RESUMEN
BACKGROUND AND OBJECTIVES: Ovarian metastases (OM) are a common site for metastases in gastrointestinal tumours with peritoneal disease. This study aimed to evaluate perioperative complications between patients with and without OM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal/colorectal cancer. METHODS: Female patients undergoing CRS ± HIPEC for appendiceal/colorectal tumours at a single centre from 2009 to 2020 were analysed. Patients were grouped according to presence or absence of OM at the time of CRS. RESULTS: The study included 318 patients, 72 (22.6%) had OM. Operation duration was longer for patients with OM (332 vs. 276 min, p < 0.0001). Patients with OM achieved higher rates of complete cytoreduction (93% vs. 79%, p = 0.006) despite a higher peritoneal carcinomatosis index (13 vs. 7, p < 0.001) and were more likely to require a blood transfusion (32% vs. 19%, p = 0.024) and a stoma (24% vs.10%, p = 0.005). Increasing age and presence of abdominal symptoms were independent predictors of major and all-cause morbidity, respectively. The presence of abdominal symptoms was independently associated with all-cause morbidity in the OM group. CONCLUSION: These results may assist with preoperative counselling. Prospective multicentre datasets are needed to evaluate morbidity in one- versus two-stage approaches for those with abdominal symptoms and OM.
Asunto(s)
Neoplasias del Apéndice , Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Femenino , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Estudios Prospectivos , Neoplasias Peritoneales/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias del Apéndice/patología , Hipertermia Inducida/efectos adversos , Terapia Combinada , Tasa de Supervivencia , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Although several studies compare the clinical outcomes and costs of laparoscopic and robotic proctectomy, most of them reflect the outcomes of the utilisation of older generation robotic platforms. The aim of this study is to compare the financial and clinical outcomes of robotic and laparoscopic proctectomy within a public healthcare system, utilising a multi-quadrant platform. METHODS: Consecutive patients undergoing laparoscopic and robotic proctectomy between January 2017 and June 2020 in a public quaternary centre were included. Demographic characteristics, baseline clinical, tumour and operative variables, perioperative, histopathological outcomes and costs were compared between the laparoscopic and robotic groups. Simple linear regression and generalised linear model analyses with gamma distribution and log-link function were used to determine the impact of the surgical approach on overall costs. RESULTS: During the study period, 113 patients underwent minimally invasive proctectomy. Of these, 81 (71.7%) underwent a robotic proctectomy. A robotic approach was associated with a lower conversion rate (2.5% versus 21.8%;P = 0.002) at the expense of longer operating times (284 ± 83.4 versus 243 ± 89.8 min;P = 0.025). Regarding financial outcomes, robotic surgery was associated with increased theatre costs (A$23,019 ± 8235 versus A$15,525 ± 6382; P < 0.001) and overall costs (A$34,350 ± 14,770 versus A$26,083 ± 12,647; P = 0.003). Hospitalisation costs were similar between both approaches. An ASA ≥ 3, non-metastatic disease, low rectal cancer, neoadjuvant therapy, non-restorative resection, extended resection, and a robotic approach were identified as drivers of overall costs in the univariate analysis. However, after performing a multivariate analysis, a robotic approach was not identified as an independent driver of overall costs during the inpatient episode (P = 0.1). CONCLUSION: Robotic proctectomy was associated with increased theatre costs but not with increased overall inpatient costs within a public healthcare setting. Conversion was less common for robotic proctectomy at the expense of increased operating time. Larger studies will be needed to confirm these findings and examine the cost-effectiveness of robotic proctectomy to further justify its penetration in the public healthcare system.
