Fusobacterium nucleatum, immune responses, and metastatic organ diversity in colorectal cancer liver metastasis.

The presence of Fusobacterium nucleatum is associated with an immunosuppressive tumor immune microenvironment (TIM) in primary colorectal cancer (CRC), contributing to tumor progression. Its persistence in CRC liver metastasis tissues raises questions about its role in modulating local and systemic immune responses and influencing recurrence patterns. This retrospective cohort study of 218 patients with CRC liver metastasis investigated the association of F. nucleatum in CRC liver metastasis tissues with systemic inflammation, TIM alterations, and the number of metastatic organs involved in recurrence. Two-step polymerase chain reaction (PCR), including digital PCR, detected F. nucleatum in 42% (92/218) of fresh-frozen specimens of CRC liver metastases. Compared with the F. nucleatum-none group, the F. nucleatum-high group showed higher C-reactive protein levels (0.82 vs. 0.22 mg/dL; Ptrend = 0.02), lower numbers of CD8+ cells (33.2 vs. 65.3 cells/mm2; Ptrend = 0.04) and FOXP3+ cells (11.3 vs. 21.7 cells/mm2; Ptrend = 0.01) in the TIM, and a greater number of metastatic organs involved in recurrence (1.6 vs. 1.1; p < 0.001). The presence of F. nucleatum in CRC liver metastasis tissues was associated with increased systemic inflammation, TIM alterations, and a greater number of metastatic organs involved in recurrence. These findings suggest a potential contribution of F. nucleatum to the metastatic propensity of CRC cells and could inform future research to enhance understanding of the interaction between tumor, host, and microbes in the metastatic process.

Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Robot-Assisted Pancreaticoduodenectomy with Hemicircumferential Dissection of Nerve Plexus Around the Superior Mesenteric Artery.

BACKGROUND: Pancreatic head cancer with perineural invasion of the superior mesenteric artery (SMA) requires dissection of the nerve plexus around the SMA (PLsma, superior mesenteric nerve plexus) to obtain cancer-free margins.1,2 Technically challenging robot-assisted pancreaticoduodenectomy with PLsma resection is rarely performed owing to the technical limitations of the robot. In this multimedia article, we present our approach to robot-assisted pancreaticoduodenectomy with PLsma dissection.3-5 METHODS: We performed a robot-assisted pancreaticoduodenectomy with resection of the hemicircle of the PLsma in a 78-year-old woman with resectable pancreatic cancer extending to the root of the inferior pancreaticoduodenal artery. In this video, we show how to obtain an optimal view using the multiple scope transition method,4 and technical tips to perform a PLsma dissection with a robot to perform this difficult surgery safely. RESULTS: The operative time was 568 min and 300 mL of blood was lost. The pathological diagnosis was invasive pancreatic ductal carcinoma with lymph node metastasis, and R0 resection was performed. The distance margin from the SMA was 2 mm. The patient was discharged on the 18th postoperative day without postoperative complications. CONCLUSIONS: Robot-assisted pancreaticoduodenectomy with dissection of the hemicircle of the PLsma, which is difficult to perform, can be performed safely with an optimal view using the multiple-scope transition method, and delicate dissection using a robot.

Unique Biology of Pancreatic Ductal Adenocarcinoma Accompanied by Rapidly Impaired Diabetes: A Favorable Long-Term Survival Following Curative Resection.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained. METHODS: Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated. RESULTS: Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01). CONCLUSIONS: PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology.

Fusobacterium Detected in Barrett's Esophagus and Esophageal Adenocarcinoma Tissues.

We examined Fusobacterium nucreatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) in non-neoplastic Barrett's esophagus (BE) from patients without cancer (n = 67; N group), with esophageal adenocarcinoma (EAC) (n = 27) and EAC tissue (n = 22). F. nucleatum was only detectable in 22.7% of EAC tissue. Pan-fusobacterium was enriched in EAC tissue and associated with aggressive clinicopathological features. Amount of Pan-fusobacterium in non-neoplastic BE was correlated with presence of hital hernia and telomere shortening. The result suggested potential association of Fusobacterium species in EAC and BE, featuring clinicpathological and molecular features.

