Endometrioid adenocarcinoma arising from inguinal endometriosis during follow-up for gastric cancer surgery: a case report and literature review.

Malignant transformation of inguinal endometriosis is rare. A 56-year-old woman underwent surgery for advanced gastric cancer 5 years ago and received postoperative adjuvant chemotherapy. She had no recurrence since then. However, 5 years after surgery, contrast-enhanced computed tomography (CT) showed a mass in the right inguinal region suspected to be a hydrocele of the canal of Nuck, with a blood test showing a slightly elevated CA19-9 level (63.0 U/mL). Six months later, CT showed an enlarged mass in the right inguinal region and inflammation in the surrounding area. In addition, both inguinal lymph nodes and those in the right iliac artery area were enlarged, suggesting the possibility of malignancy. For diagnostic purposes, a right inguinal mass was excised. Histopathological examination revealed that it was endometrioid adenocarcinoma with ectopic endometriois as the origin. The differential diagnoses for inguinal masses in women include an inguinal hernia, hydrocele of the canal of Nuck, ectopic endometriosis, lymphoma, and metastatic malignancy. The presence of a primary malignancy in the inguinal region is sporadic but must be differentiated. This is the first case of malignant transformation of inguinal endometriosis developed during postoperative follow-up of another cancer.

Inhibition of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition in Melanoma Tumors and May Improve Immunotherapy Efficacy by Reducing T-cell Exhaustion.

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited similar tumorigenicity to that of COX-2-deficient cells, despite a lower ability to suppress PGE2 synthesis by mPGES-1 depletion, indicating the presence of factors other than PGE2 that are likely to regulate tumor immunity. RNA-sequencing analysis revealed that mPGES-1 depletion reduced the expressions of collagen-related genes, which have been found to be associated with immunosuppressive signatures. In our mouse model, collagen was reduced in mPGES-1-deficient tumors, and phenotypic analysis of tumor-infiltrating lymphocytes indicated that mPGES-1-deficient tumors had fewer TIM3+ exhausted CD8+ T cells compared with COX-2-deficient tumors. CAY10678, an mPGES-1 inhibitor, was equivalent to celecoxib, a selective COX-2 inhibitor, in reinforcing anti-PD-1 treatment. Our study indicates that mPGES-1 inhibitors represent a promising adjuvant for immunotherapies in melanoma by reducing collagen deposition and T-cell exhaustion. Significance: Collagen is a predominant component of the extracellular matrix that may influence the tumor immune microenvironment for cancer progression. We present here that mPGES-1 has specific roles in regulating tumor immunity, associated with several collagen-related genes and propose that pharmacologic inhibition of mPGES-1 may hold therapeutic promise for improving immune checkpoint-based therapies.

Preoperative diagnosis of tumor depth in gastric cancer using transabdominal ultrasonography compared to using endoscopy and computed tomography.

BACKGROUND: An accurate evaluation method for preoperative diagnosis has not yet been established in patients with gastric cancer (GC), though it is essential for optimal treatment. Current standard modalities are endoscopy and contrast computed tomography (CT). In this study, we investigated the efficacy and limitations of transabdominal ultrasonography (TUS) for the assessment of tumor invasion. METHODS: We enrolled 178 consecutive patients with GC evaluated by TUS, endoscopy, and contrast CT before gastrectomy. For the TUS examination, patients ingested water to fill their stomachs. The clinical staging determined using these modalities was compared to the pathological staging. RESULTS: The overall accuracy of clinical T staging using TUS was 47.8% (pT1a: 5.8% (2/35); pT1b: 58.8% (20/35); pT2: 69.6% (16/23); pT3: 66.7% (22/33); pT4a: 46% (23/50); pT4b: 100% (2/2)). Using endoscopy, contrast CT, and TUS, the overall accuracy was 60.7%. The accuracy of TUS was associated with the tumor region (U region: 50% (14/28); M: 31.8% (14/44); L: 53.7% (57/106); P = 0.048), but not with the cross-sectional parts (P = 0.49). Multivariate analysis identified inaccurate TUS as independently correlating with tumor region (M vs. U/L, odds ratio (OR) = 3.11, 95% confidence interval (CI) 1.41-6.87; P = 0.005) and pT (pT1 vs. pT2-4, OR = 3.00, 95%CI 1.31-6.87; P = 0.009). CONCLUSIONS: The present study demonstrated the importance of TUS in evaluating GC. Thus, TUS may be useful for clinical T staging in certain circumstances, leading to treatment optimization.

