Advancements and Challenges in Robot-Assisted Bone Processing in Neurosurgical Procedures.

OBJECTIVE: Practical applications of nerve decompression using neurosurgical robots remain unexplored. Our ongoing research and development initiatives, utilizing industrial robots, aim to establish a secure and efficient neurosurgical robotic system. The principal objective of this study was to automate bone grinding, which is a pivotal component of neurosurgical procedures. METHODS: To achieve this goal, we integrated an endoscope system into a manipulator and conducted precision bone machining using a neurosurgical drill, recording the grinding resistance values across 3 axes. Our study encompassed 2 core tasks: linear grinding, such as laminectomy, and cylindrical grinding, such as foraminotomy, with each task yielding unique measurement data. RESULTS: In linear grinding, we observed a proportional increase in grinding resistance values in the machining direction with acceleration. This observation suggests that 3-axis resistance measurements are a valuable tool for gauging and predicting deep cortical penetration. However, problems occurred in cylindrical grinding, and a significant error of 10% was detected. The analysis revealed that multiple factors, including the tool tip efficiency, machining speed, teaching methods, and deflection in the robot arm and jig joints, contributed to this error. CONCLUSION: We successfully measured the resistance exerted on the tool tip during bone machining with a robotic arm across 3 axes. The resistance ranged from 3 to 8 Nm, with the measurement conducted at a processing speed approximately twice that of manual surgery performed by a surgeon. During the simulation of foraminotomy under endoscopic grinding conditions, we encountered a -10% error margin.

Transoral Robotic-Assisted Neurosurgery for Skull Base and Upper Spine Lesions.

OBJECTIVE: The application of the da Vinci Surgical System in neurosurgery is limited due to technical difficulties requiring precise maneuvers and small instruments. This study details the advantages and disadvantages of robotics in neurosurgery and the reachable range of the transoral approach to lesions of the skull base and upper cervical spine. METHODS: In a cadaver study, the da Vinci Xi robot, lacking haptic feedback, was utilized for sagittal and coronal approaches on 5 heads, facilitating dura suturing in 3, with a 30°-angled drill for bone removal. RESULTS: Perfect exposure of all the nasopharyngeal sites, clivus, sellar, and choana, including the bilateral eustachian tubes, was achieved without any external incisions using this palatal split approach of transoral robotic surgery. The time required to perform a single stitch, knot, and complete single suture in robotic suturing of deep-seated were significantly less compared to manual suturing via the endonasal approach. CONCLUSION: This is the first report to show the feasibility of suturing the dural defect in deep-seated lesions transorally and revealed that the limit of reach in the coronal plane via a transoral approach with incision of the soft palate is the foramen ovale. This preclinical investigation also showed that the transoral robotic approach is feasible for lesions extending from the sellar to the C2 in the sagittal plane. Refinement of robotic instruments for specific anatomic sites and future neurosurgical studies are needed to further demonstrate the feasibility and effectiveness of this system in treating benign and malignant skull base lesions.

Green Hospital as A New Standard in Japan: How far can Neurosurgery go in Japan?

BACKGROUND: Climate change is a significant challenge that the medical community must address. Hospitals are large facilities with high water and energy consumption, as well as high levels of waste generation, which makes it important to pursue green hospital initiatives. Neurosurgery requires substantial energy for surgeries and tests. METHODS: Based on the keywords "Climate change," "green hospital," "neurosurgery," "energy consumption," "environmental impact" listed in this paper, we extracted representative manuscripts, and the practices employed in the authors' hospital were assessed. RESULTS: The "Guidelines for Environmental Consideration in Hospitals" and "Guidelines for the Sustainability of Hospital Environments" have been developed; however, they are not implemented in most hospitals in Japan. Inhalational anaesthetics were found to contribute significantly to greenhouse gas emissions. Educating patients and staff and employing the "8 Rs" (rethink, refuse, reduce, reuse, recycle, research, renovation and revolution) showed promise in achieving green hospital standards. CONCLUSION: The advent of 'green hospitals' in Japan is imminent. The active participation of neurosurgeons can play a crucial role in diminishing the environmental footprint of health care while simultaneously enhancing medical standards. Given the pressing challenges posed by climate change, there is a critical need for an overhaul of medical practices. It is imperative for neurosurgeons to pioneer the adoption of new, sustainable medical methodologies.