Effects of titration speed, gender, obesity and concomitant medications on the risk and onset time of clozapine-associated fever among Japanese patients with schizophrenia: retrospective review of charts from 21 hospitals.

BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. AIMS: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. METHOD: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. CONCLUSION: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

Feasibility of Colorectal Endoscopic Submucosal Dissection in Elderly Patients: The Impact of Sarcopenia.

INTRODUCTION: Colorectal cancer is a public health concern associated with high incidence rates. Sarcopenia is a known risk factor for postoperative complications, although an association between increased complications after colorectal endoscopic submucosal dissection (ESD) and sarcopenia remains undocumented. Herein, we aimed to explore the feasibility of colorectal ESD in patients with sarcopenia. METHODS: This retrospective study included 499 patients (69 with and 430 without sarcopenia). We evaluated the short- and long-term outcomes of colorectal ESD. RESULTS: There were no significant differences between the two groups regarding en bloc, R0, or curative resection rates. However, poor bowel preparation was significantly more common in the sarcopenia group. Moreover, patients with sarcopenia exhibited a significant increase in complications (37.7% vs. 10.5%). Multivariate analysis revealed that sarcopenia (odds ratio [OR]: 3.78, 95% confidence interval [Cl]: 1.85-7.73, p < 0.001), anticoagulation therapy (OR: 3.59, 95% Cl: 1.86-6.92, p < 0.001), procedure time (OR: 1.28, 95% Cl: 1.11-1.47, p < 0.001), and resection size (OR: 1.25, 95% Cl: 1.03-1.52, p = 0.02) were significantly correlated with the Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 2. The correlation between sarcopenia and CTCAE ≥ grade 2 was maintained after matching, resulting in more extended hospital stays in patients with sarcopenia. However, we detected no association between sarcopenia and overall survival and ESD-related death. CONCLUSION: Sarcopenia is a risk factor for complications in colorectal ESD, suggesting that colorectal ESD could be performed for patients with sarcopenia, although much caution should be taken.

Scope transition and early arterial inflow control provide safe and comfortable dissection in robotic distal pancreatectomy.

PURPOSE: We describe details and outcomes of a novel technique for optimizing the surgical field during robotic distal pancreatectomy (RDP) for distal pancreatic lesions, which has become common with potential advantages over laparoscopic surgery. METHODS: For suprapancreatic lymph node dissection and splenic artery ligation, we used the basic center position with a scope through the midline port. During manipulation of the perisplenic area, the left position was used by moving the scope to the left medial side. The left lateral position is optionally used by moving the scope to the left lateral port when scope access to the perisplenic area is difficult. In addition, early splenic artery clipping and short gastric artery dissection for inflow block were performed to minimize bleeding around the spleen. We evaluated retrospectively the surgical outcomes of our method using a scoring system that allocated one point for blood inflow control and one point for optimizing the surgical view in the left position. RESULTS: We analyzed 34 patients who underwent RDP or R-radical antegrade modular pancreatosplenectomy (RAMPS). The left position was applied in 14 patients, and the left lateral position was applied in 6. Based on the scoring system, only the 0-point group (n = 8) had four bleeding cases (50%) with splenic injury or blood pooling; the other 1-point or 2-point groups (n = 13, respectively) had no bleeding cases (p = 0.0046). CONCLUSION: Optimization of the surgical field using scope transition and inflow control ensured safe dissection during RDP.