Asunto(s)
Laparoscopía , Proctectomía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Estudios RetrospectivosRESUMEN
AIM: Resection of diverticular disease can be technically challenging. Tissue planes can be difficult to identify intraoperatively due to inflammation or fibrosis. Robotic surgery may improve identification of tissue planes and dissection which can facilitate difficult minimally invasive resections. This systematic review and meta-analysis evaluates the role of robotic surgery compared to laparoscopic surgery in diverticular resection. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. The search was completed using PubMed, OVID MEDLINE and EMBASE. A total of 490 articles were retrieved, and studies reporting primary outcomes for robotic diverticular resection were included in the final analysis. A meta-analysis of studies comparing robotic and laparoscopic surgery was performed on rate of conversion to open surgery and complications. RESULTS: Fifteen articles (8 cohort studies and 7 case series) reporting 3711 robotic diverticular resections were analysed. In comparison to laparoscopic, robotic surgery for diverticular disease was associated with a reduced conversion to open and a longer operating time. Meta-analysis showed robotic resection was associated with a lower conversion rate compared to laparoscopic surgery (OR: 0.57; 95% CI: 0.49-0.66, p < 0.001). There was no significant difference in grade III and above complications (OR: 0.74; 95% CI: 0.49-1.13, p = 0.17). Operating time was longer with a robotic approach (Hedge's G: 0.43; 95% CI: 0.04-0.81, p = 0.03). CONCLUSION: Robotic resection is a feasible and safe option in diverticular disease. Although associated with a longer operating time, robotic surgery may render diverticular disease resectable with a minimally invasive approach that would have otherwise necessitated a laparotomy. Randomised controlled data is required to better define the role of robotic surgery for diverticular disease resections.
Asunto(s)
Enfermedades Diverticulares , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Conversión a Cirugía Abierta/efectos adversos , Enfermedades Diverticulares/cirugía , Enfermedades Diverticulares/complicaciones , Laparoscopía/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.
Asunto(s)
Pancreatectomía , Sarcoma , Humanos , Morbilidad , Recurrencia Local de Neoplasia/cirugía , Pancreatectomía/efectos adversos , Fístula Pancreática/etiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Sarcoma/cirugíaRESUMEN
BACKGROUND: How well imaging size agrees with pathologic size of gastric gastrointestinal stromal tumors (GISTs) is unknown. GIST risk stratification is based on pathologic size, location, and mitotic rate. To inform decision making, the size discrepancy between imaging and pathology for gastric GISTs was investigated. METHODS: Imaging and pathology reports were reviewed for 113 patients. Bland-Altman analyses and intraclass correlation (ICC) assessed agreement of imaging and pathology. Changes in clinical risk category due to size discrepancy were identified. RESULTS: Computed tomography (CT) (n = 110) and endoscopic ultrasound (EUS) (n = 50) underestimated pathologic size for gastric GISTs by 0.42 cm, 95% confidence interval (CI): (0.11, 0.73), p = 0.008 and 0.54 cm, 95% CI: (0.25, 0.82), p < 0.001, respectively. ICCs were 0.94 and 0.88 for CT and EUS, respectively. For GISTs ≤ 3 cm, size underestimation was 0.24 cm for CT (n = 28), 95% CI: (0.01, 0.47), p = 0.039 and 0.56 cm for EUS (n = 26), 95% CI: (0.27, 0.84), p < 0.0001. ICCs were 0.72 and 0.55 for CT and EUS, respectively. Spearman's correlation was ≥0.84 for all groups. For GISTs ≤ 3 cm, 6/28 (21.4% p = 0.01) on CT and 7/26 (26.9% p = 0.005) on EUS upgraded risk category using pathologic size versus imaging size. No GISTs ≤ 3 cm downgraded risk categories. Size underestimation persisted for GISTs ≤ 2 cm on EUS (0.39 cm, 95% CI: [0.06, 0.72], p = 0.02, post hoc analysis). CONCLUSION: Imaging, particularly EUS, underestimates gastric GIST size. Caution should be exercised using imaging alone to risk-stratify gastric GISTs, and to decide between surveillance versus surgery.