Presentation and Management of Cerebral Venous Sinus Thrombosis After Supratentorial Craniotomy.

BACKGROUND AND OBJECTIVES: Cerebral venous sinus thrombosis (CVST) after supratentorial craniotomy is a poorly studied complication, for which there are no management guidelines. This study assessed the incidence, associated risk factors, and management of postoperative CVST after awake craniotomy. METHODS: This is an observational, retrospective, monocentric analysis of patients who underwent a supratentorial awake craniotomy. Postoperative CVST was defined as a flow defect on the postoperative contrast-enhanced 3D T1-weighted sequence and/or as a T2* hypointensity within the sinus. RESULTS: In 401 supratentorial awake craniotomies (87.3% of diffuse glioma), the incidence of postoperative CVST was 4.0% (95% CI 2.5-6.4): 14/16 thromboses located in the superior sagittal sinus and 12/16 located in the transverse sinus. A venous sinus was exposed during craniotomy in 45.4% of cases, and no intraoperative injury to a cerebral venous sinus was reported. All thromboses were asymptomatic, and only two cases were diagnosed at the time of the first postoperative imaging (0.5%). Postoperative complications, early postoperative Karnofsky Performance Status score, and duration of hospital stay did not significantly differ between patients with and without postoperative CVST. Adjusted independent risk factors of postoperative CVST were female sex (adjusted Odds Ratio 4.00, 95% CI 1.24-12.91, P = .021) and a lesion ≤1 cm to a venous sinus (adjusted Odds Ratio 10.58, 95% CI 2.93-38.20, P < .001). All patients received standard prophylactic-dose anticoagulant therapy, and none received treatment-dose anticoagulant therapy. No thrombosis-related adverse event was reported. All thromboses presented spontaneous sinus recanalization radiologically at a mean of 89 ± 41 days (range, 7-171). CONCLUSION: CVST after supratentorial awake craniotomy is a rare event with satisfactory clinical outcomes and spontaneous sinus recanalization under conservative management without treatment-dose anticoagulant therapy. These findings are comforting to neurosurgeons confronted with postoperative MRI reports suggesting CVST.

A fluorescence imaging technique suggests that sweat leakage in the epidermis contributes to the pathomechanism of palmoplantar pustulosis.

Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology.

Shorter survival time of adolescents and young adult patients than older adults with spinal cord glioblastoma: a multicenter study.

