Pharmaceutical Quality by Design Approach to Develop High-Performance Nanoparticles for Magnetic Hyperthermia.

Magnetic hyperthermia holds significant therapeutic potential, yet its clinical adoption faces challenges. One obstacle is the large-scale synthesis of high-quality superparamagnetic iron oxide nanoparticles (SPIONs) required for inducing hyperthermia. Robust and scalable manufacturing would ensure control over the key quality attributes of SPIONs, and facilitate clinical translation and regulatory approval. Therefore, we implemented a risk-based pharmaceutical quality by design (QbD) approach for SPION production using flame spray pyrolysis (FSP), a scalable technique with excellent batch-to-batch consistency. A design of experiments method enabled precise size control during manufacturing. Subsequent modeling linked the SPION size (6-30 nm) and composition to intrinsic loss power (ILP), a measure of hyperthermia performance. FSP successfully fine-tuned the SPION composition with dopants (Zn, Mn, Mg), at various concentrations. Hyperthermia performance showed a strong nonlinear relationship with SPION size and composition. Moreover, the ILP demonstrated a stronger correlation to coercivity and remanence than to the saturation magnetization of SPIONs. The optimal operating space identified the midsized (15-18 nm) Mn0.25Fe2.75O4 as the most promising nanoparticle for hyperthermia. The production of these nanoparticles on a pilot scale showed the feasibility of large-scale manufacturing, and cytotoxicity investigations in multiple cell lines confirmed their biocompatibility. In vitro hyperthermia studies with Caco-2 cells revealed that Mn0.25Fe2.75O4 nanoparticles induced 80% greater cell death than undoped SPIONs. The systematic QbD approach developed here incorporates process robustness, scalability, and predictability, thus, supporting the clinical translation of high-performance SPIONs for magnetic hyperthermia.

Video-assisted thoracoscopic versus open sleeve lobectomy for non-small cell lung cancer: A systematic review and meta-analysis from six comparative studies.

BACKGROUND: Lung sleeve resection is indicated for centrally located lung tumors, especially for patients who cannot tolerate pneumonectomy. With video-assisted thoracoscopic surgery (VATS) being increasingly implemented for a wide variety of thoracic pathologies, this study aims to compare the intraoperative, postoperative, and long-term outcomes of VATS and open bronchial sleeve lobectomy for non-small cell lung cancer (NSCLC). METHODS: The MEDLINE (via PubMed), Cochrane Library, and Scopus databases were searched. Original clinical studies, comparing VATS and open sleeve lobectomy for NSCLC were included. Evidence was synthesized as odds ratios for categorical and weighted mean difference (WMD) for continuous variables. RESULTS: Our analysis included six studies with non-overlapping populations reporting on 655 patients undergoing bronchial sleeve lobectomy for NSCLC (229 VATS and 426 open). VATS sleeve lobectomy was associated with significantly longer operative time ((WMD): 45.85 min, 95% confidence interval (CI): 12.06 to 79.65, p = 0.01) but less intraoperative blood loss ((WMD): -34.57 mL, 95%CI: -58.35 to -10.78, p < 0.001). No significant difference was found between VATS and open bronchial sleeve lobectomy in margin-negative resection rate, number of lymph nodes resected, postoperative outcomes (drainage duration, length of hospital stay, 30-day mortality), postoperative complications (pneumonia, bronchopleural fistula/empyema, prolonged air leakage, chylothorax, pulmonary embolism, and arrhythmia), and long-term outcomes (overall survival, recurrence-free survival). CONCLUSIONS: The limitation of our study arises mainly due to the heterogeneity of the included studies. Nevertheless, VATS bronchial sleeve lung resection constitutes a feasible and safe alternative to the open sleeve lung resection surgery for the management of centrally located lung tumors.

Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties.

Silicon nitride (Si3N4) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to higher fusion rates, and reduce the incidence of pseudarthrosis. In this study, it was hypothesized that creating a highly negatively charged Si3N4 surface would enhance its bioactivity without affecting the antibacterial nature of the material. To this end, samples were thermally, chemically, and thermochemically treated. Apatite formation was examined for a 21-day immersion period as an in-vitro estimate of bioactivity. Staphylococcus aureus bacteria were inoculated on the surface of the samples, and their viability was investigated. It was found that the thermochemically and chemically treated samples exhibited enhanced bioactivity, as demonstrated by the increased spontaneous formation of apatite on their surface. All modified samples showed a reduction in the bacterial population; however, no statistically significant differences were noticed between groups. This study successfully demonstrated a simple method to improve the in vitro bioactivity of Si3N4 implants while maintaining the bacteriostatic properties.