Asunto(s)
Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/patología , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Anciano , Toma de Decisiones Clínicas , Endosonografía , Femenino , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Tiempo de Tratamiento , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
BACKGROUND: Emergency general surgery (EGS) services are gaining popularity in Canada as systems-based approaches to surgical emergencies. Despite the high volume, acuity and complexity of the patient populations served by EGS services, little has been reported about the services' structure, processes, case mix or outcomes. This study begins a national surveillance effort to define and advance surgical quality in an important and diverse surgical population. METHODS: A national cross-sectional study of EGS services was conducted during a 24-hour period in January 2017 at 14 hospitals across 7 Canadian provinces recruited through the Canadian Association of General Surgeons Acute Care Committee. Patients admitted to the EGS service, new consultations and off-service patients being followed by the EGS service during the study period were included. Patient demographic information and data on operations, procedures and complications were collected. RESULTS: Twelve sites reported resident coverage. Most services did not include trauma. Ten sites had protected operating room time. Overall, 393 patient encounters occurred during the study period (195/386 [50.5%] operative and 191/386 [49.5%] nonoperative), with a mean of 3.8 operations per service. The patient population was complex, with 136 patients (34.6%) having more than 3 comorbidities. There was a wide case mix, including gallbladder disease (69 cases [17.8%]) and appendiceal disease (31 [8.0%]) as well as complex emergencies, such as obstruction (56 [14.5%]) and perforation (23 [5.9%]). CONCLUSION: The characteristics and case mix of these Canadian EGS services are heterogeneous, but all services are busy and provide comprehensive operative and nonoperative care to acutely ill patients with high levels of comorbidity.
CONTEXTE: Les services de chirurgie générale d'urgence (CGU) gagnent en popularité au Canada en tant qu'approches systémiques aux urgences chirurgicales. Malgré le volume élevé, le caractère urgent et la complexité des populations de patients desservies en CGU, peu de rapports ont porté sur la structure, les processus, les clientèles ou les résultats de ces services. La présente étude instaure une démarche de surveillance nationale qui servira à définir et à améliorer la qualité des chirurgies destinées à cette population importante et hétérogène. MÉTHODES: Une étude transversale nationale sur les services de CGU a été réalisée sur une période de 24 heures en janvier 2017 dans 14 hôpitaux de 7 provinces canadiennes recrutés par l'entremise du comité pour les soins aigus de l'Association canadienne des chirurgiens généraux. On y a inclus les patients admis dans les services de CGU, les nouvelles consultations et les patients de l'extérieur suivis par les services de CGU pendant la période de l'étude. On a recueilli les caractéristiques démographiques des patients et les données sur les interventions, les procédures et les complications. RÉSULTATS: Douze sites ont fait état de la couverture assurée par les résidents. La plupart des services ont exclu la traumatologie. Dix sites disposaient de temps protégé au bloc opératoire. En tout, 393 rencontres avec des patients ont eu lieu pendant la période de l'étude (195/386 [50,4 %] chirurgicales, 191/386 [49,5 %] non chirurgicales), avec une moyenne de 3,8 chirurgies par service. La population regroupait des cas complexes : 136 patients (34,6 %) présentaient plus de 3 comorbidités. La clientèle était diversifiée et comprenait des cas de maladie de la vésicule biliaire (69 cas [17,8â¯%]) et de l'appendice (31 [8,0 %]), de même que des situations d'urgence délicates, telle qu'obstruction (56 [14,5 %]) et perforation (23 [5,9 %]). CONCLUSION: Leurs caractéristiques et leurs clientèles sont hétérogènes, mais les services de CGU sont tous achalandés et ils offrent tous des soins chirurgicaux et non chirurgicaux complets à des patients gravement malades porteurs d'importantes comorbidités.
Asunto(s)
Cirugía General/organización & administración , Traumatología/organización & administración , Canadá , Estudios Transversales , Grupos Diagnósticos Relacionados , Humanos , Flujo de TrabajoRESUMEN
BACKGROUND: Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program. METHODS: We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data. RESULTS: We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%. CONCLUSION: In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.
