Low-CO2-inducible bestrophins outside the pyrenoid sustain high photosynthetic efficacy in diatoms.

Anion transporters sustain a variety of physiological states in cells. Bestrophins (BSTs) belong to a Cl- and/or HCO3- transporter family conserved in bacteria, animals, algae, and plants. Recently, putative BSTs were found in the green alga Chlamydomonas reinhardtii, where they are upregulated under low CO2 (LC) conditions and play an essential role in the CO2-concentrating mechanism (CCM). The putative BST orthologs are also conserved in diatoms, secondary endosymbiotic algae harboring red-type plastids, but their physiological functions are unknown. Here, we characterized the subcellular localization and expression profile of BSTs in the marine diatoms Phaeodactylum tricornutum (PtBST1 to 4) and Thalassiosira pseudonana (TpBST1 and 2). PtBST1, PtBST2, and PtBST4 were localized at the stroma thylakoid membrane outside of the pyrenoid, and PtBST3 was localized in the pyrenoid. Contrarily, TpBST1 and TpBST2 were both localized in the pyrenoid. These BST proteins accumulated in cells grown in LC but not in 1% CO2 (high CO2 [HC]). To assess the physiological functions, we generated knockout mutants for the PtBST1 gene by genome editing. The lack of PtBST1 decreased photosynthetic affinity for dissolved inorganic carbon to the level comparable with the HC-grown wild type. Furthermore, non-photochemical quenching in LC-grown cells was 1.5 to 2.0 times higher in the mutants than in the wild type. These data suggest that HCO3- transport at the stroma thylakoid membranes by PtBST1 is a critical part of the CO2-evolving machinery of the pyrenoid in the fully induced CCM and that PtBST1 may modulate photoprotection under CO2-limited environments in P. tricornutum.

Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.

BACKGROUND: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. METHODS: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. RESULTS: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. CONCLUSION: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.

Pancreaticoduodenectomy with celiac artery resection (PD-CAR) for unresctable locally advanced pancreatic ductal adenocarcinoma.

PURPOSE: Locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) involving the celiac artery (CeA), the common hepatic artery and the gastroduodenal artery (GDA) is considered unresectable. We developed the novel procedure of pancreaticoduodenectomy with celiac artery resection (PD-CAR) for such LA-PDACs. METHODS: From 2015 to 2018, we performed curative pancreatectomy with major arterial resection for 13 LA-PDACs as a clinical study (UMIN000029501). Of those, four patients with pancreatic neck cancer involving the CeA and GDA were candidates for PD-CAR. Prior to surgery, blood flow alterations were performed to unify the blood flow to the liver, stomach, and pancreas, resulting in feeding from the cancer-free artery. During PD-CAR, arterial reconstruction of the unified artery was performed as needed. Based on the records of PD-CAR cases, we retrospectively analyzed the validity of the operation. RESULTS: R0 resection was achieved in all patients. Arterial reconstruction was performed in three patients. In another patient, the hepatic arterial flow was maintained by preserving of the left gastric artery. The mean operative time was 669 min, and the mean blood loss was 1003 ml. Although Clavien-Dindo classification III-IV postoperative morbidities occurred in three patients, no reoperations nor mortalities occurred. Although two patients died of cancer recurrence, one patient survived for 26 months without recurrence (died of cerebral infarction), and another is alive at 76 months without recurrence. CONCLUSION: PD-CAR, which enabled R0 resection and preservation of the residual stomach, pancreas, and spleen, provided acceptable postoperative outcomes.