OBJECTIVE: Cancers in adolescents and young adults (AYAs) (age 15-39 years) often present with unique characteristics and poor outcomes. To date, spinal cord glioblastoma, a rare tumor, remains poorly understood across all age groups, including AYAs. This comparative study aimed to investigate the clinical characteristics and outcomes of spinal cord glioblastoma in AYAs and older adults (age 40-74 years), given the limited availability of studies focusing on AYAs. METHODS: Data from the Neurospinal Society of Japan's retrospective intramedullary tumor registry (2009-2020) were analyzed. Patients were dichotomized on the basis of age into AYAs and older adults. Univariate and multivariate Cox proportional hazards regression models were utilized to explore risk factors for overall survival (OS). RESULTS: A total of 32 patients were included in the study, with a median (range) age of 43 (15-74) years. Of these, 14 (43.8%) were AYAs and 18 (56.2%) were older adults. The median OS was 11.0 months in AYAs and 32.0 months in older adults, and the 1-year OS rates were 42.9% and 66.7%, respectively, with AYAs having a significantly worse prognosis (p = 0.017). AYAs had worse preoperative Karnofsky Performance Status (KPS) than older patients (p = 0.037). Furthermore, AYAs had larger intramedullary tumors on admission (p = 0.027) and a significantly higher frequency of intracranial dissemination during the clinical course (p = 0.048). However, there were no significant differences in the degrees of surgical removal or postoperative radiochemotherapy between groups. The Cox proportional hazards regression model showed that AYAs (HR 3.53, 95% CI 1.17-10.64), intracranial dissemination (HR 4.30, 95% CI 1.29-14.36), and no radiation therapy (HR 57.34, 95% CI 6.73-488.39) were risk factors for mortality for patients of all ages. Worse preoperative KPS did not predict mortality in AYAs but did in older adults. The high incidence of intracranial dissemination may play an important role in the poor prognosis of AYAs, but further studies are needed. CONCLUSIONS: The clinical characteristics of AYAs with spinal cord glioblastoma differ from those of older adults. The prognosis of AYAs was clearly worse than that of older adults. The devastating clinical course of spinal glioblastoma in AYAs was in line with those of other cancers in this age group.

A Case of Pneumothorax Required Surgical Treatment as a Complication of Paclitaxel with Bevacizumab Treatment.

A 63-year-old woman had a history of neoadjuvant chemotherapy, mastectomy, and adjuvant endocrine therapy for 5 years before being diagnosed with recurrent lesions involving the right anterior chest wall, multiple lymph nodes, and pulmonary metastases. The patient was subsequently initiated on a paclitaxel and bevacizumab regimen. During this treatment, the patient complained of palpitations and malaise. Chest radiography revealed a left pneumothorax. Despite attempts at conservative treatment, the pneumothorax did not improve and a thoracoscopic approach was required. One of the metastatic tumors in the left lower lobe appeared to rupture, and this area was estimated to be the cause of air leak. The tumor was covered with a tissue seal sheet, and the patient's condition improved with no recurrence of pneumothorax. This case highlights the importance of early conversion to surgical treatment when conservative treatment for pneumothorax is unresponsive due to the potential side effects of bevacizumab. The findings of this case report may be of interest to oncologists, pulmonologists, and other healthcare professionals involved in the care of patients with breast cancer and pulmonary metastases who are undergoing bevacizumab chemotherapy.

Tumor-to-thoracic height ratio as an easy method to predict the feasibility of reduced-port video-assisted thoracic surgery for mediastinal lesions in children: a single-center experience.

In the last few decades, reduced-port video-assisted thoracic surgery (RP-VATS) has been developed to minimize surgical invasiveness. Nevertheless, VATS in children can occasionally be difficult because the lesion occupies a small thoracic cavity, limiting the working space. This study aimed to assess the feasibility of RP-VATS for the resection of mediastinal lesions in children in association with the tumor-to-thoracic height ratio (TTH ratio). We reviewed all patients aged ≤10 years who underwent resection for mediastinal lesions in our institute between January 2008 and August 2022. Patients who underwent diagnostic procedures were excluded from this study. The TTH ratio was calculated as tumor height divided by thoracic height. Seven patients in the RP-VATS group and six in the conventional procedures (multi-portal VATS or open surgery) group were included in this study. The TTH ratio was significantly lower in the RP-VATS group than in the conventional procedures group (median, 26.3% vs. 50.8%; P=0.007). The operating time (P=0.01) and duration of drainage (P=0.003) were significantly shorter and the blood loss (P=0.001) was significantly lower in the RP-VATS group than in the conventional procedures group. After adjusting for age, a lower TTH ratio was significantly associated with the completion of RP-VATS (odds ratio: 0.776; 95% confidence interval: 0.529-0.926; P=0.048). In conclusion, RP-VATS can be performed appropriately in carefully selected cases of pediatric mediastinal lesions. A low TTH ratio may predict the feasibility of RP-VATS. Further studies are warranted to determine the criteria for the indications of RP-VATS in children, so that more children can benefit from RP-VATS.