Management of potential portal vein thrombus during laparoscopic right hemihepatectomy following portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) is often performed prior to right hemihepatectomy (RH) to increase the future liver remnants. However, intraoperative removal of portal vein thrombus (PVT) is occasionally required. An algorithm for treating the right branch of the PV using laparoscopic RH (LRH) after PVE is lacking and requires further investigation. METHODS: In our department, after the confirmation of a lack of extension of PVT to the main portal trunk or left branch on preoperative examination (ultrasound and contrast-enhanced computed tomography), a final evaluation was performed using intraoperative ultrasonography (IOUS). Here we present the cases of eight patients who underwent LRH after PVE and examine the safety of our treatment strategies. RESULTS: IOUS revealed PVT extension into the main portal trunk in two cases. For the other six patients without PVT extension, we continued the laparoscopic procedure. In contrast, in the two cases with PVT extension, we converted to laparotomy after hepatic transection and removed the PVT. The median operation time for hepatectomy was 562 min (421-659 min), the median blood loss was 293 mL (85-1010 mL), no liver-related postoperative complications were observed, and the median length of stay was 10 days (6-34 days). CONCLUSIONS: PVT evaluation and removal are important in cases of LRH after PVE. Our strategy is safe and IOUS is particularly useful for laparoscopically evaluating PVT extension.

Does Preoperative Manual Reduction (Omoto Technique) Affect Surgical Outcomes for Calcaneal Fractures? A Multicenter (TRON Group) Retrospective Study.

The Omoto technique is a well-known method that is commonly used for noninvasive manual repair of calcaneal fractures. However, there have been no detailed studies on its clinical outcomes in preoperative closed reduction for surgical cases. This multicenter retrospective study aimed to compare the clinical and radiographic outcomes of calcaneal fractures treated with and without the preoperative Omoto technique, assessing its effectiveness. We extracted 335 patients with calcaneal fracture who underwent surgery between 2015 and 2020 from our multicenter database, named TRON. We evaluated the clinical outcomes using the American Orthopedic Foot and Ankle Society (AOFAS) score, the Böhler angle (BA) for radiographic analysis, and noted any complications. We divided the patients into those managed with the Omoto technique (group O) and those managed without the Omoto technique (group N). Patients were matched by age, sex, and fracture type, resulting in 43 patients per group. The use of the Omoto technique at the time of injury significantly improved the Böhler angle (BA). Furthermore, there were no significant differences in AOFAS, postoperative complications, or BA values at the final follow-up. In conclusion, our study demonstrates that the Omoto technique, when used preoperatively for calcaneal fractures, does not negatively impact the outcomes of subsequent surgical treatments. For patients who prefer to avoid surgery, the Omoto technique can be an effective initial intervention. Additionally, our findings suggest that the Omoto technique may facilitate less invasive surgical options in certain cases.

Alterations in driving ability and their relationship with morphometric magnetic resonance imaging indicators in patients with amnestic mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Drivers with dementia are at a higher risk of motor vehicle accidents. The characteristics of driving behaviour of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have not been fully elucidated. We investigated driving ability and its relationship with cognitive function and magnetic resonance imaging (MRI) morphometry indicators. METHODS: The driving abilities of 19 patients with AD and 11 with amnestic MCI (aMCI) were evaluated using a driving simulator. The association between each driving ability parameter and the Mini-Mental State Examination (MMSE) score or voxel-based specific regional analysis system for AD (VSRAD) was assessed. RESULTS: Patients with AD made a significantly higher number of operational errors than those with aMCI in attention allocation in the complex task test (P = 0.0008). The number of operational errors in attention allocation in the complex task test significantly and negatively correlated with MMSE scores in all participants (r = -0.4354, P = 0.0162). The decision time in the selective reaction test significantly and positively correlated with the severity and extent of medial temporal structural atrophy (r = 0.4807, P = 0.0372; r = 0.4862, P = 0.0348; respectively). CONCLUSION: An increase in the operational errors for attention allocation in the complex task test could be a potential indicator of progression from aMCI to AD. Atrophy of the medial temporal structures could be a potential predictor of impaired judgement in driving performance in aMCI and AD. A driving simulator could be useful for evaluating the driving abilities of individuals with aMCI and AD.

