Pancreaticoenterostomy With Seromuscular-parenchymal Anastomosis for Prevention of Postoperative Pancreatic Fistula in Distal Pancreatectomy.

BACKGROUND/AIM: There have been several attempts to prevent the development of a postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP); however, there is no established method yet. In the present study, we investigated whether POPF can be prevented using pancreaticoenterostomy with seromuscular-parenchymal anastomosis. PATIENTS AND METHODS: We evaluated the incidence of POPF and complications in 20 patients who underwent DP since August 2014, wherein pancreaticoenterostomy with seromuscular-parenchymal anastomosis was performed. RESULTS: No patient developed POPF, and only 4 patients developed a biochemical leak. Postoperative complications (Clavien-Dindo classification: CD) occurred in 5 patients (Grade IIIa in 2 cases, Grade II in 2 cases, and Grade I in 1 case). In a case of CD Grade II, a gastric ulcer was formed at the pancreatico-gastric anastomosis. CONCLUSION: Although new complications, such as the formation of ulcers, consistent with pancreatic anastomosis, were noted, the present method was useful in preventing POPF.

[A Case of Pancreatoduodenectomy for Pancreatic Head Cancer with Invasion to the Hepatic Artery from the Pancreatic Arcade].

This case pertained a 53-year-old man who underwent nab-PTX plus GEM therapy for BR-A pancreatic head cancer. He achieved a partial response and underwent pancreatoduodenectomy. Dynamic CT showed blockage of the original common hepatic artery branching from the celiac artery. Hepatic blood flow was maintained by a pancreatic arcade branching from the superior mesenteric artery which ran along the ventral side of the pancreatic head. The cancer had invaded the same location; therefore, the hepatic artery and portal vein were both resected and reconstructed. The patient had no complications, such as postoperative pancreatic fistula, and was discharged 45 days postoperatively. Currently(5 months postoperatively), postoperative S-1-based adjuvant chemotherapy is being administered, and the patient had a recurrence-free survival.

[A Case of Laparoscopic Hepatectomy and Combined Resection of Lymph Nodes and Ureter for Liver Metastasis after Colorectal Cancer Surgery, with Local Lymph Node Recurrence and Bilateral Hydronephrosis].

A 65-year-old man with sigmoid colon cancer underwent sigmoidectomy, followed by 8 courses of oral S-1 as postoperative adjuvant chemotherapy. Three years and 3 months after surgery, the patient developed liver metastasis, lymphadenopathy at the root of the inferior mesenteric artery, and bilateral hydronephrosis. The left hydronephrosis was believed to be due to invasion by lymph node metastasis at the root ofthe inferior mesenteric artery. The patient underwent laparoscopic partial resection ofsegment 5 ofthe liver, excision ofthe lymph nodes at the root ofthe inferior mesenteric artery(combined resection ofthe left ureter), bilateral ureteral stent placement, and left ureteral reconstruction. The postoperative course was without complications, and he was discharged 12 days after surgery. Follow-up observation without postoperative adjuvant chemotherapy was planned, according to the patient's wishes.

[Two Cases of Afferent Loop Obstruction Treated with Percutaneous Bowel Drainage(PBD)].

Here, we report our experiences with 2 cases of afferent loop obstruction with percutaneous bowel drainage(PBD)and present a review of the literature. Case 1 involved a 60-year-old woman. She underwent pancreaticoduodenectomy for pancreatic cancer. Eighteen months postoperatively, a recurrence marked by a jejunal elevation and expansion on the cecal side near the porta hepatic lymph nodes appeared. We performed PBD because intestinal depression via the endoscopic approach was difficult. She was discharged from the hospital 7 days after PBD. Case 2 involved a 51-year-old woman. She underwent total gastrectomy and Roux-en-Y reconstruction for progressive stomach cancer. We detected a local recurrence in the Y anastomosis following a chief complaint of vomiting 10 months postoperatively. Fifteen months postoperatively, she developed acute pancreatitis with afferent loop syndrome. We performed PBD via a trans-liver route. The patient was discharged from the hospital 11 days after PBD. By devising a puncture route, we could safely perform PBD for an afferent loop obstruction.