Interleukin-8 produced from cancer-associated fibroblasts suppresses proliferation of the OCUCh-LM1 cancer cell line.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort. METHODS: We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines on cancer cell proliferation. RESULTS: PDAC patients with positive αSMA expression showed significantly shorter overall survival and recurrence-free survival than αSMA-negative patients (p = 0.003, p = 0.009, respectively). BTC patients with positive αSMA expression showed better recurrence-free survival than αSMA-negative patients (p = 0.03). CAF-conditioned medium suppressed the proliferation of cancer cells for only OCUCh-LM1 cells and not PDAC cells. Blockage of Interleukin-8 (IL-8) or its receptor C-X-C motif chemokine receptor 2 (CXCR2) by antibodies canceled the suppressive effect of the IL-8. CONCLUSIONS: CAFs are a good prognostic factor in BTC, but not for PDAC. Moreover, CAF-produced Interleukin-8 suppresses the proliferation of OCUCh-LM1 cell lines.

Laparoscopic liver resection reduces postoperative infection in patients with hepatocellular carcinoma: a propensity score-based analysis.

BACKGROUND: This study is aimed to compare the occurrence of postoperative infections between patients with hepatocellular carcinoma (HCC) undergoing laparoscopic liver resection (LLR) and those undergoing open liver resection (OLR). METHODS: This study included 446 patients who underwent initial curative liver resection for HCC 5 cm or less in size without macroscopic vascular invasion. To adjust for confounding factors between the LLR and OLR groups, propensity score matching and inverse probability weighting (IPW) analysis were performed. The incidence rates of postoperative infection, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI), were compared between the two groups. RESULTS: An imbalance in several confounding variables, including period of surgery, extent of liver resection, difficult location, proximity to a major vessel, tumor size ≥ 3 cm, and multiple tumors, was observed between the two groups in the original cohort. After matching and weighting, the imbalance between the two groups significantly decreased. Compared with OLR, LLR was associated with a lower volume of intraoperative blood loss (140 vs. 350 mL, P < 0.001 in the matched cohort; 120 vs. 320 mL, P < 0.001 in the weighted cohort) and reduced risk of postoperative infection (2.0% vs. 12%, P = 0.015 in the matched cohort; 2.9% vs. 14%, P = 0.005 in the weighted cohort). Of the types of postoperative infections, organ/space SSI and RI were less frequently observed in the LLR group than in the OLR group in the matched cohort (1.0% vs. 6.0%, P = 0.091 for organ/space SSI; 0% vs. 6.0%, P < 0.001 for RI) and in the weighted cohort (1.2% vs. 7.8%, P < 0.001 for organ/space SSI; 0.3% vs. 5.1%, P = 0.009 for RI). CONCLUSIONS: Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI.

Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer.

BACKGROUND: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. METHODS: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. RESULTS: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. CONCLUSIONS: Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

Postoperative direct-acting antiviral treatment after liver resection in patients with hepatitis C virus-related hepatocellular carcinoma.

AIM: We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. METHODS: Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded. RESULTS: Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC-DAA and DAA-HCC groups. The number of HCC-DAA patients with albumin-bilirubin (ALBI) grade 1 increased from 11 to 15. The disease-free survival rate did not differ between HCC-DAA group (3 years, 60%) and the other two groups (DAA-HCC group, 92% and control group, 60%). The 3-year overall survival rates were better in the DAA-HCC group (84%) and HCC-DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA-induced SVR was neither. CONCLUSIONS: Although postoperative DAA-induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival.

Impact of Advancing Age on the Status and Risk of Postoperative Infections After Liver Resection.

BACKGROUND: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status. METHODS: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively). RESULTS: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29). CONCLUSIONS: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.

[A Case of Synchronous Double Cancer including Borderline Resectable Pancreatic Body Cancer and Breast Carcinoma with Osseous/Cartilaginous Differentiation Treated with Neoadjuvant Chemotherapy and Radical Resection].