Indirect cholecystoduodenal fistula via hepatoduodenal ligament secondary to gangrenous cholecystitis: a case report.

BACKGROUND: Cholecystoduodenal fistula is an infrequent complication of gallbladder diseases. In the majority of cases, the fistula is formed by direct communication between the gallbladder and duodenum due to gallstone impaction in the gallbladder neck. We herein report a rare case of indirect cholecystoduodenal fistula via the hepatoduodenal ligament secondary to gangrenous cholecystitis. CASE PRESENTATION: An 80-year-old woman suspected of having emphysematous cholecystitis by a previous doctor was referred to our hospital for urgent surgery. The initial diagnosis based on additional examinations was gangrenous cholecystitis penetrating the hepatoduodenal ligament. Since she did not complain of signs of peritonitis and was taking an anticoagulant medicine, we avoided surgery and selected percutaneous gallbladder drainage (PTGBD) instead. Contrast imaging of the PTGBD tube and upper endoscopy identified the indirect cholecystoduodenal fistula via the hepatoduodenal ligament. Despite repeated attempts at endoscopic fistula closure using clips, the fistula did not close successfully. We therefore performed laparoscopic cholecystectomy and fistula closure. The postoperative clinical course was uneventful, and she left the hospital on postoperative day 15. The resected gallbladder contained small black stones, and a histological examination revealed gangrenous cholecystitis with no malignant signatures. CONCLUSION: We encountered a rare case of indirect cholecystoduodenal fistula via the hepatoduodenal ligament secondary to gangrenous cholecystitis that was successfully treated by laparoscopic cholecystectomy and fistula closure. It is important to recognize the possible formation of indirect cholecystoduodenal fistula in cases of gangrenous cholecystitis penetrating the hepatoduodenal ligament.

Pancreatic fibrosis by extracellular volume fraction using Contrast-enhanced computed tomography and relationship with pancreatic cancer.

PURPOSE: This study aimed to assess the relationship between pancreatic fibrosis measured by the extracellular volume fraction (ECV) using contrast-enhanced computed tomography (CT) and the histologic pancreatic fibrosis fraction and investigate the relationship between pancreatic fibrosis and pancreatic cancer. METHOD: The study included 88 consecutive patients (48 males, 40 females; median age, 69 years; range, 17-89 years); 47 had pancreatic cancer, and 41 had other diseases. Fifty-two cases were evaluated pathologically for pancreatic fibrosis. The histologic pancreatic fibrosis fraction was quantified using image analysis software in nontumorous pancreatic tissue at the resection stump using 2-µm-thick Azan-stained slides. Two board-certified radiologists measured ECV in the pancreatic parenchyma at an estimated transection line. The correlation between histologic pancreatic fibrosis fraction and ECV was investigated, and whether the ECV value could be used as a biomarker for pancreatic cancer was investigated. RESULTS: The histologic pancreatic fibrosis fraction was significantly correlated with the ECV (r = 0.64, P < 0.01). Pancreatic fibrosis evaluated by ECV was higher in pancreatic cancer patients than in other patients (P < 0.01). On receiver-operating characteristic curve analysis, the ECV had good diagnostic accuracy for the development of pancreatic cancer (cut-off value 32.8%; sensitivity 61.0%, specificity 85.1%). ECV was identified on multivariate analysis as an independent risk factor for pancreatic cancer (odds ratio 1.16; P < 0.01). CONCLUSIONS: Extracellular volume fraction was strongly related to the histologic pancreatic fibrosis fraction, which was independently associated with pancreatic cancer. Thus, extracellular volume fraction is an imaging biomarker that reflects the progression of pancreatic fibrosis and may potentially help predict the development of pancreatic cancer, although further investigation will be needed.

Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma.

Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of sCD74 was observed primarily in melanoma cell lines as well as a THP-1 line of macrophages from monocytes and primary macrophages, especially in response to interferon-γ (IFN-γ). A predominant form that showed clinical relevance was the 25-KDa sCD74, which originated from the 33-KDa isoform of CD74. The release of this sCD74 was regulated by either a disintegrin and metalloproteinase-mediated cell-surface cleavage or cysteine-protease-mediated lysosomal cleavage, depending on cell types. Both recombinant and THP-1 macrophage-released endogenous sCD74 suppressed melanoma cell growth and induced apoptosis under IFN-γ stimulatory conditions via inhibiting the MIF/CD74/AKT-survival pathway. Our findings demonstrate that the interplay between sCD74 and MIF regulates tumor progression and determines patient outcomes in advanced melanoma.

[A Case of Peritoneal Lymphomatosis Diagnosed by Single-Port Laparoscopic Biopsy].

Peritoneal lymphomatosis is an extremely rare presentation of non-Hodgkin lymphoma. We report a case of peritoneal lymphomatosis diagnosed by single-port laparoscopic biopsy. A 70-year-old woman presented to our hospital with a 2-day history of increasing abdominal distension. Abdominal CT and positron emission tomography/CT(PET-CT)demonstrated extensive disseminated disease with marked thickening of the peritoneal surfaces, and a large omental cake with large volume ascites. Under the diagnosis of peritoneal carcinoma, single-port laparoscopic biopsy was performed. Pathological and immunohistochemical examination revealed diffuse large B-cell lymphoma presenting as peritoneal lymphomatosis. She was treated with a combination chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, and prednisolone(R- CHOP), and no recurrence was reported for 1 year and 6 months. Single-port laparoscopic biopsy was minimally invasive, and helpful for an urgent and accurate diagnosis and treatment of the disseminated peritoneal disease.

Three-dimensional Vascularized ß-cell Spheroid Tissue Derived From Human Induced Pluripotent Stem Cells for Subcutaneous Islet Transplantation in a Mouse Model of Type 1 Diabetes.

BACKGROUND: Islet transplantation is an effective replacement therapy for type 1 diabetes (T1D) patients. However, shortage of donor organ for allograft is obstacle for further development of the treatment. Subcutaneous transplantation with stem cell-derived ß-cells might overcome this, but poor vascularity in the site is burden for success in the transplantation. We investigated the effect of subcutaneous transplantation of vascularized ß-cell spheroid tissue constructed 3-dimensionally using a layer-by-layer (LbL) cell-coating technique in a T1D model mouse. METHODS: We used MIN6 cells to determine optimal conditions for the coculture of ß-cell spheroids, normal human dermal fibroblasts, and human umbilical vein endothelial cells, and then, under those conditions, we constructed vascularized spheroid tissue using human induced pluripotent stem cell-derived ß-cells (hiPS ß cells). The function of insulin secretion of the vascularized hiPS ß-cell spheroid tissue was evaluated in vitro. Furthermore, the function was investigated in T1D model NOD/SCID mice subcutaneously transplanted with the tissue. RESULTS: In vitro, the vascularized hiPS ß-cell spheroid tissue exhibited enhanced insulin secretion. The vascularized hiPS ß-cell spheroid tissue also significantly decreased blood glucose levels in diabetic immunodeficient mice when transplanted subcutaneously. Furthermore, host mouse vessels were observed in the explanted vascularized hiPS ß-cell spheroid tissue. CONCLUSIONS: Vascularized hiPS ß-cell spheroid tissue decreased blood glucose levels in the diabetic mice. This therapeutic effect was suggested due to host angiogenesis in the graft. This method could lead to a promising regenerative treatment for T1D patients.

