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-a 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.

Although achieving the critical view of safety (CVS) is useful for avoiding vasculobiliary injury during laparoscopic cholecystectomy (LC), the CVS cannot always be achieved in cases of severe cholecystitis because of technical difficulties. Herein, we focused on segment IV of the liver and its diagonal line (D‐line) as a feasible landmark for carrying out difficult LC. The D‐line connects the right dorsal and left ventral corners of segment IV and is used as the vectoral landmark, which is where the gallbladder is first dissected to achieve CVS without misidentification. Conversion to subtotal cholecystectomy along the D‐line is also feasible when gallbladder wall scarring is severe. We named this procedure the segment IV approach for LC. Sixty‐two consecutive difficult LC (including 27 scheduled LC after percutaneous transhepatic gallbladder drainage [PTGBD] and 35 conservatively treated cases of Tokyo Guidelines [TG] grade II cholecystitis) were managed by the segment IV approach. Successful gallbladder extraction along the D‐line was achieved in 44 (71%) cases; all of these cases also achieved CVS following total cholecystectomy. The other 18 (29%) cases were converted to subtotal cholecystectomy because gallbladder extraction along the D‐line failed as a result of severe cholecystitis with inflammatory adhesion with surrounding structures. Median operative time and intraoperative blood loss were 135 (range, 54‐290) min and 10 (range, 0‐100) mL, respectively. No intra‐ or postoperative complications were observed. The segment IV approach is feasible for achieving CVS and for considering subtotal cholecystectomy in difficult LC cases where scarring of the gallbladder wall is present.

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.

DGE, especially grade C, negatively affects cancer-specific survival.

The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA -Foxp3 þþ CCR4 þ 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.