Clinical evaluation of a surgical difficulty score for laparoscopic cholecystectomy for acute cholecystitis proposed in the Tokyo Guidelines 2018.

BACKGROUND/PURPOSE: We evaluated the difficulty score of laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) proposed in the Tokyo guidelines 2018 (TG18) and analyzed the most appropriate scoring method. METHODS: We reviewed 127 patients who underwent LC for AC from January 2018 to March 2022. According to TG18, surgical difficulty was scored for five categories consisting of 25 intraoperative findings. The median, highest, and mean score of the five categories were analyzed for their association with surgical outcomes. RESULTS: The difficulty score distribution (0/1/2/3/4/5/6) was as follows: median (8/34/43/30/12/0/0), highest (1/1/32/42/36/15/0) and mean (19/49/49/10/0/0/0). In all three scoring methods, higher difficulty scores were significantly correlated with longer operative time, more blood loss, and higher occurrence of subtotal cholecystectomy in trend tests. The areas under the curve (AUCs) for prediction of prolonged operative time minutes and increased blood loss were similar in all three scoring methods. For conversion to subtotal cholecystectomy, the AUC was significantly better for the highest than median and mean score (p = .015 and p = .002, respectively). CONCLUSIONS: The difficulty score in TG18 appropriately reflects the surgical difficulty of LC for AC. The median, highest, and mean scores of the five categories are all available, and the highest scores are simple and versatile.

Matrix metalloproteinase­1 expression is regulated by HIF­1­dependent and epigenetic mechanisms and serves a tumor­suppressive role in gastric cancer progression.

The matrix metalloproteinase (MMP) family is associated with degradation of the extracellular matrix and is known to promote cancer invasion. The present study aimed to investigate the biological role of MMP­1 in gastric cancer cells and analyze the association between MMP­1 expression and the clinical outcomes of gastric cancer patients. In the present study, hypoxia accelerated invasion, accompanied by elevated MMP­1 expression in the gastric cancer cell line 58As9. Additionally, hypoxia­inducible factor­1α (HIF­1α) knockdown in 58As9 cells reduced MMP­1 expression under hypoxic conditions. Treatment with 5­aza­2­deoxycytidine and trichostatin A restored MMP­1 expression in the MMP­1­deficient cell lines MKN45 and MKN74. These results indicated that MMP­1 expression was controlled by both HIF­1α­dependent and epigenetic mechanisms in gastric cancer cell lines. In addition, MMP­1 knockdown impaired the hypoxia­induced invasiveness of 58As9 cells, implicating MMP­1 in the elevated invasion. By contrast, knockdown enhanced the proliferative ability of 58As9 cells, whereby expression of cell cycle­related genes was subsequently altered. In nude mouse models, the knockdown accelerated the growth of xenograft tumor and the development of peritoneal dissemination. In an immunohistochemical study using 161 surgically resected cancer tissues, the Ki67 score was significantly higher in the group with low MMP­1 expression (P<0.001). Disease­free survival (DFS) and disease­specific survival (DSS) were both significantly reduced in patients with low MMP­1 expression (log­rank test; DFS: P=0.005; DSS: P=0.022). Multivariate analysis demonstrated that MMP­1 expression was an independent prognostic factor for DFS and DSS [DFS: HR=2.11 (1.22­3.92) P=0.005, DSS: HR=2.90 (1.23­8.50) P=0.012]. In conclusion, the present study indicated that MMP­1 may serve as a tumor­suppressive factor that inhibits gastric cancer progression, although it promoted invasion in vitro.

Antitumor effects of low-dose tipifarnib on the mTOR signaling pathway and reactive oxygen species production in HIF-1α-expressing gastric cancer cells.