Ischemia reperfusion-induced metastasis is resistant to PPARγ agonist pioglitazone in a murine model of colon cancer.

Ischemia reperfusion injury (IRI) during liver-metastasis resection for treatment of colon cancer may increase the risk of further metastasis. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been observed to exert a protective effect against IRI and IRI-induced metastasis of hepatocellular carcinoma. The present study aimed to investigate the effect of the PPARγ agonist pioglitazone on tumor metastasis and liver injury following IRI in a mouse model of colon cancer. Pioglitazone (30 mg/kg weight) was administered orally 1.5 h before and 2 h after the initiation of ischemia and was orally administrated daily to mice from day 0-21. SL4-cancer cells expressing red fluorescent protein (SL4-RFP) (1 × 106) were injected into the spleen. Fifteen minutes after injection, the hepatoduodenal ligament was clamped with a vessel clip, and released 5 min later. Liver, blood and tumor samples were taken from mice in order to determine if inflammation was induced by IRI. The effect of pioglitazone on liver metastasis was assessed. Furthermore, the effect of pioglitazone to control the inflammatory response during IRI progression was examined. Liver metastasis along with MMP-9 activation and the production of inflammatory cytokines were resistant to pioglitazone. Our results indicate that liver metastasis and associated inflammation in mice were resistant to pioglitazone.

Endogenous CXCL9 affects prognosis by regulating tumor-infiltrating natural killer cells in intrahepatic cholangiocarcinoma.

CXCL9, an IFN-γ inducible chemokine, has been reported to play versatile roles in tumor-host interrelationships. However, little is known about its role in intrahepatic cholangiocarcinoma (iCCA). Here, we aimed to elucidate the prognostic and biological implications of CXCL9 in iCCA. Endogenous CXCL9 expression and the number of tumor-infiltrating lymphocytes were immunohistochemically assessed in resection specimens. These data were validated in mice treated by silencing CXCL9 with short hairpin RNA. In addition, the induction of endogenous CXCL9 and the effects of CXCL9 on tumor biological behaviors were evaluated in human cholangiocarcinoma cell lines. Immunohistochemical analyses revealed that high CXCL9 expression was closely correlated with prolonged postoperative survival and a large number of tumor-infiltrating natural killer (NK) cells. In fact, due to the trafficking of total and tumor necrosis factor-related apoptosis-inducing ligand-expressing NK cells into tumors, CXCL9-sufficient cells were less tumorigenic in the liver than CXCL9-deficient cells in mice. Although CXCL9 involvement in tumor growth and invasion abilities differed across cell lines, it did not exacerbate these abilities in CXCL9-expressing cell lines. We showed that CXCL9 was useful as a prognostic marker. Our findings also suggested that CXCL9 upregulation might offer a therapeutic strategy for treating CXCL9-expressing iCCA by augmenting anti-tumor immune surveillance.

Evaluation of fatty pancreas by proton density fat fraction using 3-T magnetic resonance imaging and its association with pancreatic cancer.

