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Sarocladium kiliense is ubiquitous in the human environment and is an emerging opportunistic pathogen, especially among immunocompromised hosts. A 77-year-old man diagnosed with aplastic anemia suffered from non-valvular endocarditis. After he passed away, fungal hyphae were observed in several lesions on a postmortem examination. Polymerase chain reaction (PCR) and a DNA sequence analysis revealed S. kiliense as the causative organism. This is the first case report of non-valvular fungal endocarditis caused by S. kiliense identified by PCR and a DNA sequence analysis in an immunocompromised patient. Although rare, invasive fungal infection caused by S. kiliense should be considered in immunocompromised hosts.

Adaptor ligation and PCR primer sequences

Histopathological findings of the skin rash and the brain (Case 2)

The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA–Foxp3++CCR4+ phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644–9. ©2016 AACR.

The numbers of sequence reads

Histopathological findings of the skin (Case 1)

Introduction Liver metastasis of submandibular gland carcinoma is not uncommon, yet its optimal management is still unclear. We report a case of resection of liver metastasis from submandibular gland carcinoma five years after the primary operation. Case presentation The patient was a 76-year-old male who had undergone resection of primary adenoid cystic carcinoma of the submandibular gland in 2012. On follow-up computed tomography (CT) five years after the initial operation, a tumor was found incidentally in hepatic segment 6. Magnetic resonance imaging (MRI) confirmed the lesion's presence. Based on imaging findings and medical history, the lesion was suspected to be a liver metastasis of the previous submandibular gland carcinoma. The patient underwent hepatic posterior sectionectomy. His postoperative course was uneventful except for minor bile leakage that subsided without surgical intervention, and he was discharged on postoperative day 25. Postoperative pathological examinations of the hepatic tumor showed exactly the same features seen in the primary submandibular gland carcinoma, and the diagnosis as metastasis from this carcinoma was confirmed. Discussion Liver resection may be a reasonable choice of treatment for liver metastasis of submandibular gland carcinoma. Further evidence from studies with larger patient populations must be accumulated to confirm this. Conclusion We report our experience with a case of liver metastasis from submandibular gland carcinoma, which was resected five years after the primary operation., Highlights • We report a case in which a tumor was found incidentally in hepatic segment 6. • The submandibular gland was resected five years ago for adenoid cystic carcinoma. • Postoperative pathological diagnosis was metastasis from the previous carcinoma. • Liver resection may be useful for liver metastasis of submandibular gland carcinoma.

A cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreER

Sarocladium kiliense is ubiquitous in the human environment and is an emerging opportunistic pathogen, especially among immunocompromised hosts. A 77-year-old man diagnosed with aplastic anemia suffered from non-valvular endocarditis. After he passed away, fungal hyphae were observed in several lesions on a postmortem examination. Polymerase chain reaction (PCR) and a DNA sequence analysis revealed S. kiliense as the causative organism. This is the first case report of non-valvular fungal endocarditis caused by S. kiliense identified by PCR and a DNA sequence analysis in an immunocompromised patient. Although rare, invasive fungal infection caused by S. kiliense should be considered in immunocompromised hosts.

Background Intraoperative hypothermia is a common adverse event. For avoiding the complication due to hypothermia, many warming devices and methods have been used in perioperative period. It has been reported that more patients undergoing laparoscopic surgery tend to have hypothermia than with open surgery. To avoid intraoperative hypothermia, many kinds of warming tools have been used. But, it was also reported that some warming methods increased perceptions of distraction and physical demand. Methods To achieve both patients’ normothermia and surgeons’ comfort, new air conditioning (AC) system was designed with considering the characteristics of laparoscopic surgery. The temperature of the airflows to the patient and to the surgeons can be adjusted independently in this new system. The new system has two parts. One controls the temperature of the central area over the operation table. The air from this part falls on the patients. The other part is the lateral area beside the operating table; the air from this part falls on the surgeons. The subjects of this study were 160 gastric cancer patients and 316 colorectal cancer patients undergoing laparoscopic surgery. The temperature of the central flow was set 23.5 °C, and the temperature of the lateral flow was set 22 °C just after the anesthesia. The number of timepoints the patient spent in hypothermic state, defined as a temperature cooler by 0.5 °C or more than that at the starting point of surgery, was determined in each patient. Results In the results, the rate of hypothermic state in old operation rooms was 23.8% and that in new operation rooms was 2.7% in male gastric cancer patients (p p p p Conclusions Thus, the usefulness of the new air conditioning system for achieving both patients’ normothermia and comfort of surgeons could be verified in this study.