Epichordal vertebral column formation in Xenopus laevis.

Although Xenopus Laevis is the most widely used model amphibian, skeletal development of its vertebral column has not been well illustrated so far. The mode of vertebral column development in anurans has been classified into two modes: perichordal and epichordal. Xenopus vertebral column formation is believed to follow the epichordal mode, but this aspect has been underemphasized, and illustrative examples are currently unavailable to the scientific community. This study documents the entire process of vertebral column formation in X. laevis, from the initial neural arch formation to the completion of metamorphosis. These images reveal that the neural arch arises from the dorsal lamina and lateral pedicle primordia, with no strict adherence to an anteroposterior sequence. Unlike other species, Xenopus centrum primordia exclusively form at the expanded ventral margins of neural arches, rather than from the cartilaginous layer surrounding the notochord. These paired centrum primordia then fuse at the ventral midline, dorsal to the notochord, and subsequently the notochord degenerates. This mode of centrum formation differs from the traditional epichordal mode, indicating that Xenopus might have lost the ability to form a cartilaginous layer around the notochord. Instead, the neural arch's ventral margin appears to have evolved to incorporate centrum precursor cells at its base, thereby forming a centrum-like structure compensating for the absence of a true centrum. It is widely accepted that postsacral vertebrae lack centra, only possessing neural arches, and eventually fuse with the hypochord to form the urostyle. However, we have shown that the paired ventral ends of the postsacral vertebrae also fuse at the midline to form a centrum-like structure. This process might extend to the trunk region during centrum formation. In addition to these findings, we offer evolutionary insights into the reasons why Xenopus retains centrum primordia at the base of neural arches.

The effectiveness of palliative middle meningeal artery embolization prior to craniotomy for large acute epidural hematoma: A case report.

INTRODUCTION AND IMPORTANCE: Acute epidural hematoma is typically managed with craniotomy. However, there are a few reports on transcatheter arterial embolization (TAE) as an adjunctive therapy. CASE PRESENTATION: A 70-year-old female with no obvious history of trauma was transported to our hospital. Computed tomography scan revealed an epidural hematoma of approximately 80 ml with a midline shift of 5 mm. We decided to perform an emergency craniotomy. However, the operating room (OR) was already occupied by a scheduled surgery and it would take 30 min to an hour to prepare it. We opted to wait for our OR, considering that, even if the patient was transferred to another hospital, it would take time for the craniotomy to commence. CLINICAL DISCUSSION: We performed TAE for the middle meningeal artery (MMA) as a palliative measure to prevent hematoma enlargement. The MMA was selectively embolized with 20 % n-butyl-2-cyanoacrylate (NBCA), resulting in no hematoma enlargement or observed complications. The criteria for endovascular treatment of acute epidural hematoma are not yet well-established. This case demonstrates the potential role of endovascular treatment for large acute epidural hematomas in carefully selected patients. CONCLUSION: If there is a time gap before craniotomy, TAE could be considered a viable option for large acute epidural hematomas as a palliative intervention before craniotomy.

Clinical Features of Cardiac Calcified Amorphous Tumor: A Narrative Review.

A cardiac calcified amorphous tumor (CAT) is a non-neoplastic cardiac mass composed of calcified nodules surrounded by amorphous fibrous tissue in a context of degeneration and chronic inflammation. Although CAT cases are increasingly reported, its clinical manifestation remains unclear. We aimed to conduct a narrative review of CAT and identify its clinical characteristics. We conducted a comprehensive literature search using PubMed, with the keyword "Cardiac Calcified Amorphous Tumor" to identify relevant articles. A total of 113 articles published between 1997 and 2022 were retrieved. The clinical features allowing for assess patient background, differences with and without end-stage renal disease (ESRD), symptom-related factors, risk factors for embolism caused by CAT, and features of CAT, such as shape, location, mobility, pathology, and treatment, were statistically analyzed in 106 criteria-matched cases. The mean patient age was 60.2 ± 18.6 years, with 45 men and 61 women. Of the data collected from 21 countries, 52 patients were from Japan. Mobile CAT was more common in the chronic renal failure group. Linear, club-shaped, and spindle-shaped CAT tended to be mobile and more common in the ESRD group as well as located in the mitral valve region. The shape, mobility, location, and underlying mechanism of CAT depended on the presence or absence of ESRD. The risk of embolism was considered high because mobile CAT was more common in the ESRD group, and CAT originated in the mitral valve region. Hence, early diagnosis based on periodic examination in patients with ESRD and aggressive surgical treatment are necessary.