BACKGROUND: Au Canada, la chirurgie bariatrique est effectuée principalement dans des cliniques spécialisées financées par le secteur public. Des études ont démontré que les interventions de cette nature sont supérieures à la prise en charge médicale intensive pour la perte de poids et la réduction des affections comorbides liées à l'obésité. L'objectif de notre étude était de comparer l'efficacité et l'innocuité de la dérivation gastrique Roux-en-Y par laparoscopie (DGRY), de la gastrectomie longitudinale (GL) et de la gastroplastie par anneau gastrique modulable (GAGM) dans le cadre d'un programme de traitement bariatrique basé sur la population financé par les deniers publics. METHODS: Nous avons suivi pendant 2 ans des patients ayant subi une chirurgie bariatrique. Le résultat primaire à l'étude était la variation pondérale (en kilogrammes). Nous avons analysé la variation intergroupe au moyen d'une régression multivariable et utilisé la méthode d'imputation des données manquantes par report de la dernière observation. RESULTS: Nous avons retenu 150 patients consécutifs (51 DGRY; 51 GL; 48 GAGM). Au début de l'étude, l'âge moyen était de 43,5 ± 9,5 ans, 87,3 % des patients étaient des femmes, et leur indice de masse corporelle (IMC) avant l'opération était de 46,2 ± 7,4. Après 2 ans, la perte de poids moyenne (pourcentage du poids de départ) était de 36,6 ± 19,5 kg (26,1 ± 12,2 %) pour la DGRY, de 21,4 ± 16,0 kg (16,4 ± 11,6 %) pour la GL, et de 7,0 ± 9,7 kg (5,8 ± 7,9 %) pour la GAGM (p < 0,001). La variation de l'IMC était plus grande pour le groupe DGRY (13,0 ± 6,6) que pour les 2 autres groupes (7,6 ± 5,7 pour la GL et 2,6 ± 3,5 pour la GAGM; p < 0,001). L'incidence sur le diabète, l'hypertension et la dyslipidémie était également plus grande après la DGRY qu'après la GAGM (p < 0,05 pour tous). Il n'y a eu aucun décès. Le taux de fuites anastomotiques et liées aux sutures était de 1,3 %. CONCLUSION: Dans le cadre d'un programme de chirurgie bariatrique basé sur une population et financé par le secteur public, la DGRY et la GL ont entraîné une plus grande perte de poids que la GAGM. La dérivation a donné lieu à la plus forte réduction des affections comorbides liées à l'obésité. Toutes les interventions se sont avérées sécuritaires.
Asunto(s)
Gastrectomía/métodos , Derivación Gástrica/métodos , Gastroplastia/métodos , Obesidad/cirugía , Evaluación de Resultado en la Atención de Salud , Pérdida de Peso , Adulto , Canadá , Femenino , Estudios de Seguimiento , Gastrectomía/efectos adversos , Derivación Gástrica/efectos adversos , Gastroplastia/efectos adversos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AI (anaemia of inflammation) often manifests in patients with chronic immune activation due to cancer, chronic infections, autoimmune disorders, rheumatoid arthritis and other diseases. The pathogenesis of AI is complex and involves cytokine-mediated inhibition of erythropoiesis, insufficient erythropoietin production and diminished sensitivity of erythroid progenitors to this hormone, and retention of iron in haemoglobin-processing macrophages. NO (nitric oxide) is a gaseous molecule produced by activated macrophages that has been identified as having numerous effects on iron metabolism. In the present study, we explore the possibility that NO affects iron metabolism in reticulocytes and our results suggest that NO may also contribute to AI. We treated reticulocytes with the NO donor SNP (sodium nitroprusside). The results indicate that NO inhibits haem synthesis dramatically and rapidly at the level of erythroid-specific 5-aminolaevulinic acid synthase 2, which catalyses the first step of haem synthesis in erythroid cells. We also show that NO leads to the inhibition of iron uptake via the Tf (transferrin)-Tf receptor pathway. In addition, NO also causes an increase in eIF2α (eukaryotic initiation factor 2α) phosphorylation levels and decreases globin translation. The profound impairment of haem synthesis, iron uptake and globin translation in reticulocytes by NO raises the possibility that this gas may also contribute to AI.
