Gata6+ Pericardial Cavity Macrophages Relocate to the Injured Heart and Prevent Cardiac Fibrosis.

Macrophages play an important role in structural cardiac remodeling and the transition to heart failure following myocardial infarction (MI). Previous research has focused on the impact of blood-derived monocytes on cardiac repair. Here we examined the contribution of resident cavity macrophages located in the pericardial space adjacent to the site of injury. We found that disruption of the pericardial cavity accelerated maladaptive post-MI cardiac remodeling. Gata6+ macrophages in mouse pericardial fluid contributed to the reparative immune response. Following experimental MI, these macrophages invaded the epicardium and lost Gata6 expression but continued to perform anti-fibrotic functions. Loss of this specialized macrophage population enhanced interstitial fibrosis after ischemic injury. Gata6+ macrophages were present in human pericardial fluid, supporting the notion that this reparative function is relevant in human disease. Our findings uncover an immune cardioprotective role for the pericardial tissue compartment and argue for the reevaluation of surgical procedures that remove the pericardium.

A monocyte-leptin-angiogenesis pathway critical for repair post-infection.

During infection, inflammatory monocytes are thought to be key for bacterial eradication, but this is hard to reconcile with the large numbers of neutrophils that are recruited for each monocyte that migrates to the afflicted tissue, and the much more robust microbicidal functions of the neutrophils. However, unlike neutrophils, monocytes have the capacity to convert to situationally specific macrophages that may have critical functions beyond infection control1,2. Here, using a foreign body coated with Staphylococcus aureus and imaging over time from cutaneous infection to wound resolution, we show that monocytes and neutrophils are recruited in similar numbers with low-dose infection but not with high-dose infection, and form a localization pattern in which monocytes surround the infection site, whereas neutrophils infiltrate it. Monocytes did not contribute to bacterial clearance but converted to macrophages that persisted for weeks after infection, regulating hypodermal adipocyte expansion and production of the adipokine hormone leptin. In infected monocyte-deficient mice there was increased persistent hypodermis thickening and an elevated leptin level, which drove overgrowth of dysfunctional blood vasculature and delayed healing, with a thickened scar. Ghrelin, which opposes leptin function3, was produced locally by monocytes, and reduced vascular overgrowth and improved healing post-infection. In sum, we find that monocytes function as a cellular rheostat by regulating leptin levels and revascularization during wound repair.

iNKT Cells Orchestrate a Switch from Inflammation to Resolution of Sterile Liver Injury.

After traumatic injury, some cells function as detectors to sense injury and to modulate the local immune response toward a restitution phase by affecting the local cytokine milieu. Using intravital microscopy, we observed that patrolling invariant natural killer T (iNKT) cells were initially excluded from a site of hepatic injury but subsequently were strategically arrested first via self-antigens and then by cytokines, circumscribing the injured site at exactly the location where monocytes co-localized and hepatocytes proliferated. Activation of iNKT cells by self-antigens resulted in the production of interleukin-4 (IL-4) but not interferon-γ (IFN-γ). This promoted increased hepatocyte proliferation, monocyte transition (from Ly6Chi to Ly6Clo), and improved healing where IL-4 from iNKT cells was critical for these processes. Disruption of any of these mechanisms led to delayed wound healing. We have shown that self-antigen-driven iNKT cells function as sensors and orchestrators of the transformation from inflammation to tissue restitution for essential timely wound repair.

Is Robotic Surgery Beneficial for Rectal Cancer Patients with Unfavorable Characteristic After Neoadjuvant Chemoradiotherapy?

BACKGROUND: The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection. METHODS: This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups. RESULTS: After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m2, and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group. CONCLUSIONS: Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer.

Pulmonary Metastasis as the First Site of Metastasis After Curative Surgery for Colon Cancer: Incidence and Risk Factors According to the TNM Stage.

