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To investigate halogen heterogeneity in the subcontinental lithospheric mantle (SCLM), we measured the concentrations of Cl, Br, and I in kimberlites and their mantle xenoliths from South Africa, Greenland, China, Siberia, Canada, and Brazil. The samples can be classified into two groups based on halogen ratios: a high-I/Br group (South Africa, Greenland, Brazil, and Canada) and a low-I/Br group (China and Siberia). The halogen compositions were examined with the indices of crustal contamination using Sr and Nd isotopes and incompatible trace elements. The results indicate that the difference between the two groups was not due to different degrees of crustal contamination but from the contributions of different mantle sources. The low-I/Br group has a similar halogen composition to seawater-influenced materials such as fluids in altered oceanic basalts and eclogites and fluids associated with halite precipitation from seawater. We conclude that the halogens of the high-I/Br group are most likely derived from a SCLM source metasomatized by a fluid derived from subducted serpentinite, whereas those of the low-I/Br group are derived from a SCLM source metasomatized by a fluid derived from seawater-altered oceanic crust. The SCLM beneath Siberia and China could be an important reservoir of subducted, seawater-derived halogens, while such role of SCLM beneath South Africa, Greenland, Canada, and Brazil seems limited.

The neural plexus and lymph nodes around the superior mesenteric artery (LN#14), are the most frequent sites involved by pancreatic head cancer. However the influence of metastases to LN#14 on patients’ prognosis has rarely been evaluated. The patients who underwent pancreatectomy for pancreatic head cancer between January 2010 and December 2018 were selected. The patients with nodal metastases were classified into an LN#14 + or LN#14−group according to LN#14 metastasis. Clinical and pathological characteristics and prognosis were compared between the two groups. In total, 99 patients underwent pancreatectomy. Ninety-four patients were positive for lymph node metastases and 14 and 80 were classified as LN#14 + and LN#14 − , respectively. Postoperative median overall survival (OS) of the LN#14 + and LN#14 − groups was 10.2 and 31.1 months, respectively (P

A modified Fong clinical score (m-Fong CS) that includes the RAS mutation status has recently been proposed and offered an improved survival stratification of patients who undergo surgery and systemic chemotherapy for colorectal liver metastases (CLM). The aim of this study is to assess whether a CS that includes RAS status is influenced by whether patients receive perioperative chemotherapy. We created a new CS using multivariate analysis of data of patients who underwent hepatectomy for CLM for the first time between 2010 and 2016 at a single hospital (n = 341, 79% received perioperative chemotherapy). The resulting CS and m-Fong CS were then validated in the patient cohort at three other hospitals (n = 309). Furthermore, the applicability of the two CS in the total cohort (n = 650) was tested according to whether the patients received perioperative chemotherapy. The new CS comprised mutant RAS status, ≥4 CLMs, and a CA19-9 level ≥100 U/mL (1 point per factor). Both the new CS and m-Fong CS failed to stratify the survival of the 309 patients in the validation cohort, including those who did not receive perioperative chemotherapy (29%). Both of the CS accurately stratified the survival of patients who underwent perioperative chemotherapy but not of those who underwent surgery alone. A CS that includes the RAS mutation status can stratify the survival of patients who undergo hepatectomy combined with perioperative chemotherapy, but it has limited value for patients who undergo surgery alone.

Background and aim Lipopolysaccharide (LPS) preconditioning drastically augments bactericidal activity but reduces the host inflammatory response. Therefore, it may be beneficial to prevent postoperative infectious complications and mitigate host damage by surgical stress. Considering its clinical application, how LPS preconditioning influences the antitumor effect in the liver is an important issue. We then investigated the effect of LPS preconditioning on antitumor activity against Colon26 tumor cells in mice. Methods Lipopolysaccharide preconditioning was induced in mice by the intraperitoneal injection of 5 μg/kg LPS for three consecutive days. Intraportal inoculation of Colon26 cells, which express luminescent protein called Nano-lantern, was performed to evaluate the effect of LPS preconditioning on tumor liver metastasis. The antitumor activities of cytotoxic liver lymphocytes, especially natural killer (NK) cells and natural killer T (NKT) cells, against Colon26 cells were also examined in LPS preconditioned mice. Results Lipopolysaccharide preconditioning remarkably prevented liver metastasis of Colon26 cells, as observed by IVIS imaging system, and prolonged survival after tumor inoculation. LPS preconditioning increased the proportions and number of liver NK cells and NKT cells and augmented their intracellular perforin and granzyme B expression, while reducing their intracellular expression of IFN-γ. An in vitro antitumor cytotoxicity assay revealed that LPS preconditioning significantly augmented antitumor cytotoxicities of the liver NK cells and NKT cells, especially NKT cells, against Colon26 cells. Conclusions Lipopolysaccharide preconditioning potently augmented antitumor cytotoxicity of liver NK cells and NKT cells, thereby improving mouse survival after intraportal inoculation of Colon26 tumor cells. It may be useful for perioperative care in oncological patients.

