RESUMO
BACKGROUND: Frailty is common in older patients with cancer; however, its clinical impact on the survival outcomes has seldom been examined in these patients. This study aimed to investigate the association of frailty with the survival outcomes and surgical complications in older patients with cancer after elective abdominal surgery in Taiwan. METHODS: We prospectively enrolled 345 consecutive patients aged ≥65 years with newly diagnosed cancer who underwent elective abdominal surgery between 2016 and 2018. They were allocated into the fit, pre-frail, and frail groups according to comprehensive geriatric assessment (CGA) findings. RESULTS: The fit, pre-frail, and frail groups comprised 62 (18.0%), 181 (52.5%), and 102 (29.5%) patients, respectively. After a median follow-up of 48 (interquartile range, 40-53) months, the mortality rates were 12.9%, 31.5%, and 43.1%, respectively. The adjusted hazard ratio was 1.57 (95% confidence interval [CI], 0.73-3.39; p = 0.25) and 2.87 (95% CI, 1.10-5.35; p = 0.028) when the pre-frail and frail groups were compared with the fit group, respectively. The frail group had a significantly increased risk for a prolonged hospital stay (adjusted odds ratio, 2.22; 95% CI, 1.05-4.69; p = 0.022) compared with the fit group. CONCLUSION: Pretreatment frailty was significantly associated with worse survival outcomes and more surgical complications, with prolonged hospital stay, in the older patients with cancer after elective abdominal surgery. Preoperative frailty assessment can assist physicians in identifying patients at a high risk for surgical complications and predicting the survival outcomes of older patients with cancer.
Assuntos
Fragilidade , Neoplasias , Idoso , Humanos , Fragilidade/complicações , Fragilidade/diagnóstico , Idoso Fragilizado , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Avaliação Geriátrica , Neoplasias/complicações , Neoplasias/cirurgiaRESUMO
Multicolor labeling for monitoring the intracellular localization of the same target type in the native environment using chemical fluorescent dyes is a challenging task. This approach requires both bioorthogonal and biocompatible ligations with an excellent fluorescence signal-to-noise ratio. Here, we present a metabolic glycan labeling technique that uses homemade fluorogenic dyes to investigate glycosylation patterns in live cells. These dyes allowed us to demonstrate rapid and efficient simultaneous multilabeling of glycoconjugates with minimum fluorescence noise. Our results demonstrate that this approach is capable of not only probing sialylation and GlcNAcylation in cells but also specifically labeling the cell-surface and intracellular sialylated glycoconjugates in live cells. In particular, we performed site-specific dual-channel fluorescence imaging of extra and intracellular sialylated glycans in HeLa and PC9 cancer cells as well as identified fluorescently labeled sialylated glycoproteins and glycans by a direct enrichment approach combined with an MS-based proteomic analysis in the same experiment. In conclusion, this study provides multilabeling tools in cellular systems for simultaneous site-specific glycan imaging and glycoproteomic analysis to study potential cancer- and disease-associated glycoconjugates.
Assuntos
Glicoproteínas , Proteômica , Humanos , Corantes Fluorescentes/metabolismo , Glicoconjugados/metabolismo , Polissacarídeos/metabolismoRESUMO
Intercellular heterogeneity occurs widely under both normal physiological environments and abnormal disease-causing conditions. Several attempts to couple spatiotemporal information to cell states in a microenvironment were performed to decipher the cause and effect of heterogeneity. Furthermore, spatiotemporal manipulation can be achieved with the use of photocaged/photoactivatable molecules. Here, we provide a platform to spatiotemporally analyze differential protein expression in neighboring cells by multiple photocaged probes coupled with homemade photomasks. We successfully established intercellular heterogeneity (photoactivable ROS trigger) and mapped the targets (directly ROS-affected cells) and bystanders (surrounding cells), which were further characterized by total proteomic and cysteinomic analysis. Different protein profiles were shown between bystanders and target cells in both total proteome and cysteinome. Our strategy should expand the toolkit of spatiotemporal mapping for elucidating intercellular heterogeneity.