Farnesyltransferase inhibitors (FTIs) suppress tumor aggressiveness in several malignancies by inhibiting Ras signaling. However, treatment of cells with a low dose of the FTI tipifarnib suppresses the expression of hypoxia-inducible factor-1α (HIF-1α) and results in antitumor effects without inhibiting the Ras pathway. Although we previously reported that elevated HIF-1α expression is associated with an aggressive phenotype in gastric cancer (GC), little is known about the antitumor effects of FTIs on GC. In this study, we examined the relationship between the antitumor effects of low-dose tipifarnib and HIF-1α expression in GC cells. Under normoxic conditions, HIF-1α was expressed only in MKN45 and KATOIII cells. The inhibitory effect of tipifarnib on HIF-1α was observed in HIF-1α-positive cells. Low-dose tipifarnib had antitumor effects only on HIF-1α-positive cells both in vitro and in vivo. Furthermore, low-dose tipifarnib inactivated ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) signaling and decreased intracellular reactive oxygen species (ROS) levels in HIF-1α-positive GC cells. Our results that the antitumor effects of low-dose tipifarnib are at least partially mediated through suppression of mTOR signaling and HIF-1α expression via inhibition of Rheb farnesylation and reduction in ROS levels. These findings suggest that low-dose tipifarnib may be capable of exerting an antitumor effect that is dependent on HIF-1α expression in GC cells. Tipifarnib may have potential as a novel therapeutic agent for HIF-1α-expressing GC exhibiting an aggressive phenotype.

Incidence of postoperative complications in transabdominal preperitoneal repair for groin hernia is influenced by poor performance status rather than by old age.

AIM: The present study was designed to evaluate the safety and feasibility of transabdominal preperitoneal (TAPP) repair for very old patients with groin hernia and to identify the risk factors predicting perioperative complications. METHODS: A total of 140 patients treated by TAPP were reviewed retrospectively. They were divided into two groups: patients ≥80 years of age (≥80 years group; n = 26) and those <80 years of age (<80 years group; n = 114). Patient characteristics and surgical outcomes were then statistically compared between the two groups. RESULTS: Number of patients with any comorbidities was significantly higher in the ≥80 years group than in the <80 years group (96.2% vs 61.4%, P = 0.003). There were no significant differences in surgical outcomes between the two groups. In the univariate analysis of perioperative complications, poor performance status (PS) (P = 0.014), lower hemoglobin level (P = 0.038) and lower albumin level (P = 0.016) were significantly associated with the occurrence of postoperative complications, and multivariate analysis showed that only poor PS was an independent factor (PS 0-2 vs 3-4: P = 0.034, OR 5.192 [95% CI; 1.137 to 23.71]). CONCLUSIONS: This is the first report to show that the incidence of postoperative complications in TAPP repair for groin hernia is influenced by poor PS rather than old age. TAPP can be a safe surgical procedure for very old patients with a good PS, with benefits that are equal to those in young patients.

Mieap-induced accumulation of lysosomes within mitochondria (MALM) regulates gastric cancer cell invasion under hypoxia by suppressing reactive oxygen species accumulation.

Mitochondrial quality control (MQC) protects against potentially damaging events, such as excessive generation of mitochondrial reactive oxygen species (mtROS). We investigated the contribution of the two major MQC processes, namely, mitophagy and Mieap-induced accumulation of lysosomes within mitochondria (MALM), to the response to hypoxia of two human gastric cancer (GC) cell lines. We found that hypoxia increased mtROS generation and cell invasion in 58As9, but not in MKN45, although the transcription factor hypoxia-inducible factor 1α was induced in both cell lines. Colocalisation of lysosomes with mitochondria was found only in hypoxic MKN45 cells, suggesting that hypoxia-induced MQC functions normally in MKN45 but may be impaired in 58As9. Hypoxia did not lead to decreased mitochondrial mass or DNA or altered appearance of autophagosomes, as judged by electron microscopy, suggesting that mitophagy was not induced in either cell line. However, western blot analysis revealed the presence of the MALM-associated proteins Mieap, BNIP3 and BNIP3L, and the lysosomal protein cathepsin D in the mitochondrial fraction of MKN45 cells under hypoxia. Finally, Mieap knockdown in MKN45 cells resulted in increased mtROS accumulation and cell invasion under hypoxia. Our results suggest that hypoxia-induced MALM suppresses GC cell invasion by preventing mtROS generation.

Andrographolide induces degradation of mutant p53 via activation of Hsp70.