Robot-Assisted Minimally Invasive Esophagectomy versus Open Esophagectomy for Esophageal Cancer: A Systematic Review and Meta-Analysis.

Robot-assisted minimally invasive esophagectomy (RAMIE) was introduced as a further development of the conventional minimally invasive esophagectomy, aiming to further improve the high morbidity and mortality associated with open esophagectomy. We aimed to compare the outcomes between RAMIE and open esophagectomy, which remains a popular approach for resectable esophageal cancer. Ten studies meeting our inclusion criteria were identified, including five retrospective cohort, four prospective cohort, and one randomized controlled trial. RAMIE was associated with significantly lower rates of overall pulmonary complications (odds ratio (OR): 0.38, 95% confidence interval (CI): [0.26, 0.56]), pneumonia (OR: 0.39, 95% CI: [0.26, 0.57]), atrial fibrillation (OR: 0.53, 95% CI: [0.29, 0.98]), and wound infections (OR: 0.20, 95% CI: [0.07, 0.57]) and resulted in less blood loss (weighted mean difference (WMD): -187.08 mL, 95% CI: [-283.81, -90.35]) and shorter hospital stays (WMD: -9.22 days, 95% CI: [-14.39, -4.06]) but longer operative times (WMD: 69.45 min, 95% CI: [34.39, 104.42]). No other statistically significant difference was observed regarding surgical and short-term oncological outcomes. Similar findings were observed when comparing totally robotic procedures only to OE. RAMIE is a safe and feasible procedure, resulting in decreased cardiopulmonary morbidity, wound infections, blood loss, and shorter hospital stays compared to open esophagectomy.

An extremely rare clinical manifestation of acute appendicitis in a nonagenarian patient: lessons still to be learned.

Abstract.

Statins and statin intensity in peripheral artery disease.

Background: Peripheral artery disease (PAD) affects more than 202 million people worldwide. Several studies have shown that patients with PAD are often undertreated, and that statin utilization is suboptimal. European and American guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on lower extremities PAD endpoints and examine whether statin dose (high vs. low intensity) impacts outcomes. Patients and methods: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of use of statins vs. no statins for PAD patients or studies comparing high vs. low intensity statins were considered to be potentially eligible. We excluded studies with only critical limb threatening ischemia (CLTI) patients. The Medline (PubMed) database was searched up to January 31, 2021. A random effects meta-analysis was performed. Results: In total, 39 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) patients were on statins vs. 139,645 (50.66%) who were not on statins. Statin use was associated with a reduction in all cause-mortality by 42% (HR: 0.58, 95% CI: 0.49-0.67, p<0.01) and cardiovascular death by 43% (HR: 0.57, 95% CI: 0.40-0.74, p<0.01). Statin use was associated with an increase in amputation-free survival by 56% (HR: 0.44, 95% CI: 0.30-0.58, p<0.01). The risk of amputation and loss of patency were reduced by 35% (HR: 0.65, 95% CI: 0.41-0.89, p<0.01) and 46% (HR: 0.54, 95% CI: 0.34-0.74, p<0.01), respectively. Statin use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR: 0.65, 95% CI: 0.51-0.80, p<0.01) and myocardial infarction rates by 41% (HR: 0.59, 95% CI: 0.33-0.86, p<0.01). Among patients treated with statins, the high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR: 0.64, 95% CI: 0.54-0.74, p<0.01) compared to patients treated with low intensity statins. Conclusions: Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MACE, risk for amputation, or loss of patency. Higher statin dose seems to be associated with improved outcomes.

Surgical management of familial pancreatic cancer: a systematic review of the literature.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related mortality. The fact that the vast majority of patients with PDAC are diagnosed at an advanced stage highlights the need of early diagnosis. As hereditary factors are associated with approximately 5% of all PDAC cases, a screening programme to these high-risk individuals (HRI) has been proposed. The aim of screening methods is to identify selected group of patients with morphological abnormalities at an early stage, in order to be treated promptly. In this study, we evaluate the surgical outcomes and the appropriateness of pancreatic resection in HRIs who were selected for screening. METHODS: A systematic literature search of the PubMed, Embase, and Cochrane databases was performed. The clinicopathological features were recorded and evaluated. RESULTS: Six studies were selected for data collection. A total number of 77 patients were identified. Twenty-one patients had a germline mutation, with CDKN2A being the most prominent one (15.6%). Distal pancreatectomy was the most common surgical procedure (42.8%), followed by pancreaticoduodenectomy (33.8%). The mean disease-free survival was 23.6 months and tumour recurrence occurred in 9 patients (11.7%). Disease-specific mortality was 17.8%, while overall mortality was 19.5%. The most frequently reported postoperative diagnosis was PDAC (28 cases, 38.9%), followed by IPMN (23 cases, 31.9%), whereas high-grade PanIN lesions were found in 13 patients (18.1%). CONCLUSION: High-risk individuals for pancreatic cancer, who are eventually operated may have a relatively uneventful postoperative course, however the oncological outcomes are comparable to the general population.