Assuntos
Proteômica , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Omental wrapping (OW) is the leading cause of obstruction of the peritoneal dialysis (PD) catheter, which interferes with dialysis treatment. Routinely or selectively performing omentopexy during laparoscopic PD catheter placement has been suggested to prevent OW. However, most of the published techniques for performing this adjunctive procedure require additional incisions and suturing. Herein, we aimed to report our experience in performing omentopexy with a sutureless technique during dual-incision PD catheter insertion. We also performed a comparative analysis to assess the benefit/risk profile of routine omentopexy in these patients. METHODS: This retrospective study enrolled 469 patients who underwent laparoscopic PD catheter insertion. Their demographic characteristics and operative details were collected from the database of our institution. Omentopexy was performed by fixing the inferior edge of the omentum to the round ligament of the liver using titanium clips. For analysis, the patients were divided into the omentopexy group and the non-omentopexy group. We also reviewed the salvage management and outcomes of patients who experienced OW. RESULTS: The patients were categorized into the omentopexy (n = 81) and non-omentopexy (n = 388) groups. The patients in the non-omentopexy group had a higher incidence of OW, whereas no patient in the omentopexy group experienced this complication (5.2% vs. 0.0%, p = 0.033). The median operative time was 27 min longer in patients who underwent omentopexy than in those who did not [100 (82-118) min vs. 73 (63-84) min, p < 0.001]. One patient had an intra-abdominal hematoma after omentopexy and required salvage surgery to restore catheter function. The complication rate of omentopexy was 1.2% (1/81). CONCLUSION: Sutureless omentopexy during laparoscopic PD catheter insertion is a safe and reliable technique that does not require additional incisions and suturing. Routinely performing omentopexy provides clinical benefits by reducing the risk of catheter dysfunction due to OW.
Assuntos
Falência Renal Crônica , Laparoscopia , Diálise Peritoneal , Feminino , Humanos , Omento/cirurgia , Estudos Retrospectivos , Diálise Peritoneal/métodos , Catéteres , Laparoscopia/métodos , Falência Renal Crônica/cirurgia , Cateteres de DemoraRESUMO
Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.
Assuntos
Laparoscopia , Diálise Peritoneal , Humanos , Estudos Retrospectivos , Cateteres de Demora , Diálise Renal , Diálise Peritoneal/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , PeritônioRESUMO
OBJECTIVE: This international multicenter study by the Upper GI International Robotic Association aimed to gain insight in current techniques and outcomes of RAMIE worldwide. BACKGROUND: Current evidence for RAMIE originates from single-center studies, which may not be generalizable to the international multicenter experience. METHODS: Twenty centers from Europe, Asia, North-America, and South-America participated from 2016 to 2019. Main endpoints included the surgical techniques, clinical outcomes, and early oncological results of ramie. RESULTS: A total of 856 patients undergoing transthoracic RAMIE were included. Robotic surgery was applied for both the thoracic and abdominal phase (45%), only the thoracic phase (49%), or only the abdominal phase (6%). In most cases, the mediastinal lymphadenectomy included the low paraesophageal nodes (n=815, 95%), subcarinal nodes (n = 774, 90%), and paratracheal nodes (n = 537, 63%). When paratracheal lymphadenectomy was performed during an Ivor Lewis or a McKeown RAMIE procedure, recurrent laryngeal nerve injury occurred in 3% and 11% of patients, respectively. Circular stapled (52%), hand-sewn (30%), and linear stapled (18%) anastomotic techniques were used. In Ivor Lewis RAMIE, robot-assisted hand-sewing showed the highest anastomotic leakage rate (33%), while lower rates were observed with circular stapling (17%) and linear stapling (15%). In McKeown RAMIE, a hand-sewn anastomotic technique showed the highest leakage rate (27%), followed by linear stapling (18%) and circular stapling (6%). CONCLUSION: This study is the first to provide an overview of the current techniques and outcomes of transthoracic RAMIE worldwide. Although these results indicate high quality of the procedure, the optimal approach should be further defined.