The tumor suppressor gene p53 encodes a transcription factor that regulates various cellular functions, including DNA repair, apoptosis and cell cycle progression. Approximately half of all human cancers carry mutations in p53 that lead to loss of tumor suppressor function or gain of functions that promote the cancer phenotype. Thus, targeting mutant p53 as an anticancer therapy has attracted considerable attention. In the current study, a small-molecule screen identified andrographlide (ANDRO) as a mutant p53 suppressor. The effects of ANDRO, a small molecule isolated from the Chinese herb Andrographis paniculata, on tumor cells carrying wild-type or mutant p53 were examined. ANDRO suppressed expression of mutant p53, induced expression of the cyclin-dependent kinase inhibitor p21 and pro-apoptotic proteins genes, and inhibited the growth of cancer cells harboring mutant p53. ANDRO also induced expression of the heat-shock protein (Hsp70) and increased binding between Hsp70 and mutant p53 protein, thus promoting proteasomal degradation of p53. These results provide novel insights into the mechanisms regulating the function of mutant p53 and suggest that activation of Hsp70 may be a new strategy for the treatment of cancers harboring mutant p53.

A case of Mirizzi syndrome that was successfully treated by laparoscopic choledochoplasty using a gallbladder patch.

The use of laparoscopic surgery in the treatment of Mirizzi syndrome is considered controversial due to the degree of technical difficulty. We herein describe the case of a 36-year-old woman who was admitted to our hospital due to appetite loss, nausea and back pain. Endoscopic retrograde cholangiography revealed a round-shaped filling defect at the confluence of the bile duct. The patient was diagnosed with Mirizzi syndrome Type II according to the Csendes classification. Before surgery, an endoscopic nasobiliary drainage tube was placed for intraoperative cholangiography. Based on the intraoperative findings, the anterior wall of Hartmann's pouch was excised to remove the impacted gallstone. The neck portion of the gallbladder wall was then used to make a gallbladder patch, which was sutured to cover the anterior wall of the common hepatic bile duct. Laparoscopic choledochoplasty using a gallbladder patch was a technically feasible treatment for Mirizzi syndrome Type II.

Double cystic duct preoperatively diagnosed and successfully treated with laparoscopic cholecystectomy: A case report.

INTRODUCTION: A single gallbladder with a double cystic duct is a very rare finding. In addition, few cases with this rare condition are preoperatively diagnosed. However, the preoperative confirmation or suspicion of this rare condition could facilitate safe laparoscopic cholecystectomy, which is a minimally invasive therapeutic modality for gallbladder disease. We herein present a case of gallstone disease in a patient with a double cystic duct who was preoperatively diagnosed and successfully treated with laparoscopic cholecystectomy. PRESENTATION OF CASE: A 57-year-old woman was admitted to our hospital with epigastric pain. Gallstone disease in the gallbladder and common bile duct was diagnosed by ultrasonography and computed tomography. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiography (ERC) revealed that the aberrant cystic duct arose from the cystic duct and communicated with the intrahepatic bile duct of the posterior segmental branch. Laparoscopic cholecystectomy was successfully performed in combination with intraoperative cholangiography. DISCUSSION: If an anomaly of the biliary duct system is not identified during surgery, it may turn out to be a bile leak. The preoperative diagnosis of a double cystic duct allows laparoscopic cholecystectomy to be performed safely in combination with intraoperative cholangiography. CONCLUSIONS: A single gallbladder with double cystic duct is a very rare anomaly. However, laparoscopic surgery can be facilitated by the use of preoperative and intraoperative images.

Traumatic Gallbladder Rupture Treated by Laparoscopic Cholecystectomy.

Gallbladder rupture due to blunt abdominal injury is rare. There are few reports of traumatic gallbladder injury, and it is commonly associated with other concomitant visceral injuries. Therefore, it is difficult to diagnose traumatic gallbladder rupture preoperatively when it is caused by blunt abdominal injury. We report a patient who underwent laparoscopic cholecystectomy after an exact preoperative diagnosis of traumatic gallbladder rupture. A 43-year-old man was admitted to our hospital due to blunt abdominal trauma. The day after admission, abdominal pain and ascites increased and a muscular defense sign appeared. Percutaneous drainage of the ascites was performed, and the aspirated fluid was bloody and almost pure bile. He was diagnosed with gallbladder rupture by the cholangiography using the endoscopic retrograde cholangiopancreatography technique. Laparoscopic cholecystectomy was performed safely, and he promptly recovered. If accumulated fluids contain bile, endoscopic cholangiography is useful not only to diagnose gallbladder injury but also to determine the therapeutic strategy.