Asunto(s)
Hemo/biosíntesis , Hierro/metabolismo , Óxido Nítrico/metabolismo , Reticulocitos/metabolismo , 5-Aminolevulinato Sintetasa/metabolismo , Anemia/metabolismo , Anemia/patología , Animales , Factor 2 Eucariótico de Iniciación/metabolismo , Femenino , Ratones , Fosforilación , Receptores de Transferrina/metabolismo , Reticulocitos/patologíaRESUMEN
With the exception of well-differentiated liposarcoma, dedifferentiated liposarcoma, leiomyosarcoma, solitary fibrous tumour, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma, the majority of the ≈70 histologic subtypes of retroperitoneal sarcoma are defined as 'ultra-rare' sarcomas, with an incidence of ≤1-5/1,000,000 persons/year. For most of these ultra-rare RPS subtypes, diagnosis and treatment follows international guidelines for the management of more common RPS histologies, with en bloc surgical resection as the mainstay of curative treatment, and enrolment in clinical trials where possible. Because the treatment of RPS is heavily driven by histology, the surgeon must be familiar with specific issues related to the diagnosis and management of ultra-rare sarcoma subtypes. Expert radiological and surgeon reviews are required to differentiate similarly presenting tumours where surgery can be avoided (e.g., angiomyolipoma), or where upfront systemic therapy is indicated (e.g., extraosseous Ewing's sarcoma). Thus, the management of all retroperitoneal sarcomas should occur at a sarcoma referral centre, with a multidisciplinary team of experts dedicated to the surgical and medical management of these rare tumours. In this focused review, we highlight how diagnosis and management of the ultra-rare primary RPS histologies of malignant perivascular epithelioid cell tumour (PEComa), extraosseous Ewing sarcoma (EES), extraosseous osteosarcoma (EOS), and rhabdomyosarcoma (RMS) critically diverge from the management of more common RPS subtypes.
Asunto(s)
Neoplasias Renales , Neoplasias Retroperitoneales , Sarcoma de Ewing , Sarcoma , Neoplasias de los Tejidos Blandos , Adulto , Humanos , Sarcoma de Ewing/diagnóstico por imagen , Sarcoma de Ewing/terapia , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/patología , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/terapia , Neoplasias Retroperitoneales/patologíaRESUMEN
Lateral pelvic lymph node dissection (LPLND) in rectal cancer has gained increasing traction worldwide. Robotic LPLND is an emerging technique. Utilising the IDEAL (idea, development, exploration, assessment and long-term follow-up) framework for surgical innovation, robotic LPLND is currently at the IDEAL 2A stage (development) mainly limited to case reports, case series and videos. A systematic literature review was performed for videographic robotic LPLND. Pubmed, Ovid and Web of Science were searched with a predefined search strategy. The LapVEGAS score for peer review of video surgery was adapted for the robotic approach (RoVEGAS) and applied to measure video quality. Two reviewers independently reviewed videos and consensus reached on technical steps and learning points. Data are presented as a narrative synthesis of results. The IDEAL 2A framework was applied to videos to assess their content at the present stage of innovation. A total of 83 abstracts were identified. In accordance with the PRISMA statement, nine videos were analysed. Adherence to the complete IDEAL 2a framework was low. All videos demonstrated LPLND; however, reporting of clinical outcomes was heterogeneous and completed in six of nine videos. Histopathology was reported in six videos, with other outcomes variably reported. No videos presented patient-reported outcome measures. Two videos reported presence or absence of recurrence on follow-up. Video articles provide a valuable educational resource in dissemination and adoption of robotic techniques. Standardisation of reporting objectives are needed. Complete reporting of pathology and oncologic outcomes is required in videographic procedural-based publications to meet the IDEAL 2A framework criteria.
