Masaki Wakasugi

Dominant-negative mutant of BIG2, an ARF-guanine nucleotide exchange factor, specifically affects membrane trafficking from the trans-Golgi network through inhibiting membrane association of AP-1 and GGA coat proteins.

BIG2 is one of the guanine nucleotide exchange factors (GEFs) for the ADP-ribosylation factor (ARF) family of small GTPases, which regulate membrane association of COPI and AP-1 coat protein complexes and GGA proteins. Brefeldin A (BFA), an ARF-GEF inhibitor, causes redistribution of the coat proteins from membranes to the cytoplasm and membrane tubulation of the Golgi complex and the trans-Golgi network (TGN). We have recently shown that BIG2 overexpression blocks BFA-induced redistribution of the AP-1 complex but not TGN membrane tubulation. In the present study, we constructed a dominant-negative BIG2 mutant and found that when expressed in cells it induced redistribution of AP-1 and GGA1 and membrane tubulation of the TGN. By contrast, the mutant did not induce COPI redistribution or Golgi membrane tubulation. These observations indicate that BIG2 is involved in trafficking from the TGN by regulating membrane association of AP-1 and GGA through activating ARF.

Different Distribution Patterns of the Two Mannose 6-phosphate Receptors in Rat Liver

Two mannose 6-phosphate receptors, cation-dependent and -independent receptors (CDMPR and CIMPR), play an important role in the intracellular transport of lysosomal enzymes. To investigate functional differences between the two in vivo, their distribution was examined in the rat liver using immunohistochemical techniques. Positive signals corresponding to CIMPR were detected intensely in hepatocytes and weakly in sinusoidal Kupffer cells and interstitial cells in Glissons capsule. In the liver acinus, hepatocytes in the perivenous region showed a more intense immunoreactivity than those in the periportal region. On the other hand, positive staining of CDMPR was detected at a high level in Kupffer cells, epithelial cells of interlobular bile ducts, and fibroblast-like cells, but the corresponding signal was rather weak in hepatocytes. In situ hybridization analysis also revealed a high level of expression of CIMPR mRNAs in hepatocytes and of CDMPR mRNA in Kupffer cells. By double immunostaining, OX6-positive antigen-presenting cells in Glissons capsule were co-labeled with the CDMPR signal but were only faintly stained with anti-CIMPR. These different distribution patterns of the two MPRs suggest distinct functional properties of each receptor in liver tissue.

Predominant expression of the short form of GGA3 in human cell lines and tissues

Three GGAs (GGA1-3) were found in humans, among which GGA3 has short and long forms of spliced variants (GGA3-S and GGA3-L). The present study analyzed expression patterns of both GGA3 variants in human tissues and cell lines. Western blot analysis revealed that the brain contained both GGA3-S and -L, while other tissues and cell lines examined predominantly expressed GGA3-S. By double immunofluorescence microscopy, GGA1 and GGA3 were localized with slightly different patterns in both the trans-Golgi network (TGN) and peripheral region. When the dominant-negative mutant, VHS-GAT domain, of GGA1 or GGA3-L was overexpressed, TGN-associated GGA1 was redistributed into the cytoplasm. However, the GGA3 distribution was not affected by the expression of either VHS-GAT domain. These results indicate that GGA3-S which would not be directly involved in the cargo protein recognition is predominantly expressed in human tissues except the brain and in cell lines.

Comparison of perioperative and short-term oncological outcomes after single- or multiport surgery for colorectal cancer.

The aim of this retrospective study was to compare the short‐term surgical results of single‐port surgery (SPS) with those of multiport surgery (MPS) for colorectal cancer.

Short-term outcome of single-incision laparoscopic totally extra-peritoneal inguinal hernia repair.

We performed single‐incision laparoscopic surgery for totally extra‐peritoneal (SILS‐TEP) repair using a lightweight mesh fixed by absorbable tacks and without balloon dilation. Thirty‐four patients (mean age, 66.5 years) underwent SILS‐TEP repair in our hospital between September 2011 and April 2012; 30 patients had unilateral hernia and 4 had bilateral hernias. Mean operative time was 85.6 min for unilateral hernia and 137.7 min for bilateral hernias. All patients underwent successful SILS‐TEP repair. Mean hospital stay was 3.4 days. Mean duration of follow‐up was 7.1 months. Four seromas were observed, but no recurrences or major complications occurred. SILS‐TEP is an economical and useful method for decreasing postoperative complications, such as neuralgia and recurrence, and it could be an attractive approach for inguinal hernia.