The Impact of Adjuvant Radiotherapy on Clinical Performance Status in Patients With Grade II Spinal Cord Astrocytoma - A Nationwide Analysis by the Neurospinal Society of Japan.

OBJECTIVE: The impact of adjuvant radiotherapy on overall survival (OS) and progression-free survival (PFS) of patients with grade II spinal cord astrocytomas remains controversial. Additionally, the relationship between progression and clinical deterioration after radiotherapy has not been well investigated. METHODS: This study included 53 patients with grade II intramedullary spinal cord astrocytomas treated by either subtotal, partial resection or open biopsy. Their clinical performance status was assessed immediately before operation and 1, 6, 12, 24, and 60 months after surgery by Karnofsky Performance Scale (KPS). Patients with and without adjuvant radiotherapy were compared. RESULTS: The groups with and without radiation comprised 23 and 30 patients with a mean age of 50.3 ± 22.6 years (range, 2-88 years). The mean overall disease progression rate was 47.1% during a mean follow-up period of 48.4 ± 39.8 months (range, 2.5-144.5 months). In the radiation group, 11 patients (47.8%) presented with progressive disease, whereas 14 patients (46.7%) presented with progressive disease in the group without radiation. There were no significant differences in OS or PFS among patients with or without adjuvant radiotherapy. KPS in both groups, especially radiation group, gradually decreased after operation and deteriorated before the confirmation of disease progression. CONCLUSION: Adjuvant radiotherapy did not show effectiveness regarding PFS or OS in patients with grade II spinal cord astrocytoma according to classical classification based on pathohistological findings.

Clinical Characteristics and Long-term Outcomes of Spinal Pilocytic Astrocytomas: A Multicenter Retrospective Study by the Neurospinal Society of Japan.

OBJECTIVE: The characteristics, imaging features, long-term surgical outcomes, and recurrence rates of primary spinal pilocytic astrocytomas (PAs) have not been clarified owing to their rarity and limited reports. Thus, this study aimed to analyze the clinical presentation, radiological features, pathological findings, and long-term outcomes of spinal PAs. METHODS: Eighteen patients with spinal PAs who were surgically treated between 2009 and 2020 at 58 institutions were included in this retrospective multicenter study. Patient data, including demographics, radiographic features, treatment modalities, and long-term outcomes, were evaluated. RESULTS: Among the 18 consecutive patients identified, 11 were women and 7 were men; the mean age at presentation was 31 years (3-73 years). Most PAs were located eccentrically, were solid or heterogeneous in appearance (cystic and solid), and had unclear margins. Gross total resection (GTR), subtotal resection (STR), partial resection (PR), and biopsy were performed in 28%, 33%, 33%, and 5% of cases, respectively. During a follow-up period of 65 ± 49 months, 4 patients developed a recurrence; however, the recurrence-free survival did not differ significantly between the GTR and non-GTR (STR, PR, and biopsy) groups. CONCLUSION: Primary spinal PAs are rare and present as eccentric and intermixed cystic and solid intramedullary cervical tumors. The imaging features of spinal PAs are nonspecific, and a definitive diagnosis requires pathological support. Surgical resection with prevention of neurological deterioration can serve as the first-line treatment; however, the resection rate does not affect recurrence-free survival. Investigation of relevant molecular biomarkers is required to elucidate the regrowth risk and prognostic factors.

A split Hopkinson pressure bar for experimental investigation of dynamic pulverization under very high strain rates.

