Prediction of extensive necrotic change in acute gangrenous cholecystitis.

PURPOSE: Gangrenous cholecystitis (GC) is a severe type of acute cholecystitis that implies higher mortality and morbidity rates than uncomplicated cholecystitis. The characteristics of GC are various for each case. However, preoperative predictors of GC with extensive necrotic change have not been investigated well. METHODS: A total of 239 patients who were pathologically diagnosed with GC underwent laparoscopic cholecystectomy at our hospital between January 2013 and December 2021. Of these, 135 patients were included in this study and were subdivided into the extensive necrosis group (patients with necrotic change extending to the neck of the gallbladder, n = 18) and the control group (patients with necrotic change limited to the fundus or body, not extending to the neck, n = 117) according to each operation video. Patient characteristics and perioperative factors predicting extensive necrotic change were investigated. RESULTS: Pericholecystic fat stranding (83.3 vs. 53.8%, p = 0.018) and absence of wall enhancement on preoperative CT images (50.0 vs. 24.7%, p = 0.026) were significantly associated with extensive necrosis. Seven of 18 patients in the extensive necrosis group showed necrotic changes beyond the infundibulum. The absence of wall enhancement on preoperative CT images (71.4 vs. 28.8%, p = 0.018) was significantly associated with necrotic changes beyond the infundibulum. CONCLUSIONS: Pericholecystic fat stranding and absence of wall enhancement on preoperative enhanced CT are predictors of extensive necrotic change in patients with GC. In addition, the absence of wall enhancement also predicts the presence of necrotic changes beyond the infundibulum.

Does preoperative MRCP imaging predict risk for conversion to subtotal cholecystectomy in patients with acute cholecystitis?

BACKGROUND: Subtotal cholecystectomy (SC) is a useful procedure for avoiding bile duct injury in patients with difficult gallbladder. However, risk factors for conversion to SC, especially preoperative magnetic resonance cholangiopancreatography (MRCP) findings that predict conversion to SC, have not been investigated in detail. METHODS: A total of 290 patients with acute cholecystitis who underwent laparoscopic cholecystectomy at our hospital between November 2011 and March 2020 were included. Patient characteristics and perioperative outcomes were reviewed, and preoperative clinical factors predicting conversion to SC were investigated. RESULTS: Forty-three patients underwent SC, whereas the remaining 247 patients underwent total cholecystectomy. An American Society of Anesthesiologists (ASA) score of 3 or greater (p = 0.011), surgery on or after 9 days from symptom onset (p < 0.001), obscuration of the gallbladder wall around the neck on MRCP images (p = 0.010) and disruption of the common hepatic duct on MRCP images (p < 0.001) were significantly associated with conversion to SC. Logistic regression analyses revealed that an ASA score of 3 or greater (odds ratio = 2.667, p = 0.020), surgery on or after 9 days from symptom onset (odds ratio = 4.229, p < 0.001) and disruption of the common hepatic duct on MRCP images (odds ratio = 4.478, p = 0.002) were independent predictors for conversion to SC. CONCLUSIONS: Early surgery yielded a lower risk for conversion to SC. Disruption of the common hepatic duct on preoperative MRCP images is associated with a risk for conversion to SC.

Risk factors for postoperative bile leak in patients who underwent subtotal cholecystectomy.