Assuntos
Boehmeria , Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Sistema de Registros , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Esophagectomy remains the standard treatment for esophageal cancer or esophagogastric junction cancer. The stomach, or the gastric conduit, is currently the most commonly used substitute for reconstruction instead of the jejunum or the colon. Preservation of the right gastric and the right gastroepiploic vessels is a vital step to maintain an adequate perfusion of the gastric conduit. Compromise of these vessels, especially the right gastroepiploic artery, might result in ischemia or necrosis of the conduit. Replacement of the gastric conduit with jejunal or colonic interposition is reported when a devastating accident occurs; however, the latter procedure requires a more extensive dissection and multiple anastomosis. CASE PRESENTATION: A 61-year-old male with a lower third esophageal squamous cell carcinoma (cT3N1 M0) who received neoadjuvant chemoradiation with a partial response. He underwent esophagectomy with a gastric conduit reconstruction. However, the right gastroepiploic artery was accidentally transected during harvesting the gastric conduit, and the complication was identified during the pull-up phase. An end-to-end primary anastomosis was performed by the plastic surgeon under microscopy, and perfusion of the conduit was evaluated by the ICG scope, which revealed adequate vascularization of the whole conduit. We continued the reconstruction with the revascularized gastric conduit according to the perfusion test result. Although the patient developed minor postoperative leakage of the esophagogastrostomy, it was controlled with conservative drainage and antibiotic administration. Computed tomography also demonstrated fully enhanced gastric conduit. The patient resumed oral intake smoothly later without complications and was discharged at postoperative day 43. CONCLUSION: Although the incidence of vascular compromise during harvesting of the gastric conduit is rare, the risk of conduit ischemia is worrisome whenever it happens. Regarding to our presented case, with the prompt identification of the injury, expertized vascular reconstruction, and a practical intraoperative evaluation of the perfusion, a restored gastric conduit could be applied for reconstruction instead of converting to more complicated procedures.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Anastomose Cirúrgica/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Junção Esofagogástrica/cirurgia , Humanos , Isquemia/cirurgia , Masculino , Pessoa de Meia-Idade , Perfusão , Estômago/patologiaRESUMO
A mycotic aneurysm is a life-threatening disease that usually presents with nonspecific symptoms. A prompt diagnosis is essential because of the risk of aneurysm rupture and high mortality rate. We describe a case of an abdominal mycotic aortic aneurysm presenting as chronic constipation for 3 weeks, without fever or abdominal pain. Point-of-care ultrasound has the ability to detect silent abdominal aortic aneurysms and serves as a follow-up tool for patients under medical treatment.
Assuntos
Aneurisma Infectado/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/etiologia , Constipação Intestinal/etiologia , Aneurisma Infectado/terapia , Antibacterianos/uso terapêutico , Aneurisma da Aorta Abdominal/terapia , Ruptura Aórtica/cirurgia , Procedimentos Endovasculares , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , UltrassonografiaRESUMO
PURPOSE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for fluorouracil-based adjuvant chemotherapy in colorectal cancer has been a paradigm shift. However, whether this applies to gastric cancer is questionable. Furthermore, we herein investigated whether and how autophagy plays a role in MSI-relevant chemoresistance. MATERIALS AND METHODS: A total of 929 patients with deficient MMR (dMMR) and proficient MMR (pMMR) gastric cancers who underwent curative-intent gastrectomy were enrolled. We compared clinicopathological variables and survival among dMMR and pMMR cohorts and tested the responses of MSI-high and microsatellite stable (MSS) gastric cancer cell lines to 5-fluorouracil (5-FU) with or without chloroquine, an autophagy inhibitor. RESULTS: We identified an 8.9% prevalence of dMMR cases (83 out of 929) in our cohort. This was associated with old age, tumor site at the distal stomach, an intestinal phenotype, fewer nodal metastasis, and early pathological stages. MMR was an independent prognostic factor after multivariate adjustment. Overall survival (OS) of dMMR patients was better than that of the pMMR patients but was only applicable to stage III patients. There was no difference in OS between dMMR patients treated with or without adjuvant chemotherapy, although the latter showed more medical morbidities. The MSI-high gastric cancer cell lines, versus the MSS counterparts, displayed increased resistance to 5-FU and increased autophagy. Interestingly, autophagy inhibition abrogated the chemoresistance. CONCLUSION: Our data show that fluorouracil-based adjuvant chemotherapy does not work for dMMR cases, if not worse. Autophagy inhibition and/or immune checkpoint inhibition might be promising alternative strategies for gastric cancer treatment. IMPLICATIONS FOR PRACTICE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for adjuvant chemotherapy in colorectal cancer has caused a paradigm shift in cancer therapy, although its implications in gastric cancer are still questionable. The data obtained in the current study indicate that MSI-MMR is an independent prognostic factor for gastric cancer. Standard fluorouracil-based adjuvant chemotherapy did not work for deficient MMR cases, and was likely worse. Instead, strategies like autophagy inhibition and/or immune checkpoint inhibition should be taken into consideration in the future.
