Discovery of Transcription Factors Involved in the Maintenance of Resident Vascular Endothelial Stem Cell Properties.

A resident vascular endothelial stem cell (VESC) population expressing CD157 has been identified recently in mice. Herein, we identified transcription factors (TFs) regulating CD157 expression in endothelial cells (ECs) that were associated with drug resistance, angiogenesis, and EC proliferation. In the first screening, we detected 20 candidate TFs through the CD157 promoter and gene expression analyses. We found that 10 of the 20 TFs induced CD157 expression in ECs. We previously reported that 70% of CD157 VESCs were side population (SP) ECs that abundantly expressed ATP-binding cassette (ABC) transporters. Here, we found that the 10 TFs increased the expression of several ABC transporters in ECs and increased the proportion of SP ECs. Of these 10 TFs, we found that six (Atf3, Bhlhe40, Egr1, Egr2, Elf3, and Klf4) were involved in the manifestation of the SP phenotype. Furthermore, the six TFs enhanced tube formation and proliferation in ECs. Single-cell RNA sequence data in liver ECs suggested that Atf3 and Klf4 contributed to the production of CD157+ VESCs in the postnatal period. We concluded that Klf4 might be important for the development and maintenance of liver VESCs. Our work suggests that a TF network is involved in the differentiation hierarchy of VESCs.

Cancer apelin receptor suppresses vascular mimicry in malignant melanoma.

Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin-apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin-APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin-APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial-mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-ß/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.

Open abdominal management for perforative peritonitis with septic shock: a retrospective analysis on usefulness of a standardized treatment protocol.

BACKGROUND: Damage control surgery (DCS) with open abdominal management (OAM) has been increasingly expanded to include critically ill non-trauma patients. However, there is limited data regarding the usefulness of this protocol for the treatment of severe perforative peritonitis (PP), especially with septic shock (SS). Here, we retrospectively evaluated the usefulness of our OAM protocol for PP with SS. METHODS: We retrospectively reviewed patients with from June 2015 to September 2018. The proposed protocol was composed of the following steps: (1) rapid control of contamination; (2) temporary abdominal closure; (3) repeated washout of the abdominal cavity; and (4) delayed definitive surgery. For temporary abdominal closure, a negative pressure wound therapy device was used. The end points were the morbidity and 30-day mortality rates. Logistic backward regression was performed to identify factors associated with complications. RESULTS: The mortality rate was 4% (1/25) and the overall morbidity rate of surviving patients was 58.3% (14/24). The mean duration of the first DCS was 67.36 ± 22.83 min. The median durations of ventilation and intensive care unit stay were 5 and 7 days, respectively. Although not significant, morbidity might be associated with age, diabetes mellitus, initial operative time, and OAM duration. CONCLUSIONS: A standardized protocol for OAM may improve the outcomes of patients with SS due to PP. This damage control approach can be applied for the treatment of severe abdominal sepsis.

Perioperative Factors Associated With Respiratory Complications Following Open Abdomen Management.

BACKGROUND: Postoperative respiratory complications are often severe and associated with a high risk of mortality in patients who undergo open abdomen (OA) management following emergency damage-control surgery. The causes of postoperative respiratory complications remain unknown. Therefore, we evaluated postoperative factors associated with respiratory complications in nontrauma patients who had undergone OA management using propensity score matching, with a focus on OA-related risk factors. METHODS: This retrospective analysis included subjects who underwent OA management during a 4-y study period. Age, body mass index, and smoking history were selected as covariates. After propensity score matching, we compared postoperative factors (ie, first operative time, duration of OA, initial 3-d fluid balance, length of ICU stay, and in-hospital mortality) in 2 groups of subjects: those who had post-OA respiratory complications (PORCs) and those who did not. RESULTS: 60 subjects (33 men and 27 women) were identified; 38.3% of these subjects had PORCs. After propensity score matching, 18 subjects were matched. The 3-d fluid balance was significantly higher in subjects with PORCs than in those without PORCs (3,513 mL vs 1,087 mL; P = .03). CONCLUSIONS: To our knowledge, this is the first study to examine factors associated with respiratory complications following OA in nontrauma subjects. After adjusting for known co-factors associated with postoperative respiratory complications, the 3-d fluid balance was identified as a significant risk factor for PORCs in subjects who had undergone OA. Clinicians should pay attention to the incidence of PORCs in OA subjects with a positive fluid balance after emergency abdominal surgery.

Novel laparoscopic methods for inguinal hernia post pelvic fracture: A case report.

