious complications such as pancreatic fistula and portal venous thrombosis (PVT) sometimes occur. We investigated the clinical significance of splenic vessels and anatomical features in LS. Methods: Patient data were collected from 32 patients who underwent LS. The indications for LS were hypersplenism due to liver cirrhosis, idiopathic thrombocytopenic purpura, hereditary spherocytosis, and others. Close contact of pancreatic tail with splenic hilum, spleen volume, and diameters of splenic vessels were evaluated on computed tomography images. Results: Close contact of pancreatic tail with splenic hilum was recognized in 15 of the patients. The close contact was significantly associated with operation time (P = .038), spleen volume (P = .021), and spleen volume/body surface area (BSA) ratio (P = .001). In multivariate analysis, spleen volume/BSA ratio was an independent factor for close contact (P = .022). PVT occurred in 3 cirrhosis patients, and the diameter of the splenic vein (SV) was significantly associated with PVT as a result of multivariate analysis (P = .027). Conclusion: Close contact of the pancreatic tail with the splenic hilum may cause a longer operation time at LS and be associated with spleen volume/BSA ratio. A larger SV diameter in cirrhosis patients may be related to PVT after LS.

Characteristics of spontaneous calcium oscillations in renal tubular epithelial cells.

BACKGROUND: The kidney is a major organ involved in calcium (Ca(2+)) metabolism. Ca(2+) is transported through renal tubular epithelial cells. The intracellular free calcium concentration ([Ca(2+)](i)) is tightly controlled at a low concentration, but transient increases and oscillations in [Ca(2+)](i) are induced by various conditions. In this study, we investigated the mechanisms underlying the spontaneous [Ca(2+)](i) oscillations observed in MDCK cells. METHODS: [Ca(2+)](i) was monitored in fura-2-loaded Madin-Darby canine kidney (MDCK) cells using a calcium imaging system. We investigated the mechanism by which [Ca(2+)](i) changed by applying drugs or by changing the extracellular Ca(2+) concentration. RESULTS: Spontaneous [Ca(2+)](i) oscillations occurred in MDCK cells. The oscillations occurred irregularly and were not transmitted to neighboring cells. Spontaneous [Ca(2+)](i) oscillations in MDCK cells were initiated by Ca(2+) release from ryanodine/IP(3)-sensitive intracellular calcium stores, and their frequency was largely unaffected by the extracellular Ca(2+) concentration. Moreover, the frequency of the oscillations was increased by extracellular nucleotide, but was decreased when the nucleotides were removed. CONCLUSIONS: Our study suggested that [Ca(2+)](i) release from ryanodine/IP(3)-sensitive intracellular calcium stores mediates spontaneous [Ca(2+)](i) oscillations in MDCK cells. Calcium oscillations may be associated with the function of the renal tubular epithelial cells.

Phosphoinositide 3-kinase signaling pathway mediated by p110α regulates invadopodia formation.

Invadopodia are extracellular matrix-degrading protrusions formed by invasive cancer cells that are thought to function in cancer invasion. Although many invadopodia components have been identified, signaling pathways that link extracellular stimuli to invadopodia formation remain largely unknown. We investigate the role of phosphoinositide 3-kinase (PI3K) signaling during invadopodia formation. We find that in human breast cancer cells, both invadopodia formation and degradation of a gelatin matrix were blocked by treatment with PI3K inhibitors or sequestration of D-3 phosphoinositides. Functional analyses revealed that among the PI3K family proteins, the class I PI3K catalytic subunit p110α, a frequently mutated gene product in human cancers, was selectively involved in invadopodia formation. The expression of p110α with cancerous mutations promoted invadopodia-mediated invasive activity. Furthermore, knockdown or inhibition of PDK1 and Akt, downstream effectors of PI3K signaling, suppressed invadopodia formation induced by p110α mutants. These data suggest that PI3K signaling via p110α regulates invadopodia-mediated invasion of breast cancer cells.

Long-term facilitation of spontaneous calcium oscillations in astrocytes with endogenous adenosine in hippocampal slice cultures.

It is well established that astrocytes release gliotransmitters and moderate neuronal activity in the central nervous system via intracellular Ca(2+) dynamics. Astrocytic Ca(2+) oscillations are one type of spontaneous Ca(2+) mobilization that occurs in astrocytes. However, the modulation of spontaneous astrocytic Ca(2+) oscillations, especially in pathophysiological conditions, is not yet fully understood. Here, we demonstrate that activation of adenosine receptors induces a long-lasting increase in the frequency of astrocytic Ca(2+) oscillations in rat hippocampal slice cultures. The long-term facilitation of the frequency of Ca(2+) oscillations was mediated by endogenous adenosine generated via breakdown of extracellular ATP by ecto-ATPase. We also demonstrate that local tissue injury with ultraviolet irradiation can cause this long-term facilitation of Ca(2+) oscillations via endogenous adenosine. Our data suggest that endogenous adenosine is one of the modulators of spontaneous astrocytic Ca(2+) oscillations in the rat hippocampus, and may play a significant role in altered Ca(2+) dynamics in astrocytes observed during pathophysiological conditions.