The associations of the immunological status of the pancreatic ductal adenocarcinoma (PDA) microenvironment with prognosis were assessed. A high tumor-infiltrating lymphocyte (TIL) density was associated with a better prognosis. Importantly, even with a high density of TILs, the PDA cells with programed cell death-ligand 1 (PD-L1) expression showed a worse prognosis than the patients with negative PD-L1 expression. A significant association between a better prognosis and a tumor microenvironment with a high TIL density/negative PD-L1 expression was observed. Assessments of a combined immunological status in the tumor microenvironment may predict the prognosis of PDA patients following surgical resection.

Background/aim Organ/space surgical site infections (SSIs) are critical complications of pancreaticoduodenectomy. We investigated the impact of the time between division of the common hepatic duct and completion of biliary reconstruction [bile exposure (BE) time] on the occurrence of post-pancreaticoduodenectomy organ/space SSI. Patients and methods Sixty-one patients who underwent pancreaticoduodenectomy were retrospectively studied. The impact of perioperative variables and BE time on organ/space SSI occurrence was analyzed. Results Organ/space SSIs occurred in 17 patients (28%). Patients were divided into two groups according to BE time. The incidence of organ/space SSIs was significantly higher in the long BE time group than in the short BE time group (42% versus 13%, p=0.0127). Multivariate analysis revealed that long BE times [odds ratio (OR)=4.8; p=0.0240] and soft pancreatic texture (OR=16.5; p=0.0106) were independent risk factors for organ/space SSIs. Conclusion Long BE time is a risk factor for post-pancreaticoduodenectomy organ/space SSIs. Shortening BE time may reduce organ/space SSI occurrence.

What We Already Know about This Topic What This Article Tells Us That Is New Background Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. Methods Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy. Results Recombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg−1 · h−1; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg−1 · h−1; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg−1 · h−1; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide. Conclusions Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.

Introduction Recent advances in single-incision laparoscopic surgery (SILS) have caused increased difficulties when tying knots because of the limited working space. Although extracorporeal knot-tying techniques may be a practical alternative choice in SILS, it is not always appropriate. For example, sliding resistance may be encountered when tying knots for a Z-shaped suture, and it could damage the sutured tissue. Materials and surgical technique The clinch knot is a kind of slipknot that has been historically used by fishermen. We modified it for SILS so that it has a locking mechanism caused by knot deformation. We apply pre-tied modified clinch (MC) knots in the peritoneal cavity with a needle driver. After the suture, the needle is pulled through the knot and exits out the trocar. After the MC knot has been tightened, locking is achieved by pulling the other end of the axial thread and folding the thread in an acute angle. Because both ends of the suture thread leave the trocar together, every step can be carried out quickly through a single trocar. The MC knot can also be used to tie knots for Z-shaped sutures because of its short sliding distance. Twelve simple interrupted sutures and 55 Z-shaped sutures were tied by MC knot in SILS. All knots were successfully tied, and the mean required time to tie a knot was 27 s. Discussion The MC knot is feasible knot-tying procedure especially for a Z-shaped suture during SILS.

Solitary bone plasmacytoma (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy. Consequently, bortezomib treatment was stopped and a stringent complete response has been maintained.

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Off-flavor events in tap water have been reported from various regions of Japan. Fishy smell is the second most common off-flavor in Japan and Uroglena americana (U. americana) is known to be a major contributor to the smell. However, the causative compound of the smell it produces still remains unrevealed to the best of our knowledge. In this study, an exploration of odorous aldehydes and ketones originating from U. americana was performed with a view to discovering a possible candidate substance of causative compounds. Environmental samples containing U. americana colony and cultured media with U. americana were analyzed with two high resolution mass spectrometers, one of them is coupled with liquid chromatography (LC-HRMS), and the other is with gas chromatography and a sniffing port (GC-O-HRMS). Multivariate analyses (MVA) were utilized to explore a compound that is likely to be odorous aldehydes or ketones with a reduced time of exploration. A combination of LC-HRMS and MVA resulted in the selection of one candidate substance and its formula was determined to be C13H20O3 on the basis of its accurate mass and natural isotopic pattern. The candidate substance underwent GC-O-HRMS analyses and milk-like smell was detected at around its retention time. Although the detected smell was different from fishy smell, it is expected that the fishy smell is caused by multiple compounds to which the candidate substance belongs. First generation product ion spectra of the candidate substance suggested that it contains a hydroxyl group, a cyclohexene ring, and a ketone moiety.

Tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 fusion protein, encoded by the Philadelphia chromosome, have drastically improved the outcomes for patients with chronic myeloid leukemia (CML). Although several real-time quantitative polymerase chain reaction (RQ-PCR) kits for the detection of BCR-ABL1 transcripts are commercially available, their accuracy and efficiency in laboratory practice require reevaluation. We have developed a new in-house RQ-PCR method to detect minimal residual disease (MRD) in CML cases. MRD was analyzed in 102 patients with CML from the DOMEST study, a clinical trial to study the rationale for imatinib mesylate discontinuation in Japan. The BCR-ABL1/ABL1 ratio was evaluated using the international standard (IS) ratio, where IS < 0.01% was defined as a major molecular response. At enrollment, BCR-ABL1 transcripts were undetectable in all samples using a widely-applied RQ-PCR method performed in the commercial laboratory, BML (BML Inc., Tokyo, Japan); however, the in-house method detected the BCR-ABL1 transcripts in five samples (5%) (mean IS ratio: 0.0062 ± 0.0010%). After discontinuation of imatinib, BCR-ABL1 transcripts were detected using the in-house RQ-PCR in 21 patients (21%) that were not positive using the BML method. Nineteen samples were also tested using a commercially available RQ-PCR assay kit with a detection limit of IS ratio, 0.0007% (ODK-1201, Otsuka Pharmaceutical Co., Tokyo, Japan). This method detected low levels of BCR-ABL1 transcripts in 14 samples (74%), but scored negative for five samples (26%) that were positive using the in-house method. These data suggest that our new in-house RQ-PCR method is effective for monitoring MRD in CML.

Urine output is widely used as a criterion for the diagnosis of AKI. Although several potential mechanisms of septic AKI have been identified, regulation of urine flow after glomerular filtration has not been evaluated. This study evaluated changes in urine flow in mice with septic AKI. The intratubular urine flow rate was monitored in real time by intravital imaging using two-photon laser microscopy. The tubular flow rate, as measured by freely filtered dye (FITC-inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2 hours, the tubular flow rate was slower in mice injected with LPS than in mice injected with saline, whereas BP and GFR were similar in the two groups. Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal tubules that showed reduced tubular flow at 2 hours and luminal obstruction with cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor 4 in mice abolished these effects, whereas neutralization of TNF-α had little effect on LPS-induced tubular flow retention. Rapid intravenous fluid resuscitation within 6 hours improved the tubular flow rate only when accompanied by the dilation of obstructed proximal tubules with accumulated LPS. These findings suggest that LPS reduces the intratubular urine flow rate during early phases of endotoxemia through a Toll-like receptor 4–dependent mechanism, and that the efficacy of fluid resuscitation may depend on the response of tubules with LPS accumulation.

Portal vein thrombosis (PVT) is caused by several conditions including infection, malignancies, surgery, medications, and coagulation disorders. However, PVT caused by low-energy injury is very rare. A 51-year-old man visited a clinic with a 2-day history of abdominal pain following blunt abdominal trauma. Contrast-enhanced computed tomography (CT) revealed thrombosis in both the portal vein and splenic vein, and he was transferred to our hospital with a diagnosis of PVT. Anticoagulant therapy was initiated using unfractionated heparin. A repeat CT scan revealed enlargement of the thrombus, which occluded the main trunk and first right branch of the portal vein. Laboratory data before heparin administration suggested low protein C activity. Anticoagulation therapy was continued with intermittent assessment of the size of the thrombus and degree of coagulation. On day 23, enhanced CT showed marked shrinkage of the thrombus compared with that on day 8. On day 30, the patient was discharged with a therapeutic prothrombin time–international normalized ratio. Here we present a case of PVT caused by low-energy trauma of the upper abdomen in a patient with a background of low protein C activity that was successfully treated without invasive surgery.

Aim Pancreaticoduodenectomy (PD) is still the only curative treatment for periampullary cancer. Confirming the outcomes of PD in elderly patients is important as the aging population continues to grow. Patients and methods We analyzed 340 patients with periampullary cancer who underwent PD, dividing them into three groups by age: group A: aged 64 years or younger, n=115; group B: 65-74 years, n=144; and group C: 75 years or older, n=81. Results Group C had a significantly higher 60-day mortality of 6.3% (p=0.04), the lowest 5-year overall survival rate of 9.9% (p=0.02), and there was no impact of staging of the Union for International Cancer Control classification on overall survival of patients with pancreatic cancer. Independent prognostic factors of group C in the multivariate analysis were pancreatic cancer and reoperation. Conclusion For elderly patients aged 75 years or over, caution should be exercised in selecting PD for patients with pancreatic cancer.