PURPOSE: To evaluate whether pancreatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) correlates with histological pancreatic fat fraction and its possible usefulness as a biomarker of pancreatic cancer compared with pancreatic index (PI) using computed tomography (CT number of the pancreas divided by that of the spleen). METHOD: We included 55 consecutive patients (24 with pancreatic cancer and 31 controls; median age, 72 years) who preoperatively underwent MRI-PDFF using IDEAL-IQ and unenhanced CT and did not receive preoperative therapy. Histologic pancreatic fat fraction was measured in non-tumorous pancreatic tissues at the resection stump. A board-certified radiologist evaluated MRI-PDFF and PI. Correlations were evaluated among MRI-PDFF, PI, and histologic pancreatic fat fraction; the usefulness of MRI-PDFF as a predictor of pancreatic cancer was assessed. RESULTS: Histologic pancreatic fat fraction significantly correlated with MRI-PDFF and PI (r = 0.802 and -0.534, respectively; P < 0.01). The absolute correlation coefficient was significantly higher for MRI-PDFF than for PI (P < 0.01). Compared with the control group, the pancreatic cancer group had higher MRI-PDFF and histologic pancreatic fat fraction (P < 0.01) but lower PI (P < 0.01). In multivariate analysis, MRI-PDFF was found to be the sole independent risk factor for pancreatic cancer (odds ratio: 1.19; P < 0.01). CONCLUSIONS: Pancreatic fat, which was associated with pancreatic cancer, could be quantified by MRI-PDFF measurement; therefore, MRI-PDFF should be considered as a promising and superior imaging biomarker for estimating the probability of pancreatic cancer than PI.

Laparoscopy-assisted extended right hepatectomy for giant hemorrhagic hepatic cyst mimicking biliary cystadenocarcinoma: a case report.

BACKGROUND: Hemorrhagic hepatic cysts infrequently involve several iconographic changes requiring a differential diagnosis, primarily with a cystic malignancy. We herein report a case of laparoscopy-assisted extended right hepatectomy for a giant hemorrhagic hepatic cyst with an enhancing mural nodule that was clinically suspected of being biliary cystadenocarcinoma. CASE PRESENTATION: A 73-year-old woman was followed up for giant hepatic cyst occupying the right lobe of the liver. During the follow-up, an enhancing mural nodule was newly noted on computed tomography in 2016. Based on additional clinical examinations, biliary cystadenocarcinoma was undeniable, and laparoscopy-assisted extended right hepatectomy was performed for diagnostic and therapeutic purposes. She had no perioperative complications and was discharged on postoperative day 13. A histological examination of the mural nodule showed neovascularization within an organized hematoma. CONCLUSION: We herein report a rare case of giant hemorrhagic hepatic cyst mimicking biliary cystadenocarcinoma that was successfully treated with laparoscopy-assisted extended right hepatectomy. Laparoscopic surgery in our case was an effective procedure performed with the utmost care.

Endoscopy-assisted laparoscopic submucosal dissection for a duodenal epithelial tumor.

We present the case of a 46-year-old obese woman with a 3.5-cm adenoma in the descending part of the duodenum who was treated with a totally laparoscopic approach. The preoperative examination revealed a pedunculated superficial tumor on the side of pancreas from the inferior duodenal angulus to 5 cm proximal to the papilla that was associated with massive blood flow. We chose not to perform endoscopic submucosal dissection, pancreaticoduodenectomy, or transduodenal tumor excision with laparotomy for this obese patient because of the poor exposure, risk of bleeding, and substantial invasiveness. We performed endoscopy-assisted laparoscopic submucosal dissection as a novel laparoscopic-endoscopic cooperative surgical approach in this patient. This surgery was surgically and oncologically safe.

Clinical Impact of Preoperative Sarcopenia on the Postoperative Outcomes After Pancreas Transplantation.