Asunto(s)
Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patologíaRESUMEN
Natural resistance-associated macrophage protein 1 (Nramp1) is a divalent metal transporter expressed exclusively in phagocytic cells. We hypothesized that macrophage Nramp1 may participate in the recycling of iron acquired from phagocytosed senescent erythrocytes. To evaluate the role of Nramp1 in vivo, the iron parameters of WT and KO mice were analyzed after acute and chronic induction of hemolytic anemia. We found that untreated KO mice exhibited greater serum transferrin saturation and splenic iron content with higher duodenal ferroportin (Fpn) and divalent metal transporter 1 (DMT1) expression. Furthermore, hepatocyte iron content and hepcidin mRNA levels were dramatically lower in KO mice, indicating that hepcidin levels can be regulated by low-hepatocyte iron stores despite increased transferrin saturation. After acute treatment with the hemolytic agent phenylhydrazine (Phz), KO mice experienced a significant decrease in transferrin saturation and hematocrit, whereas WT mice were relatively unaffected. After a month-long Phz regimen, KO mice retained markedly increased quantities of iron within the liver and spleen and exhibited more pronounced splenomegaly and reticulocytosis than WT mice. After injection of (59)Fe-labeled heat-damaged reticulocytes, KO animals accumulated erythrophagocytosed (59)Fe within their liver and spleen, whereas WT animals efficiently recycled phagocytosed (59)Fe to the marrow and erythrocytes. These data imply that without Nramp1, iron accumulates within the liver and spleen during erythrophagocytosis and hemolytic anemia, supporting our hypothesis that Nramp1 promotes efficient hemoglobin iron recycling in macrophages. Our observations suggest that mutations in Nramp1 could result in a novel form of human hereditary iron overload.
Asunto(s)
Proteínas de Transporte de Catión/fisiología , Eritrocitos/inmunología , Hierro/metabolismo , Macrófagos/metabolismo , Fagocitosis , Anemia Hemolítica , Animales , Hemoglobinas/metabolismo , Hierro/análisis , Hígado/metabolismo , Ratones , Ratones Noqueados , Bazo/metabolismoRESUMEN
Retroperitoneal liposarcomas are a rare entity and are comprised mostly of the well-differentiated and dedifferentiated subtypes. Eight-year survival ranges from 30% to 80% depending on histologic subtype and grade. Surgery is the cornerstone of treatment and compartment resection is the current standard. Mesenteric liposarcomas are extremely rare and comprise more high-grade lesions, with poorer prognosis of 50% 5-year overall survival. They are managed with a similar aggressive surgical approach. This review presents the current management of retroperitoneal and mesenteric liposarcomas.
Asunto(s)
Liposarcoma , Neoplasias Retroperitoneales , Humanos , Liposarcoma/patología , Liposarcoma/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/cirugíaRESUMEN
Objectives: Small bowel adenocarcinoma (SBA) with peritoneal metastasis (PM) is rare and despite treatment with systemic chemotherapy, the prognosis is poor. However, there is emerging evidence that cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a survival benefit over systemic therapy alone. This systematic review will assess the effectiveness of CRS-HIPEC for SBA-PM. Content: Three databases were searched from inception to 11/10/21. Clinical outcomes were extracted and analysed. Summary: A total of 164 cases of SBA-PM undergoing CRS-HIPEC were identified in 12 studies. The majority of patients had neoadjuvant chemotherapy (87/164, 53%) and complete cytoreduction (143/164, 87%) prior to HIPEC. The median overall survival was 9-32 months and 5-year survival ranged from 25 to 40%. Clavien-Dindo grade III/IV morbidity ranged between 19.1 and 50%, while overall mortality was low with only 3 treatment-related deaths. Outlook: CRS-HIPEC has the potential to improve the overall survival in a highly selected group of SBA-PM patients, with 5-year survival rates comparable to those reported in colorectal peritoneal metastases. However, the expected survival benefits need to be balanced against the intrinsic risk of morbidity and mortality associated with the procedure. Further multicentre studies are required to assess the safety and feasibility of CRS-HIPEC in SBA-PM to guide best practice management for this rare disease.