Off-fault damage or pulverized rocks found in large-scale strike-slip faults are of great interest in earthquake research. In order to experimentally investigate rock pulverization, we developed a split Hopkinson pressure bar with compact dimensions and high-speed imaging. The developed experimental setup is capable of generating very high strain rates up to 1320 s-1 with the satisfaction of stress equilibrium, which are essential to reproduce the dynamic pulverization observed in nature and obtain dynamic stress-strain responses accurately. High-speed imaging revealed that cracks initiate and propagate along the grain boundaries at very high speeds, while the dynamic stress-strain response suggested that energy dissipated into the fracture increases with stronger impacts. In addition, we show that the apparatus is capable of producing particle size distributions partly similar to those in naturally pulverized rocks of large-scale strike-slip faults. Thus, our developed system with compact dimensions opens new ways to understand the dynamics of the rock pulverization in off-fault regions of large-scale strike-slip faults.

Absence of anti-rabphilin-3A antibodies in children and young adults with idiopathic central diabetes insipidus: a potential clue to elucidating a tumor etiology.

BACKGROUND: Central diabetes insipidus (CDI) is a rare condition caused by various underlying diseases, including neoplasms, autoimmune diseases, and infiltrative diseases. Differentiating between CDI etiologies is difficult. What has initially been classified as "idiopathic" central diabetes insipidus might in fact underlie various pathogenic mechanisms that are less understood to date and/or are not obvious at initial presentation. Therefore, even if idiopathic CDI is diagnosed at the time of onset, it is common for tumors such as germinoma to develop during surveillance. Crucially, a delayed diagnosis of germinoma may be associated with a worse prognosis. Recently, the presence of anti-rabphilin-3A antibodies has been found to be a highly sensitive and specific marker of lymphocytic infundibuloneurohypophysitis, an autoimmune-mediated CDI. CASE PRESENTATION: We herein present two cases, namely, a 13-year-old boy (patient 1) and a 19-year-old young man (patient 2) who were diagnosed with idiopathic CDI. In both patients, panhypopituitarism developed. Magnetic resonance imaging revealed pituitary stalk thickening and pituitary swelling approximately 1 1/2 years after the onset of CDI. Western blotting did not reveal the presence of anti-rabphilin-3A antibodies in serum in either patient, suggesting that autoimmune mechanisms might not be involved. Both patients were subsequently diagnosed with germinoma on pathological examination. They received chemotherapy, followed by radiation therapy. Notably, testosterone and insulin-like growth factor-1 levels normalized, and libido and beard growth recovered after chemoradiotherapy in patient 2. CONCLUSION: Our data suggest that the absence of anti-rabphilin-3A antibodies in young patients clinically diagnosed with idiopathic CDI may increase the probability of the development of non-lymphocytic lesions, including germinoma. We thus recommend a more attentive approach at the onset of these diseases.

[Transoral Robot-Assisted Surgery for Pituitary Gland].

Robotic surgery has been introduced into various surgical fields and is expected to be useful in neurosurgery. Robotic surgery is a technology used to safely and reliably perform minimally invasive surgeries. There are three main types of robotic surgery in neurosurgery: 1)Aids to improve the performance and efficiency of stereotactic surgery; 2)Leader-follower types, such as Da Vinci and hinotori, which enable operations under endoscopy, surgical maneuvers in deep-seated lesions, and operations in areas that are difficult to reach with tools; and 3)Aids to assist the surgeon. Many neurosurgical procedures have shifted from microscopy to endoscopy. One such case is pituitary lesions, where transsphenoidal sinus surgery is currently performed. Originally, Hardy's surgery using microscopy was performed, whereas now endoscopic surgery is mainstream, with the possibility of robotic surgery being used in the near future. This report describes the history of the development of robots, including neurosurgery, the advantages and disadvantages of robotic surgery, and the DaVinci Xi approach to the pituitary gland.

Nuclear IL-33 Plays an Important Role in EGFR-Mediated Keratinocyte Migration by Regulating the Activation of Signal Transducer and Activator of Transcription 3 and NF-κB.

