Bilateral laparosocopic lateral lymph node dissection by the totally extraperitoneal approach after intersphincteric resection of the lower rectum: report of a case.

Introduction and Importance: Lateral lymph node dissection (LLND) for recurrent lateral pelvic lymph node metastasis could be the only surgical treatment to improve its prognosis, but is difficult and challenging technically. Case Presentation: A 75-year-old Japanese man who underwent a radical laparoscopic intersphincteric resection to treat double lower rectal cancer. Computed tomography and MRI showed lower rectal wall thickening and bilateral lateral lymph node swelling. The authors scheduled and performed the LLND for recurrent lateral pelvic lymph nodes after ISR by the totally extraperitoneal (TEP) approach. The bottom of the obturators lymph node (#263D) were positive for metastasis histologically. Clinical Discussion: The TEP approach is an especially effective option for the treatment of bilateral LLND. Conclusion: Herein, the authors introduce our surgical technique: successful challenging treatment of the LLND by the TEP approach after intersphincteric resection of the lower rectum.

Successful treatment for sports hernia by total extraperitoneal repair with intraperitoneal examination: Report a case.

Introduction: and importance: TEP might be one of options for treating such a sports hernia. Case presentation: An 18-year-old Japanese male presented with right groin pain for approximately two years. The pain was initially felt on the right side only, especially on kicking. We assessed the patient using laparoscopic examination with an intra-abdominal scope and subsequently diagnosed a sports hernia with a bilateral internal inguinal hernia. We then performed total extraperitoneal repair (TEP) for its treatment. The patient had a good postoperative course and was discharged from our hospital in remission after 3 days. Finally, the patient was able to play soccer without groin pain. Clinical discussion: Chronic groin pain in athletes can be caused by a bulge in the posterior inguinal wall, consistent with an incipient direct inguinal hernia. Conclusion: We show that intraperitoneal examination with TEP might be one of options for treating such a sports hernia. Endoscopic placement of the retropubic mesh must be considered an important option for this type of hernia.

Laparoscopic intraperitoneal mesh repair of an incisional hernia after transverse rectus abdominis myocutaneous flap reconstruction for breast cancer.

Breast reconstruction with transverse rectus abdominis myocutaneous (TRAM) flap is performed for the treatment of large defects of the breast. However, this may result in an abdominal wall hernia or bulging. A 53-year-old Japanese woman with left breast cancer underwent left skin-sparing mastectomy, sentinel node lymph node dissection, and immediate reconstruction with a contralateral pedicled TRAM flap. Thirty-two months following surgery, right lower abdominal wall hernia (15.5 × 12 cm) and bulging were observed at the suprapubic region. The patient was diagnosed with an incisional hernia and was scheduled for laparoscopic intraperitoneal mesh repair. The mesh was coated with an absorbable hydrogel barrier and was trimmed to 26 × 22 cm, with a 5 cm overlap around the defect. The patient demonstrated a good postoperative course. In conclusion, intraperitoneal onlay mesh with hernia repair closure (IPOM-Plus) is a simple and useful method for hernia repair following TRAM flap reconstruction.

Granular cell tumor coexisting with adenocarcinoma in the stomach: Report of a rare case.

INTRODUCTION: and importance: Granular cell tumor (GCT) is a benign, mesenchymal tumor that originates from Schwann cells. CASE PRESENTATION: A 75-year-old Japanese woman was referred to our hospital due to epigastric discomfort. Upper gastrointestinal endoscopy revealed an ulcerated cancer lesion, approximately 1.2 cm in diameter, at the angle of the stomach in the posterior gastric wall and a yellowish submucosal tumor, 5 mm in diameter, near an anal ulcerated lesion. Based on these findings, the patient was scheduled for laparoscopic distal gastrectomy and lymph node dissection. The pathological diagnosis was a moderately differentiated tubular adenocarcinoma invading mucosal stroma without lymph node metastasis and GCT in the stomach. Tumor cells were positive for S-100 and were consistent with the characteristics of GCT. CLINICAL DISCUSSION: To the best of our knowledge, this is an extremely rare case with reports of only 6 cases of such a combination, including our case. CONCLUSIONS: We believe that the coexistence of a GCT and gastric cancer in our patient was accidental and that there was no relation between them.

Clinical characteristics and molecular analysis of USA300 and ST 764 methicillin-resistant Staphylococcus aureus isolates from outpatients in Japan by PCR-Based open reading frame typing.

INTRODUCTION: USA300 is the most common community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain. Sequence type (ST) 764 MRSA is a new local variant of the ST 5 lineage. The objective of this study was to determine the clinical characteristics of USA300 and ST 764 infections among outpatients in Japan. METHODS: We obtained MRSA isolates from 132 outpatients who visited our hospital from January 2016 to December 2017 and compared USA300 infection group to ST 764 infection group. Molecular analysis, including that of various toxins and other virulence factors, of the MRSA isolates were performed. In particular, we investigated the relationships among PCR-based open reading frame typing (POT) scores, MRSA clones, and virulence factors. RESULTS: Twenty-seven USA300 isolates (20.5%) and 16 ST 764 isolates (12.1%) were identified. Although USA300 and ST 764 had lower rates of risk factors, their infection rates were higher. USA300-infected patients had higher rates of deep skin and soft tissue infections compared with the non-USA300 CA-MRSA-infected patients. Notably, the USA300 and ST 764 isolates had unique POT scores. CONCLUSIONS: Our results indicated that USA300 MRSA was spreading in an area 120 km west of Tokyo, Japan. We observed multiple cases of ST 764 MRSA infection, raising concerns about the antimicrobial resistance of ST 764, as it limits the choices of antibiotics to treat infection. The POT score can predict the presence of toxins and virulence factors, as well as the clone identity of MRSA with high accuracy.

Laparoscopic cholecystectomy for cholecystitis using direct gallbladder indocyanine green injection fluorescence cholangiography: A case report.

: Laparoscopic cholecystectomy is the treatment of choice for almost all biliary diseases. We present a novel technique using near-infrared fluorescence imaging for laparoscopic cholecystectomy. : A 78-year-old woman diagnosed with acute cholecystitis (Grade II) was scheduled for emergency laparoscopy according to Tokyo Guidelines 2018. We performed a direct percutaneous drainage of the gallbladder to grasp the gallbladder itself. Subsequently, indocyanine green was administered into the gallbladder through the same tube, and the cystic and common bile ducts could be easily detected. The postoperative course was good, and the patient was discharged in remission nine days after the surgery. : Real-time fluorescence cholangiography with indocyanine green is reliable for biliary anatomy visualization before the dissection of the Calot's triangle. Our method of indocyanine green injection into the same drainage catheter does not require pre-preparation and can be simultaneously performed with drainage intraoperatively. This surgical technique is simple, straightforward, and effective and can be useful in intraoperative decision-making, especially during laparoscopic cholecystectomy.

Ultimate Stomaless Technique of Two-Stage Operation for Lower Rectal Cancer Performed on a Patient with a High Body Mass Index: The Reborn Operation (Novel Pull-Through Method).

A 58-year-old Japanese man, with a body mass index of 41.7 kg/m2 (height: 179.8 cm; weight: 133.8 kg), underwent a laparoscopic pull-through procedure with delayed coloanal anastomosis performed in two surgical stages for lower rectal cancer. This method was selected because the volume of the abdominal wall was fairly thick and it would have been impossible to perform diverting ileostomy and colostomy, which are routinely conducted. First, a colonic pull-through segment of about 10 cm was left outside the anal canal without any tension and was fixed by sutures under indocyanine green fluorescence imaging (ICG FI). The second surgical stage was performed 10 days after the first operation under general anesthesia. Final coloanal anastomosis was performed with near-infrared light without diverting the stoma under ICG FI. The patient demonstrated a good postoperative course and was discharged from our hospital in remission 15 days after the latest operation. We could inspect the coloanal flow of the anastomosis under ICG FI before the reconstruction. This procedure was considered to be a standard method, but it was overtaken by new technology, ICG FI. This procedure is an ultimate stomaless surgery for ultralow rectal cancer that can be performed in selected cases, such as in patients with a high body mass index and with hope for stomaless operation.

