Thick mesopancreas is a novel predictor of surgical outcomes of patients who undergo pancreaticoduodenectomy.

PURPOSE: Mesopancreas resection is a crucial but difficult procedure when performing pancreaticoduodenectomy. This study evaluated the influence of mesopancreas thickness on surgical outcomes in patients undergoing pancreaticoduodenectomy. METHODS: We measured the thickness of the fat tissue on the right side of the superior mesenteric artery from the dorsal margin of the confluence of the superior mesenteric vein and portal vein to the ventral margin of the left renal vein on preoperative contrast-enhanced computed tomography and defined it as the mesopancreas thickness. We evaluated the correlation between mesopancreas thickness and intraoperative and postoperative variables in 357 patients who underwent pancreaticoduodenectomy. RESULTS: Multivariate analysis revealed that a thick mesopancreas was significantly associated with a long operative time (ß = 10.361; 95% confidence interval, 0.370-20.353, p = 0.042), high estimated blood loss (ß = 36.038; 95% confidence interval, -27.192-99.268, p = 0.013), and a low number of resected lymph nodes (ß = -1.551; 95% confidence interval, -2.662--0.439, p = 0.006). This analysis further revealed that thick mesopancreas was a significant risk factor for overall morbidity (odds ratio 2.170; 95% confidence interval 1.340-3.520, p = 0.002), major morbidity (odds ratio 2.430; 95% confidence interval 1.360-4.340, p = 0.003), and a longer hospital stay (ß = 2.386; 95% confidence interval 0.299-4.474, p = 0.025). CONCLUSION: A thick mesopancreas could predict a longer operation time, higher estimated blood loss, fewer resected lymph nodes, more frequent overall and major morbidities, and a longer hospital stay in patients who underwent pancreaticoduodenectomy more precisely than the body mass index.

Superiority trial for the development of an ideal method for the closure of midline abdominal wall incisions to reduce the incidence of wound complications after elective gastroenterological surgery: study protocol for a randomized controlled trial.

BACKGROUND: The recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure. The wound closure technique is an important determinant of the risk of wound complications, and a comprehensive approach to prevent wound complications should be developed. METHODS: We propose a single-institute, prospective, randomized, blinded-endpoint trial to assess the superiority of the combination of continuous suturing of the fascia without peritoneal closure and continuous suturing of the subcuticular tissue (study group) over that of interrupted suturing of the fascia together with the peritoneum and interrupted suturing of the subcuticular tissue (control group) for reducing the incidence of midline abdominal wall incision wound complications after elective gastroenterological surgery with a clean-contaminated wound. Permuted-block randomization with an allocation ratio of 1:1 and blocking will be used. We hypothesize that the study group will show a 50% reduction in the incidence of wound complications. The target number of cases is set at 284. The primary outcome is the incidence of wound complications, including incisional surgical site infection, hemorrhage, seroma, wound dehiscence within 30 days after surgery, and incisional hernia at approximately 1 year after surgery. DISCUSSION: This trial will provide initial evidence on the ideal combination of fascial and skin closure for midline abdominal wall incision to reduce the incidence of overall postoperative wound complications after gastroenterological surgery with a clean-contaminated wound. This trial is expected to generate high-quality evidence that supports the current guidelines for the closure of abdominal wall incisions from the European and American Hernia Societies and to contribute to their next updates. TRIAL REGISTRATION: UMIN-CTR UMIN000048442. Registered on 1 August 2022. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055205.

Intraspecific divergence in a coastal plant, Euphorbia jolkinii, at a major biogeographic boundary in East Asia.

PREMISE: Quaternary climatic fluctuations and long-distance seed dispersal across the sea are critical factors affecting the distribution of coastal plants, but the spatiotemporal nature of population expansion and distribution change of East Asian coastal plants during this period are rarely examined. To explore this process, we investigated the genome-wide phylogenetic patterns of Euphorbia jolkinii Boiss. (Euphorbiaceae), which grows widely on littoral areas of Japan, Korea, and Taiwan. METHODS: We used plastome sequences and genome-wide single nucleotide polymorphisms in samples across the species range to reveal phylogeographic patterns and spatiotemporal distributional changes. We conducted ecological niche modeling for the present and the last glacial maximum (LGM). RESULTS: Genetic differentiation was observed between the northern and southern populations of E. jolkinii, separated by the major biogeographic boundary, the Tokara Gap. These two groups of populations differentiated during the glacial period and subsequently intermingled in the intermorainic areas of the central Ryukyu Islands after the LGM. Ecological niche models suggested that the potential range of E. jolkinii was restricted to southern Kyushu; however, it was widespread in the southern Ryukyu Islands and Taiwan during the LGM. CONCLUSIONS: This study provides evidence of genetic differentiation among coastal plant populations separated by the prominent biogeographical boundary. Although coastal plants are typically expected to maintain population connectivity through sea-drifted seed dispersal, our findings suggest that genetic differences may arise because of a combination of limited gene flow and changes in climate during the glacial period.

Synthesis and Biological Evaluations of Novel Human Parathyroid Hormone 1 Receptor (hPTHR1) Agonists Bearing Bicyclic Aromatic Moiety.

We have previously shown that the small molecule hPTHR1 agonist PCO371 (1) orally and dose-dependently induces PTH-like calcemic and hypophostemic activity in thyroparathyroidectomized rats. Compound 2a, bearing a bicyclic aromatic ring, was identified as a novel hPTHR1 agonist during hit to lead modification. It showed moderate PTHR1 agonistic activity with an EC20 value of 15 µM, and its metabolic stability in human liver microsome (hLM) as well as its solubility in phosphate buffer (PPb) and Fasted state simulated intestinal fluid (FaSSIF) were found to be poor. As results of the initial derivatization of 2a, we identified the indole derivatives as another scaffold. In this article, we report on the structure-activity relationship (SAR), structure-metabolism relationship (SMR), and structure-solubility relationship (SSR) of bicyclic aromatic derivatives, and the in vivo efficacy of 2j.

A postoperative body weight increase is a novel risk factor for incisional hernia of midline abdominal incision after elective gastroenterological surgery.

PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.

Molecular aggregation in liquid-crystalline layers crucially affects their physics: smectic A (SmA)-nematic (N) phase transition.

Recently, two molecular packing modes of the alkyl chain in smectic A (SmA) liquid crystal phases were revealed: normal and tilted types, which are named by the orientation relative to the layer normal. This study reveals the relationship between the packing mode and thermodynamic order of the SmA-nematic (N) phase transition. Two normal type and three tilted type mesogens were subject to thermodynamic and structural experiments. The DSC results showed that the SmA-N phase transitions of the normal and tilted types are of the second and first order, respectively. The analysis of the intensities of reflections in wide-angle X-ray diffraction related to the periodicity of the SmA layer yielded the distribution of the mass centers of molecules along the normal to the SmA layers. The resultant distribution offered a rationale for the correlation of the thermodynamic order of the SmA-N phase transition and molecular packing modes in the SmA phases based on the Meyer-Lubensky theory.

Class B1 GPCR activation by an intracellular agonist.