Background Delayed gastric emptying (DGE), a common postoperative complication of pancreaticoduodenectomy, is not considered a life-threatening complication. In the present study, we analyzed the risk factors for DGE and its impact on long-term prognosis. Methods We analyzed 383 patients who underwent pancreaticoduodenectomy between 2003 and 2010, dividing them into two groups according to DGE grade as defined by the International Study Group of Pancreatic Surgery: 243 without DGE (non-DGE group) and 140 with DGE of any grade (DGE group). Results The 5-year overall survival was 32.7% in the DGE group, and 41% in the non-DGE group (P = 0.02). Cox proportional hazards analyses showed that pancreatic cancer (compared with ampulla of Vater cancer: hazard ratio [HR] 3.4, 95% confidence interval [CI] 1.82–6.34, P < 0.001), bile duct cancer (HR 2.1, 95% CI 1.08–4.06, P = 0.03), the Union for International Cancer Control stage (compared with stages I and II: HR 2.98, 95% CI 1.66–5.35, P < 0.001; compared with stage III: HR 4.71, 95% CI 2.51–8.86, P < 0.001), and DGE grade (grade C; HR 1.6, 95% CI 1.04–2.46, P = 0.03) were independent risk factors for cancer-specific survival. Conclusions DGE, especially grade C, negatively affects cancer-specific survival.

Recent advances in single-incision laparoscopic surgery (SILS) have caused increased difficulties when tying knots because of the limited working space. Although extracorporeal knot-tying techniques may be a practical alternative choice in SILS, it is not always appropriate. For example, sliding resistance may be encountered when tying knots for a Z-shaped suture, and it could damage the sutured tissue.The clinch knot is a kind of slipknot that has been historically used by fishermen. We modified it for SILS so that it has a locking mechanism caused by knot deformation. We apply pre-tied modified clinch (MC) knots in the peritoneal cavity with a needle driver. After the suture, the needle is pulled through the knot and exits out the trocar. After the MC knot has been tightened, locking is achieved by pulling the other end of the axial thread and folding the thread in an acute angle. Because both ends of the suture thread leave the trocar together, every step can be carried out quickly through a single trocar. The MC knot can also be used to tie knots for Z-shaped sutures because of its short sliding distance. Twelve simple interrupted sutures and 55 Z-shaped sutures were tied by MC knot in SILS. All knots were successfully tied, and the mean required time to tie a knot was 27 s.The MC knot is feasible knot-tying procedure especially for a Z-shaped suture during SILS.

We report our first case of single-incision laparoscopic hepatectomy in a 43-year-old woman with a 30-mm solitary combined hepatocellular-cholangiocarcinoma. A port of single-incision laparoscopic surgery was inserted through the abdominal wall using a 2.5-cm single incision in the umbilical area. To obtain adequate operative view for the tumor in segment 6, a 5-mm flexible endoscope, roticulated instruments, and a miniloop retractor were used. After precoagulation with a 5-mm flexible microwave probe, liver resection was performed using laparoscopic ultrasonic shears, soft-coagulation devices, and a tissue-sealing knife. Subsequently, cholecystectomy was carried out for a gallbladder polyp. The procedure was successfully completed without conversion to conventional laparoscopic technique. The operation time was 180 minutes and operative blood loss was uncountable. Transumbilical single-incision laparoscopic hepatectomy using precoagulation and clipless techniques is feasible and seems to provide better cosmetic appearance in selected cases by qualified endoscopic liver surgeons.

Introduction Recent interest in improving cosmetic outcomes has led to single-incision laparoscopic surgery (SILS) being performed in a variety of organs. However, this innovative technique has rarely been introduced in pancreatic surgery, as it is considered to be a challenging procedure. We report herein our technique of single-incision laparoscopic distal pancreatectomy with or without splenic preservation. Materials and Surgical Technique A 2.5-cm intraumbilical mini-laparotomy was made for the placement of a SILS Port as a single access site. The overall procedures were similar to those performed in the standard laparoscopic distal pancreatectomy with multiple trocars. To obtain better exposure of the operative field, we made technical refinements by employing gastric suspension with sutures, the tug-exposure technique, a balloon retractor, and gravity by changing the patient's position. The pancreas was transected with a linear stapler, and the specimen was extracted through the umbilical wound. Discussion Patients were discharged without any complications. The umbilical wounds were almost invisible 1 month after surgery. We believe that SILS, with some technical refinements, can be safely applied for distal pancreatectomy. Although the cosmetic benefits of single-incision laparoscopic distal pancreatectomy are obvious, several issues such as the extent of invasiveness, cost, indications, and learning curve need to be investigated.

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