Combined Intraoperative Identification and Monitoring of Recurrent Laryngeal Nerve Paresis during Minimally Invasive Esophagectomy: Surgical Technique Using Nerve Integrity Monitoring for Esophageal Carcinoma.

Recurrent laryngeal palsy occurs after No. 106 rec RL lymphadenectomy procedure, which is assumed to cause postoperative respiratory complications. A 71-year-old Japanese man with T1b N0 M0 stage 1 esophageal cancer was scheduled for thoracoscopic esophagectomy with two-field lymph node dissection using nerve integrity monitoring (NIM). The patient demonstrated an uneventful postoperative course with 56 days remission. Under general anesthesia conditions, a single-lumen intubation tube was inserted for NIM. The automatic periodic stimulation electrode was placed on the bilateral vagus nerves on the left and right, respectively. The NIM had set and enabled the identification of the nerve accurately and continuous intraoperative nerve monitoring using impulses from the stimulation probe. The postoperative outcomes and comparison of the potential amplitudes of electromyography were observed while no postoperative vocal cord paresis was present. Combined intraoperative identification and monitoring of recurrent laryngeal nerve significantly changes the quality of the lymphadenectomy procedure and is a promising optical imaging technique. It has gained recognition for being able to reduce or prevent recurrent laryngeal nerve paralysis. It was considered a reasonable method, but it has been superseded by NIM, which is a novel technology.

Usefulness of repair using Hem-o-lok™ for peritoneal tear as a complication of totally extraperitoneal repair: Case series.

INTRODUCTION: Peritoneal tear (PT) is a frequent intraoperative event during totally extraperitoneal repair (TEP). We aimed to introduce our surgical technique for PT during TEP to avoid the more difficult TEP procedure.MethodsOne surgeon with 10 years of experience performed our TEP method in 147 TEP cases from January 2012 to June 2019. We investigated the repair time of each repair technique using endoscopic suturing (suturing group, SG) and endoscopic Hem-o-lok stapling (CG). RESULTS: Twenty-three (15.6%) PT cases occurred as TEP complication. The mean repair times (with standard deviation) of the PT were 16.2 ± 13 and 7.6 ± 7.0 min in the SG and CG, respectively, indicating a significant difference (P = 0.043). The repair time of the PT using Hem-o-lok (Teleflex, Wayne, PA, USA) stapling was shorter than that using endoscopic suturing, which was significantly different despite the length of the PT. CONCLUSION: Hem-o-lok stapling is feasible in case of PT during TEP.

Novel technique with the IRIS U kit to prevent urethral injury in patients undergoing transanal total mesorectal excision.

BACKGROUND: Low anterior resection of the rectum with total mesorectal excision (TME) has been the gold standard for the surgical treatment of rectal cancer as it has the lowest recurrence rates. The key issue while performing transanal TME (TaTME) is avoiding iatrogenic urethral injury. We introduce our surgical technique for TaTME. SURGICAL TECHNIQUE: Intraurethral indocyanine green injection using the IRIS U kit with subsequent visualization under NIR was safely utilized during the TaTME. We were able to easily detect and visualize the IRIS urethral kit. The prostatic segment of the urethra can be identified in real-time using the infrared illumination system urethral kit (IRIS U kit). BENEFITS: The prostatic segment of the urethra was easily and quickly identified by the green fluorescence during TaTME. CONCLUSION: Our TaTME technique is an easy and feasible approach that provides real-time urethral images.

Laparoscopic Total Devascularization of the Upper Stomach and Splenectomy (Hassab's Procedure) Under Indocyanine Green Fluorescence Imaging: Initial Experience.