A 78-year-old woman with a left breast cancer was examined at our institute. Ultrasonography showed 48 mm sized mass at zone C of the left breast, and left axillary lymph node swelling. Pathological examination of core needle biopsy revealed invasive ductal carcinoma and lymph node metastasis. In addition, contrast computed tomography showed 30 mm sized an hypovascular mass at pancreatic body involved the portal vein. Endoscopic ultrasound guided fine needle aspiration biopsy of the pancreas revealed adenocarcinoma. The diagnosis was synchronous double cancer including borderline resectable pancreatic body cancer and left breast cancer, and she received neoadjuvant chemotherapy consisting of gemcitabine and nab-paclitaxel. The effect of neoadjuvant chemotherapy was judged to be stable disease for breast cancer, partial response for pancreatic cancer. Then, she underwent pancreatosplenectomy with portal vein and gastroduodenal artery resection and reconstruction, left mastectomy and axillary lymph node dissection. Pathologic examination of the excised specimen revealed the diagnosis of breast cancer with osseous/cartilaginous differentiation and pancreatic moderately differentiated adenocarcinoma. She was treated with fluorouracil, epirubicin, and cyclophosphamide as adjuvant therapy, and there has been no recurrence.

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment.

BACKGROUND: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. METHODS: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. RESULTS: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. CONCLUSIONS: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Surgical outcomes for hepatocellular carcinoma detected after hepatitis C virus eradiation by direct-acting antivirals.

OBJECTIVE: To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA). METHODS: Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups. RESULTS: After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period. CONCLUSIONS: SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.

Predictive Value of the Age-Adjusted Charlson Comorbidity Index for Outcomes After Hepatic Resection of Hepatocellular Carcinoma.

BACKGROUND: This study aimed to evaluate the impact of the age-adjusted Charlson comorbidity index (ACCI) on outcomes after hepatic resection for hepatocellular carcinoma (HCC). METHODS: We assessed 763 patients who underwent hepatic resection for HCC. The ACCI scores were categorized as follows: ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7. RESULTS: A multivariate analysis showed that the odds ratios for postoperative complications in ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 0.71 (p = 0.41) and 4.15 (p < 0.001), respectively. The hazard ratios for overall survival of ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 1.52 (p = 0.023) and 2.45 (p < 0.001), respectively. The distribution of deaths due to HCC-related, liver-related, and other causes was 68.2%, 11.8%, and 20% in ACCI ≤ 5 group, 47.2%, 13.9%, and 38.9% in ACCI = 6 group, and 27.3%, 9.1%, and 63.6% in ACCI ≥ 7 group (p = 0.053; ACCI ≤ 5 vs. = 6, p = 0.19; ACCI = 6 vs. ≥ 7, p < 0.001; ACCI ≤ 5 vs. ≥ 7). In terms of the treatment for HCC recurrence in ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7 groups, adaptation rate of surgical resection was 20.1%, 7.3%, and 11.1% and the rate of palliative therapy was 4.3%, 12.2%, and 22.2%, respectively. CONCLUSIONS: The ACCI predicted the short-term and long-term outcomes after hepatic resection of HCC. These findings will help physicians establish a treatment strategy for HCC patients with comorbidities.

The prognostic significance of the advanced lung cancer inflammation index in patients with unresectable metastatic colorectal cancer: a retrospective study.

BACKGROUND: Growing evidence indicates that inflammation contributes to cancer progression, and several inflammatory markers have been reported to be associated with the clinical outcomes in patients with various types of cancer. Recently, the advanced lung cancer inflammation index (ALI) has been developed as a prognostic marker in patients with lung cancer. The difference between the ALI and the inflammatory markers reported in the previous studies is that the ALI contains not only indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. The aim of this study was to evaluate the prognostic significance of the ALI in patients with unresectable metastatic colorectal cancer. METHODS: We retrospectively reviewed a database of 159 patients who underwent combination chemotherapy for unresectable metastatic colorectal cancer between 2008 and 2016. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated from a blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI × serum albumin concentration/NLR. RESULTS: The overall survival rate was significantly worse in the low-ALI group than in the high-ALI group (p < 0.0001). Furthermore, the ALI was an independent prognostic factor for the overall survival (hazard ratio: 2.773, 95% confidence interval: 1.773-4.335, p < 0.001). CONCLUSIONS: A newly developed prognostic marker, the ALI, was found to be a novel prognostic marker in patients with unresectable metastatic colorectal cancer as well as in patients with lung cancer.