BACKGROUND The TNM (Tumor, Node, Metastasis) classification of the 8th Union for International Cancer Control and the 6th Japanese classification of biliary tract cancer were made on the premise that the prognostic effect of each regional lymph node station is similar. However, some studies have reported different effects of lymph node metastasis location on post-resection prognosis. This study aimed to investigate outcome following radical resection of ampullary carcinoma according to station of lymph node metastasis. METHODS Patients who underwent surgical resection for ampullary carcinoma between January 2007 and December 2017 at two separate Japanese institutions were included. Regional lymph nodes were subclassified as follows: Pancreatoduodenal lymph nodes (PD) and others (OT). RESULTS Of the 101 patients analyzed, 34 had regional lymph node metastasis. OT metastasis was found in eight patients. Significant differences were found in relapse-free survival (RFS) and overall survival (OS) between the three study groups (no nodal metastasis, only PD metastasis and OT metastasis; P

Many patients undergoing hepatectomy for colorectal liver metastases (CRLM) experience recurrence. However, no criteria for screening candidates to undergo repeat hepatectomy (RH) for CRLM have been established. Budding, one form by which colorectal carcinoma malignancies are expressed, is a new pathologic index. This study aimed to analyze prognostic factors, including budding, and to provide criteria for screening candidates to undergo RH for recurrent CRLM. Data of 186 consecutive patients who underwent hepatectomy for CRLM between April 2008 and December 2015 were collected. Survival was calculated using the Kaplan–Meier method. Uni- and multivariate analyses were performed to determine factors significantly affecting mortality. Of 186 patients, 131 experienced recurrence after hepatectomy, with 83 of the 131 patients showing recurrence in the liver, and 52 of these 83 patients undergoing primary surgery at the authors’ institution and having information on budding grade. In the univariate analysis, preoperative chemotherapy, budding grade, extrahepatic metastases, and number of liver metastases at the time of recurrence were associated with overall survival (OS) for the 52 patients. In the multivariate analysis, budding grade and number of liver metastases at the time of recurrence were associated with OS. The study examined simple prognostic factors that could help to screen patients better for RH. Repeat hepatectomy improved the prognosis for patients with recurrent CRLM. The independent prognostic factors for OS were number of liver metastases at recurrence as a conventional factor and budding grade as a new pathologic factor. With budding used as an index, patients who could benefit from hepatectomy can be screened more precisely.

Purpose 18F-Fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) is an important diagnostic tool in breast cancer. The utility of maximum standardized uptake values (SUVmax) of primary tumors has been evaluated to predict sentinel node (SN) and non-SN metastasis in clinically node-negative (cN0) patients. Patients and Methods 18F-FDG PET/CT was performed on 414 cN0 patients. The following parameters were evaluated: SUVmax at 60 min (SUVmax1), SUVmax at 120 min (SUVmax2), percent change between SUVmax1 and SUVmax2 (ΔSUVmax%), SN metastasis foci maximum size (SN meta size), and ratio of metastatic SNs to total SNs or SN ratio (SNR). It was assessed whether these were risk factors for SN metastasis. The relationship between these parameters and the status of SN and/or non-SN metastasis was retrospectively explored to predict non-SN metastasis. Results All SUV parameters significantly correlated with pathological T factor (pT), nuclear grade, lymphatic invasion (Ly), and Ki-67 labeling index. On multivariate analysis, pT and Ly were independent predictive factors for SN metastasis. In SN meta-positive cases, SN meta size, SNR, and ΔSUVmax% were predictors for non-SN metastasis on univariate analyses, and the former two were independent predictors on multivariate analysis. The combination of SUVmax2 and ΔSUVmax% was an independent predictor of non-SN metastasis (P = 0.0312) and was associated with prediction of non-SN metastasis negative status with high probability (92.3%). Conclusions In patients with cN0 breast cancer, SUV parameters of the primary tumor were correlated with pathological features. The combination of SUVmax2 and ΔSUVmax% may be useful for predicting non-SN metastasis.