Analysis of Calcaneal Avulsion Fractures Treated Surgically and Nonsurgically: A Retrospective Multicenter Study.

Background: Calcaneal avulsion fractures (CAvFs) at the Achilles tendon insertion are among the more challenging fractures to treat. Although rare, they often require reoperation. The optimal treatment, including nonsurgical procedures and better implants for surgical procedures in the treatment of CAvFs, remains to be established. Therefore, our study aimed to (1) perform a descriptive evaluation of CAvFs, including cases managed nonsurgically, and (2) assess surgical procedures, including the incidence of complications and reoperation for surgically treated CAvFs. Methods: In this multicenter retrospective study, we collected data of patients with CAvFs treated at 9 hospitals from 2012 to 2022. We performed a descriptive study of CAvFs and compared postoperative complications and reoperation rates for multiple surgical techniques and implants. The size of the bone fragments was quantified. Results: The data of 70 patients with CAvFs were analyzed; 20 patients were treated nonsurgically, and 50 were treated surgically. The mean age of patients was 68.5 years; 67% of the patients were female. Nineteen percent of the patients had diabetes, and 19% had osteoporosis. The incidence of postoperative complications was 30%, with infection in 14%, necrosis in 26%, and loss of reduction in 18%. The reoperation rate was 22%. Surgical techniques with use of cannulated cancellous screws were performed in 80% of the surgical cases. Cannulated cancellous screw (CCS) fixation alone resulted in a reoperation rate of 35%, whereas additional augmentation, including washers with CCS fixation, resulted in a reoperation rate of 10%. CCS fixation was successfully performed, although suture anchors were used in some cases with smaller fragments. Conclusions: CAvFs occurred more frequently in older women and had a high rate of postoperative complications. A combination of CCS with augmentation was more effective at reducing postoperative complications than CCS fixation alone, even when the bone fragment size was small. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The association between CD34 expression status and the clinicopathological behavior of dedifferentiated liposarcoma.

Lipogenic and fibrous tumors are thought to originate from CD34-positive stromal fibroblastic/fibrocystic cells. Well-differentiated lipogenic tumors typically express CD34, whereas dedifferentiated liposarcoma (DDLPS) often loses it. We conducted survival analyses involving 59 patients with DDLPS. Males comprised 53% of the cohort, and the median age at the time of wide resection of primary DDLPS was 60 years. Loss of CD34 expression was defined as when ≥50% of the dedifferentiated area was immunohistochemically negative for CD34. As a result, 39 of the 59 patients showed loss of CD34 expression during the initial operation for DDLPS. In the univariate analyses, the tumor site in the retroperitoneum/abdominal cavity and loss of CD34 expression were significantly associated with poor overall survival. In the multivariate analyses, loss of CD34 expression (HR = 2.26; 95% CI = 1.02-5.02; p = 0.04) and the tumor site in the retroperitoneum/abdominal cavity (HR = 3.11; 95% CI = 1.09-8.86; p = 0.03) were retained as independent prognostic factors. Six CD34-positive cases lost CD34 expression when they developed metastasis and/or local recurrence, suggesting that the loss was associated with the later stage of the tumor. Therefore, an association existed between the loss of CD34 expression and clinicopathological behaviors such as poorer prognoses and recurrence.