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BACKGROUND: Ileal neuroendocrine tumors (i-NETs) are characterized by their multifocality and bulky mesenteric mass. Having shown that minimally invasive surgery (MIS) utilizing a hand-access port device has favorable short-term outcomes and achieves the goals of surgery for i-NETs, we sought to analyze long-term survival outcomes of MIS. METHODS: One hundred and sixty-eight patients who underwent resection of primary i-NETs at a single institution between January 2007 and February 2023 were retrospectively studied. Patients were categorized into the MIS or open surgery cohorts on an intention-to-treat basis. Open surgery was selected mainly based on the need for hepatectomy or bulky mesenteric mass resection. Overall survival was analyzed using log-rank tests with propensity score matching (PSM) and Cox proportional hazards regression. PSM was performed to reduce standardized mean differences of the variables to

BACKGROUND: In 2023 alone, its estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

PURPOSE: Minimal residual disease (MRD) detection can identify the recurrence in patients with colorectal cancer (CRC) following definitive treatment. We evaluated a plasma-only MRD assay to predict recurrence and survival in patients with metastatic CRC who underwent curative intent procedures (surgery and/or radiotherapy), with or without (neo)adjuvant chemotherapy. The primary objective of this study was to assess the correlation of postprocedure tumor cell-free DNA detection status with radiographic disease recurrence. EXPERIMENTAL DESIGN: Preprocedure and postprocedure longitudinal samples were collected from 53 patients and analyzed with a multiomic MRD assay detecting circulating tumor DNA (ctDNA) from genomic and epigenomic signals. Preprocedure and postprocedure ctDNA detection correlated with recurrence-free and overall survival (OS). RESULTS: From 52 patients, 230/233 samples were successfully analyzed. At the time of data cutoff, 36 (69.2%) patients recurred with median follow-up of 31 months. Detectable ctDNA was observed in 19/42 patients (45.2%) with ctDNA analyzed 3 weeks postprocedure. ctDNA detection 3 weeks postprocedure was associated with shorter median recurrence-free survival (RFS; HR, 5.27; 95% CI, 2.31-12.0; P < 0.0001) and OS (HR, 12.83; 95% CI, 3.6-45.9; P < 0.0001). Preprocedure ctDNA detection status was not associated with RFS but was associated with improved OS (HR, 4.65; 95% CI, 1.4-15.2; P = 0.0111). Undetectable ctDNA preprocedure had notable long-term OS, >90% 3 years postprocedure. CONCLUSIONS: In this cohort of oligometastatic CRC, detection of ctDNA preprocedure or postprocedure was associated with inferior outcomes even after accounting for known prognostic clinicopathologic variables. This suggests ctDNA may enhance current risk stratification methods helping the evaluation of novel treatments and surveillance strategies toward improving patient outcomes.

BACKGROUND: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. CASE PRESENTATION: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. CONCLUSIONS: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.

Background: There is a dearth of data on outcomes of postoperative chemotherapy after neoadjuvant therapy followed by surgery in patients with locally advanced non-small cell lung cancer (NSCLC). The objective of this study was to compare survival outcomes in patients who did and did not receive adjuvant chemotherapy. Methods: A retrospective chart review was performed using our multicenter database to identify patients who received neoadjuvant therapy followed by surgery for clinical T3 N0 or N1-N2 resectable NSCLC between 2009 and 2016. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. Propensity score matching (PSM) was used to control for selection bias in evaluation of overall survival (OS) and recurrence-free survival (RFS) by matching age, sex, smoking history, Charlson Comorbidity Index, histologic type, and pathologic nodal status and stage. Results: The participants were 156 patients with a median age of 65 years. The median RFS of the whole cohort was 66.3 months; OS was not reached. Before PSM, patients receiving adjuvant chemotherapy had significantly shorter RFS (hazard ratio [HR], 1.79; 95% CI, 1.13-2.82) and showed a trend for shorter OS (HR, 1.37; 95% CI, 0.78-2.39). After PSM, 50 patients were used for comparison in each group, and those receiving adjuvant chemotherapy did not have a more favorable RFS (HR, 1.33; 95% CI, 0.75-2.34) or OS (HR, 1.25; 95% CI, 0.62-2.51). Conclusions: Adjuvant chemotherapy was not associated with favorable survival outcomes in patients treated with surgery after neoadjuvant therapy for locally advanced NSCLC.