G protein-coupled receptors (GPCRs) generally accommodate specific ligands in the orthosteric-binding pockets. Ligand binding triggers a receptor allosteric conformational change that leads to the activation of intracellular transducers, G proteins and ß-arrestins. Because these signals often induce adverse effects, the selective activation mechanism for each transducer must be elucidated. Thus, many orthosteric-biased agonists have been developed, and intracellular-biased agonists have recently attracted broad interest. These agonists bind within the receptor intracellular cavity and preferentially tune the specific signalling pathway over other signalling pathways, without allosteric rearrangement of the receptor from the extracellular side1-3. However, only antagonist-bound structures are currently available1,4-6, and there is no evidence to support that biased agonist binding occurs within the intracellular cavity. This limits the comprehension of intracellular-biased agonism and potential drug development. Here we report the cryogenic electron microscopy structure of a complex of Gs and the human parathyroid hormone type 1 receptor (PTH1R) bound to a PTH1R agonist, PCO371. PCO371 binds within an intracellular pocket of PTH1R and directly interacts with Gs. The PCO371-binding mode rearranges the intracellular region towards the active conformation without extracellularly induced allosteric signal propagation. PCO371 stabilizes the significantly outward-bent conformation of transmembrane helix 6, which facilitates binding to G proteins rather than ß-arrestins. Furthermore, PCO371 binds within the highly conserved intracellular pocket, activating 7 out of the 15 class B1 GPCRs. Our study identifies a new and conserved intracellular agonist-binding pocket and provides evidence of a biased signalling mechanism that targets the receptor-transducer interface.

Update of risk factors for surgical site infection in clean-contaminated wounds after gastroenterological surgery: An analysis of 1,878 participants enrolled in 2 recent randomized control trials for the prevention of surgical site infection.

BACKGROUND: Clean-contaminated wounds should be the main target for reducing the burden of harm caused by surgical site infection after gastroenterological surgery. METHODS: The present study targeted 1,973 patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional surgical site infection prevention after gastroenterological surgery with clean-contaminated wounds. Patients were reassessed, and preoperative and postoperative variables were collected. Risk factors for surgical site infection were identified by univariate and multivariate analyses. RESULTS: The study population included 1,878 patients, among whom 213 (11.3%) developed overall surgical site infection and 119 (6.3%) developed incisional surgical site infection. A multivariate analysis revealed that steroid or immunosuppressant use (odds ratio 3.03; 95% confidence interval 1.37-6.73, P = .0064), open surgery (odds ratio 1.77; 95% confidence interval 1.11-2.83, P = .0167), and long operative time (odds ratio 2.31; 95% confidence interval 1.5-3.56, P < .001) were independent risk factors for incisional surgical site infection. Steroid or immunosuppressant use (odds ratio 2.62; 95% confidence interval 1.29-5.33, P = .0078), open surgery (odds ratio 2.13; 95% confidence interval 1.44-3.16, P < .001), and long operative time (odds ratio 2.92; 95% confidence interval 2.08-4.10, P < .001) were also independent risk factors for overall surgical site infection in the multivariate analysis. Furthermore, a multivariate analysis revealed that a long operative time (odds ratio 3.21; 95% confidence interval 1.69-6.1, P = .00378) was an independent risk factor for incisional surgical site infection in patients who underwent laparoscopic surgery. CONCLUSION: Even under current measures for surgical site infection prevention, surgeons should continue to make efforts to appropriately expand the indication of laparoscopic surgery and to reduce operative times even when performing laparoscopic surgery.

A case of needle tract seeding that seemed to be caused by endoscopic ultrasound-guided fine-needle aspiration.

A 66-year-old man underwent a single endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) session and distal pancreatectomy for the pancreatic body adenocarcinoma measuring 12 mm in diameter. At 3 years after surgery, we diagnosed needle tract seeding (NTS) and performed total gastrectomy. NTS can occur with small tumors or after a single session of EUS-FNA.

Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging.

Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable disease; mPD, progressive disease. Of 61 patients, 14 diagnosed with PD after initial CT imaging showed significantly worse therapeutic outcomes than 47 patients with disease control. In these 47 patients, initial molecular assessment exhibited significant differences in therapeutic outcomes between patients with and without ctDNA (mPD + mSD vs. mCR + mNT; 13.2 M vs. 21.7 M, P = 0.0029) but no difference between those with mPD and mSD + mCR + mNT, suggesting that the presence of ctDNA had more impact on the therapeutic outcomes than change in its number. Multivariate analysis revealed that it was the only independent prognostic factor (P = 0.0405). The presence of ctDNA in initial molecular assessment predicted early tumor progression and identified PC patients more likely to benefit from chemotherapy.

Implementation of intraoperative wound irrigation with aqueous 10% povidone-iodine and triclosan-coated sutures is not effective for reducing the incidence of incisional surgical site infection after major hepato-biliary-pancreatic surgery in patients with preoperative biliary drainage.

BACKGROUND/PURPOSE: Patients who receive preoperative biliary drainage (PBD) and biliary reconstruction are most at risk for incisional surgical site infection (SSI) in major hepatobiliary-pancreatic (HBP) surgery. METHODS: We evaluated 72 patients with PBD who underwent major HBP surgery and received intraoperative wound irrigation (IOWI) with saline and standard sutures between March 2014 and March 2017 (Cohort 1) and 63 patients with PBD who underwent major HBP surgery and received IOWI with aqueous 10% povidone-iodine and antibacterial sutures between June 2019 and February 2022 (Cohort 2). We compared the incidence of incisional SSI between the two cohorts. RESULTS: Twenty-seven (20.0%) of 135 patients developed incisional SSIs. The rate of current smoking was more frequent in patients who developed incisional SSIs than in those who did not (37.0% vs. 14.8%, p = .012). A total of 18 (25%) of 72 patients developed incisional SSI in Cohort 1, and nine (14.3%) of 63 developed incisional SSI in Cohort 2. Cohort 2 had a 10% lower incidence of incisional SSI than Cohort 1, a nonsignificant difference (p = .09). CONCLUSION: The implementation of IOWI with aqueous 10% PVP-I and antibacterial sutures failed to significantly reduce the incidence of incisional SSI in comparison to IOWI with saline and standard sutures in major HBP surgery.

Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial.

OBJECTIVE: This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI). BACKGROUND: IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low. METHODS: This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set. RESULTS: Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154). CONCLUSION: The current recommendation of IOWI with aqueous PVP-I should be reconsidered.

Molecular dynamics and kinetics of isothermal cold crystallization with tunable dimensionality in a molecular glass former, 5'-(2,3-difluorophenyl)-2'-ethoxy-4-pentyloxy-2,3-difluorotolane.

This paper characterizes the molecular mobility that triggers the cold crystallization abilities in 5'-(2,3-difluorophenyl)-2'-ethoxy-4-pentyloxy-2,3-difluorotolane (short name DFP25DFT) material by broadband dielectric spectroscopy (BDS). We analyze the properties of identified molecular motions by referring to the Vogel-Fulcher-Tammann (VFT) model for the structural α-process associated with molecular rotation in isotropic liquid and the Eyring and Starkweather approach for the thermally activated processes, ß-process related to intramolecular movement in liquid and glassy state and emerging during cold crystallization α'-process ascribed to confined movements of molecules located adjacent to crystalline surfaces. To characterize the material, we employ single-crystal X-ray diffraction, differential scanning calorimetry (DSC), adiabatic calorimetry, and polarizing optical microscopy (POM), while we utilize molecular mechanics simulations (MM2) to explore molecular flexibility. Our study focuses on inter- and intramolecular interactions that determine the cold-crystallization tendency. We demonstrate that the solidification path is controlled by the fragility of the system, the dipole-dipole attraction, and the intramolecular dynamics. The study of cold crystallization kinetics under isothermal conditions reveals the complexity of the process: the formation of two crystalline phases, Cr2 and Cr3, proceeding in different modes. This feature discloses the possibility of switching the crystal growth between three- and two-dimensional in the cold-crystallization process driven by different mechanisms.

Liquid biopsy leads to a paradigm shift in the treatment of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most cancers. Its 5-year survival rate is very low. The recent induction of neoadjuvant chemotherapy and improvements in chemotherapy for patients with pancreatic cancer have resulted in improved survival outcomes. However, the prognosis of pancreatic cancer is still poor. To dramatically improve the prognosis, we need to develop more tools for early diagnosis, treatment selection, disease monitoring, and response rate evaluation. Recently, liquid biopsy (circulating free DNA, circulating tumor DNA, circulating tumor cells, exosomes, and microRNAs) has caught the attention of many researchers as a new biomarker that is minimally invasive, confers low-risk, and displays an overall state of the tumor. Thus, liquid biopsy does not employ the traditional difficulties of obtaining tumor samples from patients with advanced PDAC to investigate their molecular biological status. In addition, it allows for long-term monitoring of the molecular profile of tumor progression. These could help in identifying tumor-specific alterations that use the target structure for tailor-made therapy. Through this review, we highlighted the latest discoveries and advances in liquid biopsy technology in pancreatic cancer research and showed how it can be applied in clinical practice.

Temporal association of vitreous hemorrhage and hypertension after COVID-19 mRNA vaccines.

Vitreous hemorrhage as common eye presentation and hypertension as common systemic presentation are difficult to designate whether they are coincidental or causal in terms of adverse events of COVID-19 vaccinations. Temporal association of hypertension and vitreous hemorrhage was noted in a patient repeatedly after the second and third COVID-19 vaccinations.

Genome­wide DNA hypomethylation drives a more invasive pancreatic cancer phenotype and has predictive occult distant metastasis and prognosis potential.

Genome­wide DNA hypomethylation is the most common molecular feature in human cancers associated with chromosomal instability (CIN), which is involved in the mechanisms that regulate pancreatic cancer (PC) metastasis. It was investigated whether genome­wide DNA hypomethylation affects the phenotype in PC via CIN in vitro, and its significance on the biological behavior of PC was verified. The relative demethylation level (RDL) of long interspersed nucleotide element­1 (LINE­1) in human PC cell lines was used to characterize DNA hypomethylation using methylation­specific quantitative (q)PCR. CIN was estimated by changes in chromosomal copy number using comparative genomic hybridization analysis. Abnormal segregation of chromosomes was assessed by immunocytochemistry, and the DNA damage response was evaluated using the number of anti­Î³H2AX positive cells. Invasion ability was assessed using a Matrigel invasion assay. Clinical specimens from 49 patients with PC who underwent curative surgery were evaluated for a correlation of DNA hypomethylation with clinical outcome. Successful induction of genome­wide DNA hypomethylation in PC cells led to copy number changes in specific chromosomal regions. The number of cells with abnormal segregation of chromosomes significantly increased with the number of anti­Î³H2AX positive cells. The invasive potential of these cells also significantly increased. The occurrence of occult distant metastasis in the clinical specimens and receiver operating characteristic analysis clearly identified those who were and were not likely to have occult distant metastasis, with high LINE­1 RDL significantly correlated with the presence of occult distant metastasis (P=0.035) and poor prognosis (P=0.048). The significance of genome­wide DNA hypomethylation on the biological behavior of PC, which promotes a more invasive phenotype via CIN in vitro and predicts the susceptibility to occult distant metastasis and poor prognosis in patients with PC was revealed.

Multiple origins of two Ochrosia (Apocynaceae) species endemic to the Bonin (Ogasawara) Islands.

The genus, Ochrosia, is widely distributed from the West Indian Ocean throughout tropical Asia to the Middle Southern Pacific region. Ochrosia comprises many island-endemic species, suggesting that long-distance dispersal and isolation after migration are key factors for clarifying the diversification process. However, the phylogeny and biogeography of endemic Ochrosia species have not been evaluated well due to the difficulty of adequate sampling from the entire distribution range of the genus. In this study, we focused on two Ochrosia species endemic to the Bonin (Ogasawara) Islands in the northwest Pacific. The Bonin Islands are of volcanic origins and consist of two islands groups, the Ogasawara and Volcano Islands groups, approximately 300 km apart. Ochrosia nakaiana is endemic to the Ogasawara Islands group, whereas O. hexandra is endemic to the Volcano Islands group. To elucidate the phylogenetic positions of these two endemic Ochrosia species, we conducted molecular phylogenetic studies with dating and biogeographic analyses including other Ochrosia species. The phylogenetic trees showed that the two endemic species had distinct origins; O. nakaiana was closely related to O. oppositifolia and O. iwasakiana, whereas O. hexandra was related to O. mariannensis. Based on the chloroplast DNA phylogeny, the genus, Ochrosia, divided into two major lineages 36.6 million years ago. Further, the two endemic species of the Bonin Islands were independently derived approximately 1-2 million years ago. Ochrosia nakaiana originated from the Southeast Asia, New Caledonia, or other Pacific Islands, while O. hexandra derived from O. mariannensis in Micronesia. We demonstrated different origins of the two endemic Ochrosia species on the Bonin Islands. This study provided an excellent example of the complex origins and speciation of flora in the oceanic islands.

A case report: Dual-lead deep brain stimulation of the posterior subthalamic area and the thalamus was effective for Holmes tremor after unsuccessful focused ultrasound thalamotomy.

Holmes tremor is a symptomatic tremor that develops secondary to central nervous system disorders. Stereotactic neuromodulation is considered when the tremors are intractable. Targeting the ventral intermediate nucleus (Vim) is common; however, the outcome is often unsatisfactory, and the posterior subthalamic area (PSA) is expected as alternative target. In this study, we report the case of a patient with intractable Holmes tremor who underwent dual-lead deep brain stimulation (DBS) to stimulate multiple locations in the PSA and thalamus. The patient was a 77-year-old female who complained of severe tremor in her left upper extremity that developed one year after her right thalamic infarction. Vim-thalamotomy using focused ultrasound therapy (FUS) was initially performed but failed to control tremor. Subsequently, we performed DBS using two leads to stimulate four different structures. Accordingly, one lead was implanted with the aim of targeting the ventral oralis nucleus (Vo)/zona incerta (Zi), and the other with the aim of targeting the Vim/prelemniscal radiation (Raprl). Electrode stimulation revealed that Raprl and Zi had obvious effects. Postoperatively, the patient achieved good tremor control without any side effects, which was maintained for two years. Considering that she demonstrated resting, postural, and intention/action tremor, and Vim-thalamotomy by FUS was insufficient for tremor control, complicated pathogenesis was presumed in her symptoms including both the cerebellothalamic and the pallidothalamic pathways. Using the dual-lead DBS technique, we have more choices to adjust the stimulation at multiple sites, where different functional networks are connected. Intractable tremors, such as Holmes tremor, may have complicated pathology, therefore, modulating multiple pathological networks is necessary. We suggest that the dual-lead DBS (Vo/Raprl and Vim/Zi) presented here is safe, technically feasible, and possibly effective for the control of Holmes tremor.

A Comparative Study of Endoscopic Ultrasonography and Histopathology Images for the Diagnosis of Early Chronic Pancreatitis.

OBJECTIVE: The concept of early chronic pancreatitis (ECP) and its diagnostic criteria were first proposed by Japan, using endoscopic ultrasonography (EUS) findings for diagnosis. However, these findings have not been supported by pathological findings. We aimed to examine the association between the EUS and pathological findings of the same area of the pancreas. METHODS: In 12 patients who underwent pancreaticoduodenectomy for distal bile duct cancer without accompanying pancreatitis, a comparative analysis between preoperative EUS and pathological findings was performed. The part of the pancreas adjoining the portal vein was evaluated. RESULTS: In 7 cases, abnormal EUS findings included in the diagnostic criteria for ECP were seen; the correlation of the accuracy of lobularity seen on EUS compared with the pathological findings of the pancreatic parenchyma (inflammatory cell infiltration, atrophy of acinar cells, and fibrosis) was high (83.3%-91.7%). Pancreatic duct findings revealed that the accuracy of the hyperechoic margin of the pancreatic duct on EUS compared with pathological findings (wall thickness of pancreatic duct) was high (83.3%). CONCLUSIONS: Endoscopic ultrasonography findings for ECP, according to Japan's 2019 revised criteria, lobularity, and the hyperechoic margin of the pancreatic duct may highly correspond to the pathological findings of chronic inflammation.

Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients.

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.