BACKGROUND: The importance of evaluating sarcopenia is increasingly being recognized in the field of transplantation because sarcopenia can have an adverse effect on the treatment outcomes. However, the clinical significance of preoperative sarcopenia on the postoperative outcomes following pancreas transplantation (PTx) has been largely unknown. The objective of this study was to investigate the role of preoperative sarcopenia in predicting the postoperative outcomes following PTx in recipients with type 1 diabetes mellitus (T1D). METHODS: Forty-one recipients with severe T1D who underwent PTx were retrospectively reviewed. The psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), as determined by preoperative computed tomography, were substituted for the quantity and quality of skeletal muscle for the definition of sarcopenia, respectively. Gender-specific quartiles were generated, and PMI lower than the first quantile or IMAC higher than the third quantile was considered to represent sarcopenia. The postoperative outcomes included postoperative surgical complications and pancreas graft survival. RESULTS: Sarcopenia was identified in 11 recipients according to both the PMI and IMAC stratifications. The multivariate analyses revealed that high IMAC was independently associated with the development of postoperative surgical complications (odds ratio, 9.35; p = 0.016). In addition, the recipients with high IMAC showed unfavorable graft survival compared to those with normal IMAC (log-rank test; p = 0.038). In contrast, low PMI was not significantly associated with the postoperative outcomes. CONCLUSIONS: Our data suggested that preoperative sarcopenia, especially a decline in the quality of skeletal muscle, predicted poorer postoperative outcomes in T1D recipients undergoing PTx.

Layer-by-layer cell coating technique using extracellular matrix facilitates rapid fabrication and function of pancreatic ß-cell spheroids.

Tissue engineering of insulin-secreting cells using alternatives to islet transplantation has been fueled by the development of available materials and fabrication techniques. We have established a cell coating technique that enables the cell surface to be coated with extracellular matrix based on the concept of a layer-by-layer (LbL) assembly. The present study evaluated whether this technique is beneficial for fabricating pancreatic ß-cell spheroids using a mouse ß-cell line. The well-structured and dense spheroids could immediately be constructed by the LbL-coated cells. In the functional analysis, spheroids with the LbL-coated cells had greater insulin secretion ability with increased expression of the insulin and glucose transporter 2 genes versus spheroids with non-coated cells. In addition, we found that the expression of connexin 36, a gap junction molecule, was upregulated by the LbL cell coating. When spheroids with the LbL-coated cells were syngeneically transplanted in diabetic mice, blood glucose levels immediately decreased and glucose sensitivity significantly improved after intraperitoneal glucose stimulation compared to spheroids with non-coated cells. This cell coating technique would be a clinically applicable approach for fabricating pancreatic ß-cell spheroids and treating type 1 diabetes mellitus.

[A Case of Repeated Surgical Resections for Tumor Seeding of Hepatocellular Carcinoma after Radiofrequency Ablation].

We report a case of repeated surgical resections for the tumor seeding of hepatocellular carcinoma(HCC)after radiofrequency ablation(RFA). A 79-year-old man, who had an intrahepatic recurrence of HCC(segment 2)5 months after RFA, was referred to our hospital for surgery, and underwent a laparoscopic lateral segmentectomy. Histological examination showed a poorly differentiated HCC(pStage II). Eight months after RFA, subcutaneous nodules along the RFA needle tract were pointed out by abdominal CT, and a tumorectomy was performed. Nineteen months after RFA, abdominal CT showed a 33mm tumor on the side of the spleen, leading to the diagnosis of the peritoneal dissemination following RFA. The tumor has been growing up to 49mm in size in spite of a radiation therapy. Accordingly, a laparoscopic tumorectomy was performed 26 months after RFA. His resected tumors were morphologically identical to the intrahepatic recurrence of HCC. The patient had remained recurrence-free for 4 months after the second tumorectomy. Our case demonstrated the utility of surgical resection for the tumor seeding of HCC following RFA.

Plasma ghrelin suppression as an early predictor for postoperative complications after pancreatoduodenectomy.