INTRODUCTION: Pelvic fractures can occur in minor injuries, such as falls, in the elderly. Extensive adhesion of preperitoneal space is common after pelvic fracture surgery; hence, surgical interventions for inguinal hernia may be challenging. We treated a case of inguinal hernia after pelvic fracture surgery, using novel laparoscopic methods: iliopubic tract repair (IPTR) and modified intraperitoneal onlay mesh (mIPOM) approach. PRESENTATION OF CASE: This is the case of an elderly male with pelvic fracture. Open reduction and internal fixation were performed. Eighteen months after the procedure, a right inguinal bulge appeared, swelling increased, and he opted for surgery. We chose laparoscopic surgery to determine the status of the hernia and anatomy around the pelvis. He was diagnosed with an indirect inguinal hernia, and the inner inguinal ring was widely open. We chose the mIPOM approach and IPTR. He was discharged on day 3 post-operation. He developed a seroma after surgery, which disappeared after a month. Six months post-operation, no recurrence or neurologic pain observed. DISCUSSION: The transabdominal preperitoneal approach (TAPP) was initiated at first; however, the adhesion inside the inferior epigastric vessels was very strong, challenging to break into the preperitoneal space. We switched to the mIPOM method because the peritoneum was fragile and difficult to suture. Additionally, the internal ring was widely opened; hence, we proceeded with IPTR on confirmation that no tension on the abdominal wall was applied. CONCLUSIONS: Laparoscopic surgery is useful in flexibility of surgical options, such as TAPP, IPTR, IPOM, in addition to hybrid conversion.

Gallstone ileus: a review.

Background Gallstone ileus is an important complication of cholecystolithiasis. In general, surgery is the treatment of choice for such cases, but clinicians face difficulty in the selection of an appropriate approach. Closure of a cholecystoenteric fistula can be achieved through one-stage or two-stage operation. Two-stage operation has a lower mortality rate than a one-stage procedure, but persistence of the cholecystoenteric fistula is associated with the risk of carcinogenesis and recurrence of gallstone ileus. Objective This study reviews the different surgical approaches according to the impaction site of the gallstone, using data of previous studies by our group and clinical reports in the literature. Conclusions First, for cases involving impaction at the duodenum, the cholecystoenteric fistula can be repaired in the same surgical field, and one-stage operation obtains favourable outcome; hence, one-stage operation is considered as treatment of choice. Second, for cases involving impaction at the small intestine, natural closure of the cholecystoenteric fistula or low mortality is expected; hence, two-stage operation may be performed, possibly using minimally invasive laparoscopy. Third, for cases involving impaction at the colon, natural closure of the cholecystocolonic fistula is unlikely, and patients have a high risk of reflux cholangitis due to faecal fluid; hence, one-stage operation is considered as treatment of choice.

Predictive Factors for a Long Postoperative Stay after Emergency Laparoscopic Cholecystectomy Using the 2013 Tokyo Guidelines: A Retrospective Study.

Laparoscopic cholecystectomy (LC) is widely used for treating early acute cholecystitis (AC) and substantially reduces hospital costs. This study aimed to identify and evaluate risk factors associated with long postoperative hospital stays (PHSs) in patients undergoing emergency LC for AC according to the 2013 Tokyo Guidelines (TG13). Clinical data of patients who underwent emergency LC for AC between 2011 and 2017 were retrospectively collected. Patients were divided into early discharge (ED, discharge in three days or less postoperatively) and late discharge (LD, discharge in more than three days postoperatively) groups based on clinical progression and PHS after LC. Preoperative characteristics and perioperative outcomes were analysed as potential risk factors for LD. Among 149 patients, 104 (69.8%) were discharged within 3 days postoperatively, whereas 45 (30.2%) had long PHSs. Main causes of LD were fever and inflammation. Univariate analysis of preoperative risk factors revealed significant differences in age, white blood cell count, C-reactive protein, total bilirubin (T-bil), and alkaline phosphatase (ALP) levels; anticoagulation therapy; and TG13 severity grade. Multivariate analysis revealed that TG13 severity grade II, age >65 years, and elevated T-bil and ALP levels are independent factors for long PHS. Older age, worse biliary function, and increased TG13 severity grade might predict prolonged PHSs in AC patients undergoing emergency LC.

Simultaneous transabdominal preperitoneal hernia repair and laparoscopic cholecystectomy: A report of 17 cases.