The use of surgical treatment for refractory isolated gastric varices has decreased owing to the development of endoscopic and radiologic procedures, although surgeries are sometimes required as the final method. A 75-year-old Japanese woman was diagnosed with solitary gastric varices. Initially, intraoperative splenic artery embolization was performed using the balloon transcatheter technique under general anesthesia. Laparoscopic splenectomy was performed safely owing to preoperative splenic artery embolization. Intraoperative indocyanine green (ICG) fluorescence angiography was performed following the injection of 5 mL of ICG; the remnant stomach was observed using laparoscopic equipment with an ICG imaging system, and blood flow from the remnant gastric artery was confirmed. The blood did not pool or wash out immediately, which confirmed successful devascularization of the stomach. The total operative time was 269 minutes, and the intraoperative blood loss was 500 mL. The patient's postoperative course was good, and at 21 days after the last operation, she was discharged from our hospital in remission. Real-time fluorescence angiography with ICG is a reliable and objective technique of assessing blood flow of the stomach. Accurate, extensive devascularization in the lower esophagus and upper stomach was performed using Hassab's procedure in combination with ICG imaging.

Surgical strategy for suspected early gallbladder carcinoma including incidental gallbladder carcinoma diagnosed during or after cholecystectomy.

PURPOSE: This paper presents an overview of the surgical strategy for patients with suspected gallbladder carcinoma (GBC), including incidental GBC cases, preoperatively or intraoperatively, as well as their outcomes. METHODS: Between April 2009 and December 2017, 529 patients underwent cholecystectomy for gallbladder disease at our hospital. Both intraoperative and postoperative histological examinations of the excised gallbladder facilitated the diagnosis of GBC. Surgery-related variables and surgical approaches were evaluated according to the extent of tumor invasion. RESULTS: Of 529 patients, eight were diagnosed with GBC during/after cholecystectomy, including four women and four men. Mean age was 75.4 (range, 59-89) years. Five patients had gallbladder stones and three had cholecystitis. Three patients with stages T1b and T2 underwent additional liver bed wedge resections with or without prophylactic common bile duct excision. Five of the eight patients are still alive and two of the remaining three died from other diseases; one patient with pT3 died of recurrent GBC (peritonitis carcinomatosa). CONCLUSION: Because of the ability to obtain full-thickness frozen biopsies during laparoscopic cholecystectomy, we could diagnose GBC intraoperatively, allowing for rapid diagnosis and tumor resection. We recommend developing a surgical treatment strategy for suspected early GBC in advance of cholecystectomy.

Surgical technique of laparoscopic hybrid approach for recurrent inguinal hernia: Report a case.

INTRODUCTION: Currently, laparoscopic surgery (LS) is a widely accepted surgical treatment for inguinal hernias, and it has major advantages, especially for recurrent cases. PRESENTATION OF CASE: We diagnosed the recurrent inguinal hernia after wound infection and performed the laparosocopic approach. We would like to introduce our method. We distinguished between the presence and absence of bilateral inguinal hernia with an intra-abdominal scope using the transabdominal preperitoneal inguinal hernia repair (TAPP) technique, which we call laparoscopic examination. Thus, we can distinguish between the types of inguinal hernias and whether they are bilateral or not. We dissected the Retzius space on the inside of an epigastric arteriovenous fistula as part of TEP part A, and dissection was performed without a balloon. We separated and dissected the Retzius space. We also performed lateral dissection of the preperitoneal space. We made an incision in the peritoneum at the inner groin ring (hernia sac). We isolated the cord structures (parietalization) using TAPP. We finally checked this operation from the abdominal space (TAPP filed) and determined whether the repair was satisfactorily completed or not. DISCUSSION: Our hybrid method is not special but the conventional laparoscopic approach adapted each merits both TAPP and TEP. CONCLUSION: Our method is effective for difficult recurrent inguinal hernias.

Laparoscopic Excisional Cholecystectomy with Full-Thickness Frozen Biopsy in Suspected Gallbladder Carcinoma.

