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.

Intussusception of the cecum due to the acute appendicitis: A case report.

INTRODUCTION AND IMPORTANCE: Intussusception of the cecum due to acute appendicitis is rare condition. PRESENTATION OF CASE: A 17-year-old male patient presented to our hospital with a chief complaint of right lower abdominal pain, which had lasted for two days. Computed tomography (CT) revealed a "target sign" from the cecum to the ascending colon, leading to a diagnosis of cecocolic intussusception. Colonoscopy revealed an erythematous, edematous, and internally distorted cecum in the ascending colon, which was difficult to repair with air insufflation. Laparoscopic surgery was performed to remove the bowel obstruction. Repositioning of the invaginated cecum was difficult due to the presence of a hard and edematous colic wall. Therefore, laparoscopic ileocecal resection was performed to release the obstruction. The pathological diagnosis was appendicitis and abscess within the cecum wall, with no malignant findings. DISCUSSION: In our case, intussusception was considered to have caused thickening of the intestinal wall of the cecum due to inflammation of the appendix, and the thickened area became the leading point. CONCLUSION: Considering that malignancy is a frequent leading point in adult patients with intussusception, a preoperative endoscopic examination is important for minimizing bowel resection.

The strategy for Mirizzi syndrome type II with laparoscopic surgery: A case report.

INTRODUCTION: Mirizzi syndrome is an unusual condition involving gallstones. Laparotomy is recommended for the treatment of Mirizzi syndrome type II due to the risk of biliary duct injury. We herein report tips for performing laparoscopic surgery for Mirizzi syndrome type II as a treatment option. PRESENTATION OF CASE: A 72-year-old woman was admitted to our hospital due to abdominal pain and a fever. The diagnosis of Mirrizi syndrome type II was made. Therefore, an endoscopic retrograde biliary drainage tube was placed, and laparoscopic surgery was performed. During the operation, the gallbladder wall was excised at the Hartmann's pouch, and a gallstone was extracted. A fistula between the gallbladder and bile duct was confirmed, and the diagnosis of Mirizzi syndrome type II was made. Partial resection of the gallbladder was performed, and the neck of the gallbladder was sutured. The postoperative course was uneventful. DISCUSSION: The preoperative diagnosis is important for Mirizzi syndrome, and the combination of various modalities, including endoscopic retrograde cholangiopancreatography, can increase the diagnostic rate. It is often difficult to recognize the anatomy during surgery for Mirizzi syndrome due to severe inflammation. Therefore, it is best to dissect the gallbladder from the bottom, perform excision at the Hartmann's pouch, remove the gallstone and suture the gallbladder wall. Replacement of the biliary tube can aid in recognizing the anatomy and bile duct. CONCLUSION: Laparoscopic surgery for Mirizzi syndrome is a viable treatment option following an accurate preoperative diagnosis and the recognition of the anatomy during the operation.

Relation of Colloidal and Conformational Stabilities to Aggregate Formation in a Monoclonal Antibody.

Aggregation of therapeutic monoclonal antibodies has a potential risk of immunogenicity, requiring minimization of aggregate formation. We have developed a fitting formula for antibody aggregation at 40°C based on physicochemical parameters, including colloidal and conformational stabilities. An IgG1 monoclonal antibody, MAb-T, was formulated in 24 combinations of different buffer types and pH with or without sodium chloride. The fitting formula for monomer loss was successfully established by nonlinear regression analysis of the results from accelerated stability testing. Calculated monomer fraction values by the fitting formula were strongly correlated with experimental values (R2 = 0.92). The model includes secondary virial coefficient, B22, as the representative parameter of colloidal stability, and aggregation temperature, Tagg, representing conformational stability. Then, we examined charge state, conformational flexibility, and thermal unfolding profile of MAb-T to clarify the molecular basis for the different aggregation propensities in sodium acetate buffer and in sodium citrate buffer at the same pH and buffer concentration. We concluded that the accumulation of citrate anions on the surface of MAb-T is the primary source of the less colloidal and conformational stabilities, resulting in the higher aggregation propensity in sodium citrate buffer.