Assuntos
Neoplasias Colorretais , Neoplasias Gástricas , Autofagia , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Humanos , Instabilidade de Microssatélites , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Submucosal tumors (SMTs) of different etiologies exist from esophagus to rectum. Esophagogastric junction (EGJ) is one of the known difficult locations for tumor resection. Although minimally invasive surgery (MIS) is a well-established approach for gastrointestinal surgery, there is no consensus that MIS for resection of SMTs around EGJ is superior to laparotomy. We tried to clarify the factors that determine the surgeons' choices between these two approaches. METHODS: From January 2002 to June 2016, 909 patients with SMTs underwent resection in our department. Among them, 119 patients (13%) had SMTs around EGJ were enrolled by retrospective review. The clinicopathological features and tumor-related parameters were reviewed and analyzed. RESULTS: The cohort was stratified into three groups according to the extent of gastrectomy and surgical approaches. The three groups are as following: major gastrectomy (n = 13), minor gastrectomy by laparotomy (n = 51), and minor gastrectomy with MIS (n = 55). The average tumor size was significantly larger in the major gastrectomy group than in the two minor gastrectomy groups; however, there was no difference between the two minor gastrectomy groups (5.33 cm, 4.07 cm, and 3.69 cm, respectively). The minor gastrectomy with MIS required least hospital stay and operation duration also. We re-stratify the two minor gastrectomy groups (n = 106) according to the orientation of SMTs around the EGJ into 4 zones. Most of SMTs located on the greater curvature side of the EGJ were resected with MIS (82% versus 18%), whereas SMTs in the other zones were resected more often by laparotomy (59% versus 41%). There was no surgical mortality within the cohort, while minor gastrectomy with MIS yielded least number of leakages among the three groups. CONCLUSIONS: For SMTs around the EGJ, larger tumors (diameter of more than 5 cm) are more likely to be resected with major gastrectomy. To resect SMTs around the EGJ in a wedge-like (minor gastrectomy) fashion, tumors located other than the greater curvature side were more often resected by laparotomy. However, MIS yielded acceptable safety and surgical outcomes compared to conventional laparotomy for SMTs around the EGJ of the same size.