Owing to the advantages of a laparoscopic approach, laparoscopic cholecystectomy (LC) is thought to be the treatment of choice in gallbladder disease, even in cases of suspected malignancy. However, it is difficult to differentiate between cholecystitis and gallbladder carcinoma (GBC). We performed radical hepatectomy in patients with pT2 GBC diagnosed by full-thickness frozen biopsy. A 75-year-old Japanese man presented to our hospital with discomfort in the right upper quadrant of the abdomen. This patient was diagnosed with suspected GBC and was scheduled to undergo LC and intraoperative histological examination. Following the procedure, we made a diagnosis of GBC with negative invasion of the cystic duct stump. We converted the laparoscopic procedure to an open surgery involving wedge liver resection with lymphadenectomy. The patient was discharged from our hospital in remission 14 days following the radical hepatectomy. Histological examination showed that the GBC had invaded the liver (T3a), but there was no lymph node metastasis (N0): stage IIIA. Between April 2009 and September 2018, 580 patients underwent cholecystectomy for gallbladder disease at our hospital. Among these, 8 (1.4%) were suspected to have GBC preoperatively and underwent laparoscopic excisional cholecystectomy. We performed elective surgery in the early stage in two patients and second-look surgery in two patients recently. We were able to perform what we termed a laparoscopic excisional cholecystectomy, involving LC with a full-thickness frozen biopsy, even in situations where intraoperative histological examination was not available. Altogether, laparoscopic excisional cholecystectomy is an effective surgical treatment for suspected early GBC.

Clinical outcomes of self-expandable metal stent (SEMS) placement as palliative treatment for malignant colorectal obstruction: A single-center study from Japan.

OBJECTIVES: We aimed to assess the efficacy of self-expanding metal stent (SEMS) implantation as palliative treatment for malignant colorectal obstruction. METHODS: We retrospectively reviewed the records of patients with malignant colorectal obstruction who underwent SEMS insertion as palliative treatment in our hospital between March 2013 and December 2016. We analyzed demographic, clinical, and operative characteristics. RESULTS: A total of 13 patients (8 males, 5 females; median age, 80.1 years) were reviewed. Tumor location included the left colon, rectum, and right colon in 38.5%, 38.5%, and 23% of the patients, respectively. Advanced and early colorectal cancer were noted in 7 (63.6%) and 4 (36.4%) cases, respectively. The mean ColoRectal Obstruction Scoring System score was 0.92 before stenting and 3.92 after stenting. Oral intake was resumed at a median of 2.1 days after SEMS placement. Median stent patency was 7.6 months, and 69.2% of patients maintained stent patency until death or the end of follow-up. Stent-related adverse effects included: re-occlusion (4 cases, 30.8%); stent migration (1 case, 7.7%), and pain with tenesmus (2 cases, 15.4%). In patients with re-occlusion (median follow-up interval, 1.3 months), stent patency was maintained for a median of 10.3 months (early failure, within 3 months; late failure, >11 months). CONCLUSION: SEMS placement as a palliative treatment is likely to fail within a year, leading to re-occlusion. It is very important to maintain vigilant monitoring using X-ray, CT, and colonoscopy after SEMS placement, with close cooperation between the endoscopist and surgeon. A logistic framework involving careful follow-up, even in the absence of symptoms, and a combined team involving endoscopists and surgeons should be established to support re-intervention and surgery. We recommend vigilant monitoring of patients who received SEMS placement for palliation of malignant colorectal obstruction.

Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.

Hot Water Extracts of the Royal Sun Mushroom, Agaricus brasiliensis (Higher Basidiomycetes), Inhibit Platelet Activation via the P2Y1 Receptor.

Hot water extracts of the medicinal mushroom Agaricus brasiliensis were investigated for their inhibition of platelet aggregation. The extracts significantly inhibited human platelet aggregation induced by adenosine 5'-diphosphate (ADP), but not by collagen or thrombin receptor-activating peptide. The extracts also had a significant inhibitory effect on shape change and intracellular calcium mobilization induced by ADP via inhibition of ADP binding to the P2Y1 receptor. In addition, oral administration of the extracts resulted in prolonged tail bleeding time in mice. The marked antiplatelet activity of the mushroom extracts involving the P2Y1 receptor suggests their potential therapeutic use against vascular disorders.

VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets.

Platelets were activated under the infection with H. pylori in human and mice. We investigated the role of VacA, an exotoxin released by H. pylori in this context. Acid-activated VacA, but not heated VacA, induced platelet CD62P expression. However, VacA reacted with none of the alleged VacA receptors present on platelet membranes. We therefore analyzed VacA associated proteins obtained through VacA affinity chromatography, using MALDI-TOF-MS. Multimerin1 was detected in two consecutive experiments, as the binding protein for VacA. Plasmon resonance confirmed their binding, and dot blot analysis revealed that the peptide sequence AA 321-340 of multimerin 1 is the binding site for VacA. In conclusion, we propose a new interaction between multimerin1 and VacA , which may give another insight into H. pylori-induced platelet activations under H. pylori infection.

Molecular cloning and characterization of the α-glucosidase II from Bombyx mori and Spodoptera frugiperda.

The α-glucosidase II (GII) is a heterodimer of α- and ß-subunits and important for N-glycosylation processing and quality control of nascent glycoproteins. Although high concentration of α-glucosidase inhibitors from mulberry leaves accumulate in silkworms (Bombyx mori) by feeding, silkworm does not show any toxic symptom against these inhibitors and N-glycosylation of recombinant proteins is not affected. We, therefore, hypothesized that silkworm GII is not sensitive to the α-glucosidase inhibitors from mulberry leaves. However, the genes for B. mori GII subunits have not yet been identified, and the protein has not been characterized. Therefore, we isolated the B. mori GII α- and ß-subunit genes and the GII α-subunit gene of Spodoptera frugiperda, which does not feed on mulberry leaves. We used a baculovirus expression system to produce the recombinant GII subunits and identified their enzyme characteristics. The recombinant GII α-subunits of B. mori and S. frugiperda hydrolyzed p-nitrophenyl α-d-glucopyranoside (pNP-αGlc) but were inactive toward N-glycan. Although the B. mori GII ß-subunit was not required for the hydrolysis of pNP-αGlc, a B. mori GII complex of the α- and ß-subunits was required for N-glycan cleavage. As hypothesized, the B. mori GII α-subunit protein was less sensitive to α-glucosidase inhibitors than was the S. frugiperda GII α-subunit protein. Our observations suggest that the low sensitivity of GII contributes to the ability of B. mori to evade the toxic effect of α-glucosidase inhibitors from mulberry leaves.

Platelet aggregometry in the presence of PGE(1) provides a reliable method for cilostazol monitoring.

INTRODUCTION: Cilostazol has been shown to be effective for prevention and treatment of cerebral infarction. However, there appears to be no widely accepted method appropriate for monitoring cilostazol. We attempted to establish an assay system for cilostazol monitoring, using platelet aggregation induced by arachidonic acid (AA) in the presence of PGE(1) which upregulates intracellular cyclic AMP. METHODS: Blood was drawn from stroke patients before and after cilostazol intake. AA-induced platelet aggregation after pretreatment with 0~30nM PGE(1) for 2minutes was measured by light transmittance aggregometry. RESULTS: AA-induced platelet aggregation was 73.1±2.2% in the absence of PGE(1), and pretreatment with 30nM PGE(1) had virtually no inhibitory effect on platelet aggregation prior to cilostazol intake. In contrast, after cilostazol intake, 30nM PGE(1) significantly inhibited platelet aggregation to 12.7±4.5% (p=7.8×10(-11)) , while in the absence of PGE(1) platelet aggregation remained similar to that of prior-to-cilostazol value (70.6±3.5%). The plasma concentration of cilostazol ranged from 0.55 to 3.51µM. In the presence of 30nM PGE(1), all the patients with cilostazol concentrations exceeding 1µM had their platelet aggregation inhibited almost completely. ROC analysis suggests that AA-induced platelet aggregation in the presence of 30nM PGE(1) had the excellent sensitivity (90.5%) and specificity (88.4%) for monitoring cilostazol. CONCLUSIONS: AA-induced platelet aggregation in the presence of 30nM PGE(1) could give good estimate on plasma concentrations of cilostazol. It is suggested that this system is a good tool for monitoring cilostazol.