Perioperative management of continuous ambulatory peritoneal dialysis patients undergoing inguinal hernia surgery

Management of patients undergoing dialysis after inguinal hernia surgery has not been standardized. This report presents the results of 9 patients with inguinal hernias (11 hernias) who were undergoing continuous ambulatory peritoneal dialysis (CAPD). All patients treated in this hospital since 2007 have returned to CAPD within 3 days after surgery without switching to hemodialysis (HD). The mean durations for resuming CAPD after surgery were 7.6 days from 1998 through 2007 and 2.3 days since 2008. The surgical procedure was performed with a polypropylene mesh in all cases. Local anesthesia was utilized for one patient with low cardiac function. All patients recovered rapidly, with no uremia or dialysis-related complications. No leakage or hernia recurrence was observed over the subsequent observation period (56.2 months). This experience suggests the possibility that interim HD can therefore be skipped in patients undergoing CAPD if the hernia sacs are closed tightly. Local anesthesia seems to be safe for high-risk hernia patients undergoing CAPD.

Single-port laparoscopic colectomy is safe and feasible in patients with previous abdominal surgery.

BACKGROUND The aim of this study was to assess the impact of previous abdominal surgery (PAS) on single-port laparoscopic colectomy (SPLC). METHODS We studied 429 consecutive patients who underwent SPLC in our department from May 2009 to December 2013. Patients were divided into 2 groups: those with PAS (PAS group) and those with NPAS (NPAS group). Operative parameters and outcomes were analyzed between the 2 groups retrospectively. RESULTS SPLC was performed in 152 PAS patients and 277 NPAS patients. Eight patients in the PAS group and 6 patients in the NPAS group were converted to multiport laparoscopic colectomy (5.3% vs. 2.2%, respectively; P = .077). Three patients in the PAS group and 2 patients in the NPAS group had inadvertent enterotomy (2.0% vs. .7%, respectively; P = .352). No patients were converted to open surgery. There were no significant differences between the 2 groups in terms of blood loss, operative time, and postoperative outcomes. CONCLUSION Our experience has demonstrated the safety and feasibility of SPLC in patients with PAS.

Multiple hepatic sclerosing hemangioma mimicking metastatic liver tumor successfully treated by laparoscopic surgery: Report of a case.

Highlights • Sclerosing hemangioma should be included among the differential diagnoses of multiple liver tumors in patients with colorectal cancer.• Laparoscopic hepatectomy is useful for diagnostic therapy for undiagnosed multiple liver tumors.• This report is the first to describe multiple hepatic sclerosing hemangiomas treated by laparoscopic surgery.

Laparoscopic Distal Pancreatectomy for Multiple Epithelial Cysts in an Intrapancreatic Accessory Spleen. A Case Report and Review of Literature

CONTEXT Accessory spleen is a congenital abnormality consisting of normal splenic tissue in ectopic sites that is found in approximately 10-15% of the general population. However, an intrapancreatic accessory spleen has seldom been reported and multiple epithelial cysts in the intrapancreatic accessory spleen are extremely rare. CASE REPORT A 37-year-old woman with no clinical manifestations presented with two cystic lesions in the tail of the pancreas. The tumor markers CA 19-9 (251 U/mL) and SPAN-1 (38 U/mL) were increased. Computed tomography showed a multilocular cyst, 40 mm in size, and a unilocular cyst, 20 mm in size, in the tail of the pancreas and gallstones. The cystic component was hypointense on T1-weighted magnetic resonance images and hyperintense on T2-weighted magnetic resonance images. A laparoscopic distal pancreatectomy was performed with the presumptive diagnosis of a mucinous cystic neoplasm or an intraductal papillary mucinous neoplasm with gallstones. The pathological examination showed that the walls of the two cysts were covered with non-keratinized stratified squamous epithelium, surrounded by normal splenic tissue. The final pathological diagnosis was two epithelial cysts originating from an intrapancreatic accessory spleen. CONCLUSIONS Even though multiple masses were detected in the pancreatic tail, the possibility of epithelial cysts originating from an accessory spleen should be considered. Laparoscopic distal pancreatectomy might be a safe and effective procedure and provide good cosmetic result for a benign or low-grade malignant tumor in the pancreas.

Signet ring cell carcinoma of the ampulla of vater: Report of a case and a review of the literature

Highlights • Signet ring cell carcinoma in the ampulla of vater is extremely uncommon.• Investigation to confirm the histological origin of signet ring cell carcinoma by immunohistochemical staining might inform the treatment strategy and identify patients with ampullary signet ring cell carcinoma who may have a good prognosis.