Bochdalek hernias in the adult population: a systematic review of the literature.

BACKGROUND: Bochdalek hernia (BH) is characterized by the protrusion of viscera into thorax through the posterolateral section of the diaphragm. The aim of this study was to systematically review current literature concerning Bochdalek hernias in adults and elucidate their clinical characteristics and preferable treatment approach. METHODS: A search of PubMed and Cochrane bibliographical databases for studies regarding BHs was conducted (last search: 31st March 2021). RESULTS: Predefined inclusion criteria were met by 173 articles and concerned collectively 192 patients (50.5% males) with a mean age of 45.41 ± 20.26 years. Abdominal pain (62.0%) and pulmonary symptoms (41.1%) were the predominant symptomatology of included cases. BHs protruded mainly through the left side of the diaphragm (70.7%), with large intestine (42.7%) and stomach (37.1%) being the most commonly herniated abdominal organs. Most patients (53.8%) underwent an open surgical approach, while abdominal approach was preferred (64.8%). to the thoracic one. Thirty-day postoperative complication were encountered at 21.5% of patients, while 30-day mortality reached 4.4%. CONCLUSION: BH is an extremely rare type of congenital diaphragmatic hernia. It rarely concerns adults, and it manifests with vague gastrointestinal or pulmonary symptoms. Surgical approach is the preferred method for their management with open procedures being preferable at emergency cases, while minimal invasive approach necessitates experienced centers. Further research is needed in order to clarify their true incidence and optimal therapeutic strategy.

Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives.

Gastric and gastroesophageal junction (GEJ) cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage, with an increasing incidence both in Asia and in Western countries. These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses. Accordingly, the understanding of phenotypic and genotypic correlations/classifications has been improved. Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone, with the incorporation of other treatment modalities, such as radiation and chemotherapy (including biologics). Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival. Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate, which is associated with improved long-term outcomes. Several studies have defined various chemotherapy regimens to accompany radiation (before and after surgery). Recently, addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval. Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results. The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers, highlight the remaining questions and present the current research effort addressing them.

Primary Squamous Cell Carcinoma of Colon and Rectum: A Systematic Review of the Literature.

Background - Objective: Primary colorectal squamous cell carcinoma is an extremely rare neoplasm with an incidence of 0.1 to 0.25 per 1,000 diagnosed colorectal carcinomas.The objective of this study was to evaluate its biological behavior and highlight the role of a surgical approach for its management.MethodsPubMed and Cohrane databases were independently searched (last search: April 10th, 2020) for articles concerning colorectal squamous cell carcinoma in adult population.Results: Seventy-one studies met predefined inclusion criteria and involved 99 patients (54.5% females) with an age of 56.98 ± 12.19 years (mean ± SD). The most frequent site of occurrence was the rectum (63.5%). Open surgery was conducted at 95% of patients, while 21.4% and 30.3% received neoadjuvant and adjuvant therapy respectively.Postoperative complications were developed in 31.3% of patients, while 6.1% died withing the first month following operation. Five-years survival rate was 49.5% (95% CI: 33.7%-63.4%). Female sex (HR: 0.24; 95% CI: 0.11-0.54; p-value: 0.001) and presence of postoperative complications (HR: 4.10; 95%CI: 1.47-1.46; p-value: 0.007) significantly affected the survival.Conclusions Colorectal Squamous Cell Carcinoma is a rare tumor with an aggressive behavior. Surgery is the standard of treatment for the colontumors, while the role of chemoradiotherapy is promising especially for rectal tumors. Further clinical trials are necessary to determine the preferred treatment approach.

Primary Angiosarcoma of the Gastrointestinal Tract: A Systematic Review of the Literature.