Assuntos
Gastrectomia , Laparoscopia , Neoplasias Gástricas , Adulto , Idoso , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. METHODS: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. RESULTS: Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. CONCLUSION: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The present study assessed the impact of the retrieval of >25 lymph nodes (LNs) on the survival outcome of patients with advanced gastric cancer after curative-intent gastrectomy. PATIENTS AND METHODS: A total of 5,386 patients who had undergone curative gastrectomy for gastric cancer from 1994 to 2011 were enrolled. The clinicopathological parameters and overall survival (OS) were analyzed according to the number of LNs examined (≤15, n = 916; 16-25, n = 1,458; and >25, n = 3,012). RESULTS: The percentage of patients with >25 LNs retrieved increased from 1994 to 2011. Patients in the LN >25 group were more likely to have undergone total gastrectomy and to have a larger tumor size, poorer tumor differentiation, and advanced T and N stages. Hospital mortality among the LN ≤15, LN 16-25, and LN >25 groups was 6.1%, 2.7%, and 1.7%, respectively (p < .0001). The LN >25 group consistently exhibited the most favorable OS, in particular, with stage II disease (p = .011) when OS was stratified according to tumor stage. Similarly, the LN >25 group had significantly better OS in all nodal stages (from N1 to N3b). The discrimination power of the lymph node ratio (LNR) for the LN ≤15, LN 16-25, and LN >25 groups was 483, 766, and 1,560, respectively. Multivariate analysis demonstrated that the LNR was the most important prognostic factor in the LN >25 group. CONCLUSION: Retrieving more than 25 lymph nodes during curative-intent gastrectomy substantially improved survival and survival stratification of advanced gastric cancer without compromising patient safety. The Oncologist 2017;22:97-106Implications for Practice: D2 lymph node (LN) dissection is currently the standard of surgical management of gastric cancer, which is rarely audited by a third party. The present study, one of the largest surgical series worldwide, has shown that the traditionally recognized retrieval of ≥16 LNs during curative-intent gastrectomy might not be adequate in regions in which locally advanced gastric cancers predominate. The presented data show that retrieval of >25 LNs, which more greatly mimics D2 dissection, improves long-term outcomes and survival stratification without compromising patient safety.
Assuntos
Excisão de Linfonodo , Linfonodos/cirurgia , Prognóstico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Portal vein embolization is essential for patients with biliary cancer who undergo extended hepatectomy to induce hypertrophy of the future remnant liver. Over 830 patients have undergone the portal vein embolization at our institution since 1990. Non-alcoholic fatty liver disease is an entity of hepatic disease characterized by fat deposition in hepatocytes. It has a higher prevalence among persons with morbid obesity, type 2 diabetes, and hyperlipidemia. Neither the mechanism of hepatic hypertrophy after portal vein embolization nor the pathophysiology of non-alcoholic fatty liver disease has been fully elucidated. Some researchers integrated the evident insults leading to progression of fatty liver disease into the multiple-hit hypothesis. Among these recognized insults, the change of hemodynamic status of the liver was never mentioned. CASE PRESENTATION: We present the case of a woman with perihilar cholangiocarcinoma who received endoscopic biliary drainage and presented to our institute for surgical consultation. A left trisectionectomy with caudate lobectomy and extrahepatic bile duct resection was indicated for curative treatment. To safely undergo left trisectionectomy, she underwent selective portal vein embolization of the liver, in which uneven acute fatty change subsequently developed. The undrained left medial sector of the liver with dilated biliary tracts was spared the fatty change. The patient underwent planned surgery without any major complications 6 weeks after the event and has since resumed a normal life. The discrepancies in fatty deposition in the different sectors of the liver were confirmed by pathologic interpretations. CONCLUSION: This is the first report of acute fatty change of the liver after portal vein embolization. The sparing of the undrained medial sector is unique and extraordinary. The images and pathologic interpretations presented in this report may inspire further research on how the change of hepatic total inflow after portal vein embolization can be one of the insults leading to non-alcoholic fatty liver disease/ change.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Embolização Terapêutica/efeitos adversos , Fígado Gorduroso/etiologia , Embolização Terapêutica/métodos , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Veia Porta , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND AIM: Epstein-Barr virus (EBV) is suggested to actively utilize its ebv-microRNAs (miRNAs) to manipulate viral and cellular functions during neoplasia transformation. A systemic profiling of ebv-miRNAs expressed in EBV-associated gastric carcinoma (EBVa GC) helps understand its epigenetic regulation of carcinogenesis. METHODS: A total of 1039 patients with gastric cancer were screened for EBVa GC using EBV-encoded RNAs in situ hybridization. A comprehensive profiling of ebv-miRNAs expressed in EBVa GC was constructed using stem-loop quantitative polymerase chain reaction. Functional assay of specific ebv-miRNA was conducted. Expression of epithelial-to-mesenchymal transition (EMT) markers among EBVa GC and non-EBVa GC was compared. RESULTS: The prevalence of EBVa GC was 5.0% (52 out of 1039) in our series. The most abundant ebv-miRNAs of EBVa GC were Bart4, followed by Bart11, Bart2, Bart6, Bart9, and Bart18, in the decreasing order. Of them, Bart9 exhibited the same seed sequence as to hsa miR-200a and miR-141. Expression of E-cadherin of EBV-positive SNU-719 was increased after BART9 knockdown. Depleting endogenous Bart9 of SNU-719 induced a surged expression of miR-200a and miR-141, accompanied by decreased proliferative and invasive ability. Expression of mesenchymal markers in EBVa GC was increased compared with those of non-EBVa GC, albeit the two cohorts exhibited a comparable long-term survival. CONCLUSIONS: We constructed a comprehensive profiling of ebv-miRNAs in EBVa GC. BART9 plays an important role during carcinogenesis through EMT. Inherent mesenchymal phenotype of EBVa GC represents a unique virus-induced morphology and microenvironment rather than being able to predict the prognosis.