BACKGROUND/OBJECTIVES: The gut peptide hormone ghrelin induces appetite and exhibits an anti-inflammatory effect. Serial perioperative changes in ghrelin have been examined in several surgical procedures, but few in pancreatectomy. The present study analyzed perioperative changes in plasma ghrelin levels after pancreaduodenectomy (PD). METHODS: The study included 24 patients undergoing PD between May 2015 and January 2016 at Osaka University Hospital. Plasma ghrelin and interleukin-6 (IL-6) levels, as well as white blood cells (WBCs) and C-reactive protein (CRP), were measured preoperatively and on postoperative day (POD) 1, 3, 7, and 14 by enzyme-linked immunosorbent assay. The relationship between the individual ghrelin ratio relative to preoperative value (IGR) and the development of grade IIIa-V Clavien-Dindo (CD) complications was examined. RESULTS: Twelve patients (50%) developed grade IIIa CD complications (n = 6 [25%] pancreatic fistula, n = 7 [29%] intraabdominal abscess, n = 3 [13%] post-pancreatectomy hemorrhage, n = 5 [21%] wound infection, and n = 1 [4%] lymphorrhea). The IGR on POD 1 was significantly lower (p = 0.014) in patients who developed the complications compared to those who did not, but no significant differences were found in terms of WBC, CRP, or IL-6 on POD 1. When the IGR cut-off was set to 82% by receiver operative curve analysis, the sensitivity was 83%, specificity 75% and area under the curve 0.80. The lower IGR group (≤82%) had more postoperative complications and longer hospital stay. CONCLUSIONS: The IGR on POD 1 after PD is a useful marker for predicting postoperative complications.

CT Density in the Pancreas is a Promising Imaging Predictor for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Fatty pancreas (FP) was recently recognized as a risk factor for pancreatic ductal adenocarcinoma (PDAC). It is unclear whether computed tomography (CT) can be used to make a FP diagnosis. This study investigated whether CT could provide a predictive value for PDAC by diagnosing FP. METHODS: The study included 183 consecutive patients who underwent distal pancreatectomy from February 2007 to January 2017, including 75 cases of PDAC and 108 cases of other pancreatic disease. Pancreatic CT density (pancreatic index; PI) at the initial diagnosis was calculated by dividing the CT number in the pancreas by the number in the spleen. To assess whether CT could be used to detect FP, 43 cases were evaluated pathologically for FP. We investigated the correlation between FP and PI, and determined the optimal PI cutoff value for detecting FP using receiver operating characteristics analysis. We then investigated whether the PI value could be used as a predictor for PDAC. RESULTS: Fourteen cases (32.6%) were pathologically diagnosed with FP. PI was significantly lower in the FP group versus the non-FP group (0.51 vs. 0.83; p = 0.0049). ROC analysis indicated that the PI had good diagnostic accuracy for FP diagnosis (cutoff value 0.70; sensitivity 0.79, specificity 0.79). Low PI (≤0.70) was identified in the multivariate analysis as an independent risk factor for PDAC (odds ratio 2.31; p = 0.023). CONCLUSIONS: PI was strongly associated with pathological FP, which was independently associated with PDAC. PI shows promise as an imaging predictor for PDAC.

Construction of three-dimensional vascularized functional human liver tissue using a layer-by-layer cell coating technique.

The creation of artificial liver tissue is an active area of research due to the shortage of donors for liver transplantation. Here we investigated whether a simple and efficient cell coating technique developed in our laboratory could be used to generate functional vascularized liver tissue. This technique creates three-dimensional tissue by loading cells sterically onto other cells that have been coated with layer-by-layer (LbL) nanofilms of fibronectin and gelatin, two extracellular matrix proteins. We used this technique to construct homogenous, dense, well-vascularized liver tissue from cryopreserved human primary hepatocytes, human umbilical vein endothelial cells, and normal human dermal fibroblasts. Using LbL cell coating technique resulted in higher cellular function in terms of human albumin production (P < 0.01) and cytochrome P450 activity (P < 0.01) in vitro. Furthermore, after being transplanted subcutaneously into NOD/SCID mice, the vascularized liver tissue showed greater albumin production in the early stage than non-vascularized tissue or a hepatocyte suspension (P < 0.01). Histological examination demonstrated that compare to non-vascularized tissue, there were many less-morphologically changed and intact hepatocytes in the vascularized tissue. This cell coating technique would be applicable to the generation of vascularized functional liver tissue for regenerative medicine in the future.