RESUMEN
BACKGROUND: The role of en bloc vascular resection and reconstruction (EVRR) is controversial in colorectal adenocarcinoma (CRC), but well-established in retroperitoneal sarcoma (RPS). Sparse data exists regarding these complex procedures. METHODS: Patients undergoing curative intent EVRR for advanced CRC and RPS between 2014 and 2021 at a tertiary centre were included. Morbidity, margins, recurrence, and survival were evaluated. RESULTS: 24 patients underwent EVRR with 48 reconstructions (11 CRC and 13 RPS). For CRC, 100% of patients underwent Iliac system reconstructions. For RPS, inferior vena cava reconstructions were the most common (69.2%). There were 2 arterial and 1 venous graft thromboses. Primary graft patency was 89.4% arterial and 93.1% venous, while secondary patency was 100% arterial and 96.5% venous at last follow up. 1 venous and 1 arterial graft required reoperation for bleeding. There were no compromised limbs. Major complications occurred in 6 patients (25.0%) with no observed difference between CRC and RPS (OR 0.43 95%CI[0.60,3.19], P = 0.41). R1 margins occurred 1 CRC (90.9%) and 3 RPS (76.9%), with no R2 resections. All vascular resection margins were clear. There were 6 CRC (50%) and 4 RPS (33.3%) recurrences. Median recurrence time was 20.9 months for CRC and 'not yet reached' for RPS. Median follow-up was 19.4 months for CRC and 21.4 months for RPS. CONCLUSION: EVRR for locally advanced CRC or RPS is safe and achieves favorable R0 resection rates. CRC patients with major vascular invasion can still be considered for curative intent surgery. Larger cohorts with longer follow up are needed to assess oncologic outcomes.
Asunto(s)
Adenocarcinoma , Neoplasias Colorrectales , Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Estudios Retrospectivos , Márgenes de Escisión , Centros de Atención Terciaria , Resultado del Tratamiento , Neoplasias Retroperitoneales/patología , Sarcoma/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Adenocarcinoma/cirugía , Recurrencia Local de Neoplasia/cirugíaRESUMEN
How does the brain represent the passage of time at the subsecond scale? Although different conceptual models for time perception have been proposed, its neurophysiological basis remains unknown. We took advantage of a visual duration illusion produced by stimulus novelty to link changes in cortical activity in monkeys with distortions of duration perception in humans. We found that human subjects perceived the duration of a subsecond motion pulse with a novel direction longer than a motion pulse with a repeated direction. Recording from monkeys viewing identical motion stimuli but performing a different behavioral task, we found that both the duration and amplitude of the neural response in the middle temporal area of visual cortex were positively correlated with the degree of novelty of the motion direction. In contrast to previous accounts that attribute distortions in duration perception to changes in the speed of a putative internal clock, our results suggest that the known adaptive properties of neural activity in visual cortex contributes to subsecond temporal distortions.