BACKGROUND: The lungs are one of the most common sites for colon cancer metastasis. A few studies reported that approximately 2% to 10% of patients with colon cancer developed pulmonary metastasis. However, among these studies, patient characteristics were heterogeneous, and information on pulmonary metastasis incidence by the TNM stage was scarce. OBJECTIVE: This study evaluated the incidence of pulmonary metastasis in colon cancer without synchronous metastasis treated with radical surgery and identified risk factors for pulmonary metastasis according to the TNM stage. DESIGN AND SETTINGS: This retrospective study included all patients with colon cancer without metastasis who underwent radical surgery for primary tumor at Samsung Medical Center between January 2007 and December 2016. PATIENTS: A total of 4889 patients who underwent radical surgery for stage I and III colon cancer were included. MAIN OUTCOME MEASURES: The main outcome measures were the incidence of pulmonary metastasis and overall survival. RESULTS: A total of 156 patients (3.2%) were diagnosed with pulmonary metastasis after a median of 16 months from the time of radical surgery for colon cancer to detection of pulmonary metastasis. The pulmonary metastasis incidence rate by the TNM stage was 0.5% in stage I, 1.6% in stage II, and 6% in stage III. Risk factors for pulmonary metastasis were preoperative CEA >5 ng/mL, cancer obstruction, N stage, vascular invasion, perineural invasion, and adjuvant chemotherapy for primary colon cancer in multivariable analysis. LIMITATION: This was a retrospective single-center study. CONCLUSIONS: Preoperative CEA >5 ng/mL, cancer obstruction, pN stage, vascular invasion, perineural invasion, and receiving adjuvant chemotherapy for primary colon cancer were risk factors for pulmonary metastasis in colon cancer. Therefore, patients with risk factors for pulmonary metastasis should be recommended for intensive follow-up to detect lung metastases. See Video Abstract . METSTASIS PULMONAR EN EL PRIMER SITIO TRAS CIRUGA CURATIVA DEL CNCER DE COLON INCIDENCIA Y FACTORES DE RIESGO SEGN ESTADIO TNM: ANTECEDENTES:Los pulmones son uno de los sitios más comunes de metástasis del cáncer de colon. Algunos estudios informaron que aproximadamente entre el 2% y el 10% de los pacientes con cáncer de colon desarrollaron metástasis pulmonar. Sin embargo, entre estos estudios, las características de los pacientes fueron heterogéneas y la información sobre la incidencia de metástasis pulmonares según el estadio TNM fue escasa.OBJETIVO:Este estudio evaluó la incidencia de metástasis pulmonar en cáncer de colon sin metástasis sincrónica tratada con cirugía radical e identificó factores de riesgo para metástasis pulmonar según el estadio TNM.DISEÑO Y AJUSTES:Este estudio retrospectivo incluyó a todos los pacientes con cáncer de colon sin metástasis que se sometieron a cirugía radical por tumor primario en el Samsung Medical Center entre enero de 2007 y diciembre de 2016.PACIENTES:Se incluyó un total de 4.889 pacientes sometidos a cirugía radical por cáncer de colon en estadio I-III.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la incidencia de metástasis pulmonar y la supervivencia general.RESULTADOS:Un total de 156 pacientes (3,2%) fueron diagnosticados con metástasis pulmonar con una duración media de 16 meses desde el momento de la cirugía radical por cáncer de colon hasta la detección de la metástasis pulmonar. La tasa de incidencia de metástasis pulmonares por estadio TNM fue del 0,5% en el estadio I, del 1,6% en el estadio II y del 6% en el estadio III. Los factores de riesgo de metástasis pulmonar fueron CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio N, invasión vascular, invasión perineural y quimioterapia adyuvante para el cáncer de colon primario en un análisis multivariable.LIMITACIÓN:Este fue un estudio retrospectivo de un solo centro.CONCLUSIÓN:CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio pN, invasión vascular, invasión perineural y recibir quimioterapia adyuvante para el cáncer de colon primario fueron factores de riesgo de metástasis pulmonar en el cáncer de colon. Por lo tanto, se debe recomendar un seguimiento intensivo a los pacientes con factores de riesgo de metástasis pulmonares para detectar metástasis pulmonares. (Traducción-Dr Yolanda Colorado ).

A prospective single-arm clinical trial to assess the safety and efficacy of monofilament polydioxanone barbed suture, MONOFIX®, on abdominal fascial closure.

BACKGROUND: For abdominal fascial closure, the choice of optimal suture material and appropriate suture technique are of paramount importance to prevent the incidence of incisional hernia. Although barbed sutures are widely used in various surgical fields, their safety and feasibility on abdominal fascial closure which requires the most tensile strength for security have not been established yet. METHODS: We conducted a prospective, single-arm, interventional clinical trial to present the postoperative outcomes of using barbed sutures in abdominal fascial closure between April 2021 and August 2021. Patients with colorectal cancer who underwent minimally invasive surgery in elective setting were included. For all participants, monofilament polydioxanone barbed suture, MONOFIX®, was used to secure the abdominal fasica. The primary outcome was the 1-year incidence of incisional hernia assessed by computed tomography. RESULTS: A total of 30 patients were included. The median fascial incision length and suture length were 6.5 cm (range, 6-7.5 cm) and 31 cm (range, 27.5-39.0 cm), respectively. The median procedure time of abdominal fascial closure was 4 min (range, 3-9 min). There was no incidence of unexpected event related to suturing including suture cutting, stopper separation from threads, and suture loosening. One case of superficial surgical site infection occurred during postoperative hospital stays. There was no fascial dehiscence, incisional hernia, and adhesive ileus during a median follow-up period of 17.5 months. CONCLUSION: Monofilament polydioxanone barbed suture, MONOFIX®, may be used safely and effectively on abdominal fascial closure. GOV NUMBER: NCT05872334.

Diaphragm-sparing efficacy of subparaneural upper trunk block for arthroscopic shoulder surgery: A randomised controlled trial.