Clinical Features, Prognosis, Diagnostic Approaches and Treatment of Multiple Primary Malignancies in the Digestive System.

BACKGROUND/AIM: Additional primary malignancy (APM) risk is increasing with improved prognosis of cancer survivors. In order to clarify risk factors and patients susceptible to develop APMs, we investigated the clinical features, prognosis, and approaches for diagnosis and treatment in these patients. PATIENTS AND METHODS: Among 874 patients newly diagnosed with gastrointestinal tract (GIT) or hepato-biliary-pancreatic (HBP) cancers between 2011 and 2014, 124 with a synchronous and/or metachronous APM were identified. Patient characteristics, time interval between the malignancies, clue to detect APMs, treatment approaches, and prognosis were investigated. RESULTS: Patients with APMs were older and predominantly male. Half of the metachronous APMs were detected within 3 years after the first primary malignancy (PM). The main clue to detect synchronous and metachronous APMs was preoperative screening for current PM, and follow-up of prior PM, respectively. There was no significant difference in the overall survival between colon cancer patients with or without APMs. CONCLUSION: Multiple PMs were present in 14.2% of patients. Male and old age were identified to be risk factors for APM. Pre-operative screening and post-operative regular follow-ups are important for detecting synchronous or metachronous APMs.

Quantitative Laser Diffraction for Quantification of Protein Aggregates: Comparison With Resonant Mass Measurement, Nanoparticle Tracking Analysis, Flow Imaging, and Light Obscuration.

In the past, analysis of micron-sized (>1.0 µm) aggregates of therapeutic proteins has been limited to light obscuration (LO), and appropriate quantitative methods of evaluating protein aggregates need to be developed. Recently, novel methods with enhanced reliability and sensitivity, such as nanoparticle tracking analysis (NTA), resonant mass measurement (RMM), and flow imaging (FI), have emerged. We have found that quantitative laser diffraction (qLD) is also effective for quantitative evaluation of protein aggregates over a wide size range. However, the different detection principles of the methods potentially lead to inconsistencies in results. This study aimed to compare particle size distributions and concentrations of protein aggregates using the orthogonal methods. Protein aggregates were generated by stirring an immunoglobulin solution. Serial dilutions of the aggregates stock were analyzed by RMM, FI, and qLD to obtain the particle size distribution and concentration using each method. In addition, size distribution of a protein aggregates solution was compared by RMM, NTA, FI, LO, and qLD. Both particle size distribution and concentration were in good agreement between RMM and qLD (0.3-2 µm) and between FI and qLD (2-20 µm). Thus, we concluded that qLD enables covering of the overlapping particle size range between RMM and FI.

A long-term survivor of undifferentiated carcinoma of the liver successfully treated with surgical treatments: A case report and literature review.

INTRODUCTION: Undifferentiated carcinoma of the liver is extremely rare. The biological characteristics and standard strategy for its treatment have not been established yet. PRESENTATION OF CASE: A 45-year-old man was admitted because of fever elevation and shivering. Abdominal computed tomography revealed a hypovascular cystic mass in segments 6 and 7 of the liver measuring 11.5 × 9.0 cm with ring enhancement and partial solid component. A diagnosis of liver abscess was made, and percutaneous transhepatic abscess drainage was performed. Reddish brown-colored pus showed no bacteria or amoebas. However, cytology demonstrated malignant cells. After additional examinations of magnetic resonance imaging and the positron emission tomography, extended posterior sectionectomy with cholecystectomy was performed. The excised specimen showed a solid and irregular tumor with extensive central necrosis. A pathological examination revealed diffuse proliferation of oval- and spindle-shaped malignant cells. Immunohistochemically, the malignant cells were diffusely positive for AE1/AE3 and vimentin and focally positive for granulocyte colony-stimulating factor and cytokeratin 19; however, hepatocyte-specific antigen, glypican 3, cytokeratin 7, and CD56 were negative. Therefore, a diagnosis of undifferentiated carcinoma of the liver was made. He has remained well without any recurrence for three years since the operation. DISCUSSION: Undifferentiated carcinoma of the liver might grow rapidly, resulting in necrosis with a cystic component. Therefore, it can be difficult to distinguish from liver abscess. CONCLUSION: This disease has markedly different clinical and biological features from common primary malignant tumor of the liver. However, if the tumor is a solitary mass, surgical resection might lead to a good prognosis.

Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas.

AIM: To investigate the association between smoking habits and surgical outcomes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients. METHODS: We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups' clinicopathological features and surgical outcomes, i.e., disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients. RESULTS: The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS (P = 0.0039) and DSS (P = 0.0416). In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS, or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status. CONCLUSION: A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes.

Occult HBV infection status and its impact on surgical outcomes in patients with curative resection for HCV-associated hepatocellular carcinoma.

BACKGROUND: We sought to clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and to determine whether OBI affects the surgical outcomes in curatively resected Japanese patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: A total of 257 patients with HCV-related HCC who underwent curative surgical resection were enrolled. All enrolled patients were serologically negative for HBV surface antigen and positive for HCV antibody. DNA was extracted from formalin-fixed paraffin-embedded liver tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Surgical outcomes were evaluated according to overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: OBI was identified in 15 of the 257 (5.8%) cases. In the multivariate analyses, the factors significantly correlated with OS were BMI >25 (P=0.0416), portal vein invasion (P=0.0065), and multiple tumors (P=0.0064). The only factor significantly correlated with DSS was T-stage (P=0.0275). The factors significantly correlated with DFS were liver fibrosis (P=0.0017) and T-stage (P=0.0001). The status of OBI did not show any significant correlation with OS, DSS or DFS, but a weak association with DSS (P=0.0603) was observed. CONCLUSIONS: The prevalence of OBI was 5.8% in 257 cases of HCV-related HCC. Although a weak association between DSS and OBI was observed, and statistical analyses were limited by small number of OBI cases, no significant correlation between OBI and surgical outcomes was detected.

Beyond the subjective experience of colour: An experimental case study of grapheme-texture synesthesia.

This study was a case investigation of grapheme-texture synestheste TH, a female who subjectively reported experiencing a visual association between grapheme and colour/texture. First, we validated the existence of a synesthetic association in an objective manner. Involuntarily elicited experience is a major hallmark that is common to different types of synesthetes. Our results indicated interference between physical and synesthetic texture, suggesting the involuntary occurrence of synesthetic textural experience. We analysed the behavioural measures using the EZ diffusion model. The result suggested that TH's synesthetic experience was dissociable from that of briefly trained associative processing of non-synesthetes. Second, we investigated how the synesthetic experience of colour and texture dimensions was bound in the visual representation. We found that the interference effects of colour and texture were not independent. This suggested that in the elicited experience, the colour and texture features construct an integrated representation.

Impact of smoking habit on surgical outcomes in non-B non-C patients with curative resection for hepatocellular carcinoma.

AIM: To analyzed the correlation between smoking status and surgical outcomes in patients with non-B non-C hepatocellular carcinoma (NBNC-HCC), and we investigated the patients' clinicopathological characteristics according to smoking status. METHODS: We retrospectively analyzed the consecutive cases of 83 NBNC-HCC patients who underwent curative surgical treatment for the primary lesion at Saga University Hospital between 1984 and December 2012. We collected information about possibly carcinogenic factors such as alcohol abuse, diabetes mellitus, obesity and smoking habit from medical records. Smoking habits were subcategorized as never, ex- and current smoker at the time of surgery. The diagnosis of non-alcoholic steatohepatitis (NASH) was based on both clinical information and pathological confirmation. RESULTS: Alcohol abuse, diabetes mellitus, obesity and NASH had no significant effect on the surgical outcomes. Current smoking status was strongly correlated with both overall survival (P = 0.0058) and disease-specific survival (P = 0.0105) by multivariate analyses. Subset analyses revealed that the current smokers were significantly younger at the time of surgery (P = 0.0002) and more likely to abuse alcohol (P = 0.0188) and to have multiple tumors (P = 0.023). CONCLUSION: Current smoking habit at the time of surgical treatment is a risk factor for poor long-term survival in NBNC-HCC patients. Current smokers tend to have multiple HCCs at a younger age than other patients.

Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma.

AIM: To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus (HBV) infection (OBI) in patients with non-B, non-C (NBNC) hepatocellular carcinoma (HCC). METHODS: This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis (NASH) were examined. Surgical outcomes were evaluated according to disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). RESULTS: OBI was found in 27/78 patients (34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery (average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases (P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumor-related factors affected these surgical outcomes. CONCLUSION: Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.

Curative resection of gallbladder cancer with liver invasion and hepatic metastasis after chemotherapy with gemcitabine plus S-1: report of a case.

A 62-year-old woman diagnosed with gallbladder cancer exhibiting broad liver invasion and metastasis to Couinaud's hepatic segments 4 and 8 (S4 and S8) consulted her regular doctor. Owing to the presence of liver metastases, she received treatment with gemcitabine plus S-1. After four cycles of chemotherapy, the size of the main lesion dramatically decreased and the two liver metastases disappeared. After six cycles of chemotherapy, the patient was referred to our hospital for surgical treatment. Upon admission, there was no evidence of any distant metastasis, based on a detailed radiological examination. Therefore, we performed cholecystectomy and central bisegmentectomy of the liver after obtaining the patient's informed consent. Pathological examination demonstrated viable cancer cells with granuloma formation and calcification in the gallbladder, as well as regenerative changes without viable cancer cells in S4 and S8 of the liver. Gemcitabine plus S-1 was again administered as postoperative adjuvant chemotherapy. One and a half years after the surgery, there were no signs of recurrence. In patients selected according to their response to chemotherapy, surgical treatment might therefore be effective against gallbladder cancer with metastasis.

[A case of effective treatment with S-1/gemcitabine chemotherapy and resection for advanced pancreatic cancer with peritoneal dissemination].

A 69-year-old man was admitted to our hospital for abdominal pain. An abdominal computed tomography(CT)scan revealed pancreatictail cancer with peritoneal dissemination. We administered systemic chemotherapy consisting of S-1 and gemcitabine. After 10 courses, the peritoneal dissemination had disappeared and tumor marker levels returned to almost normal values. Thus, we considered the patient to have an effective response, so we performed a distalpancreatectomy and partial resection of the stomach, transverse colon, and left adrenal gland. Eleven months after the operation, the patient is alive with no recurrence.

Multiple neural mechanisms for coloring words in synesthesia.

Grapheme-color synesthesia is a phenomenon in which achromatic letters/digits automatically induce particular colors. When multiple letters are integrated into a word, some synesthetes perceive that all those letters are changed into the same color, reporting lexical color to that word. Previous psychological studies found several "rules" that determine those lexical colors. The colors to most words are determined by the first letters of the words, while some words in ordinal sequences have their specific colors. Recent studies further reported the third case where lexical colors might be influenced by semantic information of words. Although neural mechanisms determining those lexical colors remained unknown, here we identified three separate neural systems in the synesthete's brain underlying three rules for illusory coloring of words. In addition to the occipito-temporal and parietal regions previously found to be associated with the grapheme-color synesthesia, neural systems for lexical coloring extended to linguistic areas in the left inferior frontal and anterior temporal regions that were engaged in semantic analyses of words. Those results indicate an involvement of wider and higher neural networks than previously assumed in a production of synesthetic colors to visual stimuli and further showed a multiplicity of synesthetic mechanisms represented in the single brain.

Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1.