Nuclear IL-33 levels are high at the epidermal edges of skin wounds and facilitate wound healing. However, IL-33-mediated regulation of keratinocyte (KC) biology during wound healing remains poorly understood. During skin-wound healing, KC migration and re-epithelialization are mediated predominantly by EGFR signaling activation and depend on the function of signal transducer and activator of transcription 3 (STAT3). We found that migrating KCs at the leading edges of mouse skin wounds exhibited concomitant induction and nuclear colocalization of IL-33 and phosphorylated STAT3. In cultured human KCs, activation of EGFR signaling caused rapid elevation of nuclear IL-33, which directly interacts with phosphorylated STAT3, promoting STAT3 activation. In vitro KC migration and wound-healing assays revealed that high nuclear IL-33 levels were required for KC migration and wound closure. KC mobility associated with a lack of suprabasal epidermal keratins and extracellular matrix degradation mediated by matrix metalloproteinases (MMPs) control cell migration at the intracellular and extracellular levels, respectively. In EGFR-activated KCs, nuclear IL-33 mediated keratin 1 and 10 downregulation and MMP9 upregulation by promoting STAT3 activation and limited MMP1, MMP3, and MMP10 induction by suppressing NF-κB transactivation. Thus, epidermal nuclear IL-33 is involved in KC migration and wound closure by regulating the STAT3 and NF-κB pathways.

Bone wax technique for full-endoscopic lumbar laminotomy.

Hemostatic procedures in endoscopic spine surgery have not yet been established, especially in full-endoscopic spine surgery (FESS) performed under continuous irrigation, which has been a major concern for surgeons. Chu et al. had previously reported a technique to convey bone wax during full-endoscopic cervical spine surgery via intracorporeal route by using ball tip of the drill in 2018. However, to the best of our knowledge, there has been no report by surgeons to adopt bone wax as a hemostatic material in full-endoscopic lumbar surgery to date, probably because of difficulty in handling bone wax under continuous irrigation and through a narrow and long working channel in endoscope. We have renewed the bone wax technique (BWT) for hemostasis in FESS, improving its handling by introducing a nozzle applicator, without which the bone wax would stick to the working channel of the endoscope on the way to the bleeding target. This would result in significant loss of bone wax and repeated bone-wax contact would cause dirt build-up on the endoscope lens, which would then be pushed out from the wall of the working channel, thereby disturbing the laminectomy procedure and obfuscating the visual field. Technical details using nozzle-loaded bone wax have been demonstrated.

Intraoperative Real-Time Near-Infrared Image-Guided Endoscopic Endonasal Surgery for Pituitary Tumors.

BACKGROUND: For endoscopic endonasal surgery of pituitary tumors, tissue identification and intraoperative judgment depend largely on surgeon expertise. In the present study, we assess whether the delayed-window indocyanine green (ICG) technique can identify pituitary gland tumors in real-time during surgery and analyze the mechanism of ICG fluorescence in the pituitary gland and tumor. METHODS: Twenty-five patients with a pituitary adenoma were administered 12.5 mg of ICG intravenously during surgery. Thereafter, near-infrared (NIR) visualization was performed from 0 to 180 minutes. Only 8 patients underwent dynamic contrast-enhanced perfusion magnetic resonance imaging (MRI) owing to predicaments with insurance coverage. Consequently, we analyzed these 8 patients extensively. RESULTS: The pituitary gland and pituitary adenoma were visualized in all 25 patients with NIR fluorescence. The relative ratio of the fluorescence emission of the normal gland to that of the tumor (signal/background ratio [SBR] of the normal gland vs. the tumor) had increased after 15 minutes, peaking (5.8) at 90 minutes, demonstrating that the pituitary gland was distinctly visualized during that period. The tumor/blood (SBR tumor) and normal gland/blood (SBR gland) NIR fluorescence was significantly and positively correlated with each transfer constant on dynamic contrast-enhanced MRI, indicating vascular permeability. CONCLUSIONS: The results from the present study exhibit the utility of the delayed-window ICG technique in distinguishing the normal pituitary gland from a tumor during endoscopic endonasal surgery from 15 to 90 minutes after ICG administration. Permeability can contribute to gadolinium enhancement on MRI, as well as ICG retention and NIR fluorescence in a normal pituitary gland and tumor.