BACKGROUND: Subtotal cholecystectomy (SC) is a procedure for avoiding the risk of bile duct injury, especially in patients with difficult gallbladders. However, recent meta-analyses have demonstrated that SC is associated with a relatively high incidence of postoperative bile leak. To our knowledge, there have been no reports that have investigated risk factors for postoperative bile leak. METHODS: A total of 76 patients underwent reconstituting SC at our hospital between January 2005 and July 2019. Patient characteristics and perioperative outcomes were reviewed, and risk factors for postoperative bile leak were investigated. In addition, in patients with acute cholecystitis (AC) (n = 60), subgroup analyses were performed. RESULTS: Bile leak developed in 11 patients with AC (18.3%), while no patients with chronic cholecystitis developed bile leak (p = 0.064). Patients with AC who underwent surgery 10 days or later from onset developed postoperative bile leak significantly more frequently than those who underwent surgery within 10 days (38.0 vs 7.6%, p = 0.003). Patients with AC who underwent gallbladder stump closure with suturing developed postoperative bile leak significantly more frequently than those who underwent ligation (37.5 vs 11.3%, p = 0.020). In the patients with AC, surgery after 10 days from onset (p = 0.022, odds ratio = 5.85) was found by logistic regression analysis to be an independent risk factor for developing postoperative bile leak. CONCLUSION: Early surgery yielded a lower incidence of postoperative bile leak in patients who underwent SC. Surgery during the subacute phase was considered to imply a higher risk for developing bile leak than surgery during the acute and chronic phases.

Calculus left in remnant gallbladder cause long-term complications in patients undergoing subtotal cholecystectomy.

BACKGROUND: There have been only a few reports that describe the long-term outcomes of Subtotal cholecystectomy (SC). METHODS: A total of 59 patients underwent "reconstituting" SC at our hospital between January 2005 and July 2017. In the 59 patients, risk factors for long-term complications were analyzed. In addition, in the patients with acute cholecystitis (AC), perioperative and long-term clinical factors were compared for patients who underwent SC (n = 48) and those who underwent total cholecystectomy (n = 378). RESULTS: In the 59 patients who underwent SC, long-term complication developed in 14 (23.7%), including residual calculus in the common bile duct (n = 12), remnant cholecystitis (n = 1), and persistent severe inflammatory response (n = 1). Postoperative magnetic resonance image was performed in 35/59 patients (59.3%) who underwent SC. In these 35 patients, the size of the remnant gallbladder calculated by magnetic resonance cholangiopancreatography was significantly associated with the occurrence of long-term complications (p = 0.009). In the patients with AC, regarding long-term complications, the incidence of residual calculus in the common bile duct (16.6 versus 0.7%) was significantly higher in the SC group. CONCLUSIONS: SC was associated with a relatively high incidence of long-term complications associated with remnant calculus.

Teneligliptin Prevents Cardiomyocyte Hypertrophy, Fibrosis, and Development of Hypertensive Heart Failure in Dahl Salt-Sensitive Rats.

BACKGROUND: We investigated the effects of the dipeptidyl peptidase 4 inhibitor teneligliptin on cardiac function and hemodynamics during heart failure in hypertensive model rats. METHODS AND RESULTS: Fifty-five male Dahl salt-sensitive rats were divided into 4 groups: control group (0.3% NaCl chow; n = 13), hypertension (HT) group (8% NaCl chow; n = 20), HT-early TNL group (8% NaCl chow and teneligliptin from 6 weeks; n = 10), and HT-late TNL group (8% NaCl chow and teneligliptin from 10 weeks; n = 12). Hemodynamic measurement and tissue analyses were performed at 18 weeks. In all of the HT groups, systolic blood pressures were similarly elevated (P = .66) and heart weights similarly increased (P = .36) with and without TNL administration. LV end-diastolic dimension was significantly enlarged only in the HT-early TNL group compared with the control group (P = .025). Histologic analysis showed less fibrosis (P = .008) and cardiomyocyte widths (P = .009) in the HT-early TNL group compared with the HT group. On hemodynamic analysis, only the HT group showed significant LV end-diastolic pressure elevation (P = .049) and lung congestion (P < .001) compared with the control group. CONCLUSIONS: These results suggest that teneligliptin prevents concentric LV hypertrophy, fibrosis, and development of congestive heart failure in Dahl salt-sensitive rats. Teneligliptin may inhibit pressure-overload hypertrophic adaption and result in LV eccentric hypertrophy with reduced LV ejection fraction.