GPR55 is a seven-transmembrane G-protein-coupled receptor that has been proposed as a novel type of cannabinoid receptor. Previously, we identified lysophosphatidylinositol (LPI), in particular 2-arachidonoyl-LPI, as an agonist for GPR55. In the present study, we examined whether intracellular phospholipase A1 (DDHD domain containing 1, or DDHD1), previously identified as phosphatidic acid (PA)-preferring PLA1 (PA-PLA1), is involved in the formation of 2-arachidonoyl-LPI. HEK293 cells expressing DDHD1 produced [(3)H]arachidonic acid-containing LPI after prelabeling with [(3)H]arachidonic acid and subsequent activation by ionomycin; the formation of [(3)H]LPI was inhibited by n-butanol and the overexpression of an inactive PLD1 mutant PLD1K898R. DDHD1 was translocated from the cytosol to membranes upon ionomycin treatment. A purified recombinant DDHD1 formed [(3)H]LPI when incubated with [(3)H]PI; the V(max) and apparent K(m) were 190 micromol/min/mg protein and 10 mol% PI, respectively. DDHD1 binds PA, and the addition of PA to DDHD1 increased the affinity for PI (K(m) ; 3 mol%) and augmented the PI-PLA1 activity. DDHD1 activated by PA was returned to a basal state by its own PA-hydrolytic activity. These results implicate DDHD1 in the formation of 2-arachidonoyl-LPI and indicate that the process is modulated by PA released by phospholipase D. Similar observations for the production of arachidonic acid-containing LPI in neuroblastoma cells suggest the DDHD1-LPI-GPR55 axis to be involved in functions in the brain.

Path generator control system and virtual compliance calculator for maxillofacial massage robots.

PURPOSE: Oral disorders such as temporomandibular joint disorders (TMD) and dry mouth are common and often require treatment. Maxillofacial massage is used as a complementary and alternative therapy for these disorders. We developed an oral rehabilitation robot that massages the maxillofacial tissues for this purpose. In this paper, we propose a control system for oral rehabilitation robots. METHOD: The control system consists of a massage path generator, virtual compliance calculator, and inverse kinematics calculator. The massage path generator computes a target massage path based on a human head model obtained from a reference MRI image of an adult male. The head model includes the shape and elastic modulus of each component, all of which were obtained experimentally. Virtual compliance control is used to control manipulators with position servo actuators. The manipulators, which have a force sensor at their end-effectors, move actively in the direction of the external force applied to their sensors via virtual compliance control. We implemented this control in WAO-1, our first prototype oral rehabilitation robot. RESULTS: WAO-1 provided massage to three adult male subjects with and without virtual compliance control. One of the subjects was the adult male whose MRI image was used to synthesize the head model in the massage path generator. Without virtual compliance control, the actual massage force was greater than the target massage force, while that with virtual compliance control was less than the target massage force. Furthermore, with virtual compliance control, the massage paths conformed to the head shape of each patient. CONCLUSION: Implementation of virtual compliance control in the WAO-1 massage robot is feasible and useful for implementation of safe and potentially effective maxillofacial massage therapy.

Subcellular localization and lysophospholipase/transacylation activities of human group IVC phospholipase A2 (cPLA2gamma).

cPLA2gamma was identified as an ortholog of cPLA2alpha, which is a key enzyme in eicosanoid production. cPLA2gamma was reported to be located in endoplasmic reticulum (ER) and mitochondria and to have lysophospholipase activity beside phospholipase A2 (PLA2) activity. However, subcellular localization, mechanism of membrane binding, regulation and physiological function have not been fully established. In the present study, we examined the subcellular localization and enzymatic properties of cPLA2gamma with C-terminal FLAG-tag. We found that cPLA2gamma was located not only in ER but also mitochondria even in the absence of the prenylation. Purified recombinant cPLA2gamma catalyzed an acyltransferase reaction from one molecule of lysophosphatidylcholine (LPC) to another, forming phosphatidylcholine (PC). LPC or lysophosphatidylethanolamine acted as acyl donor and acceptor, but lysophosphatidylserine, lysophosphatidylinositol and lysophosphatidic acid (LPA) did not. PC and phosphatidylethanolamine (PE) also acted as weak acyl donors. Reaction conditions changed the balance of lysophospholipase and transacylation activities, with addition of LPA/PA, pH>8, and elevated temperature markedly increasing transacylation activity; this suggests that lysophospholipase/transacylation activities of cPLA2gamma may be regulated by various factors. As lysophospholipids are known to accumulate in ischemia heart and to induce arryhthmia, the cPLA2gamma that is abundant in heart may have a protective role through clearance of lysophospholipids by its transacylation activity.