The adenohypophysis is composed of the anterior and intermediate lobes (AL and IL, respectively), and secretes hormones that play an important role in reproduction. CD9- and SOX2-double (CD9/SOX2) positive cells located in the marginal cell layer (MCL) facing the Rathke’s cleft in the AL and IL form the primary stem cell niche in the adult adenohypophysis of rats. In this study, we successfully obtained 3-dimensional (3D) cell aggregates that closely resembled the primary niche of MCL in vivo. After incubation in a Matrigel containing several growth factors, approximately 20% of the cells in the CD9/SOX2-positive cell aggregates were differentiated into hormone-producing cells. The cell aggregates generated in this study may provide insight into the regulation of the pituitary stem/progenitor cell niche and the turnover of hormone-producing cells.

Pancreatoblastoma is perceived to be aggressive in adults; however, data are limited due to the rarity of the disease. We benchmarked clinico-pathologic characteristics, outcomes, and survival of adult patients with pancreatoblastoma to a comparable PDAC cohort using the National Cancer Database (NCDB). This study included 301,204 patients: 35 with pancreatoblastoma and 301,169 PDAC patients. Pancreatoblastoma patients were younger than PDAC patients (56 vs. 69 years, p < 0.001). More pancreatoblastoma patients were managed at academic institutions (63.0% vs. 40.7%, p = 0.047). The most frequent primary site was the head and the neck of the pancreas. There were no differences in tumor size (4.2 cm vs. 3.7 cm, p = 0.828), lymph node positivity (14.3% vs. 26.4%, p = 0.103), or metastasis at time of diagnosis (31.4% vs. 46.1%, p = 0.081). The majority of pancreatoblastoma patients underwent resection compared to a minority of PDAC patients (69.7% vs. 15.5%, p < 0.001). Time from diagnosis to surgery was longer for pancreatoblastoma patients (33 vs. 14 days, p = 0.030). Pancreaticoduodenectomy was the most common type of resection in the pancreatoblastoma and PDAC groups (47.8% vs. 67.7%, p = 0.124). Among resected patients, pancreatoblastoma patients were less likely to receive radiation (4.8% vs. 37.0%, p = 0.002), but the use of chemotherapy was similar to PDAC patients (60.9% vs. 70.7%). After matching, median overall survival was longer for pancreatoblastoma than PDAC (59.8 months vs. 15.2 months, p = 0.014).

High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.

Abstract Background Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. Methods This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. Discussion This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. Trial registration jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.

Abstract Background Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. Case Presentation We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. Conclusions This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.

Abstract Background Centrally located lung tumours present a challenge because of their tendency to exhibit symptoms such as airway obstruction, atelectasis, and bleeding. Surgical resection of these tumours often requires sacrificing the lungs, making definitive radiotherapy the preferred alternative to avoid pneumonectomy. However, the proximity of these tumours to mediastinal organs at risk increases the potential for severe adverse events. To mitigate this risk, we propose a dual-method approach: deep inspiration breath-hold (DIBH) radiotherapy combined with adaptive radiotherapy. The aim of this single-centre, single-arm phase II study is to investigate the efficacy and safety of DIBH daily online adaptive radiotherapy. Methods Patients diagnosed with centrally located lung tumours according to the International Association for the Study of Lung Cancer recommendations, are enrolled and subjected to DIBH daily online adaptive radiotherapy. The primary endpoint is the one-year cumulative incidence of grade 3 or more severe adverse events, as classified by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Discussion Delivering definitive radiotherapy for centrally located lung tumours presents a dilemma between ensuring optimal dose coverage for the planning target volume and the associated increased risk of adverse events. DIBH provides measurable dosimetric benefits by increasing the normal lung volume and distancing the tumour from critical mediastinal organs at risk, leading to reduced toxicity. DIBH adaptive radiotherapy has been proposed as an adjunct treatment option for abdominal and pelvic cancers. If the application of DIBH adaptive radiotherapy to centrally located lung tumours proves successful, this approach could shape future phase III trials and offer novel perspectives in lung tumour radiotherapy. Trial registration. Registered at the Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/ ); registration number: jRCT1052230085 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1052230085 ).

Abstract Background Systemic edema is an adverse effect of docetaxel chemotherapy and causes distress to patients, including those receiving this agent for breast cancer. However, its characteristics and factors related to its effect on quality of life (QoL) have not been adequately investigated. In this study, we assessed systemic edema quantitatively, explored related factors, and evaluated QoL in patients receiving docetaxel for breast cancer. Methods The study had a prospective cohort design and included 37 patients with no known history of swelling who were treated with docetaxel between September 2019 and April 2022. Patients were examined at the start, middle, and end of their course of treatment and 1 and 2 months later. Body water content, body mass, fat mass, and muscle mass were quantified using bioelectrical impedance analysis. Systemic edema was evaluated with reference to the Common Terminology Criteria for Adverse Events. The timing of development of systemic edema at any anatomical site that was grade 2 or worse was recorded. QoL was assessed using the Quality of Life-Anti Cancer Drug scale. Nutrition was evaluated using the Brief-type self-administered diet history questionnaire. Multivariable logistic regression analysis was performed to identify related factors. QoL was also compared between patients with edema and those without edema. Results Systemic edema developed in 67% of the study participants and was most prevalent at the end of treatment. Body fat mass (adjusted odds ratio [aOR] 0.802, 95% confidence interval [CI] 0.651–0.988, p = 0.038), disease stage (aOR 3.279, 95% CI 0.493–21.793, p = 0.219), and history of alcohol consumption (aOR 0.141, 95% CI 0.013–1.521, p = 0.106) were identified as risk factors for docetaxel-induced edema. Participants who developed systemic edema experienced more physical, vital, and emotional distress 1 month after treatment than those who did not. There was no association between systemic edema and nutrition. Conclusions Systemic edema may develop after treatment with docetaxel and increase distress in patients with a high body fat mass. Patients at risk of systemic edema should be informed in advance about the potential frequency, location, and timing of its onset and encouraged to self-manage this condition.

Tumors rich in stroma are associated with advanced stage and poor prognosis in colorectal adenocarcinoma (CRC). Abundance of stromal cells also has implications for genomic analysis of patient tumors as it may prevent detection of somatic mutations. As part of our efforts to interrogate stroma-cancer cell interactions and to identify actionable therapeutic targets in metastatic CRC, we aimed to determine the proportion of stroma embedded in hepatic CRC metastases by performing computational tumor purity analysis based on whole exome sequencing data (WES). Unlike previous studies focusing on histopathologically prescreened samples, we used an unbiased in-house collection of tumor specimens. WES from CRC liver metastasis samples were utilized to evaluate stromal content and to assess the performance of three in silico tumor purity tools, ABSOLUTE, Sequenza and PureCN. Matching tumor derived organoids were analyzed as a high purity control as they are enriched in cancer cells. Computational purity estimates were compared to those from a histopathological assessment conducted by a board-certified pathologist. According to all computational methods, metastatic specimens had a median tumor purity of 30% whereas the organoids were enriched for cancer cells with a median purity estimate of 94%. In line with this, variant allele frequencies (VAFs) of oncogenes and tumor suppressor genes were undetectable or low in most patient tumors, but higher in matching organoid cultures. Positive correlation was observed between VAFs and in silico tumor purity estimates. Sequenza and PureCN produced concordant results whereas ABSOLUTE yielded lower purity estimates for all samples. Our data shows that unbiased sample selection combined with molecular, computational, and histopathological tumor purity assessment is critical to determine the level of stroma embedded in metastatic colorectal adenocarcinoma.

BackgroundSmall intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive.MethodsWe performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient.ResultsAbsence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we observed potential loss-of-function gene alterations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors.ConclusionsOur study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.

Limited contemporary data has compared similarities and differences between total laparoscopic (LDP), hand-assisted (HALDP), and open distal pancreatectomy (ODP). This study aimed to examine similarities and differences in outcomes between these three approaches in a contemporary cohort. Methods: Patients undergoing elective LDP, HALDP, and ODP in the NSQIP dataset (2014−2019) were included. Descriptive statistics and multivariate regression analyses were employed to compare postoperative outcomes. Results: Among 5636 patients, 33.9% underwent LDP, 13.1% HALDP, and 52.9% ODP. Compared with the LDP approach, surgical site infections were more frequent in HALDP and ODP approaches (1.2% vs. 2.6% vs. 2.8%, respectively, p < 0.01). After adjustment, the LDP approach was associated with a significantly lower likelihood of surgical site infection (OR 0.25, p = 0.03) when compared to ODP. There was no difference in the likelihood of surgical site infection when HALDP was compared to ODP (OR 0.59, p = 0.40). Unadjusted operative times were similar between approaches (LDP = 192 min, HALDP = 193 min, ODP = 191 min, p = 0.59). After adjustment, the LDP approach had a longer operative time (+10.3 min, p = 0.04) compared to ODP. There was no difference in the adjusted operative time between HALDP and ODP approaches (+5.4 min, p = 0.80). Conclusions: Compared to ODP, LDP was associated with improved surgical site infection rates and slightly longer operative times. There was no difference in surgical site infection rates between ODP and HALDP. Surgeon comfort and experience should decide the operative approach, but it is important to discuss the differences between these approaches with patients.

Background To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors.Methods This prospective, multicentre, randomised, open-label clinical study examined open-angle glaucoma patients who underwent trabeculectomy or trabeculectomy combined with cataract surgery followed by 3-month postoperative ripasudil treatments. After randomly allocating patients to ripasudil—ROCK inhibitor (ripasudil) or without ripasudil (non-ripasudil) groups. Mean intraocular pressure (IOP) changes, success rate, and number of eyedrops were compared for both groups.Results A total of 17 and 15 subjects dropped out in the ripasudil group and non-ripasudil group, respectively. At baseline, the mean IOP was 16.8±5.0 mm Hg in the ripasudil group (38 patients) and 16.2±4.4 in the non-ripasudil group (52 patients). The IOP decreased to 11.4±3.2 mm Hg, 10.9±3.9 mm Hg and 10.6±3.5 mm Hg at 12, 24 and 36 months in the ripasudil group, while it decreased to 11.2±4.1 mm Hg, 10.5±3.1 mm Hg and 10.9±3.2 mm Hg at 12, 24 and 36 months in the non-ripasudil group, respectively. There was a significant decrease in the number of IOP-lowering medications after trabeculectomy in the ripasudil group versus the non-ripasudil group at 24 (p=0.010) and 36 months (p=0.016). There was no statistically significant difference between the groups for the 3-year cumulative probability of success.Conclusion Although ripasudil application did not increase the primary trabeculectomy success rate, it did reduce IOP-lowering medications after trabeculectomy with mitomycin C.

Abstract Background The use of Bio 3D nerve conduits is a promising approach for peripheral nerve reconstruction. This study aimed to assess their safety in three patients with peripheral nerve defects in their hands. Methods We describe a single institution, non-blinded, non-randomised control trial conducted at Kyoto University Hospital. Eligibility criteria included severed peripheral nerve injuries or a defect in the region distal to the wrist joint not caused by a congenital anomaly; a defect with a length of ≤20 mm in a nerve with a diameter ≤2 mm; failed results of sensory functional tests; ability to register in the protocol within 6 months from the day of injury; refusal of artificial nerve or autologous nerve transplantation; age 20–60 years; and willingness to participate and provide informed written consent. Six weeks before transplantation, skin was harvested, dermal fibroblasts were isolated and expanded, and Bio 3D nerve conduits were created using a Bio 3D printer. Bio 3D nerve conduits were transplanted into the patients’ nerve defects. The safety of Bio 3D nerve conduits in patients with a peripheral nerve injury in the distal part of the wrist joint were assessed over a 48-week period after transplantation. Results No adverse events related to the use of Bio 3D nerve conduits were observed in any patient, and all three patients completed the trial. Conclusions Bio 3D nerve conduits were successfully used for clinical nerve reconstruction without adverse events and are a possible treatment option for peripheral nerve injuries.

Introduction: The intentional perforation of the pulp chamber floor before tooth replantation promotes pulpal healing by facilitating the revascularization of the pulp cavity. This study aimed to elucidate the effects of this method on the dynamics of quiescent dental pulp stem cells (DPSCs). Methods: The right and left maxillary first molars of Crlj:CD1 mice and TetOP-histone 2B (H2B)-green fluorescent protein (GFP) mice were extracted. The left molars were immediately replanted as the control group (CG), whereas the pulp chamber floor of the right molars were perforated before the tooth was replanted as the experimental group (EG). Immunohistochemistry for Nestin and GFP, and quantitative RT-PCR for Nestin, Opn, CD11c, and Oct3/4 mRNA were performed. Results: The rate of Nestin-positive perimeter along the pulp–dentin border in the EG tended to be higher than that of the CG at days 5 and 7 and was significantly increased between days 3 and 7. The rate of GFP-positive cells in the EG was significantly higher than that of the CG at days 5 and/or 7 in the mesial and middle coronal pulp. CD11c mRNA in the EG at day 5 was significantly higher than that of the CG and tended to be higher than that of the CG during the observation period. Oct3/4 mRNA expression in the EG was significantly higher than that of the CG at day 7. Conclusions: The current experimental model demonstrated the promotion of the survival of DPSCs and their differentiation into odontoblast-like cells (OBLCs). Thus, the use of this model is expected to clarify the crosstalk mechanism between immune cells, including macrophages and dendritic cells, and DPSCs with regards to pulpal healing after tooth replantation. It also provides insight into the differentiation process of DPSCs into OBLCs.

Abstract Minimally invasive glaucoma surgery has expanded the surgical treatment options in glaucoma, particularly when combined with cataract surgery. It is clinically relevant to understand the associated postoperative changes in biomechanical properties because they are influential on the measurement of intraocular pressure (IOP) and play an important role in the pathogenesis of open-angle glaucoma (OAG). This retrospective case–control study included OAG patients who underwent cataract surgery combined with microhook ab interno trabeculotomy (µLOT group: 53 eyes of 36 patients) or iStent implantation (iStent group: 59 eyes of 37 patients) and 62 eyes of 42 solo cataract patients without glaucoma as a control group. Changes in ten biomechanical parameters measured with the Ocular Response Analyzer and Corneal Visualization Scheimpflug Technology (Corvis ST) at 3 and 6 months postoperatively relative to baseline were compared among the 3 groups. In all the groups, IOP significantly decreased postoperatively. In the µLOT and control groups, significant changes in Corvis ST-related parameters, including stiffness parameter A1 and stress‒strain index, indicated that the cornea became softer postoperatively. In contrast, these parameters were unchanged in the iStent group. Apart from IOP reduction, the results show variations in corneal biomechanical changes from minimally invasive glaucoma surgery combined with cataract surgery.

BackgroundGuidelines recommend limiting minimally invasive pancreaticoduodenectomy (MIPD) to high-volume centers. However, the definition of high-volume care remains unclear. We aimed to objectively define a minimum number of MIPD performed annually per hospital associated with improved outcomes in a contemporary patient cohort.Patients and methodsResectable pancreatic adenocarcinoma patients undergoing MIPD were included from the National Cancer Database (2010-2017). Multivariable modeling with restricted cubic splines was employed to identify an MIPD annual hospital volume threshold associated with lower 90-day mortality. Outcomes were compared between patients treated at low-volume (≤ model-identified cutoff) and high-volume (> cutoff) centers.ResultsAmong 3079 patients, 141 (5%) died within 90 days. Median hospital volume was 6 (range 1-73) cases/year. After adjustment, increasing hospital volume was associated with decreasing 90-day mortality for up to 19 (95% CI 16-25) cases/year, indicating a threshold of 20 cases/year. Most cases (82%) were done at low-volume (< 20 cases/year) centers. With adjustment, MIPD at low-volume centers was associated with increased 90-day mortality (OR 2.7; p = 0.002). Length of stay, positive surgical margins, 30-day readmission, and overall survival were similar. On analysis of the most recent two years (n = 1031), patients at low-volume centers (78.2%) were younger and had less advanced tumors but had longer length of stay (8 versus 7 days; p < 0.001) and increased 90-day mortality (7% versus 2%; p = 0.009).ConclusionsThe cutpoint analysis identified a threshold of at least 20 MIPD cases/year associated with lower postoperative mortality. This threshold should inform national guidelines and institution-level protocols aimed at facilitating the safe implementation of this complex procedure.

The hypermetabolic and hypercatabolic responses to severe burns put nutrition support at the forefront of treatments. When left untreated, severe weight loss, increased infection, and wound healing failure can occur. Enteral nutrition is the primary method of nutrition support in such patients. Meeting caloric needs and a positive nitrogen balance are short-term goals of nutrition support, with long-term goals of minimizing lean body mass loss and maximizing wound healing. High-carbohydrate and low-fat nutrition received evidence from randomized controlled trials of aiding in decreasing pneumonia rates and was found to promote positive nitrogen balance, which lipids do not do. We go through the macronutrient and micronutrient needs of the burn patient as well as techniques for meeting these needs in the modern intensive care unit, with some discussion of alterations in these techniques that are required in the austere environment.

The adenohypophysis is comprised of the anterior and intermediate lobes (AL and IL, respectively). Cluster of differentiation 9 (CD9)- and sex-determining region Y-box 2 (SOX2)-positive cells are stem/progenitor hormone-producing cells in the AL. They are located in the marginal cell layer (MCL) facing Rathke’s cleft between the AL and IL (primary niche) and the parenchyma of the AL (secondary niche). We previously showed that, in rats, CD9/SOX2-positive cells in the IL side of the MCL (IL-side MCL) migrate to the AL side (AL-side MCL) and differentiate into prolactin-producing cells (PRL cells) in the AL parenchyma during pregnancy, lactation, and diethylstilbestrol treatment, all of which increase PRL cell turnover. This study examined the changes in CD9/SOX2-positive stem/progenitor cell niches and their proportions by manipulating the turnover of growth hormone (GH)- and thyroid-stimulating hormone (TSH)-producing cells (GH and TSH cells, respectively), which are Pit1 lineage cells, as well as PRL cells. After induction, the isolated CD9/SOX2-positive cells from the IL-side MCL formed spheres and differentiated into GH and TSH cells. We also observed an increased GH cell proportion upon treatment with GH-releasing hormone and recovery from continuous stress and an increased TSH cell proportion upon propylthiouracil treatment, concomitant with alterations in the proportion of CD9/SOX2-positive cells in the primary and secondary niches. These findings suggest that CD9/SOX2-positive cells have the potential to supply GH and TSH when an increase in GH and TSH cell populations is required in the adult pituitary gland.

Abstract Introduction The purpose of this study was to compare the surgical outcomes between ab interno trabeculotomy (LOT) and iStent inject W implantation (iStent) both combined with cataract surgery, matching the background factors including age, intraocular pressure (IOP), medication score, central corneal thickness (CCT), and axial length. Methods A total of 100 eyes from 75/79 patients with primary open-angle glaucoma were included in the LOT/iStent groups. The background factors were matched between the two groups using the propensity score. Results There were no significant differences in age, IOP, medication score, CCT, and axial length, preoperatively. The postoperative medication scores were 1.3 ± 1.2 and 1.2 ± 1.2 in the LOT and iStent groups. The postoperative IOPs were 12.8 ± 2.8 and 13.1 ± 2.4 mmHg in the LOT and iStent groups, respectively. The changes in the medication score were − 0.64 ± 1.4 and − 0.44 ± 1.6 in the LOT and iStent groups, respectively. The changes in the IOP were − 2.1 ± 3.3 and − 1.5 ± 3.0 mmHg in the LOT and iStent groups, respectively. These values were not significantly different between the two groups. The postoperative IOP and changes in the IOP were significantly associated with preoperative IOP and CCT. There was no significant difference in the occurrence of postoperative complications (hyphema, 11.0% and 6.0%, and transient ocular hypertension, 8.0% and 5.0%, in the LOT and iStent groups, respectively). Conclusion LOT and iStent have similar surgical outcomes with sufficient safety. Postoperative IOP was significantly associated with preoperative IOP and CCT in both groups.

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.