Intravenous Maxacalcitol Therapy Correlates with Serum Fibroblast Growth Factor 23 Levels in Hemodialysis Patients Independent of Serum Phosphate or Calcium Levels.

Fibroblast growth factor 23 (FGF23) is a regulator of phosphate and vitamin D homeostasis that carries out primary bone- and mineral-related physiological functions to increase renal phosphate excretion and reduce 1α-hydroxylation of 25-hydroxyvitamin D. In a negative endocrine feedback loop, 1,25-dihydroxyvitamin D also stimulates FGF23 secretion. Previous studies have assessed the correlation between vitamin D receptor activator therapy and FGF23 concentrations, and to our knowledge, none has assessed the correlation between intravenous (i.v.) maxacalcitol therapy and FGF23 concentration in hemodialysis patients. Subjects included 148 patients on maintenance hemodialysis. Serum FGF23 concentrations were measured. The correlations among serum FGF23 concentrations with i.v. maxacalcitol therapy and other clinical parameters and medications were analyzed. Mean serum log FGF23 was 3.7 ± 0.8 pg/mL. After division into two equal groups based on median serum log FGF23 level, the percentages of patients administered i.v. maxacalcitol (60/74 [81.1%] vs. 45/74 [60.8%], p < 0.01) were significantly higher in the high log FGF23 group. The amounts of serum FGF23 concentrations had been significantly higher to the amounts of i.v. maxacalcitol per week dependency. Multivariate regression analysis showed that treatment with i.v. maxacalcitol was an independent predictor of serum FGF23 levels, regardless of phosphate or calcium concentrations. i.v. maxacalcitol correlates with serum FGF23 concentration in hemodialysis patients, independent of serum phosphate or calcium concentrations.

FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells.

BACKGROUND: FGF23 plays an important role in calcium-phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium-phosphorus metabolism. METHODS: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. RESULTS: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. CONCLUSION: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells.

Preventive Strategies for Vascular Calcification in Patients with Chronic Kidney Disease.

BACKGROUND: Vascular calcification is significant because of the close association between the degree of vascular calcification and cardiovascular mortality in chronic kidney disease (CKD) patients. SUMMARY: There are 2 types of vascular calcification in CKD patients. One is endothelial vascular calcification, a common type of vascular calcification. Another is medial vascular calcification, a specific type that is common in CKD patients. The former is mainly associated with atherosclerosis due to hyperlipidemia, especially hypercholesterolemia. The latter CKD-specific type is called Moenckeberg's arteriosclerosis. A known risk factor for this type of vascular calcification is hyperphosphatemia. In this review article, we mainly discuss a preventive strategy for Moenckeberg type vascular calcification in CKD, primarily involving the treatment of hyperphosphatemia. Several possible modalities are considered. However, at present, dietary restriction of phosphate is not recommended so as to avoid malnutrition in CKD patients. The first consideration is the enhancement of phosphate removal by renal replacement therapy in dialysis patients. Various phosphate binder therapies can be beneficial and effective. Surgical and pharmacological parathyroidectomies are also useful for treating secondary hyperparathyroidism. Good quality bone provides a good pool of calcium and phosphate. Thus, bone protection is another option for preventing vascular calcification. Several therapeutic agents have been developed to manage osteoporosis. These trial agents may be reasonably effective in impeding the progression of vascular calcification in CKD patients. Key Messages: We should make full use of several modalities so as to completely prevent vascular calcification.

Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor.

AIM: Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD-mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD-mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. METHODS: Aortic segments from 7-week-old male Sprague-Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. RESULTS: Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p＜0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. CONCLUSION: These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor.

The Organo- and Cytoprotective Effects of Heat-shock Protein in Response to Injury Due to Radiofrequency Ablation in Rat Liver.