Introduction: Growing evidence indicates the prognostic importance of the crosstalk between cancer cells and stroma through the induction of epithelial-mesenchymal transition (EMT). This study aimed to clarify the prognostic value of evaluating primary tumor histology with the anatomical extent of disease in patients with colorectal liver metastasis (CRLM). Methods: Prognostic analyses were performed in 411 CRLM patients who underwent hepatectomy at two institutions. Tumors were graded into one of three histological categories based on integrated assessment of EMT-associated histology (HistologyEMT) in primary tumors, i.e., poorly differentiated clusters (PDCs) and desmoplastic reaction (DR). Results: A prognostic grouping system for the anatomical extent of disease (N stage, liver metastasis number and size, and extrahepatic disease; Gradeanatomical) stratified patients into three groups with different five-year relapse-free survival (RFS) rates after hepatectomy: A, 31% (191 patients); B, 15% (124 patients); and C, 6% (96 patients; P < 0.0001). HistologyEMT (A, G1 PDC and mature-type DR; C, G3 PDC and immature-type DR; and B, others) identified 49, 120, and 242 patients with 46%, 5%, and 22% five-year RFS, respectively (P < 0.0001). Among prognostic factors, the Akaike information criterion was most favorable in Gradeanatomical, followed by HistologyEMT. Multivariate analysis demonstrated that these two factors independently impacted RFS; two-year RFS after hepatectomy in different patient groups had a wide range (10%-76%). Conclusions: Histological assessment of dedifferentiation and the stromal environment of primary tumors contributed to effective risk stratification of early relapse after hepatectomy, which could be useful to determine clinical management for CRLM patients.

The short-term outcomes after hepatic vein reconstruction (HVR) were evaluated in 41 patients. HVR can be performed safely using autologous vein graft. HVR can increase the functional remnant liver volume, facilitating parenchyma-sparing one-step hepatectomy as well as expanding resectability even in patients with all major hepatic veins involved.

A 74-year-old man was diagnosed to have a pancreas head tumor (38mm × 32 mm) due to an obstructive jaundice. The patient presented an acute intrabiliary bleeding, while waiting for surgery. Thus, after a coil embolization of the gastroduodenal artery and the anterior/posterior pancreaticoduodenal artery an emergency pancreatoduodenectomy was performed. The patient suffered from grade B delayed gastric emptying, being discharged on postoperative day 33. The pathological diagnosis established was pancreatic angiosarcoma. The patient was re-admitted 4 days after discharge with a general malaise and the loss of appetite. A dynamic computed tomography (CT) and angiography revealed multiple liver metastases and a massive hemoperitoneum. Despite of transcatheter hepatic arterial embolization with gelfoam particles, the patient died 42 days after operation. Six patients with primary angiosarcoma of the pancreas have been reported in English literature so far and this is the first report of unique features of angiogram of multiple liver metastases. The present report allows a deeper knowledge about the aggressive behavior of angiosarcoma of the pancreas.

Hemorrhage due to a ruptured pancreaticoduodenal artery aneurysm is potentially fatal. We describe a case of a 51-year-old man, incidentally diagnosed with an inferior pancreaticoduodenal artery aneurysm associated with probable congenital hypoplasia of the celiac axis and its branches. Considering the rupture risk, we performed an ilio-hepatic artery bypass with an autologous vein graft and aneurysmorrhaphy. The postoperative course was uneventful. At the 24-month follow-up, the bypass was patent, with no aneurysm recurrence. The ilio-hepatic artery bypass is effective and preserves visceral blood flow. However, the iliac artery is susceptible to occlusive disease, and long-term follow-up is required.