Primary Gastrointestinal Angiosarcoma (PGAS) constitutes a rare malignant tumor arising from vascular or lymphatic endothelial cells. The aim of this study was to review the available literature on PGAS and to elucidate its biological behavior and optimal therapeutic approach. PubMed and Embase bibliographical databases were systematically searched (last search April 8th, 2020) for studies concerning PGAS. Ninety-eight studies met our inclusion criteria, involving 110 patients (male/female = 1.5) with an age of 62.40 ± 17.84 (mean, SD) years. They were most frequently located at small (44.5%) and large intestine (35.5%), while 12.7% were multifocal. Surgical resection of the tumor was conducted at 84.0% of the cases combined with adjuvant therapy at 12.3%. One-year cumulative survival was 55.18% (95% CI: 34.33%-71.84%) for large intestine, 30.2% (95% CI: 17.1%-44.5%) for small intestine, whereas multifocal PGAS had a 6-months cumulative survival of 23.08% (95% CI: 5.58%-47.46%). Therefore, PGAS is an extremely rare entity with atypical clinical presentation, challenging diagnosis and aggressive behavior. High clinical suspicion is crucial for its prompt management. Further studies and the development of novel therapeutic agents are required in order to improve survival.

Nonalcoholic fatty liver disease: The role of quercetin and its therapeutic implications.

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting almost one-third of the general population and 75% of obese patients with type 2 diabetes. The aim of this article is to review the current evidence concerning the role of quercetin, a natural compound and flavonoid, and its possible therapeutic effects on this modern-day disease. Despite the fact that the exact pathophysiological mechanisms through which quercetin has a hepatoprotective effect on NAFLD are still not fully elucidated, this review clearly demonstrates that this flavonoid has potent antioxidative stress action and inhibitory effects on hepatocyte apoptosis, inflammation, and generation of reactive oxygen species, factors which are linked to the development of the disease. NAFLD is closely associated with increased dietary fat consumption, especially in Western countries. The hepatoprotective effect of quercetin against NAFLD merits serious consideration and further validation by future studies.

Surgery for metachronous oligometastatic esophageal cancer: Is there enough evidence? / Cirugía para el cáncer de esófago oligometastásico metacrónico: ¿hay suficiente evidencia?

Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer. (AU)

El cáncer de esófago es la sexta causa más frequente de mortalidad relacionada con el cáncer en todo el mundo. A pesar de los avances en los medios de diagnóstico y las opciones de tratamiento, la tasa de supervivencia a los cinco años es menor del 20%. La esofagectomía con la disección de ganglios linfáticos extendida es la base del tratamiento. Más del 50% de los pacientes experimentan recurrencia dentro de 1-3 años después de la operación. La enfermedad recurrente puede presentarse como recidiva locorregional en el sitio de la anastomosis o como recidiva a través de diseminación en los ganglios linfáticos, como metástasis hematológicas o como una combinación de todos ellos. El tratamiento estándar de la recidiva se basa actualmente en la quimioterapia sistémica y/o radioterapia. La evidencia reciente sugiere que el tratamiento quirúrgico de la enfermedad oligometastásica metacrónica puede tener ventajas pronósticas superiores al tratamiento exclusivamente médico. Dada la tasa de respuesta considerablemente baja a la quimiorradioterapia, muchas instituciones han adoptado estrategias de tratamiento quirúrgico para la enfermedad oligorrecurrente caso por caso. El objetivo de este artículo es revisar la evidencia actual sobre el papel del tratamiento quirúrgico de las oligometástasis metacrónicas del cáncer de esófago. (AU)

Surgery for metachronous oligometastatic esophageal cancer: Is there enough evidence?

Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer.

Management of Morgagni's Hernia in the Adult Population: A Systematic Review of the Literature.

BACKGROUND: Morgagni's hernia (MH) is defined by the protrusion of abdominal viscera through an anterior retrosternal diaphragmatic defect. The objective of this study was to systematically review current literature on MHs in adult population and assess their clinical characteristics and therapeutic approach. METHODS: PubMed and Cochrane bibliographical databases were searched (last search: 15th January 2021) for studies concerning MHs. RESULTS: Inclusion criteria were met by 189 studies that included 310 patients (61.0% females) with an age of 57.37 ± 18.41 (mean ± SD) years. Pulmonary symptoms, abdominal pain, and nausea-vomit were among the most frequent symptomatology. MHs were predominantly right-sided (84.0%), with greater omentum (74.5%) and transverse colon (65.1%) being the most commonly herniated viscera. The majority of cases underwent an open procedure, while 42.3% of patients had a minimally invasive procedure. Abdominal approach was mostly preferred, while a thoracic one was chosen at 20.6% of cases and a thoracoabdominal at 3.2%. Thirty-day postoperative complications were recorded at 29 patients and 30-day mortality was 2.3%. CONCLUSIONS: MH is a rare type of congenital diaphragmatic hernia which rarely manifests in adult population with atypical pulmonary and gastrointestinal symptoms. Surgery is the gold standard for their management. Open surgical approach is preferable in emergency cases, while laparoscopic surgery is favored in elective setting and is associated with shorter hospitalization. Further studies are crucial in order to elucidate etiology and optimal therapeutic approach.