AIM: In treating liver tumors, preserving hepatic reserve and reducing surgical invasiveness are important for minimizing postoperative complications. Geranylgeranylacetone (GGA) is reported to selectively induce heat-shock protein 70 (HSP70), which initiates a powerful cytoprotective effect. We investigated the function of HSP70 under conditions of radiofrequency ablation (RFA) of the liver. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: a control group, a group administered GGA, and a group administered GGA plus quercetin, an HSP70 synthesis inhibitor. Expression of HSP70 and heat-shock factor-1 (HSF1) in the liver was measured at the protein level, and severity of liver damage was investigated using serum and hepatic tissue. RESULTS: The GGA-treated group had higher expression of HSP70 and HSF1 than the other groups. Peak liver damage in all groups occurred 6 h after RFA. The GGA-treated group also had significantly less liver damage and lower serum level of the inflammatory cytokine tumor necrosis factor-α, and a lower rate of apoptosis in tissue around post-ablation necrosis. Expression of HSP70 and HSF1 was suppressed in the group treated with GGA and quercetin, and this group had severe liver damage. CONCLUSION: Induction of HSP in the liver by GGA may be applicable in future treatments for hepatocellular carcinoma or liver metastasis. The present findings suggest that if preoperative administration of GGA can offer protective effects in the liver, treatment options could be increased and liver failure and other complications might be avoided.

[Treatment Strategy for Non-Functional Pancreatic Neuroendocrine Tumors (P-NETs) at Kurume University Hospital].

Pancreatic neuroendocrine tumors (P-NETs) are relatively rare. Approximately 50-90% of non-functioning P-NETs are malignant, and the only curative treatment is surgical resection. Liver and lymph node metastases often occur. In Japan, the mTOR inhibitor everolimus is now covered by the national health insurance for treatment of P-NETs, including advanced and unresectable tumors. We present a case of P-NETs with liver metastases seen at our hospital and discuss our treatment strategy for this disease. Patients with tumors≤1 cm receive follow-up observation. For G1 and G2 (other than G3) tumors, if their size is >1 cm when first discovered, resection of the primary lesion along with lymph node dissection (as for pancreatic cancer) is performed. In G1 and G2 tumors with synchronous distant metastases, the primary lesion is first resected, and depending on the pathological findings, chemotherapy (LAR plus everolimus) may be administered. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, resection is performed. When there are synchronous liver metastases, if partial resection and local treatment (such as RFA) are possible, the primary lesion and synchronous lesions are resected. If a major hepatic resection procedure such as a segmentectomy or lobectomy is possible, the primary lesion is resected, followed by chemotherapy. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, hepatic resection is performed. G3 tumors are usually highly malignant, advanced, and often associated with metastases at the time of diagnosis. Chemotherapy may be an option for treating patients with G3 tumors.

[S-1+gemcitabine (GEM) therapy was effective in a case of unresectable pancreatic head carcinoma].

OBJECTIVE: Treatment results of pancreatic head carcinoma are not good and long-term survival, especially in nonresectable cases is extremely difficult to obtain. The case reported here is of nonresectable pancreatic head carcinoma in which S-1+gemcitabine (GEM) proved to be effective. CASE: A 70-year-old male. The patient initially complained of epigastralgia. Jaundice was also noted and upon further study, pancreatic head carcinoma, portal vein and common hepatic artery infiltration along with duodenal infiltration were diagnosed. Gastrojejunostomy and cholecystectomy were performed with a preoperative diagnosis of Phb, TS2 infiltrative type T4, CH (+), DU (+), S (+), RP (-), PV (+), Ach (+), PLX, OO (-), N0, M0, and Stage IVa. Perioperative findings showed no hepatic or peritoneal metastases. Following surgery, S-1+ GEM (S-1 100 mg/day, day 1-14; GEM 1,000 mg/m(2) was administered on day 8 and day 15 for 2 weeks followed by one week of no administration) was started. After completing 2 courses, there was no change in the tumor, but after finishing the sixth course, there was a notable reduction in tumor size, and after finishing the 10th course, a further reduction was noted. Currently at the end of the 14th course, the tumors are unidentifiable upon imaging. At 1 year and 5 months from the initial diagnosis, there has been no recurrence and chemotherapy is being continued. In the case reported here, there have been no adverse side-effects from the S-1+GEM therapy, it is a safe method which does not lower QOL in patients with unresectable pancreatic carcinoma, and we can look forward to the possibility of extended survival times. CONCLUSION: In the case of unresectable pancreatic carcinoma, S-1+GEM therapy may be able to provide an improved long-term prognosis.