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC-/-) mice subjected to periaortic application of CaCl2 developed AAAs. Six weeks after CaCl2 treatment, internal and external aortic diameters were significantly increased in MURC-/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC-/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC-/- AAAs compared with WT AAAs at 5 days after CaCl2 treatment. At 6 weeks after CaCl2 treatment, MURC-/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC-/-, apolipoprotein E-/- (ApoE-/-), and MURC/Cavin-4 and ApoE double-knockout (MURC-/-ApoE-/-) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE-/- and MURC-/-ApoE-/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC-/-ApoE-/- mice compared with Ang II-infused ApoE-/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression.

Multimodality intracoronary imaging in spontaneous coronary artery dissection: impacts of intravascular ultrasound, optical coherence tomography, and coronary angioscopy.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and its etiology and pathogenesis have not been well understood. Intracoronary imaging modalities with intravascular ultrasound and optical coherence tomography would enable a precise diagnosis in this entity. Coronary angioscopy is also a unique tool for allowing direct visualization of the luminal surface of a vessel. We described an interesting case of SCAD documented with multimodality intracoronary imaging showing the presence of superficial lipid plaque nearby the coronary dissection entry point, which might have been associated with fragility of the arterial wall and the subsequent development of SCAD.

Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice.

PURPOSE: Experimental autoimmune myocarditis (EAM) is a mouse model of inflammatory cardiomyopathy, and the involvement of T helper (Th) 1 and Th17 cytokines has been demonstrated. Accumulated evidence has shown that statins have anti-inflammatory and immunomodulatory effects; however, the mechanism has not been fully elucidated. This study was designed to test the hypothesis that pitavastatin affects T cell-mediated autoimmunity through inhibiting Th1 and Th17 responses and reduces the severity of EAM in mice. METHODS: The EAM model was established in BALB/c mice by immunization with murine α-myosin heavy chain. Mice were fed pitavastatin (5 mg/kg) or vehicle once daily for 3 weeks from day 0 to day 21 after immunization. RESULTS: Pitavastatin reduced the pathophysiological severity of the myocarditis. Pitavastatin treatment inhibited the phosphorylation of signal transducer and activator of transcription (STAT)3 and STAT4, which have key roles in the Th1 and Th17 lineage commitment, respectively, in the heart, and suppressed production of Th1 cytokine interferon-γ and Th17 cytokine interleukin-17 from autoreactive CD4(+) T cells. In in vitro T-cell differentiation experiments, pitavastatin-treated T cells failed to differentiate into Th1 and Th17 cells through inhibiting the transcription of T-box expressed in T-cells (T-bet) and RAR-related orphan receptor γt (RORγT) which have critical roles in the development of Th1 and Th17 cells, respectively, and this failure was rescued by adding mevalonate. CONCLUSIONS: Pitavastatin inhibits Th1 and Th17 responses and ameliorates EAM. These results suggest that statins may be a promising novel therapeutic strategy for the clinical treatment of myocarditis and inflammatory cardiomyopathy.

Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction.

BACKGROUND: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is not normally expressed in the adult heart but transiently reappears under various pathologic conditions to play important roles in tissue remodeling. It is unclear whether serum TN-C levels add prognostic information independent from traditional prognostic markers. METHODS AND RESULTS: We assessed 239 patients with first ST-segment elevation myocardial infarction who underwent successful percutaneous coronary intervention. We measured serum TN-C and plasma B-type natriuretic peptide (BNP) levels on day 5 after admission and compared long-term clinical outcome. During the follow-up period (24.3 ± 13 months), 54 patients experienced primary composite cardiac events (cardiac death or hospitalization for worsening heart failure). Multivariable Cox proportional hazards analysis indicated that serum TN-C (hazard ratio 2.92, 95% confidence interval [CI] 1.55-5.67; P < .001) and plasma BNP levels (hazard ratio 1.84, 95% CI 1.17-2.97; P = .008) were significant independent predictors for cardiac events after adjustment for multiple confounders. The combination of TN-C and BNP resulted in an increase of the c-statistic from 0.821 to 0.877 (P < .001) and an integrated discrimination improvement gain of 14.0% (P < .001). CONCLUSIONS: Serum TN-C level on day 5 after admission is potentially useful for early risk stratification after AMI beyond established prognostic markers.