Is frequent measurement of tumor markers beneficial for postoperative surveillance of colorectal cancer?

PURPOSE: To determine whether frequent measurement of tumor markers triggers early detection of colorectal cancer recurrence. METHODS: Of 1,651 consecutive patients undergoing colorectal cancer surgery between 2010 and 2016, 1,050 were included. CEA and CA 19-9 were considered to be postoperative tumor markers and were measured every 3 months for 3 years, and then every 6 months for 2 years. Sensitivity analysis of elevated CEA and CA19-9 levels and multivariate analysis of factors associated with elevated CEA and CA19-9 levels were performed. The proportion of triggers for detecting recurrence was determined. RESULTS: The median follow-up period was 5.3 years. After applying the exclusion criteria, 1,050 patients were analyzed, 176 (16.8%) of whom were found to have recurrence. After excluding patients with persistently elevated CEA and CA19-9 levels before and after surgery from the 176 patients, 71 (43.6%) of 163 patients had elevated CEA levels and 35 (20.2%) of 173 patients had elevated CA19-9 levels. Sensitivity/positive predictive values for elevated CEA and CA19-9 levels at recurrence were 43.6%/32.3% and 20.2%/32.4%, respectively. Lymph node metastasis was a factor associated with both elevated CEA and CA19-9 levels at recurrence. Of the 176 patients, computed tomography triggered the detection of recurrence in 137 (78%) and elevated tumor marker levels in 13 (7%); the diagnostic lead interval in the latter 13 patients was 1.7 months. CONCLUSION: Tumor marker measurements in surveillance after radical colorectal cancer resection contribute little to early detection, and frequent measurements are unnecessary for stage I patients with low risk of recurrence.

Highly concentrated trehalose induces prohealing senescence-like state in fibroblasts via CDKN1A/p21.

Trehalose is the nonreducing disaccharide of glucose, evolutionarily conserved in invertebrates. The living skin equivalent (LSE) is an organotypic coculture containing keratinocytes cultivated on fibroblast-populated dermal substitutes. We demonstrated that human primary fibroblasts treated with highly concentrated trehalose promote significantly extensive spread of the epidermal layer of LSE without any deleterious effects. The RNA-seq analysis of trehalose-treated 2D and 3D fibroblasts at early time points revealed the involvement of the CDKN1A pathway, the knockdown of which significantly suppressed the upregulation of DPT, ANGPT2, VEGFA, EREG, and FGF2. The trehalose-treated fibroblasts were positive for senescence-associated ß-galactosidase. Finally, transplantation of the dermal substitute with trehalose-treated fibroblasts accelerated wound closure and increased capillary formation significantly in the experimental mouse wounds in vivo, which was canceled by the CDKN1A knockdown. These data indicate that high-concentration trehalose can induce the senescence-like state in fibroblasts via CDKN1A/p21, which may be therapeutically useful for optimal wound repair.

Utility of intraoperative real-time near-infrared fluorescence surgery for spinal schwannoma.

The authors report the first cases of fluorescence-guided spinal surgery of schwannomas using near-infrared fluorescence imaging with the delayed window indocyanine (ICG) green (DWIG) technique for accurate real-time intraoperative tumor visualization. Patients with intradural spinal schwannomas received 0.5 mg/kg ICG at the beginning of surgery. After 1 hour, using the DWIG technique, near-infrared spectroscopy (NIRS) detected the spinal schwannomas, showing the exact tumor location and boundaries. DWIG with NIRS microscopy confirmed the exact location of spinal schwannomas before and after opening of the dura mater, thereby facilitating successful tumor dissection from the surrounding tissues, tumor resection, and confirmation of tumor removal. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21158.