Hilar and suprapancreatic cholangiocarcinoma: value of 3D angiography and multiphase fusion images using MDCT.

OBJECTIVE: We evaluated the feasibility of creating 3D and multiphase fusion images of cholangiocarcinoma. The 3D rendering of the biliary tree provide valuable information for planning surgery, including the location of the obstruction and its relationship to the surrounding vessels. CONCLUSION: Our data emphasize that 3D and multiphase fusion images may be an accurate and routinely applicable tool for the diagnosis and therapeutic management of patients with biliary system abnormalities.

[A case of radiofrequency ablation therapy for recurrent hepatomas with tumor fever--efficacy of hepatic arterial infusion therapy with antibiotics and anticancer drugs].

Efficacy of hepatic arterial infusion therapy (HAI) using antibiotics for hepatic abscess has been reported. However, we effectively performed RFA therapy after HAI with antibiotics and anticancer drugs for recurrent hepatomas with tumor fever. A 67-year-old female of recurrent hepatomas with fever is presented here. She was diagnosed with a 6 cm recurrent hepatoma, both in the right and IM lobes. Her liver function was child A with hepatitis C. On her CT scan, we found an enhanced 60 mm mass at an early phase and it was washed out at a delayed phase. Initially, we gave systemic medication of antibiotics, but could not decrease the fever. Therefore, we performed HAI with antibiotics and anticancer drugs. The patient's temperature went down after 14 days, and we were able to cut down her tumor size. After HAI, we were able to completely perform RFA for recurrent hepatomas.

[Chemoradiation therapy for stage IV pancreatic cancer].

BACKGROUND: Pancreatic cancer is a malignant tumor with a poor prognosis. It frequently presents with locally advanced and distant metastasis at the time of diagnosis. Favorable results were obtained by performing intraoperative radiation therapy (IORT) and chemotherapy (administration of GEM) for the treatment of inoperable pancreatic cancer. A study was conducted on its efficacy as an adjuvant therapy for inoperable and advanced pancreatic cancer. SUBJECTS AND METHODS: Between May 1998 and December 2002, 40 patients with stage IV pancreatic cancer were treated at our institution. The study comprised background factors, adjuvant therapy and survival rate. RESULTS: According to the treatment modality, the study population was classified into four groups: group A, consisting of 3 patients with localized unresectable tumors who had been treated with IORT: group B, 5 patients who underwent curative resection of primary tumor combined with IORT: group C, 6 patients who were administered GEM combined with IORT: group D, 26 patients not falling into groups A, B or C. The mean survival for group A, B, C and D was 10.3 months, 6.7 months, 16.8 months and 9.4 months, respectively. The 1-year survival rates were 0%, 0%, 80.0% and 19.3%, respectively. The mean survival and the 1-year survival rate were significantly better in group C than in the other groups. In group C, the tumor decreased in size, invasion of large vessels and pancreatic posterior evolution was suppressed, and 4 patients survived for 17 months or more. CONCLUSIONS: Prolongation of the survival period was shown by concomitant IORT and administration of GEM for inoperable advanced pancreatic cancer. Thus, attempting to combine chemotherapy with IORT and giving additional consideration to the administration method was shown to provide adjuvant therapy that can be expected to be effective against stage IV inoperable pancreatic cancer.