Primary gastric melanoma in adult population: a systematic review of the literature.

BACKGROUND: Primary gastric melanoma (PGM) is a rare malignant tumour of the stomach with poor prognosis. The aim of this systematic review was to assess the available literature on this entity and to highlight its biological behaviour and preferred treatment approach. METHODS: PubMed and Cochrane bibliographical databases were independently searched (last search: 2 February 2020) by two investigators for articles reporting on PGM in the adult population. RESULTS: Twenty-five studies met the inclusion criteria and concerned collectively 25 patients (18 males and seven females) with an age of 63.4 ± 8.97 years (mean ± standard deviation). Main symptoms included abdominal pain (64%), weight loss (48%) and hematemesis or melena (32%). The most frequent tumour location was the body of the stomach (54.2%). All tumours were surgically resected and the majority of the patients had a partial gastrectomy (52%). Median recurrence time was 5 months and 12% of patients reached 5-year survival landmark. CONCLUSION: PGM is a rare disease characterized by an aggressive malignant behaviour. Its differential diagnosis from a metastatic lesion is crucial. A prompt diagnosis and therapeutic approach are needed. Further studies are required to elucidate the optimal management of this clinical entity.

Aortoiliac Occlusive Disease: When the Development of Arterial Collateral Network Takes Over.

This report describes the collateral pathways that restore arterial circulation in cases of aortoiliac occlusive disease and discusses the clinical and surgical importance of these systemic-systemic, visceral-systemic, and visceral-visceral anastomoses.

The role of liver transplantation for colorectal liver metastases: A systematic review and pooled analysis.

BACKGROUND: Liver transplantation (LT) has gained interest in the treatment of unresectable colorectal liver metastases (CRLM) over the last two decades. Despite the initial poor outcomes, recent reports from countries with graft abundance have provided further insights in the potential of LT as a treatment for unresectable CRLM. METHODS: A systematic literature search was conducted in the MEDLINE (PubMed), Embase, Scopus, Cochrane Library, Google Scholar, Virtual Health Library, Clinicaltrials.gov, and Web of Science databases (end-of-search date: January 27th, 2020) to identify relevant studies. Pooled overall and recurrence-free survival analysis at 6 months, 1, 2, 3, and 5 years was conducted with the Kaplan-Meier (Product Limit) method. RESULTS: Eighteen studies comprising 110 patients were included. The population consisted of 59.8% males with a mean age of 52.3 ± 9.3 years. CRLM diagnosis was synchronous in 83%, while 99% received chemotherapy, and 39% received liver resection prior to LT. The mean time from primary tumor resection to LT was 39.5 ± 32.5 months, the mean post-LT follow-up was 32.1 ± 22.2 months, and the mean time to recurrence was 15.0 ± 11.3 months. The pooled 6-month, 1-, 2-, 3-, and 5-year overall survival rates were 95.7% (95%CI: 89.1%-98.4%), 88.1% (95%CI: 79.6%-93.2%), 74.6% (95%CI: 64.2%-82.3%), 58.4% (95%CI: 47.2%-62.0%), and 50.5% (95%CI: 39.0%-61.0%), respectively. The pooled 6-months, 1-, 2-, 3-, and 5-year recurrence-free survival rates were 77.2% (95%CI: 67.2%-84.5%), 59.9% (95%CI: 49.0%-69.2%), 42.4% (95%CI: 31.8%-52.6%), 30.7% (95%CI: 20.9%-41.1%), and 25.6% (95%CI: 16.2%-36.0%), respectively. CONCLUSION: LT should be considered in patients with unresectable liver-only CRLM under strict selection criteria and only under well-designed research protocols. Ongoing studies are expected to further elucidate the indications and prognosis of patients undergoing LT for unresectable CRLM.