BACKGROUND: Inter-scalene block (ISB) is associated with an inevitable risk of hemi-diaphragmatic paresis (HDP). To reduce the risk of HDP, an upper trunk block (UTB) has been proposed at the brachial plexus division level. OBJECTIVE: We hypothesised that UTB would be associated with a lower incidence of HDP than ISB while providing sufficient analgesia following arthroscopic shoulder surgery. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. PATIENTS: Seventy patients aged 20 to 80 years undergoing arthroscopic rotator cuff repair. INTERVENTION: Ultrasound-guided ISB or UTB was performed with 5 ml 0.75% ropivacaine. MAIN OUTCOME MEASURES: The primary outcome was the incidence of complete HDP, assessed by diaphragm excursion using ultrasound, defined as a decrease to 25% or less of baseline or occurrence of paradoxical movement. Postoperative pulmonary function change, pain scores, opioid consumption and pain-related outcomes were the secondary outcomes. RESULTS: The UTB group had a significantly lower incidence of complete HDP than the ISB group [5.9% (2/34) vs. 41.7% (15/36); absolute difference, 35.8%; 95% confidence interval (CI), 17.8 to 53.7%; P  < 0.001]. The postblockade decline in pulmonary function was more pronounced in the ISB group than that in the UTB group. The pain score at 1 h postoperatively was not significantly different between the groups (ISB vs. UTB group: median 0 vs. 1; median difference, -1; 95% CI, -2 to 0.5). No significant difference was observed in any other secondary outcomes. CONCLUSION: UTB was associated with a lower incidence of HDP compared with ISB while providing excellent analgesia in arthroscopic shoulder surgery. TRIAL REGISTRATION: Clinical Trial Registry of Korea ( https://cris.nih.go.kr ) identifier: KCT0007002. IRB NUMBER: Chungnam National University Hospital Institutional Review Board No. 2021-12-069.

Can neoadjuvant chemoradiotherapy affect exfoliated cancer cells in colorectal cancer?

BACKGROUND: To prevent local recurrence caused by exfoliated cancer cells caught in the suture line, intraoperative rectal washout during surgery can be performed to eliminate exfoliated cancer cells. However, the impact of neoadjuvant chemoradiotherapy on exfoliated cancer cells is not well known. This study aimed to identify positive rate of malignant cells in rectal washout fluids of neoadjuvant chemoradiotherapy patients and to determine if neoadjuvant chemoradiotherapy could affect exfoliated cancer cells. METHODS: A total of 105 patients who underwent rectal washout intraoperatively for distal sigmoid colon and rectal cancer from April 2020 to September 2021 were analyzed. The primary outcome was positive rate of malignant cells in rectal washout fluids of patients who had received neoadjuvant chemoradiotherapy. RESULTS: The positive rate of malignant cells in washout fluids of patients who had received neoadjuvant chemoradiotherapy was 0.0% and those who had not was 32.1%. The overall positive rate was 23.8%. In the positive group, tumor sizes were bigger (4.64 ± 1.68 cm vs. 3.64 ± 2.00 cm, p = 0.026) and more patients had a fungating tumor shown in preoperative colonoscopy (96.0% vs. 71.3%, p = 0.012). Although these factors did not show statistical significance in multivariable logistic regression analysis, fungating tumor showed a trend towards significance (OR: 7.28, 95% CI: 0.90-58.77, p = 0.063). CONCLUSIONS: Our study suggests that neoadjuvant chemoradiotherapy could reduce exfoliated cancer cells, and rectal washout for the purpose of eliminating exfoliated cancer cells might be unnecessary in patients who have received neoadjuvant chemoradiotherapy.

Ductular reaction-associated neutrophils promote biliary epithelium proliferation in chronic liver disease.

BACKGROUND & AIMS: Ductular reaction expansion is associated with poor prognosis in patients with advanced liver disease. However, the mechanisms promoting biliary cell proliferation are largely unknown. Here, we identify neutrophils as drivers of biliary cell proliferation and the defective wound-healing response. METHODS: The intrahepatic localization of neutrophils was evaluated in patients with chronic liver disease. Neutrophil dynamics were analyzed by intravital microscopy and neutrophil-labeling assays in DDC-treated mice. Neutrophil depletion or inhibition of recruitment was achieved using a Ly6g antibody or a CXCR1/2 inhibitor, respectively. Mice deficient in PAD4 (peptidyl arginine deiminase 4) and ELANE/NE (neutrophil elastase) were used to investigate the mechanisms underlying ductular reaction expansion. RESULTS: In this study we describe a population of ductular reaction-associated neutrophils (DRANs), which are in direct contact with biliary epithelial cells in chronic liver diseases and whose numbers increased in parallel with disease progression. We show that DRANs are immobilized at the site of ductular reaction for a prolonged period of time. In addition, liver neutrophils display a unique phenotypic and transcriptomic profile, showing a decreased phagocytic capacity and increased oxidative burst. Depletion of neutrophils or inhibition of their recruitment reduces DRANs and the expansion of ductular reaction, while mitigating liver fibrosis and angiogenesis. Mechanistically, neutrophils deficient in PAD4 and ELANE abrogate neutrophil-induced biliary cell proliferation, thus indicating the role of neutrophil extracellular traps and elastase release in ductular reaction expansion. CONCLUSIONS: Overall, our study reveals the accumulation of DRANs as a hallmark of advanced liver disease and a potential therapeutic target to mitigate ductular reaction and the maladaptive wound-healing response. IMPACT AND IMPLICATIONS: Our results indicate that neutrophils are highly plastic and can have an extended lifespan. Moreover, we identify a new role of neutrophils as triggers of expansion of the biliary epithelium. Overall, the results of this study indicate that ductular reaction-associated neutrophils (or DRANs) are new players in the maladaptive tissue-healing response in chronic liver injury and may be a potential target for therapeutic interventions to reduce ductular reaction expansion and promote tissue repair in advanced liver disease.