[A Case of Lymph Node Recurrence Seven Years after Curative Esophagectomy for T1a(LPM)Upper Thoracic Esophageal Cancer].

Herein, we report a case of lymph node recurrence 7 years after curative esophagectomy for T1a(LPM)upper thoracic esophageal cancer. A 70's man underwent radical esophagectomy by using video-assisted thoracic surgery and hand-assisted laparoscopic surgery(VATS and HALS)with gastric tube reconstruction via a posterior mediastinal route for upper thoracic esophageal cancer cT1bN0M0, cStageⅠ in August 2010. The pathological diagnosis was pT1a(LPM), w/d, scc, ly0, v0, ie (+), inf b, pIM0, pPM0, pDM0, pRM0, pN0, pM0, pStage 0. Moreover, he was followed-up without treatment after surgery. In November 2017, 7 years after esophagectomy, follow-up CT revealed left supraclavicular lymph node swelling. FDG-PET revealed high uptake of FDG, and lymph node recurrence was suspected. In January 2018, we performed lymph node biopsy. We could not remove the lymph node completely, because the lt common carotid artery and lt jugular vein were associated with the metastatic lymph node. The pathological diagnosis was squamous cell carcinoma. Chemoradiation therapy was performed after surgery, and patient recovery was uneventful.

[Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer].

The RAINBOW trial showed that paclitaxel(PTX)plus ramucirumab(RAM)therapy improved the survival of patients with advanced gastric cancer, previously treated with chemotherapy. We retrospectively investigated 33 patients with unresectable or recurrent gastric cancer who underwent PTX plus RAM treatment as second- or third-line chemotherapy between September 2015 and December 2017. The median age was 68(45-84)years with 22 patients(67%)aged 65 years or older. Seventeen patients had unresectable and 16 patients had recurrent gastric cancer. ECOG PS was 2 in 5 patients(16%). PTX plus RAM was administered as second-line therapy for 24 patients, and as third-line therapy for 9 patients. Best overall response was partial response(PR)in 4 patients, stable disease(SD)in 14 patients, and progressive disease(PD)in 9 patients. Response rate(RR)and disease control rate(DCR)were 14.8% and 66.7%, respectively. Grade 3/4 adverse events were observed in 28(85%)of(leucopenia·neutropenia[64%], neuropathy[9%], etc). Median follow-up period was 7.3(0.4- 22.4)months. Median OS and PFS were 9.3(0.4-22.4)months and 4.7(0.4-22.4)months, respectively. We conclude that PTX plus RAM therapy is useful for treating unresectable or recurrent gastric cancer. In clinical practice, we have many opportunities to provide PTX plus RAM therapy for patients of older age and poorer PS; careful attention to adverse events is essential in such cases.

Pancreatic Cancer Cell Fraction Estimation in a DNA Sample.

OBJECTIVE: Pancreatic cancers are characterized by dense stroma. To estimate the degree of interference by coexisting noncancer cells in molecular analyses, we aimed to develop a DNA methylation marker that assesses a cancer cell fraction in DNA samples. METHODS: The microarray data of 22 pancreatic cancer tissues from the The Cancer Genome Atlas database and 9 noncancer tissues were used for genome-wide screening. Thirty-one surgical tumor samples (10 intraductal papillary mucinous neoplasms [IPMNs] and 21 pancreatic cancers), 4 normal, and 26 nontumor samples were used for validation. Gene-specific methylation analysis was conducted by bisulfite pyrosequencing. RESULTS: Genome-wide screening isolated SIM1, MIR129-2, NR1I2, and HOXB-AS4, as specifically methylated in pancreatic cancer cells. Bisulfite pyrosequencing validated that one or more of three genes (SIM1, MIR129-2, and NR1I2) were methylated in 22 (71.0%) tumor samples (8 IPMNs and 14 cancers), and all showed low levels of methylation in 26 (86.7%) normal and nontumor samples. Therefore, the three genes collectively constituted one marker for a pancreatic cancer cell fraction. The cancer cell fraction estimated by the marker was highly correlated with that estimated using the KRAS mutant allele frequency (R = 0.79). CONCLUSION: The DNA methylation marker is useful to estimate the pancreatic cancer cell fraction in DNA samples.