INTRODUCTION: Inguinal hernia repair and cholecystectomy are frequently performed in the field of gastrointestinal surgery. However, reports describing surgical procedures that involve simultaneous transabdominal preperitoneal hernia repair (TAPP) and laparoscopic cholecystectomy (LC), as well as the safety and usefulness of this combination, are limited. Herein, we report a surgical procedure involving simultaneous TAPP and LC (TAPP + LC) and present the outcomes of patients who have undergone this combined surgical procedure, with a particular focus on its safety and usefulness. METHODS: We simultaneously performed TAPP + LC in 17 patients (mean age, 66.5 ± 8.1 years) with concomitant inguinal hernia and gallbladder stones. We assessed surgical outcomes. RESULTS: The mean operative time was 157 ± 39 min, and mean postoperative hospital stay was 3.2 ± 0.6 days. The median cost was $7673 for TAPP + LC. The mean postoperative length of hospital stay was 1.1 ± 0.6 day for TAPP alone and 3.4 ± 1.4 days for LC alone. The median costs of TAPP alone and LC alone were $4932 and $5453, respectively. Regarding intraoperative complications, the inferior epigastric vessels were damaged in two patients, and seroma was detected as a postoperative complication in one; these complications were spontaneously resolved. No mesh- or infection-related complications were noted. CONCLUSION: Simultaneous TAPP + LC is safe and can be regarded as a standard surgical procedure for patients with concomitant inguinal hernia and gallbladder stones. The TAPP + LC combination appears to help prevent the need for two hospitalizations and, thereby, reduces hospital stay and economic burden.

Laparoscopic two-stage procedure for gallstone ileus.

Gallstone is a rare cause of bowel obstruction and is associated with high rates of morbidity and mortality. Here, we report a case of gallstone ileus treated by laparoscopic two-stage procedure. A 65-year-old man, without a history of any surgery, presented to our hospital with abdominal pain and vomiting. His abdominal computed tomography revealed gallstone ileus with cholecystoduodenal fistula. Then, enterolithotomy was performed as an emergency laparoscopic surgery. After 1 year of the surgery, a second laparoscopic procedure was performed for cholecystectomy and fistula closure. The patient was discharged on the 7th postoperative day. Laparoscopic two-stage procedure is a safe and an efficient approach for the management of gallstone ileus. This definitive treatment is minimally invasive, thereby suitable for treating elderly patients.

Nonoperative management of blunt liver injury in hemodynamically stable versus unstable patients: a retrospective study.

PURPOSE: The success rate of nonoperative management (NOM) of traumatic liver injury is approximately 90%. Although NOM has become the standard treatment when patients' vital signs are stable, open surgical hemostasis is often selected when these signs are unstable. At our hospital, we extensively use NOM along with transcatheter arterial embolization (TAE) to treat patients with severe abdominal trauma, as per our original protocol. We also apply NOM for severe liver injury with unstable hemodynamics. This retrospective study aimed to investigate the efficacy of NOM for blunt liver injury in hemodynamically stable and unstable patients. METHODS: We retrospectively examined 23 patients with severe liver injuries who underwent NOM after visiting our emergency outpatient department between 2007 and 2017. Patients were assigned to either the stable group with stable hemodynamics or the unstable group with unstable hemodynamics. RESULTS: The stable group comprised 13 patients, and the unstable group comprised 10 patients. All patients underwent TAE. While all patients in the stable group were discharged alive, one patient in the unstable group died during the hospital stay. The response rate to NOM was 90%, and no patient switched from NOM to open surgery. A higher rate of complications with a significantly longer average stay in the intensive care unit was observed in the unstable group. CONCLUSIONS: Even in the unstable group, NOM with TAE performed under careful general management facilitated avoidance of open surgery and provided high survival rates.

Sigmoid gallstone ileus: A case report and literature review in Japan.

INTRODUCTION: Gallstone as a cause of bowel obstruction is rare, and its occurrence in the colon is very infrequent. Here, we report the case of sigmoid gallstone ileus treated with one-stage operation. CASE PRESENTATION: A 65-year-old man visited our hospital because of abdominal pain and nausea. On the basis of the results of computed tomography, the patient was diagnosed with sigmoid gallstone ileus through cholecystocolonic fistula, and an emergency laparotomy was performed. Enterolithotomy, cholecystectomy, and fistula closure were performed in one-stage operation. Postoperatively, the patient developed biliary leakage, which rapidly recovered with conservative therapy. DISCUSSION AND CONCLUSION: The surgical treatment of gallstone ileus remains controversial. For postoperative infection control, one-stage operation can be considered for patients with gallstone ileus associated with cholecystocolonic fistula.

A rare case of secondary small bowel volvulus laparoscopically repositioned: literature review and classification.

BACKGROUND: Secondary small bowel volvulus is a rare condition caused by adhesions after laparotomy or tumors. There are no clear guidelines for indication of laparoscopic surgery. CASE PRESENTATION: A 69-year-old male visited our hospital complaining of epigastric pain. He had a history of hypopharyngeal carcinoma treated via pharyngolaryngoesophagectomy with restoration of esophageal continuity by harvesting a free jejunal autograft 6 years ago. Enhanced computed tomography revealed the whirl sign. An emergency laparoscopic operation was performed following a diagnosis of small bowel volvulus. This revealed rotation of the whole small bowel, involving the superior mesenteric artery as the center, and originating at the adhesion of the proximal and distal small bowel. Laparoscopic manipulation of volvulus and lysis of the adhesion were performed. The patient's postoperative course was uneventful, and he was discharged on hospital day 5. CONCLUSIONS: Laparoscopic surgery may be useful for treating small bowel volvulus; however, the patient's treatment indications should be judged carefully.