Association Between Distress at Diagnosis and Disease-free Survival Among Patients With Resectable Colon Cancer: A Large Cohort Study.

OBJECTIVE: This study aimed to evaluate the association between distress at initial diagnosis and disease-free survival in patients with resectable colon cancer. SUMMARY BACKGROUND DATA: Considerable research has examined the psychological impact of having a confirmed diagnosis of cancer, but relatively limited research has examined the impact of distress during the diagnostic phase on oncological outcomes. METHODS: This is a retrospective cohort study. We included newly diagnosed colon cancer patients who had resectable surgery and underwent distress screening between July 2014 and July 2021 (N=1,362). The Korean versions of the Distress Thermometer were used to assess distress and related problems. Patients were categorized into 3 groups based on distress score: low (<4), moderate (4-7), and severe (≥8). The primary outcome was disease-free survival. RESULTS: The mean distress was 5.1 (SD=2.4) and 61%, and 15% of patients had moderate and severe distress at diagnosis, respectively. The severe distress group was more likely to report fear, sadness, and concerns regarding insurance/finance, work, and childcare than the low distress group. Compared with the low distress group, the severe distress group had worse disease-free survival (Hazard Ratio=1.84, 95% CI=1.03, 3.29). The association was more evident in patients with stage IV disease (Hazard Ratio=2.53, 95% CI=1.02, 6.25). CONCLUSIONS: A substantial number of patients with colon cancer experience distress at diagnosis, and severe distress has a negative impact on oncologic outcomes. Active monitoring and appropriate management of distress at diagnosis should be adopted at clinical settings.

Revised Nodal Staging Integrating Tumor Deposit Counts With Positive Lymph Nodes in Patients With Stage III Colon Cancer.

OBJECTIVE: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging. SUMMARY BACKGROUND DATA: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered. METHODS: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared. RESULTS: Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2. CONCLUSIONS: Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with high-risk stage III colon cancer staged as N3.

Transcriptomes of the tumor-adjacent normal tissues are more informative than tumors in predicting recurrence in colorectal cancer patients.

BACKGROUND: Previous investigations of transcriptomic signatures of cancer patient survival and post-therapy relapse have focused on tumor tissue. In contrast, here we show that in colorectal cancer (CRC) transcriptomes derived from normal tissues adjacent to tumors (NATs) are better predictors of relapse. RESULTS: Using the transcriptomes of paired tumor and NAT specimens from 80 Korean CRC patients retrospectively determined to be in recurrence or nonrecurrence states, we found that, when comparing recurrent with nonrecurrent samples, NATs exhibit a greater number of differentially expressed genes (DEGs) than tumors. Training two prognostic elastic net-based machine learning models-NAT-based and tumor-based in our Samsung Medical Center (SMC) cohort, we found that NAT-based model performed better in predicting the survival when the model was applied to the tumor-derived transcriptomes of an independent cohort of 450 COAD patients in TCGA. Furthermore, compositions of tumor-infiltrating immune cells in NATs were found to have better prognostic capability than in tumors. We also confirmed through Cox regression analysis that in both SMC-CRC as well as in TCGA-COAD cohorts, a greater proportion of genes exhibited significant hazard ratio when NAT-derived transcriptome was used compared to when tumor-derived transcriptome was used. CONCLUSIONS: Taken together, our results strongly suggest that NAT-derived transcriptomes and immune cell composition of CRC are better predictors of patient survival and tumor recurrence than the primary tumor.

Prognostic Impact of Mucinous Adenocarcinoma in Stage II and III Colon Cancer.