A case of complete splenic infarction after laparoscopic spleen-preserving distal pancreatectomy.

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP), a newly developed operative procedure, is indicated for benign and low-grade malignant disease of the pancreas. However, few studies have reported on postoperative splenic infarction after LSPDP. CASE PRESENTATION: We report a case of complete splenic infarction and obliteration of the splenic artery and vein after LSPDP. The patient was a 69-year-old woman with a 35-mm cystic tumor of the pancreatic body who underwent LSPDP. Although the operation was completed with preservation of the splenic artery and vein, postoperative splenic infarction was revealed with left back pain and fluid collection around the stump of the pancreas on postoperative day 9. Fortunately, clinical symptoms disappeared within days and additional splenectomy was not needed. Splenic infarction was attributed to scattered micro-embolizations within the spleen after drawing strongly on the tape encircling the splenic vessels. CONCLUSION: Preserving splenic vessels in LSPDP is a demanding procedure. To prevent splenic infarction in LSPDP, we should carefully isolate the pancreatic parenchyma from the splenic vessels, and must avoid drawing tightly on the vessel loop encircling splenic vessels.

[A Case of Male Breast Cancer Suspected of Breast Metastasis from Pancreatic Cancer].

History of male breast cancer and pancreatic cancer are important for diagnosis of hereditary breast and ovarian cancer syndrome(HBOC), while advanced pancreatic cancer is reported to have metastasis to mammary gland tissue. A 67-year-old man visited a local hospital because fever and right hypochondrial pain. Computed tomography scan revealed pancreatic cancer with multiple liver metastasis and peritoneal metastasis. He was referred to our hospital for further evaluation and treatment. No particular family history of malignancy was formed. A palpable lump was found in his left breast. Ultrasonography revealed 2.8 cm sized mass that had heterogenous internal echo and rough border. The background mammary gland showed gynecomastia. Since it was difficult primary breast cancer with metastatic tumor originated from pancreas cancer a core needle biopsy was performed. The finding of pathological examination showed invasive carcinoma with hormonal receptor negative and HER2 negative feature. CK7 and CK19 were both positive. Although it was difficult to male differentiation whether the tumor was primary a metastatic, we diagnosed as synchronous duplicated cancer of pancreas and breast due to existence of gynecomastia. Since hepatic failure due to tumor growth advanced prior to treatment start, the treatment policy became best supportive care.

[A Case of Appendiceal Cancer Wherein the Abdominal Abscess Ruptured into the Urinary Bladder Owing to Obstructive Appendicitis].

A 73-year-old woman presented to her doctor because of lower abdominal pain and distension. A neoplastic lesion in the lower abdomen was revealed, and she was referred to our department. Enhanced CT showed wall thickening in the urinary bladder and a 6 cm mass that extended to the appendix. An appendiceal tumor invading the urinary bladder or a urinary bladder tumor invading the appendix was suspected, and we planned surgical treatment. One month later, we repeated enhanced CT scanning on admission. The mass had shrunk, but the thickening of the urinary bladder wall remained, and an enhanced appendiceal tumor was visible. Surgery was performed and we found a 1 cm appendiceal tumor. Intraoperative pathological examination revealed appendiceal cancer. Therefore, we performed ileocecal resection, D2 lymph node dissection, and partial cystectomy. Final histopathological examination revealed appendiceal cancer with pT2N0M0, pStage Ⅰ. Taking into account the patient's clinical course, we diagnosed obstructive appendicitis with an abscess due to appendiceal cancer rupture into the urinary bladder.