Two patients with spontaneous transomental hernia treated with laparoscopic surgery: a review.

Here, we report two patients with transomental hernia who were successfully treated with laparoscopic surgery. The first patient was a 58-year-old female who presented to our hospital with abdominal pain and vomiting; she had no history of abdominal surgery. Enhanced computed tomography revealed strangulation ileus due to an internal hernia. The second patient was a 36-year-old male who presented to our hospital with abdominal pain and no history of abdominal surgery. Enhanced computed tomography indicated transomental hernia. Emergency laparoscopic surgery in both patients revealed incarcerated bowel loops through defects in the greater omentum. The bowel segments were laparoscopically released, and the patients were uneventfully discharged on postoperative Days 4 and 8. Laparoscopic surgery is useful for the diagnosis and treatment of small bowel obstruction due to transomental hernia through the greater omentum.

Arteriovenous malformation in the sigmoid colon of a patient with Cowden disease treated with laparoscopy: a case report.

BACKGROUND: Cowden disease is a genetic disorder associated with a mutation of the PTEN gene and is known to be easily complicated by generalized vascular malformations and malignant tumors. However, only a few reports have investigated the relationship between Cowden disease and vascular malformations. We present a case of Cowden disease along with a review of the literature. CASE PRESENTATION: The patient was a 48-year-old man who visited our hospital complaining of fresh blood in his stools and shortness of breath. Hematological tests showed the patient had severe anemia. On physical examination, white papules-several millimeters in size-were observed between the patient's eyebrows. White papules were also observed on the left corner of his mouth and buccal mucosa. An upper gastrointestinal endoscopy showed densely-packed, white, flat protrusions in the esophagus. While lower gastrointestinal endoscopy revealed a mass accompanied by arterial pulsation in the sigmoid colon. A diagnosis of Cowden disease was confirmed and a laparoscopic sigmoidectomy was performed to address the arteriovenous malformations in the sigmoid colon. Post-surgery, the patient had an unremarkable recovery and was discharged 7 days later. CONCLUSIONS: We present a very rare case of Cowden disease with arteriovenous malformations occurring in the colon. Surgical resection is believed to be the first choice for treating congenital arteriovenous malformations of the intestines. However, the arteriovenous malformations in the colon in our patient were treated under laparoscopic guidance, making ours the first report describing laparoscopic treatment of colonic arteriovenous malformations occurring in the inferior mesenteric artery. Thus we demonstrate that laparoscopic treatment of arteriovenous malformations in the intestines is a minimally invasive and can be successfully applied in such cases.

Paracecal hernia with intestinal ischemia treated with laparoscopic assisted surgery.

INTRODUCTION: Paracecal hernia is rare, and strangulation with ischemia has been infrequently observed in the limited number of published reports on paracecal hernias. PRESENTATION OF CASE: We describe a case of an incarcerated paracecal hernia with resultant ischemic bowel that was successfully treated with laparoscopic-assisted surgery. A 54-year-old man who had not undergone any surgery previously presented to our hospital with abdominal pain and vomiting. An abdominal computed tomographic scan showed evidence of an intestinal obstruction at a paracecal site. An emergency laparoscopic surgery demonstrated incarceration of a loop of the small bowel in the paracecal fossa. We removed the incarcerated small bowel from the paracecal fossa, noted that the tissue was necrotic, and resected this segment of bowel through a mini-laparotomy incision. The patient was discharged on the 13th postoperative day. DISCUSSION AND CONCLUSION: This case is unique in that the patient presented with small bowel strangulation, causing intestinal ischemia. Laparoscopic surgery is useful in the diagnosis of internal hernias and is also useful for the treatment of small bowel obstruction due to paracecal hernias complicated by ischemic bowel.

Intraluminal Apple as a Rare Cause of Small Bowel Obstruction.

Small bowel obstruction due to ingested foreign bodies is rare in adults. A 48-year-old male visited our hospital with abdominal pain and vomiting. Computed tomography revealed intestinal obstruction by a 3 × 4 cm apple-shaped foreign body. Emergency surgery was performed to clear the obstruction which, upon inspection, was caused by a sexual toy made of rubber. Flexible rubber products that are ingested should be carefully followed after they pass thorough the pylorus. For obstructions related to sexual behavior, the patient's sense of shame often delays the process of seeking medical attention, thereby making preoperative diagnosis difficult.