The Japanese guideline for gastroenteropancreatic neuroendocrine tumor treatment recommends everolimus or sunitinib as first-line treatment for unresectable pancreatic neuroendocrine tumors (PNETs). Streptozocin (STZ) is recommended as an alternative. We encountered a patient with PNET who had multiple liver metastases and who showed a remarkable response to third-line STZ. The patient was a 50-year-old man with a pancreatic head tumor 32 mm in diameter. We planned to perform subtotal stomach-preserving pancreaticoduodenectomy, but abandoned resecting the pancreas during the surgery upon discovering a small liver tumor 3 mm in diameter, examination of frozen sections of which revealed a poorly differentiated adenocarcinoma. However, the final pathological examination revealed that the liver nodule was a PNET; hence, we completed the subtotal stomach-preserving pancreaticoduodenectomy 5 weeks after the first laparotomy. The patient received no adjuvant chemotherapy after surgery. Twenty-one months later, we discovered 20 scattered liver metastases via computed tomography; these were considered unresectable. Therefore, we administered everolimus for 7 months, but the patient developed interstitial pneumonia and experienced metastatic progression. Subsequent sunitinib administration for 6 months was ineffective. Finally, we chose STZ (1000 mg/m(2), weekly) as a third-line treatment, which produced a partial response for 10 months. The patient remains alive 38 months after the detection of recurrence. As the order in which anti-cancer drugs should be administered to treat PNET has not been determined, additional predictors of their therapeutic efficacy should be investigated.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation of precursor cells in the bone marrow and their maturation into fully differentiated neutrophils. G-CSF-producing cancers rarely occur in the digestive system, particularly the pancreas. Herein we report the rare case of a G-CSF-producing pancreatic carcinoma associated with severe anemia due to bleeding in the duodenum, which was successfully treated with surgery. A 79 year-old man presented with epigastralgia and anemia at our institution. Esophagogastroduodenoscopy revealed a duodenal tumor, which was diagnosed as a poorly differentiated adenocarcinoma. To control breeding, subtotal stomach-preserving pancreaticoduodenectomy was performed. The excised tumor measured 86×55×54 mm. It was primarily located in the pancreas and compressed the pancreatic parenchyma and main bile duct. It comprised poorly differentiated adenocarcinoma, and prominent neutrophil infiltration was noted around the tumor. Immunohistochemical examination revelaed that the tumor was positive for G-CSF expression. Based on these results, a final diagnosis of G-CSF-producing primary pancreatic cancer was made. At 18 months following surgery, the patient was alive without recurrence.

Background Non-parasitic splenic cysts are associated with elevated serum carbohydrate antigen (CA) 19–9 levels. We report a case in which a 23-year-old female exhibited a large ruptured splenic cyst and an elevated serum CA19–9 level. Case presentation The patient, who experienced postprandial abdominal pain and vomiting, was transferred to our hospital and was found to have a large splenic cyst during an abdominal computed tomography (CT) scan. On physical examination, her vital signs were stable, and she demonstrated rebound tenderness in the epigastric region. An abdominal CT scan revealed abdominal fluid and a low-density region (12 × 12 × 8 cm) with enhanced margins in the spleen. The patient’s serum levels of CA19–9 and CA125 were elevated to 17,580 U/mL and 909 U/mL, respectively. A cytological examination of the ascitic fluid resulted in it being categorized as class II. Finally, we made a diagnosis of a ruptured splenic epidermoid cyst and performed laparoscopic splenic fenestration. The patient’s postoperative course was uneventful, and she was discharged on postoperative day 5. The cystic lesion was histopathologically diagnosed as a true cyst, and the epithelial cells were positive for CA19–9. Follow-up laboratory tests performed at 4 postoperative months showed normal CA19–9 (24.6 U/L) and CA125 (26.8 U/L) levels. No recurrence of the splenic cyst was detected during the 6 months after surgery. Conclusion Laparoscopic fenestration of a ruptured splenic cyst was performed to preserve the spleen, after the results of abdominal fluid cytology and MRI were negative for malignancy.

Ultra-magnesian igneous olivine is thought to crystallize from ultramafic melts and can therefore provide information about physicochemical conditions and the geochemistry and lithology of the source in the context of extremely hot mantle activity. This study focuses on the petrology and mineralogy of the Shizuoka meimechites, a series of ultra-magnesian olivine-bearing ultramafic lava blocks embedded in middle Eocene–early Miocene accretionary sediments at Shizuoka, Japan. Olivine phenocrysts within the Shizuoka meimechites have Fo compositions of ca. 81–92.8 mol%, where Fo = 100 Mg/(Mg + Fe). These ultra-magnesian olivines have trace-element compositions that are indicative of derivation from ultramafic melts that were in equilibrium with peridotitic mantle olivine. Al-in-olivine geothermometry yielded crystallization temperatures of ~1450 °C for Fo92.5–92.8 olivine, higher than the potential temperature of present-day mid-ocean ridge basalt source mantle material and similar to the potential temperatures of some large igneous provinces and ocean island basalts. Primary melt compositions in equilibrium with Fo92.5–92.8 olivine were estimated using the whole-rock compositions of the ultramafic lavas and are meimechitic, with MgO concentrations of ~21.4–27.0 wt% and SiO2 concentrations of 45.4–44.5 wt%. The potential temperature of the source mantle region for these meimechites (Tp) is estimated to be ~1486 °C–1705 °C, which is consistent with the Al-in-olivine geothermometry when considering adiabatic cooling during magma ascent. The relationship between Tp and Al-in-olivine temperature estimates for these lavas is consistent with global examples of ultra-magnesian olivine-bearing lavas. These lavas provide evidence of hitherto unknown Late Cretaceous–early Miocene deep mantle activity beneath the western Pacific region.