BACKGROUND: Mucinous adenocarcinoma is a rare histologic feature of colorectal cancer and is characterized by oncologic features that are different from those of adenocarcinoma. However, there are conflicting views regarding the prognostic impact of mucinous adenocarcinoma on colon cancer. OBJECTIVE: This study aimed to evaluate the prognostic impact of mucinous adenocarcinoma in stage II and III colon cancer. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted between January 2010 and December 2015. Patients were divided into the mucinous adenocarcinoma and nonmucinous adenocarcinoma groups. Disease-free survival and overall survival were assessed using propensity score matching. PATIENTS: Overall, 2532 patients who underwent radical surgery for stage II and III colon cancer were included in the study. MAIN OUTCOME MEASURES: The main outcome measures were disease-free survival and overall survival. RESULTS: The median follow-up duration was 86 months. The disease-free survival and overall survival were significantly lower in the mucinous adenocarcinoma group than in the nonmucinous adenocarcinoma group. In subgroup analysis, there was no significant difference in the disease-free survival and overall survival between patients with and without mucinous adenocarcinoma with stage II colon cancer. In stage III colon cancer, the disease-free survival and overall survival were significantly lower in patients with mucinous adenocarcinoma than in those without mucinous adenocarcinoma. Multivariable analysis showed that mucinous adenocarcinoma was a poor prognostic factor for disease-free survival and overall survival. LIMITATION: The study's limitations include those that are inherently associated with retrospective single-center studies. CONCLUSIONS: Mucinous adenocarcinoma is a poor prognostic factor in stage III but not in stage II colon cancer. Therefore, mucinous adenocarcinoma might not be regarded as an independent risk factor requiring chemotherapy for favorable oncologic outcomes. However, for stage III colon cancer, patients with mucinous adenocarcinoma require close observation. IMPACTO PRONSTICO DEL ADENOCARCINOMA MUCINOSO EN LAS ETAPAS II Y III DE CNCER DE CLON: ANTECEDENTES:El adenocarcinoma mucinoso es una característica histológica rara del cáncer colorrectal, se caracteriza por propiedades oncológicas que son diferentes a las del adenocarcinoma. Sin embargo, existen puntos de vista contradictorios con respecto al impacto pronóstico del adenocarcinoma mucinoso en el cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar el impacto pronóstico del adenocarcinoma mucinoso en las etapas II y III de cáncer de cólon.DISEÑO Y CONFIGURACIONES:Este estudio de cohorte retrospectivo se realizó entre enero de 2010 y diciembre de 2015. Los pacientes se dividieron entre grupos de adenocarcinoma mucinoso y adenocarcinoma no mucinoso. La supervivencia libre de enfermedad y la supervivencia global se evaluaron utilizando emparejamiento por puntuación de propensión.PACIENTES:En general, 2,532 pacientes que se sometieron a cirugía radical para etapa II y III de cáncer de colon se incluyeron en el estudio.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana de duración del seguimiento fue de 86 meses. La supervivencia libre de enfermedad y la supervivencia global fueron significativamente menores en el grupo de adenocarcinoma mucinoso que en el grupo de adenocarcinoma no mucinoso. En el análisis de subgrupos, no hubo diferencias significativas en la supervivencia libre de enfermedad y la supervivencia global entre los pacientes con o sin adenocarcinoma mucinoso con cáncer de cólon etapa II. En el cáncer de colon etapa III, la supervivencia libre de enfermedad y la supervivencia global fueron significativamente más bajas en pacientes con adenocarcinoma mucinoso que en aquellos sin adenocarcinoma mucinoso. El análisis multivariable mostró que el adenocarcinoma mucinoso era un factor de mal pronóstico para la supervivencia libre de enfermedad y la supervivencia global.LIMITACIONES:Las limitaciones del estudio incluyen aquellas que están inherentemente asociadas con estudios retrospectivos de un solo centro.CONCLUSIONES:El adenocarcinoma mucinoso es un factor de mal pronóstico en el cáncer de colon etapa III pero no en etapa II. Por lo tanto, el adenocarcinoma mucinoso podría no considerarse un factor de riesgo independiente que requiera quimioterapia para obtener resultados oncológicos favorables. Sin embargo, para el cáncer de colon etapa III, los pacientes con adenocarcinoma mucinoso requieren observación cercana. (Traducción-Dr. Aurian Garcia Gonzalez ).

Prognostic Impact of Lymphatic Invasion, Venous Invasion, Perineural Invasion, and Tumor Budding in Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy Followed by Total Mesorectal Excision.

BACKGROUND: The diagnostic implications of lymphatic invasion, venous invasion, perineural invasion, and tumor budding in rectal cancer treated with neoadjuvant chemoradiotherapy are unknown. OBJECTIVE: This study aimed to identify the prognostic impact of lymphatic invasion, venous invasion, perineural invasion, and tumor budding in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at the Samsung Medical Center. Grouping was performed on the basis of lymphatic invasion, venous invasion, perineural invasion, and tumor budding status: no-risk group with 0 factor (n = 299), low-risk group with any 1 factor (n = 131), intermediate-risk group with any 2 factors (n = 75), and high-risk group with 3 or 4 risk factors (n = 32). PATIENTS: Patients who underwent neoadjuvant chemoradiotherapy, followed by radical operation for locally advanced rectal cancer, from January 2010 to December 2015 were included. MAIN OUTCOME MEASURES: The main outcome measures were disease-free and overall survival. RESULTS: Disease-free and overall survival varied significantly between the groups in stage III ( p < 0.001 and p < 0.001). Disease-free survival in stage I differed between the no-risk group and the intermediate-risk group ( p = 0.026). In stage II, disease-free and overall survival differed between the no-risk group and the intermediate-risk group ( p = 0.010 and p = 0.045). In multivariable analysis, risk grouping was an independent prognostic factor for both disease-free (p <0.001) and overall survival ( p < 0.001). LIMITATIONS: The inherent limitations are associated with the retrospective single-center study design. CONCLUSIONS: Lymphatic invasion, venous invasion, perineural invasion, and tumor budding are strong prognostic factors for disease-free and overall survival in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Therefore, adjuvant chemotherapy is strongly recommended in patients with positive lymphatic invasion, venous invasion, perineural invasion, and tumor budding. See Video Abstract at http://links.lww.com/DCR/B919 . IMPACTO PRONSTICO DE LA INVASIN LINFTICA, LA INVASIN VENOSA, LA INVASIN PERINEURAL Y LA GEMACIN TUMORAL EN EL CNCER DE RECTO TRATADO CON QUIMIORRADIOTERAPIA NEOADYUVANTE SEGUIDA DE ESCISIN TOTAL DEL MESORRECTO: ANTECEDENTES:Se desconocen las implicaciones diagnósticas de la invasión linfática, la invasión venosa, la invasión perineural y el crecimiento tumoral en el cáncer de recto tratado con quimiorradioterapia neoadyuvante.OBJETIVO:Este estudio fue diseñado para identificar el impacto pronóstico de la invasión linfática, la invasión venosa, la invasión perineural y la gemación tumoral en el cáncer de recto localmente avanzado tratado con quimiorradioterapia neoadyuvante.DISEÑO:Este estudio fue un estudio de cohorte retrospectivo.AJUSTES:Este estudio se realizó en el Centro Médico Samsung. La agrupación se realizó en función de la invasión linfática, la invasión venosa, la invasión perineural y el estado de crecimiento del tumor: grupo sin riesgo con 0 factores (n = 299), grupo de bajo riesgo con cualquier factor 1 (n = 131), grupo de riesgo intermedio con 2 factores cualquiera (n = 75), y un grupo de alto riesgo con 3 o 4 factores de riesgo (n = 32).PACIENTES:Se incluyeron un total de 537 pacientes que se sometieron a quimiorradioterapia neoadyuvante seguida de operación radical por cáncer de recto localmente avanzado desde enero de 2010 hasta diciembre de 2015.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana del período de seguimiento fue de 77 meses, y la supervivencia libre de enfermedad a los 5 años y la supervivencia general a los 5 años variaron significativamente entre los grupos en el estadio III (p < 0,001, p < 0,001). La supervivencia libre de enfermedad a los 5 años en el estadio I difirió entre el grupo sin riesgo y el grupo de riesgo intermedio (p = 0,026). En el estadio II, la supervivencia libre de enfermedad a 5 años y la supervivencia global a 5 años difirieron entre el grupo sin riesgo y el grupo de riesgo intermedio p = 0,010, p = 0,045). En el análisis multivariable, la agrupación de riesgo fue un factor pronóstico independiente tanto para la supervivencia libre de enfermedad (p < 0,001) como para la supervivencia global (p < 0,001).LIMITACIÓN:Las limitaciones inherentes están asociadas con el diseño de estudio retrospectivo de un solo centro..CONCLUSIÓN:La invasión linfática, la invasión venosa, la invasión perineural y la gemación tumoral son fuertes factores pronósticos para la supervivencia libre de enfermedad y la supervivencia general en el cáncer de recto localmente avanzado tratado con quimiorradioterapia neoadyuvante. Por lo tanto, se recomienda fuertemente la quimioterapia adyuvante en pacientes con invasión linfática positiva, invasión venosa, invasión perineural y tumor en en formacion. Consulte Video Resumen en http://links.lww.com/DCR/B919 . (Traducción-Dr Yolanda Colorado ).

The Prognostic Value of Micropapillary Pattern in Colon Cancer and Its Role as a High-Risk Feature in Patients With Stage II Disease.

BACKGROUND: The association of a micropapillary pattern with oncologic outcomes has not been fully studied in patients with colon cancer. OBJECTIVE: We evaluated the prognostic value of a micropapillary pattern, especially for patients with stage II colon cancer. DESIGN: A retrospective comparative cohort study using propensity score matching. SETTING: This study was conducted at a single tertiary center. PATIENTS: Patients with primary colon cancer undergoing curative resection from October 2013 to December 2017 were enrolled. Patients were grouped into micropapillary pattern positive or micropapillary pattern negative. MAIN OUTCOME MEASUREMENTS: Disease-free survival and overall survival. RESULTS: Of the eligible 2192 patients, 334 (15.2%) were with micropapillary pattern (+). After 1:2 propensity score matching, 668 patients with micropapillary pattern-negative status were selected. The micropapillary pattern-positive group showed significantly worse 3-year disease-free survival (77.6% vs 85.1%, p = 0.007). Three-year overall survival of micropapillary pattern-positive and micropapillary pattern-negative patients did not show a statistically significant difference (88.9% vs 90.4%, p = 0.480). In multivariable analysis, micropapillary pattern-positive was an independent risk factor for poor disease-free survival (HR 1.547, p = 0.008). In the subgroup analysis for 828 patients with stage II disease, 3-year disease-free survival deteriorated significantly in micropapillary pattern-positive patients (82.6% vs 93.0, p < 0.001). Three-year overall survival was 90.1% and 93.9% in patients positive and negative for micropapillary pattern, respectively ( p = 0.082). In the multivariable analysis for patients with stage II disease, micropapillary pattern-positive status was an independent risk factor for poor disease-free survival (HR 2.003, p = 0.031). LIMITATIONS: Selection bias due to the retrospective nature of the study. CONCLUSIONS: Micropapillary pattern-positive status may serve as an independent prognostic factor for colon cancer, especially for patients with stage II disease. VALOR PRONSTICO DEL PATRN MICROPAPILAR Y SU PAPEL COMO CARACTERSTICA DE ALTO RIESGO EN PACIENTES CON CNCER DE COLON EN ESTADO II: ANTECEDENTES:La asociación del patrón micropapilar con los resultados oncológicos no ha sido completamente estudiada en pacientes con cáncer de colon.OBJETIVO:Evaluamos el valor pronóstico del patrón micropapilar, especialmente en pacientes con cáncer de colon en estadio II.DISEÑO:Estudio de cohortes comparativo y retrospectivo que utilize el emparejamiento por puntuación de propensiones.AJUSTE:Estudio realizado en un solo centro terciario.PACIENTES:Se incluyeron los pacientes con cáncer de colon primario sometidos a resección curativa desde octubre de 2013 hasta diciembre de 2017. Los pacientes se agruparon en patrón micropapilar positivo ( + ) o patrón micropapilar negativo ( - ).PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida libre de enfermedad y la sobrevida global.RESULTADOS:De los 2192 pacientes elegibles, 334 (15,2%) tenían patrón micropapilar (+). Después de emparejar el puntaje de propensión 1:2, se seleccionaron 668 pacientes con patrón micropapilar (-). El grupo con patrón micropapilar (+) mostró una sobrevida libre de enfermedad significativamente inferior a los tres años (77,6% frente a 85,1%, p = 0,007). La sobrevida global a los tres años del patrón micropapilar (+) y del patrón micropapilar (-) no mostró una diferencia estadísticamente significativa (88,9 % frente a 90,4%, p = 0,480). En el análisis multivariable, el patrón micropapilar (+) fue un factor de riesgo independiente para una deficiente sobrevida libre de enfermedad (índice de riesgo 1,547, p = 0,008). En el análisis de subgrupos de 828 pacientes con enfermedad en estadio II, la sobrevida libre de enfermedad a los tres años se deterioró significativamente en los pacientes con patrón micropapilar (+) (82,6% frente a 93,0, p < 0,001). La sobrevida global a los tres años fué del 90,1% y del 93,9% en el patrón micropapilar (+) y el patrón micropapilar (-), respectivamente ( p = 0,082). En el análisis multivariable de los pacientes con enfermedad en estadio II, el patrón micropapilar (+) fue un factor de riesgo independiente para una sobrevida libre de enfermedad deficiente (índice de riesgo 2,003, p = 0,031).LIMITACIONES:Sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:El patrón micropapilar (+) sirve como factor pronóstico independiente para el cáncer de colon, especialmente para pacientes con enfermedad en estadio II. (Traducción-Dr. Xavier Delgadillo ).

Suprascapular nerve entrapment caused by a large hematoma of the scapula: a case report.

BACKGROUND: Suprascapular nerve entrapment is a rare disorder that is frequently misdiagnosed as another disease. The suprascapular nerve is commonly entrapped at the following two sites: the suprascapular and spinoglenoid notches. Nerve entrapment at the spinoglenoid notch causes infraspinatus muscle weakness and atrophy. Patients present with posterior shoulder pain and weakness. Magnetic resonance imaging is used to confirm the diagnosis of a spinoglenoid cyst and nerve compression. Open or arthroscopic aspiration or decompression is indicated for patients with cysts in whom conservative treatment has failed and those with cysts associated with suprascapular nerve compression. CASE PRESENTATION: Herein, we describe the case of a 49-year-old man with suprascapular nerve entrapment caused by a large cyst, namely, a hematoma, in the superior scapular and spinoglenoid notches. Open surgical decompression of the suprascapular nerve was performed owing to an intact rotator cuff and glenoid labrum. CONCLUSION: Posterior shoulder pain promptly resolved without complications.

Risk Factors Associated with Intraoperative Iatrogenic Fracture in Patients Undergoing Intramedullary Nailing for Atypical Femoral Fractures with Marked Anterior and Lateral Bowing.