Asunto(s)
Percepción de Movimiento/fisiología , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Potenciales de Acción/fisiología , Animales , Femenino , Humanos , Macaca mulatta , Masculino , Factores de TiempoRESUMEN
Despite advances in adjuvant immuno- and targeted therapies, the risk of relapse for stage III melanoma remains high. With 43 active entries on clinicaltrials.gov (8 July 2020), there is a surge of interest in the role of contemporary therapies in the neoadjuvant setting. We conducted a systematic review of trials performed in the last decade evaluating neoadjuvant targeted, immuno- or intralesional therapy for resectable stage III or IV melanoma. Database searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception to 13 February 2020. Two reviewers assessed titles, abstracts, and full texts. Trials investigating contemporary neoadjuvant therapies in high-risk melanoma were included. Eight phase II trials (4 randomized and 4 single-arm) involving 450 patients reported on neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 immunotherapy (3), and intralesional therapy (2). The safest and most efficacious regimens were dabrafenib/trametinib and combination ipilimumab (1 mg/kg) + nivolumab (3 mg/kg). Pathologic complete response (pCR) and adverse events were comparable. Ipilimumab + nivolumab exhibited longer RFS. Contemporary neoadjuvant therapies are not only safe, but also demonstrate remarkable pCR and RFS-outcomes which are regarded as meaningful surrogates for long-term survival. Studies defining predictors of pCR, its correlation with oncologic outcomes, and phase III trials comparing neoadjuvant therapy to standard of care will be crucial.
RESUMEN
BACKGROUND: Surgery for retroperitoneal soft tissue sarcoma (RPS) is technically challenging, often requiring perioperative red blood cell transfusion (PBT). In other cancers, controversy exists regarding the association of PBT and oncologic outcomes. No study has assessed this association in primary RPS, or identified factors associated with PBT. METHODS: Data was collected on all resected primary RPS between 2006 and 2020 at The Ottawa Hospital (Canada) and University Hospital Birmingham (United Kingdom). 'PBT' denotes transfusion given one week before surgery until discharge. Multivariable regression (MVA) identified clinicopathologic factors associated with PBT and assessed PBT association with oncologic outcomes. Surgical complexity was measured using resected organ score (ROS) and patterns of resection. RESULTS: 192 patients were included with 98 (50.8%) receiving PBT. Median follow-up was 38.2 months. High tumour grade (OR 2.20, P = 0.048), preoperative anemia (OR 2.78, P = 0.020), blood loss >1000 mL (OR 4.89, P = 0.004) and ROS >2 (OR 2.29, P = 0.026) were associated with PBT on MVA. A direct linear relationship was observed between higher ROS and increasing units of PBT (ß = 0.586, P = 0.038). Increasingly complex patterns of resection were associated with increasing odds of PBT. PBT was associated with severe post-operative complications (P = 0.008) on MVA. Univariable association between PBT and 5-year disease-free or overall survival was lost upon MVA. CONCLUSIONS: Surgical complexity and high tumour grade are potentially related to PBT. Oncologic outcomes are not predicted by PBT but are better explained by tumour grade which subsequently may increase surgical complexity. Strategies to reduce PBT should be considered in primary RPS patients.
Asunto(s)
Transfusión Sanguínea/estadística & datos numéricos , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Pérdida de Sangre Quirúrgica , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Ontario , Atención Perioperativa , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
A 79-year-old male presented with abdominal pain, incidental umbilical hernia and acute midgut volvulus that was not detected until surgical exploration. When he presented to hospital, computed tomography (CT) findings indicated perforated jejunoileal diverticulitis; however, in the operating room clockwise volvulization of the jejunum and ileum, secondarily inflamed jejunoileal diverticula, incomplete malrotation (right-sided duodenojejunal flexure), right retroperitoneal adhesions (Ladd's bands) and numerous other congenital adhesive bands were found. A modified Ladd's procedure and umbilical hernia repair were completed including detorsion, division of Ladd's bands with medialization of the cecum and lysis of other congenital adhesions without appendectomy. The patient recovered to baseline function by 3 weeks postoperatively. Acute midgut volvulus is a life-threatening surgical emergency that is exceptionally rare in the elderly. CT is relatively insensitive, so misdiagnosis is common. A high index of suspicion is required, especially in patients with a history of congenital gastrointestinal abnormalities. Prompt surgical exploration for correction and prevention is crucial.