Assuntos
Epigênese Genética/genética , Transição Epitelial-Mesenquimal/genética , Herpesvirus Humano 4/genética , MicroRNAs , RNA Viral , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Idoso , Feminino , Expressão Gênica , Humanos , Masculino , MicroRNAs/fisiologia , Pessoa de Meia-Idade , RNA Viral/fisiologiaRESUMO
BACKGROUND: Curative hepatectomy with bile duct resection is the treatment for perihilar cholangiocarcinoma. A locally advanced tumor necessitates hepatectomy with simultaneous vascular resection, and reconstruction remains an obstacle for surgeons. Studies have focused on the variations of hepatic arteries. Nevertheless, the anatomical alignment of the portal veins, bile ducts, and hepatic arteries are equally critical in surgical planning of curative resection for advanced tumors. We have reported promising outcomes of hepatectomy with simultaneous resection and reconstruction of the hepatic artery. With respect to the type of surgery, most patients undergo left hepatectomy with right hepatic artery resection and reconstruction in contrast to right hepatectomy with left hepatic artery resection and reconstruction. We present two patients who showed detoured left hepatic arteries that were invaded by the perihilar tumors. CASE PRESENTATION: A 78-year-old man who presented with epigastric pain and abnormal liver function was referred to our clinic for further examination. Serial examination resulted in the diagnosis of Bismuth type II hilar cholangiocarcinoma. The left hepatic artery ran a detoured course and was invaded by the tumor. The second patient was a 76-year-old woman who presented with jaundice and the Bismuth type II hilar cholangiocarcinoma. The left hepatic artery was along the right-lateral position of the left portal vein and was invaded by the tumor. The variant anatomical relationship of the vessel was identified preoperatively in both patients, and they underwent right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications or recurrence. CONCLUSIONS: The largely biased selection of patients is based on the following anatomical relationship: the left hepatic artery usually runs left lateral to the portal vein, which spares invasion by the perihilar cholangiocarcinoma. On the contrary, the right hepatic artery mostly runs behind the bile duct and is invaded by the tumor. This aforementioned anatomy is one of the reasons for the relatively rare left hepatic artery resections and reconstructions in right hepatectomies. By meticulous preoperative evaluation with images, we identify the anatomical variation and performed right hepatectomy with concomitant left hepatic artery resection and reconstruction without any major complications and mortalities.