Background and objectives: Iatrogenic fractures are potential complications during intramedullary (IM) nailing for atypical femoral fractures (AFFs). The risk factors associated with iatrogenic fractures remain unclear, although excessive femoral bowing and osteoporosis are hypothesized to be contributing factors. The present study aimed to determine the risk factors for the occurrence of iatrogenic fractures during IM nailing in patients with AFFs. Materials and Methods: This retrospective cross-sectional study evaluated 95 patients with AFF (all female; age range: 49-87 years) who underwent IM nailing between June 2008 and December 2017. The patients were divided into two groups: Group I (with iatrogenic fracture: n = 20) and Group II (without iatrogenic fracture: n = 75). Background characteristics were retrieved from medical records and radiographic measurements were obtained. Univariate and multivariate logistic regression analyses were performed to identify risk factors for the occurrence of intraoperative iatrogenic fractures. Receiver operating curve (ROC) analysis was conducted to determine a cut-off value for the prediction of iatrogenic fracture occurrence. Results: Iatrogenic fractures occurred in 20 (21.1%) patients. The two groups exhibited no significant differences regarding age and other background characteristics. Group I exhibited significantly lower mean femoral bone mineral density (BMD) and significantly greater mean lateral and anterior femoral bowing angles than Group II (all p < 0.05). There were no significant differences in AFF location, nonunion, and IM nail diameter, length, or nail entry point between the two groups. In the univariate analysis, femoral BMD and lateral bowing of the femur differed significantly between the two groups. On multivariate analysis, only lateral bowing of the femur remained significantly associated with iatrogenic fracture occurrence. The ROC analysis determined a cut-off value of 9.3° in lateral bowing of the femur for prediction of iatrogenic fracture occurrence during IM nailing for AFF treatment. Conclusions: The lateral bowing angle of the femur is an important predictive factor for intraoperative iatrogenic fracture occurrence in patients undergoing IM nailing for AFF treatment.

An Unusual Case of Erdheim Chester Disease (ECD) with Knee Pain: A Case Report.

Background: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown etiology that occurs in multiple organs. The clinical characteristics of ECD are unknown, making it difficult to diagnose. Case presentation: A 61-year-old woman presented with left knee pain and contracture. She had recent medical problems such as recurrent urinary tract infection, pericardial effusion, and pleural effusion. Simple radiography and magnetic resonance imaging of the knee revealed an osteosclerotic lesion. Under suspicion of malignancy, other radiologic modalities were performed, but there were no significant results showing malignancy. A bone biopsy of the knee lesion led to a final diagnosis of ECD. The patient was treated with systemic steroids and was ultimately tried on PEG-interferon. Conclusion: This report describes an unusual presentation of ECD involving the skeletal system and multiple extraskeletal organs. Owing to its non-specific nature, ECD was notably difficult to diagnose. Therefore, if a patient has knee pain and other multiorgan presentations without malignancy, clinicians should suspect ECD.

An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells.

Here we investigate the dynamics of the hepatic intravascular immune response to a pathogen relevant to invariant natural killer T cells (iNKT cells). Immobilized Kupffer cells with highly ramified extended processes into multiple sinusoids could effectively capture blood-borne, disseminating Borrelia burgdorferi, creating a highly efficient surveillance and filtering system. After ingesting B. burgdorferi, Kupffer cells induced chemokine receptor CXCR3-dependent clustering of iNKT cells. Kupffer cells and iNKT cells formed stable contacts via the antigen-presenting molecule CD1d, which led to iNKT cell activation. An absence of iNKT cells caused B. burgdorferi to leave the blood and enter the joints more effectively. B. burgdorferi that escaped Kupffer cells entered the liver parenchyma and survived despite Ito cell responses. Kupffer cell-iNKT cell interactions induced a key intravascular immune response that diminished the dissemination of B. burgdorferi.

Tacrolimus Impairs Kupffer Cell Capacity to Control Bacteremia: Why Transplant Recipients Are Susceptible to Infection.

BACKGROUND AND AIMS: Kupffer cells (KCs) are the resident intravascular phagocyte population of the liver and critical to the capture and killing of bacteria. Calcineurin/nuclear factor of activated T cells (NFAT) inhibitors (CNIs) such as tacrolimus are used to prevent rejection in solid organ transplant recipients. Although their effect on lymphocytes has been studied extensively, there are limited experimental data about if and how CNIs shape innate immunity, and whether this contributes to the higher rates of infection observed in patients taking CNIs. APPROACH AND RESULTS: Here, we investigated the impact of tacrolimus treatment on innate immunity and, more specifically, on the capability of Kupffer cells (KCs) to fight infections. Retrospective analysis of data of >2,700 liver transplant recipients showed that taking calcineurin inhibitors such as tacrolimus significantly increased the likelihood of Staphylococcus aureus infection. Using a mouse model of acute methicillin-resistant S. aureus (MRSA) bacteremia, most bacteria were sequestered in the liver and we found that bacteria were more likely to disseminate and kill the host in tacrolimus-treated mice. Using imaging, we unveiled the mechanism underlying this observation: the reduced capability of KCs to capture, phagocytose, and destroy bacteria in tacrolimus-treated animals. Furthermore, in a gene expression analysis of infected KCs, the triggering receptor expressed on myeloid cells 1 (TREM1) pathway was the one with the most significant down-regulation after tacrolimus treatment. TREM1 inhibition likewise inhibited KC bacteria capture. TREM1 levels on neutrophils as well as the overall neutrophil response after infection were unaffected by tacrolimus treatment. CONCLUSIONS: Our results indicate that tacrolimus treatment has a significant impact directly on KCs and on TREM1, thereby compromising their capacity to fend off infections.