Laparoscopic transabdominal preperitoneal inguinal hernia repair using needlescopic instruments: a 15-year, single-center experience in 317 patients.

BACKGROUND: Laparoscopic inguinal hernia repair is associated with a decrease in postoperative pain, shortened hospital stay, earlier return to normal activity, and decrease in chronic pain. Moreover, laparoscopic surgery performed with needlescopic instruments has more advantages than conventional laparoscopic surgery. However, there are few reports of large-scale laparoscopic transabdominal preperitoneal inguinal hernia repair using needlescopic instruments (nTAPP). This report reviews our experiences with 352 nTAPP in 317 patients during the 15-year period from April 1996 to April 2011. METHODS: We performed nTAPP as the method of choice in 88.5% of all patients presenting with inguinal hernia. To perform the nTAPP, 3-mm instruments were used. A 5-mm laparoscope was inserted from the umbilicus, and surgical instruments were inserted through 5- and 3-mm trocars. After reduction of the hernia sac and dissection of the preperitoneal space, we placed polyester mesh or polypropylene soft mesh with staple fixation. The peritoneum was closed with 3-0 silk interrupted sutures. RESULTS: The mean operative time was 102.9 min for unilateral hernias and 155.8 min for bilateral hernias. There was no conversion to open repair. Forty-three patients (13.6%) used postoperative analgesics, and the mean frequency of use was 0.5 times. Regarding intraoperative complications, we observed one bladder injury, but no bowel injuries or major vessel injuries. Postoperative complications occurred in 32 patients (10.1%). One patient with a retained lipoma required reoperation. There was no incidence of chronic pain or mesh infection. The operative time for experienced surgeons (≥ 20 repairs) was significantly shorter than that of inexperienced surgeons (< 20 repairs; P < 0.05). CONCLUSIONS: The nTAPP was a safe and useful technique for inguinal hernia repair. Large prospective, randomized controlled trials will be required to establish the benefit of nTAPP.

Presence of cystic duct stone is a risk for postoperative retained stones in patients with acute cholecystitis.

PURPOSE: Retained stones (RS) in the common bile duct (CBD) are one of the major problems after laparoscopic cholecystectomy and usually require endoscopic treatment. However, few reports have investigated risk factors for the development of RS in the CBD. METHODS: A total of 325 patients with acute cholecystitis underwent laparoscopic cholecystectomy at our hospital between January 2013 and Jury 2021. Patient characteristics, including radiographic factors and perioperative outcomes, were reviewed, and perioperative factors predicting RS in the CBD were investigated. RESULTS: RS in the CBD were developed in 34 patients. All 34 patients were treated endoscopically. ASA-PS class 3 or more (p = 0.029, odds ratio = 2.601), subtotal cholecystectomy performance (p = 0.004, odds ratio = 3.783) and the presence of cystic duct stones (p < 0.001, odds ratio = 11.759) were found by logistic regression analysis to be independent risk factors for developing RS in the CBD. Cystic duct stones were preoperatively detected in 60 patients. Of these, 21 cases were not detected on magnetic resonance cholangiopancreatography (MRCP) but on CT, while 15 cases were not detected on CT but on MRCP. CONCLUSIONS: The presence of cystic duct stones on preoperative CT or MRCP is a crucial risk factor for developing RS in the CBD. Both CT and MRCP are useful to avoid overlooking cystic duct stones.

Tenascin-C is expressed in abdominal aortic aneurysm tissue with an active degradation process.

Abdominal aortic aneurysm (AAA) is a common disease caused by segmental weakening of the aortic walls and progressive aortic dilation leading to the eventual rupture of the aorta. Currently no biomarkers have been established to indicate the disease status of AAA. Tenascin-C (TN-C) is a matricellular protein that is synthesized under pathological conditions. In the current study, we related TN-C expression to the clinical course and the histopathology of AAA to investigate whether the pattern of TN-C expression could indicate the status of AAA. We found that TN-C and matrix metalloproteinase (MMP)-9 were highly expressed in human AAA. In individual human AAA TN-C deposition associated with the tissue destruction, overlapped mainly with the smooth muscle actin-positive cells, and showed a pattern distinct from macrophages and MMP-9. In the mouse model of AAA high TN-C expression was associated with rapid expansion of the AAA diameter. Histological analysis revealed that TN-C was produced mainly by vascular smooth muscle cells and was deposited in the medial layer of the aorta during tissue inflammation and excessive destructive activities. Our findings suggest that TN-C may be a useful biomarker for indicating the pathological status of smooth muscle cells and interstitial cells in AAA.

Does early surgery imply a critical risk for patients with Grade III acute cholecystitis?

BACKGROUND: For patients with Grade III acute cholecystitis (AC), several factors have been proposed in the 2018 Tokyo guidelines as caution signs in performing early surgery. However, these factors have not been externally validated in detail. METHODS: This retrospective study examined 35 patients who had been diagnosed with Grade III AC and treated with laparoscopic cholecystectomy between January 2008 and July 2019. The patients were allocated into an early group (patients who underwent surgery within 7 days of admission, n = 28) and a delayed group (patients who underwent surgery at least 8 days after admission, n = 7). Comparisons were made between these groups. RESULTS: No patients died. Significantly more patients required a conversion to open surgery (0% vs 28.5%, P = .003) or conversion to subtotal cholecystectomy (25.0% vs 71.4%, P = .020) in the delayed group than in the early group, and the total length of postoperative stay was significantly longer in the delayed group (11.4 vs 27.2 days, P = .001). The presence of negative predictive factors or risk factors listed in the 2018 Tokyo guidelines was not associated with death or postoperative complications. CONCLUSIONS: Early surgery was considered appropriate and feasible for select patients who had Grade III AC and preoperative risk factors.

Generation of Transgenic Mice that Conditionally Overexpress Tenascin-C.

Tenascin-C (TNC) is an extracellular matrix glycoprotein that is expressed during embryogenesis. It is not expressed in normal adults, but is up-regulated under pathological conditions. Although TNC knockout mice do not show a distinct phenotype, analyses of disease models using TNC knockout mice combined with in vitro experiments revealed the diverse functions of TNC. Since high TNC levels often predict a poor prognosis in various clinical settings, we developed a transgenic mouse that overexpresses TNC through Cre recombinase-mediated activation. Genomic walking showed that the transgene was integrated into and truncated the Atp8a2 gene. While homozygous transgenic mice showed a severe neurological phenotype, heterozygous mice were viable, fertile, and did not exhibit any distinct abnormalities. Breeding hemizygous mice with Nkx2.5 promoter-Cre or α-myosin heavy chain promoter Cre mice induced the heart-specific overexpression of TNC in embryos and adults. TNC-overexpressing mouse hearts did not have distinct histological or functional abnormalities. However, the expression of proinflammatory cytokines/chemokines was significantly up-regulated and mortality rates during the acute stage after myocardial infarction were significantly higher than those of the controls. Our novel transgenic mouse may be applied to investigations on the role of TNC overexpression in vivo in various tissue/organ pathologies using different Cre donors.

A safe laparoscopic cholecystectomy depends upon the establishment of a critical view of safety.

Bile duct injuries (BDI) during a laparoscopic cholecystectomy (LC) occur more frequently than during an open cholecystectomy. Many expert surgeons learn to perform procedures safely based on their experience. Above all, the critical view of safety (CVS) introduced by Strasberg in 1995 is the standard practice to prevent BDI during an LC. The CVS is achieved by clearing all fat and fibrous tissue in Calot's triangle, after which the cystic structures can be clearly identified, occluded, and divided. Failure to successfully create this view may be an indication for conversion to an open cholecystectomy. The Japan Society for Endoscopic Surgery (JSES) introduced an accreditation examination in 2004. The critical view is an important factor used to judge a safe dissection. The annual ratios of successful applicants were 63% in 2004, 45% in 2005, 36% in 2006, 39% in 2007, and 44% in 2008. Biennial questionnaire surveys by JSES show that the laparoscopic BDI rates were 0.66% in 1990-2001, 0.79% in 2002, 0.77% in 2003, 0.66% in 2004, 0.77% in 2005, 0.65% in 2006, and 0.58% in 2007. Therefore, 2007 was the first year in which the rate was below 0.6%. A decreasing BDI rate is therefore expected because successful candidates will introduce technical improvements to colleagues in their hospitals and local regions.

Skill accreditation system for laparoscopic gastroenterologic surgeons in Japan.

The Japan Society for Endoscopic Surgery (JSES) has established an Endoscopic Surgical Skill Qualification System and started examination in 2004. Non-edited videotapes were assessed by two judges in a double-blinded fashion with strict criteria. Two kinds of criteria, namely common and procedure-specific, were prepared. The common criteria were designed to evaluate set-ups, autonomy of the operator, display of the surgical field, recognition of surgical anatomy, co-operation of the surgical team. The procedure-specific criteria were made to assess the operation in a step-by-step fashion. In total, out of 1.114 surgeons who were assessed by this qualification system over a period of four years, 537 (48.2%) have been accredited. The qualification rate in each surgical field has remained at the same level of 40 to 50% to date. Inter-rater agreement of two judges was low at 0.31 in the first year, but improved with revision of the criteria and consensus meetings. Surgeons assessed by this system as qualified experienced less frequent complications when compared to those who failed. This system has impacted on the improvement and standardization of laparoscopic surgery in Japan.

[Risk management for endoscopic surgery].

The number of medical accidents in endoscopic surgery has recently increased. Surgical complications caused by inadequate preparation or immature technique or those resulting in serious adverse outcomes may be referred to as medical accidents. The Nationwide Survey of Endoscopic Surgery showed that bile duct injury and uncontrollable bleeding were seen in 0.68% and in 0.58%, respectively, of cholecystectomy patients; interoperative and postoperative complications in 0.84% and in 3.8%, respectively, of gastric cancer surgery patients; and operative complications in 6.74% of bowel surgery patients. Some required open repair, and 49 patients died. The characteristic causes of complications in endoscopic surgery are a misunderstanding of anatomy, handling of organs outside the visual field, burn by electrocautery, and injuries caused by forceps. Bleeding that requires a laparotomy for hemostasis is also a complication. Furthermore, since the surgery is usually videorecorded, immature techniques resulting in complications are easily discovered. To decrease the frequency of accidents, education through textbooks and seminars, training using training boxes, simulators, or animals, proper selection of the surgeon depending on the difficulty of the procedure, a low threshold for conversion to laparotomy, and use of the best optical equipment and surgical instruments are important. To avoid malpractice lawsuits, informed consent obtained before surgery and proper communication after accidents are necessary.

Outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis performed at a single institution.

INTRODUCTION: Debate continues regarding the clinical outcomes of early laparoscopic cholecystectomy (ELC) versus delayed laparoscopic cholecystectomy (DLC) for acute cholecystitis (AC). The aim of this retrospective study was to compare clinical outcomes of ELC and DLC. METHODS: This study consisted of 465 patients who had undergone laparoscopic cholecystectomy for AC between January 2000 and February 2017. Patients were divided between an ELC group (patients who underwent laparoscopic cholecystectomy within 6 days of symptom onset, n = 288) and a DLC group (patients who underwent laparoscopic cholecystectomy at least 7 days from symptom onset, n = 177), and clinical outcomes were compared. RESULTS: Operation time (105 vs 124 min), length of postoperative hospital stay (4 vs 4 days), conversion rate (1.3% vs 10.7%), bile leak (0.3% vs 3.3%), residual calculus (2.4% vs 6.7%), and readmission (1.0% vs 6.7%) were significantly better in the ELC group. A history of upper abdominal surgery, grade II or grade III AC, preoperative percutaneous transhepatic gallbladder drainage, and time between symptom onset and surgery of more than 7 days were independent risk factors for conversion. CONCLUSIONS: ELC for AC yields more favorable clinical outcomes than DLC.

Is postponed laparoscopic cholecystectomy justified for acute cholecystitis appearing early after onset?

INTRODUCTION: Early laparoscopic cholecystectomy (ELC) is considered the standard treatment for acute cholecystitis for patients who can tolerate surgery. The ideal time for performing ELC is reported to be 72 h from onset. However, many patients undergo surgery on or after the fourth day from onset, even if they presented early after onset. A few reports have investigated the feasibility and disadvantages of this so-called "postponed laparoscopic cholecystectomy" (PLC). METHODS: This study consisted of 215 patients who had undergone laparoscopic cholecystectomy for acute cholecystitis within 6 days of onset between July 2006 and December 2017. Patients were divided into an ELC group (patients who underwent LC within 3 days of symptom onset, n = 172) and a PLC group (patients who underwent LC 4-6 days from symptom onset and on or after 3 days from admission, n = 43). Comparisons were made between these groups. RESULTS: Perioperative outcomes between the PLC and ELC groups were not significantly different, except for the requirement of subtotal cholecystectomy (SC) (16.2% vs 5.2%, P = 0.013). In the PLC group, persistent fever after admission was significantly associated with the need for SC (P = 0.036). CONCLUSIONS: PLC for acute cholecystitis performed within 6 days of onset gave acceptable perioperative outcomes, except for an increased requirement for SC. Surgeons should keep in mind that PLC may increase the need for SC. A persistent fever after admission may be a risk factor for SC in the PLC group.

Tenascin-C accelerates adverse ventricular remodelling after myocardial infarction by modulating macrophage polarization.

AIMS: Tenascin-C (TN-C) is an extracellular matrix protein undetected in the normal adult heart, but expressed in several heart diseases associated with inflammation. We previously reported that serum TN-C levels of myocardial infarction (MI) patients were elevated during the acute stage, and that patients with high peak TN-C levels were at high risk of left ventricular (LV) remodelling and poor outcome, suggesting that TN-C could play a significant role in the progression of ventricular remodelling. However, the detailed molecular mechanisms associated with this process remain unknown. We aimed to elucidate the role and underlying mechanisms associated with TN-C in adverse remodelling after MI. METHODS AND RESULTS: MI was induced by permanent ligation of the coronary artery of TN-C knockout (TN-C-KO) and wild type (WT) mice. In WT mice, TN-C was expressed at the borders between intact and necrotic areas, with a peak at 3 days post-MI and observed in the immediate vicinity of infiltrating macrophages. TN-C-KO mice were protected from ventricular adverse remodelling as evidenced by a higher LV ejection fraction as compared with WT mice (19.0 ± 6.3% vs. 10.6 ± 4.4%; P < 0.001) at 3 months post-MI. During the acute phase, flow-cytometric analyses showed a decrease in F4/80+CD206lowCD45+ M1 macrophages and an increase in F4/80+CD206highCD45+ M2 macrophages in the TN-C-KO heart. To clarify the role of TN-C on macrophage polarization, we examined the direct effect of TN-C on bone marrow-derived macrophages in culture, observing that TN-C promoted macrophage shifting into an M1 phenotype via Toll-like receptor 4 (TLR4). Under M2-skewing conditions, TN-C suppressed the expression of interferon regulatory factor 4, a key transcription factor that controls M2-macrophage polarization, via TLR4, thereby inhibiting M2 polarization. CONCLUSION: These results suggested that TN-C accelerates LV remodelling after MI, at least in part, by modulating M1/M2-macrophage polarization.