Assuntos
Variação Anatômica , Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia/métodos , Artéria Hepática/anatomia & histologia , Tumor de Klatskin/cirurgia , Idoso , Anastomose Cirúrgica , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiografia , Angiografia por Tomografia Computadorizada , Endoscopia Gastrointestinal , Feminino , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/patologia , Artéria Hepática/cirurgia , Humanos , Tumor de Klatskin/diagnóstico por imagem , Masculino , Tomografia Computadorizada Multidetectores , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Procedimentos de Cirurgia PlásticaRESUMO
BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for gallbladder lesions, but it is not a pain-free procedure. This study explored the pain relief provided by combined wound and intraperitoneal local anesthetic use for patients who are undergoing LC. METHODS: Two-hundred and twenty consecutive patients undergoing LC were categorized into 1 of the following 4 groups: local wound anesthetic after LC either with an intraperitoneal local anesthetic (W + P) (group 1) or without an intraperitoneal local anesthetic (W + NP) (group 2), or no local wound anesthetic after LC either with intraperitoneal local anesthetic (NW + P) (group 3) or without an intraperitoneal local anesthetic (NW + NP) (group 4). A visual analog scale (VAS) was used to assess postoperative pain. The amount of analgesic used and the duration of hospital stay were also recorded. RESULTS: The VAS was significantly lower immediately after LC for the W + P group than for the NW + NP group (5 vs. 6; p = 0.012). Patients in the W + P group received a lower total amount of meperidine during their hospital stay. They also had the shortest hospital stay after LC, compared to the patients in the other groups. CONCLUSION: Combined wound and intraperitoneal local anesthetic use after LC significantly decreased the immediate postoperative pain and may explain the reduced use of meperidine and earlier discharge of patients so treated.
Assuntos
Amidas/administração & dosagem , Anestesia Local/métodos , Anestésicos Locais/administração & dosagem , Colecistectomia Laparoscópica , Dor Pós-Operatória/prevenção & controle , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/uso terapêutico , Anestésicos Locais/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Ropivacaina , Resultado do TratamentoRESUMO
Earth is currently experiencing a mass extinction event. The flora and fauna of our planet are experiencing mass die-offs from a multitude of factors, with wildlife disease emerging as one parameter where medicinal chemists are equipped to intervene. While contemporary medicinal chemistry focuses on human health, many traditional pharmaceutical companies have historic roots in human health, animal health, and plant health. This trifecta of health sciences perfectly maps to the current field of One Health, which recognizes that optimal health outcomes can only be achieved through the health of humans, plants, animals, and their shared environments. This Perspective imagines a world where state-of-the-art medicinal chemistry tactics are used to prevent the extinction of endangered species and points to preliminary work in the emerging area of conservation medicine.
Assuntos
Química Farmacêutica , Humanos , Animais , Química Farmacêutica/métodos , Espécies em Perigo de ExtinçãoRESUMO
BACKGROUND: Numerous studies have demonstrated a correlation between p53 overexpression and diminished survival in gastric cancer patients. However, conflicting findings exist, and we hypothesize that these discrepancies arise from the cancer's complexity and heterogeneity, coupled with a lack of consensus on aberrant p53 expression. METHODS: We enrolled a cohort of 187 patients with surgically resected gastric cancer. Patient categorization was based on Epstein-Barr virus (EBV), microsatellite instability (MSI), and Lauren classification (intestinal, diffuse and mixed). Utilizing an incremental algorithm, we evaluated p53 immunohistochemical (IHC) patterns in all 187 cases, while next-generation sequencing was successfully performed on 152 cases to identify TP53 mutations (mutTP53). RESULTS: MutTP53 was identified in 32 % of the 152 cases, comprising 36 missense, 5 nonsense, and 7 frameshift alterations. Missense mutations predominantly correlated with p53 overexpression, while nonsense and frameshifting alterations related to null expression. Trial calculations indicated that null expression and a p53 IHC cutoff at >40 % offered the best prediction of mutTP53 (kappa coefficient, 0.427), with the highest agreement (0.524) observed in diffuse type and the lowest (0.269) in intestinal type. Null expression and a p53 IHC cutoff at >10 %, but not mutTP53 per se, provided the optimal prediction of survival outcome (p = 0.043), particularly in diffuse type (p = 0.044). Multivariate analysis showed that aberrant p53 IHC expression was not an independent prognostic factor. CONCLUSIONS: P53 IHC patterns are predictive biomarkers for mutTP53 and gastric cancer outcomes, where a prerequisite involves a nuanced approach considering cutoff values and molecular-histologic subtyping.
RESUMO
Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.
RESUMO
Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated.