Grading Complications in Pelvic Exenteration: Limitations of Current Classification Systems.

OBJECTIVE: To comprehensively report complications associated with pelvic exenteration and to determine the strength of associations between 3 different grading methodologies and length of stay, quality of life, and physical outcomes. BACKGROUND: It is generally accepted that pelvic exenteration is associated with high rates of surgical morbidity. However, methods of reporting in the literature are inconsistent, making it difficult to compare surgical outcomes across studies to determine the impact of surgery on patients. DESIGN: A retrospective study. SETTINGS: This study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. PATIENTS: It included patients who underwent pelvic exenteration between December 2016 and August 2019. MAIN OUTCOME MEASURES: Complications were classified according to the Clavien-Dindo classification, Comprehensive Complication Index, and number of postoperative complications. Correlations between length of stay, physical component score, 6-minute walk test, and sit-to-stand test, and complications as graded using the Clavien-Dindo classification, Comprehensive Complication Index, and the number of complications were explored using Pearson's or point biserial correlation tests. RESULTS: In this study, 198 patients were included. The Clavien-Dindo classification was moderately positively correlated with length of stay ( r = 0.519; p < 0.0001), whereas Comprehensive Complication Index ( r = 0.744; p < 0.0001) and the number of complications ( r = 0.751; p < 0.0001) showed a strong correlation with length of stay. All these methodologies were moderately inversely correlated with a predischarge 6-minute walk test (Clavien-Dindo classification: r = -0.359, p = 0.008; Comprehensive Complication Index: r = -0.388, p = 0.007; number of complications: r = -0.467, p < 0.0001). LIMITATIONS: This single-center retrospective study involves a small sample size. Classification of grade I and II complications in this cohort of patients who tend to have complex postoperative recovery was challenging and therefore incomplete. The incomplete data may have affected the correlations. CONCLUSIONS: Comprehensive Complication Index and the number of postoperative complications were more strongly correlated with length of stay than the Clavien-Dindo classification in patients undergoing pelvic exenteration. Comprehensive Complication Index may be a better grading system to classify postoperative complications following pelvic exenteration. See Video Abstract at http://links.lww.com/DCR/B906 . CLASIFICACIN DE LAS COMPLICACIONES EN LA EXENTERACIN PLVICA LIMITACIONES DE LOS SISTEMAS DE CLASIFICACIN ACTUALES: OBJETIVO:Este estudio tuvo como objetivo informar de manera integral las complicaciones asociadas con la exanteración pélvica y determinar la rlacion de las asociaciones entre tres metodologías de clasificación diferentes y la duración de la estadía, la calidad de vida y los resultados físicos.ANTECEDENTES:En general, se acepta que la exanteración pélvica se asocia con altas tasas de morbilidad quirúrgica. Sin embargo, los métodos de notificación en la literatura son inconsistentes, lo que dificulta la comparación de los resultados quirúrgicos entre estudios para determinar el impacto de la cirugía en los pacientes.DISEÑO:Este fue un estudio retrospectivo.AJUSTES:Este estudio se realizó en el Royal Prince Alfred Hospital, Sydney. Australia.PACIENTES:Se incluyeron pacientes a las que se les realizó exenteración pélvica entre diciembre de 2016 y agosto de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Las complicaciones se clasificaron de acuerdo con la Clasificación de Clavien-Dindo, el Índice Integral de Complicaciones y el número de complicaciones posoperatorias. Correlaciones entre la duración de la estadía, la puntuación del componente físico, la prueba de caminata de 6 minutos y la prueba de sentarse y levantarse; y las complicaciones según la clasificación de Clavien-Dindo, el CCI y el número de complicaciones se exploraron mediante las pruebas de correlación biserial de Pearson o Point.RESULTADOS:Un total de 198 pacientes fueron incluidos en este estudio. La clasificación de Clavien-Dindo se correlacionó moderadamente positivamente con la duración de la estancia ( r = 0,519, p < 0,0001), mientras que el índice de complicaciones integrales ( r = 0,744, p < 0,0001) y el número de complicaciones ( r = 0,751, p < 0,0001) mostraron una fuerte correlación con la duración de la estancia. Todas estas metodologías se correlacionaron moderadamente inversamente con la prueba de caminata de 6 minutos antes del alta (Clasificación de Clavien-Dindo: r = -0,359, p = 0,008; Índice de Complicaciones Integrales: r = -0,388, p = 0,007; número de complicaciones: r = -0,467, p < 0,0001).LIMITACIONES:Un estudio retrospectivo de un solo centro incluye un tamaño de muestra pequeño. La clasificación de las complicaciones de grado I y II en esta cohorte de pacientes que tienden a tener una recuperación postoperatoria compleja fue un desafío y, por lo tanto, incompleta. Los datos incompletos pueden haber afectado las correlaciones.CONCLUSIONES:El Índice Integral de Complicaciones y el número de complicaciones postoperatorias se correlacionaron más con la duración de la estancia que la Clasificación de Clavien-Dindo en pacientes con exenteración pélvica. El Índice Integral de Complicaciones puede ser un mejor sistema de clasificación para clasificar las complicaciones posoperatorias después de la exenteración pélvica. Consulte Video Resumen en http://links.lww.com/DCR/B906 . (Traducción-Dr. Yolanda Colorado ).

Differences in Surgical Outcomes and Quality-of-Life Outcomes in Pelvic Exenteration Between Locally Advanced Versus Locally Recurrent Rectal Cancers.

BACKGROUND: Although pelvic exenteration remains the only curative option for locally advanced rectal cancer and locally recurrent rectal cancer, only limited evidence is available on the differences in surgical and quality-of-life outcomes between the two. OBJECTIVE: This study aimed to compare surgical outcomes and identify any differences or predictors of quality of life of patients with locally advanced rectal cancer and locally recurrent rectal cancer undergoing pelvic exenteration. DESIGN: This was a cohort study. SETTING: This study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. PATIENTS: This study included patients with locally advanced rectal cancer and locally recurrent rectal cancer who underwent pelvic exenteration between July 2008 and March 2019. MAIN OUTCOME MEASURES: The main outcome measures included Short Form 36 version 2 and Functional Assessment of Cancer Therapy-Colorectal score. RESULTS: A total of 271 patients were included in this study. Locally advanced rectal cancer patients had higher rates of R0 resection ( p = 0.003), neoadjuvant chemoradiotherapy ( p < 0.001), and had greater median overall survival (75.1 vs. 45.8 months), although the latter was clinically but not statistically significant. There was a higher blood loss ( p < 0.001), longer length of stay ( p = 0.039), and longer operative time ( p = 0.002) in the locally recurrent rectal cancer group. This group also had a higher mean baseline physical component summary score and Functional Assessment of Cancer Therapy-Colorectal score; however, there were no significant differences in complications or quality-of-life outcomes between with the two groups at any time points postoperatively up to 12 months. LIMITATION: The study was from a specialized experienced center, which could limit its generalizability. CONCLUSIONS: Patients with locally recurrent rectal cancer tend to require a more extensive surgery with a longer operative time and more blood loss and longer recovery from surgery, but despite this, their quality of life is comparable to those with locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B1000 . DIFERENCIAS EN LOS RESULTADOS QUIRRGICOS Y LOS RESULTADOS DE LA CALIDAD DE VIDA EN LA EXENTERACIN PLVICA ENTRE EL CNCER DE RECTO LOCALMENTE AVANZADO Y EL CNCER DE RECTO LOCALMENTE RECIDIVANTE: ANTECEDENTES:Aunque la exenteración pélvica sigue siendo la única opción curativa para el cáncer de recto localmente avanzado y el cáncer de recto localmente recurrente, solo hay evidencia limitada disponible sobre las diferencias en los resultados quirúrgicos y de calidad de vida entre los dos.OBJETIVO:Este estudio tuvo como objetivo comparar los resultados quirúrgicos e identificar cualquier diferencia o predictor de la calidad de vida de los pacientes con cáncer de recto localmente avanzado y cáncer de recto localmente recurrente sometidos a exenteración pélvica.DISEÑO:Este fue un estudio de cohorte.AJUSTE:Este estudio se realizó en el Royal Prince Alfred Hospital, Sydney, Australia.PACIENTES:Este estudio incluyó pacientes con cáncer de recto localmente avanzado y cáncer de recto localmente recurrente que se sometieron a exenteración pélvica entre julio de 2008 y marzo de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado incluyeron el formulario corto 36 versión 2 y la puntuación de la evaluación funcional de la terapia del cáncer colorrectal.RESULTADOS:Un total de 271 pacientes fueron incluidos en este estudio. Los pacientes con cáncer de recto localmente avanzado tuvieron tasas más altas de resección R0 ( p = 0,003), quimiorradioterapia neoadyuvante ( p < 0,001) y una mediana de supervivencia general más alta (75,1 frente a 45,8 meses),a pesar de que esta última fue clínica pero no estadísticamente significativa. Hubo una mayor pérdida de sangre ( p < 0,001), una estancia más prolongada ( p = 0,039) y un tiempo operatorio más prolongado ( p = 0,002) en el grupo de cáncer de recto localmente recurrente. También tenían una puntuación de componente físico inicial media más alta y una puntuación de Evaluación funcional de la terapia del cáncer colorrectal; sin embargo, no hubo diferencias significativas en las complicaciones o los resultados de la calidad de vida entre los dos grupos en ningún momento después de la operación hasta los 12 meses.LIMITACIÓN:El estudio fue de un centro especializado con experiencia, lo que podría limitar su generalización.CONCLUSIONES:Los pacientes con cáncer de recto localmente recurrente tienden a requerir una cirugía más extensa con un tiempo operatorio más largo y más pérdida de sangre y una recuperación más prolongada de la cirugía, pero a pesar de esto, su calidad de vida es comparable a aquellos con cáncer de recto localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B1000 . (Traducción-Dr. Yolanda Colorado ).

Hand-assisted versus straight laparoscopy for colorectal surgery - a systematic review and meta-analysis.

PURPOSE: Hand-assisted laparoscopic surgery (HALS) is an alternative to straight laparoscopy (LAP) in colorectal surgery. Many studies have compared the two in terms of efficacy, complications, and outcomes. This meta-analysis aims to uncover if there are any significant differences in conversion rates, operative times, body mass index (BMI), incision lengths, intraoperative and postoperative complications, and length of stay. METHODS: Comprehensive searches were performed on databases from their respective inceptions to 16 December 2021, with a manual search performed through Scopus. Randomized controlled trials (RCTs), cohort studies, and case series involving more than 10 patients were included. RESULTS: A total of 47 studies were found fitting the inclusion criteria, with 5 RCTs, 41 cohort studies, and 1 case series. Hand-assisted laparoscopic surgery was associated with lower conversion rates (odds ratio [OR] 0.41, 95%CI 0.28-0.60, p < 0.00001), shorter operative times (Mean Difference [MD] - 8.32 min, 95%CI - 14.05- - 2.59, p = 0.004), and higher BMI (MD 0.79, 95%CI 0.46-1.13, p < 0.00001), but it was also associated with longer incision lengths (MD 2.19 cm, 95%CI 1.66-2.73 cm, p < 0.00001), and higher postoperative complication rates (OR 1.15, 95%CI 1.06-1.24, p = 0.0004). Length of stay was not different in HALS as compared to Lap (MD 0.16 days, 95%CI - 0.06-0.38 days, p = 0.16, and intraoperative complications were the same between both techniques. CONCLUSIONS: Hand-assisted laparoscopy is a suitable alternative to straight laparoscopy with benefits and risks. While there are many cohort studies comparing HALS and LAP, more RCTs would be needed for a better quality of evidence.

Survival difference between mucinous vs. non-mucinous colorectal cancer following cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND: It is believed that the oncologic behavior of mucinous colorectal adenocarcinoma (MC) is different from non-mucinous adenocarcinoma (NMC). The aim of the study is to compare long-term survivals between patients with MC and those with NMC following cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). METHODS: This was a retrospective study of prospectively collected data of patients with peritoneal metastases of colorectal origin following CRS and IPC. Group I included patients with MC which was defined as being composed of >50% extracellular mucin. Group II included those with NMC. Subgroup analysis was performed according to the location of primary tumor. RESULTS: A total of 213 patients were included in this study. The two groups had similar hospital mortality, high dependency unit stay. MC group had a significantly longer mean intensive care unit (ICU) stay (p = .037) and total hospital stay (p = .037). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups (p = .657 and p = .938, respectively). Multivariate analysis showed that the presence of mucin was not an independent negative prognostic factor for OS (p = .190). CONCLUSION: In summary, patients with MC had a similar long-term survival outcome with those with NMC following CRS and IPC.

Discrimination, Bullying and Harassment in Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: In 2015, the public media in Australia reported a series of life stories of victims who had been subjected to inappropriate behaviors in their surgical careers, bringing the profession into disrepute. Currently, limited data are available in the medical literature on discrimination, bullying and harassment (DBH) in surgery. This significant information gap prompted a systematic review to compile relevant information about DBH in surgical practice and training, in particular, its prevalence and impact. METHODS: A literature search was conducted using the MEDLINE, EMBASE and PubMed databases (May 1929-October 2017). Studies identified were appraised with standard selection criteria. Data points were extracted, and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Eight studies, comprising 5934 participants, were examined. Discrimination occurred in a pooled estimate of 22.4% [95% Confidence Interval (CI) = 14.0-33.9%]. One of the papers reported the prevalence of bullying using two methods including Revised Negative Acts Questionnaire and a definition by Einarsen. Pooled estimate of incidence rate was thus 37.7% (95% CI = 34.0-41.5%) and 40.3% (95% CI = 34.7-46.2%), respectively. In terms of harassment, pooled prevalence was 31.2% (95% CI = 10.0-65.0%). CONCLUSIONS: DBH is a significant issue in surgery. The true incidence of these issues may remain underestimated. Actions are being taken by professional bodies to create a positive culture in surgery. The effectiveness of these strategies is yet to be determined. More studies are warranted to investigate the magnitude of these issues given their psychological impact, and more importantly to monitor the effectiveness of current measures.

Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial?

BACKGROUND: There is little evidence for the use of early postoperative intraperitoneal chemotherapy (EPIC) in patients with low-grade appendiceal mucinous neoplasms (LAMNs) with pseudomyxoma peritonei (PMP). This study aims to assess the outcomes regarding the use of EPIC in a large cohort of patients with LAMNs with PMP uniformly treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC), all of whom received hyperthermic intraperitoneal chemotherapy (HIPEC), and most of whom also received EPIC. METHODS: This was a retrospective study of prospectively collected data of consecutive patients with peritoneal carcinomatosis of appendiceal origin who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia, between January 1996 and November 2015. Subgroup analyses were performed for patients with a high Peritoneal Cancer Index (PCI) >20 and also based on histopathological subtypes of LAMNs. RESULTS: A total of 250 patients formed the cohort of this study. No significant differences were observed in terms of hospital mortality (p = 0.153), major morbidity rate (i.e., grade III/IV; p = 0.593), intensive care unit stay (p = 0.764), and total hospital stay (p = 0.927); however, patients who received HIPEC + EPIC had a significantly longer stay in the high dependency unit. Multivariate analysis showed combined HIPEC with EPIC is an independent prognostic factor for better survival outcomes (hazard ratio 0.30, 95 % confidence interval 0.12-0.74; p = 0.009), adjusted for age, PCI, and histopathological subtypes. CONCLUSIONS: The combination of HIPEC + EPIC can provide additional survival benefits for patients with LAMNs with PMP compared with HIPEC alone, without increasing postoperative morbidity and mortality. EPIC should be considered following CRS and HIPEC for patients with LAMNs with PMP.

Impact of perioperative fluid administration on early outcomes after pancreatoduodenectomy: A meta-analysis.

BACKGROUND: Pancreatoduodenectomy (PD) remains a technically challenging surgical procedure with morbidity rates ranging between 30 and 50%. It is suggested that the liberal use of fluids is associated with a poor perioperative outcome. This review examines the impact of fluid administration on outcomes after PD. METHODS: A literature search was conducted using the MEDLINE, EMBASE and PubMed database (June 1966-June 2016). Studies identified were appraised with standard selection criteria. Data points were extracted and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Eleven studies, seven retrospective trials and four randomized control trials comprising 2842 patients were included. Seven studies were meta-analyzed. There was no difference in length of hospital stay (P = 0.25), pancreas specific complications (P = 0.20), pulmonary (P = 0.58), cardiovascular (P = 0.75), gastrointestinal (P = 0.49), hepatobiliary (P = 0.53), urogenital (P = 0.42), wound complication (P = 0.79), reoperation rate (P = 0.69), overall morbidity (P = 0.18), major morbidity (P = 0.91), 30-day mortality (P = 0.07) and 90-day mortality (P = 0.58) in low or high fluid groups. CONCLUSION: The current available data fails to demonstrate an association between the amount of perioperative intravenous fluid administration and postoperative complications in patients undergoing PD.

Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.

BACKGROUND: It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. OBJECTIVE: This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. DESIGN: This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. SETTING: The study was conducted by 1 surgical team at St. George Hospital. PATIENTS: A total of 444 patients formed the cohort of this study. MAIN OUTCOME MEASURES: Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. RESULTS: Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p < 0.001), adjusted for peritoneal cancer index >20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. LIMITATIONS: This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. CONCLUSIONS: Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.

Impacts of Preoperative Serum Albumin Level on Outcomes of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy.

BACKGROUND: Only few small studies in the literature have explored the impacts of preoperative serum albumin level and clinical outcomes of patients with peritoneal surface malignancy (PSM) who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). This study aimed to evaluate the value of preoperative serum albumin as a prognostic factor for long-term survival outcomes after CRS and PIC in a large patient cohort and to determine whether preoperative serum albumin is correlated with perioperative complications. METHODS: This retrospective study examined prospectively collected data for patients with PSM who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia. The study used 35 g/L as the cuffoff for normal serum albumin level. RESULTS: The study enrolled 591 patients. Hypoalbuminemia was found to be associated with a significantly higher rate of major morbidity (p < 0.001), a longer ICU stay (p = 0.003), a longer HDU stay (p < 0.001), a longer total hospital stay (p < 0.001), and a shorter overall survival (OS) (p = 0.016). Factor analysis showed preoperative serum hypoalbuminemia to be a prognostic factor for a poor perioperative outcome (p = 0.018) and a poor OS (p = 0.026). CONCLUSION: Preoperative hypoalbuminemia is associated with poor perioperative outcomes. More importantly, it is a predictor of poorer OS for patients with PSM independent of the PCI, age, and completeness of cytoreduction. In the future, strategies should be undertaken to improve preoperative nutrition of malnourished patients as a means of improving clinical outcomes for patients with PSM.

Effects of sex hormones on survival of peritoneal mesothelioma.

BACKGROUND: Previous studies have suggested the presence of steroid receptors as a favourable prognostic factor in peritoneal mesothelioma (PM). This study aims to investigate possible hormonal effects on survival of PM. METHODS: This is a retrospective study of prospectively collected data of 52 consecutive patients with PM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by the same surgical team at St George Hospital in Sydney, Australia, between April 1996 and April 2013. Females were arbitrarily divided into assumed premenopausal (< 51 years old; n = 15) and assumed postmenopausal (≥ 51 years old, n = 9). In each gender group, patients were furthered divided into three age groups (< 40, 40-60, > 60). A significant statistical difference was defined as p < 0.05. RESULTS: Females with epithelial mesothelioma had a significantly higher survival than males (p = 0.023). They also had a better overall median survival (> 60 months) than males (43 months), although this difference was not statistically significant (p = 0.098). Survival of postmenopausal females became similar to males after excluding benign cystic mesothelioma. CONCLUSIONS: The better survival in premenopausal females could probably be explained by higher levels of oestradiol and progesterone. Also, our data suggests that higher rates of benign cystic mesothelioma in females was not the key reason for the better survival in female patients, further supporting the hypothesis of hormonal links with survival of PM. Therapeutic effects of sex steroid hormones on PM may be a valuable area to explore.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis in the elderly.

BACKGROUND: Peritoneal carcinomatosis is life-threatening without cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Only a few studies in the literature addressed the relationship between age and outcomes of peritonectomy. This study was designed to review the clinical outcomes in elderly patients who underwent CRS and PIC. METHODS: This is a retrospective study of prospectively collected data of 611 consecutive patients with peritoneal carcinomatosis who underwent CRS and PIC by the same surgical team at St George Hospital in Sydney, Australia, between January 1996 and December 2013. Patients were divided into two groups; group 1 (<65 years old, n = 487) and group 2 (≥ 65 years old, n = 124). Subgroup analysis was performed in patients who were ≥75 years old (n = 20). A significant difference was defined as p < 0.05. RESULTS: There was no significant statistical difference in terms of mean total hospital stay, intensive care unit stay, high dependency unit stay and complication rates. Postoperative mortality was 2 and 3 % in groups 1 and 2, respectively. Overall survival did not reach a statistical significance between the two groups. In subgroup analysis, patients showed similar morbidity results to patients who were <65 years old. CONCLUSIONS: CRS and PIC can be safely done in the elderly. Age alone should not be the single exclusion criterion but rather taken into consideration along with other factors to determine the suitability of elderly patients.

The application and progress of stem cells in auricular cartilage regeneration: a systematic review.

Background: The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is constructing the scaffold for auricular reconstruction. As a type of cell with multiple differentiation potentials, stem cells play an essential role in the construction of cartilage scaffolds, and therefore have received widespread attention in ear reconstructive research. Methods: A literature search was conducted for peer-reviewed articles between 2005 and 2023 with the following keywords: stem cells; auricular cartilage; ear cartilage; conchal cartilage; auricular reconstruction, regeneration, and reparation of chondrocytes; tissue engineering in the following databases: PubMed, MEDLINE, Cochrane, and Ovid. Results: Thirty-three research articles were finally selected and their main characteristics were summarized. Adipose-derived stem cells (ADSCs), bone marrow mesenchymal stem cells (BMMSCs), perichondrial stem/progenitor cells (PPCs), and cartilage stem/progenitor cells (CSPCs) were mainly used in chondrocyte regeneration. Injecting the stem cells into the cartilage niche directly, co-culturing the stem cells with the auricular cartilage cells, and inducing the cells in the chondrogenic medium in vitro were the main methods that have been demonstrated in the studies. The chondrogenic ability of these cells was observed in vitro, and they also maintained good elasticity and morphology after implantation in vivo for a period of time. Conclusion: ADSC, BMMSC, PPC, and CSPC were the main stem cells that have been researched in craniofacial cartilage reconstruction, the regenerative cartilage performed highly similar to normal cartilage, and the test of AGA and type II collagen content also proved the cartilage property of the neo-cartilage. However, stem cell reconstruction of the auricle is still in the initial stage of animal experiments, transplantation with such scaffolds in large animals is still lacking, and there is still a long way to go.

Bioengineered MSC-derived exosomes in skin wound repair and regeneration.

Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

The application and progress of tissue engineering and biomaterial scaffolds for total auricular reconstruction in microtia.

Microtia is a congenital deformity of the ear with an incidence of about 0.8-4.2 per 10,000 births. Total auricular reconstruction is the preferred treatment of microtia at present, and one of the core technologies is the preparation of cartilage scaffolds. Autologous costal cartilage is recognized as the best material source for constructing scaffold platforms. However, costal cartilage harvest can lead to donor-site injuries such as pneumothorax, postoperative pain, chest wall scar and deformity. Therefore, with the need of alternative to autologous cartilage, in vitro and in vivo studies of biomaterial scaffolds and cartilage tissue engineering have gradually become novel research hot points in auricular reconstruction research. Tissue-engineered cartilage possesses obvious advantages including non-rejection, minimally invasive or non-invasive, the potential of large-scale production to ensure sufficient donors and controllable morphology. Exploration and advancements of tissue-engineered cartilaginous framework are also emerging in aspects including three-dimensional biomaterial scaffolds, acquisition of seed cells and chondrocytes, 3D printing techniques, inducing factors for chondrogenesis and so on, which has greatly promoted the research process of biomaterial substitute. This review discussed the development, current application and research progress of cartilage tissue engineering in auricular reconstruction, particularly the usage and creation of biomaterial scaffolds. The development and selection of various types of seed cells and inducing factors to stimulate chondrogenic differentiation in auricular cartilage were also highlighted. There are still confronted challenges before the clinical application becomes widely available for patients, and its long-term effect remains to be evaluated. We hope to provide guidance for future research directions of biomaterials as an alternative to autologous cartilage in ear reconstruction, and finally benefit the transformation and clinical application of cartilage tissue engineering and biomaterials in microtia treatment.

Management of appendicitis in a De Garengeot hernia: Lockwood approach.

A De Garengeot hernia is a femoral hernia containing the vermiform appendix. This extremely rare hernia is associated with appendicitis and the risk of perforation and abscess formation. Given limited data, it poses both diagnostic and management difficulties. While management is generally surgical, questions remain about the best operative approach, indications for appendicectomy and optimum hernia repair technique. We describe a case of acute appendicitis within a De Garengeot hernia that was managed with an open appendicectomy via a Lockwood incision. This case helps to illustrate the management considerations present for this rare clinical pathology and describes a method to effectively identify the hernia and resect the appendix.

Histopathological Images and Multi-Omics Integration Predict Molecular Characteristics and Survival in Lung Adenocarcinoma.

Histopathological images and omics profiles play important roles in prognosis of cancer patients. Here, we extracted quantitative features from histopathological images to predict molecular characteristics and prognosis, and integrated image features with mutations, transcriptomics, and proteomics data for prognosis prediction in lung adenocarcinoma (LUAD). Patients obtained from The Cancer Genome Atlas (TCGA) were divided into training set (n = 235) and test set (n = 235). We developed machine learning models in training set and estimated their predictive performance in test set. In test set, the machine learning models could predict genetic aberrations: ALK (AUC = 0.879), BRAF (AUC = 0.847), EGFR (AUC = 0.855), ROS1 (AUC = 0.848), and transcriptional subtypes: proximal-inflammatory (AUC = 0.897), proximal-proliferative (AUC = 0.861), and terminal respiratory unit (AUC = 0.894) from histopathological images. Moreover, we obtained tissue microarrays from 316 LUAD patients, including four external validation sets. The prognostic model using image features was predictive of overall survival in test and four validation sets, with 5-year AUCs from 0.717 to 0.825. High-risk and low-risk groups stratified by the model showed different survival in test set (HR = 4.94, p < 0.0001) and three validation sets (HR = 1.64-2.20, p < 0.05). The combination of image features and single omics had greater prognostic power in test set, such as histopathology + transcriptomics model (5-year AUC = 0.840; HR = 7.34, p < 0.0001). Finally, the model integrating image features with multi-omics achieved the best performance (5-year AUC = 0.908; HR = 19.98, p < 0.0001). Our results indicated that the machine learning models based on histopathological image features could predict genetic aberrations, transcriptional subtypes, and survival outcomes of LUAD patients. The integration of histopathological images and multi-omics may provide better survival prediction for LUAD.

Variations in intrinsic breast cancer characteristics in screen-detected breast cancer patients aged between 45 and 69 and above the age of 70.

BACKGROUND: Increasing age is a well-recognized risk factor for breast cancer. With an increase in life expectancy of women, more older patients are diagnosed with breast cancer. This study aimed to identify the variations in breast cancer attributes and mortality in different age groups in New Zealand. METHODS: This was a retrospective study of data from the Auckland Breast Cancer Register between 1 June 2000 and 28 February 2017. Patients who were diagnosed through Breast Screen were included. Group A included those aged between 45 and 69 years. Group B included individuals with an age of 70 years or above. RESULTS: From June 2000 to February 2017, a total of 6304 new cases of new breast cancer were diagnosed through Auckland Breast Screen, with 5788 patients in group A and 516 patients in group B. Group B was more likely to have the lower grade invasive cancers, with fewer grade 3 cancers. Oestrogen receptor positivity was more pronounced in group B, along with progesterone receptor positivity. Conversely, HER-2 receptor was less likely to be positive in group B. There was a significantly higher breast cancer-related mortality in group B (6.0% versus 2.7%). Mortality related to other causes was also much higher in group B as compared to that in group A (12.8% versus 2.5%). CONCLUSION: Women aged 70 years or above generally tend to have a more favourable type of breast cancer, with a lower tumour grade, oestrogen and progesterone receptor positivity, and lower rate of HER-2 overexpression.

Integrative radiogenomics analysis for predicting molecular features and survival in clear cell renal cell carcinoma.

OBJECTIVES: To assess the feasibility of predicting molecular characteristics by computed tomography (CT) radiomics features, and predicting overall survival (OS) using combination of omics data in clear cell renal cell carcinoma (ccRCC). METHODS: Genetic data of 207 ccRCC patients was retrieved from The Cancer Genome Atlas (TCGA) and matched contrast-enhanced CT images were obtained from The Cancer Imaging Archive (TCIA). Another cohort of 175 ccRCC patients from West China Hospital was used as external validation. We first applied radiomics features and machine learning algorithms to predict genetic mutations and mRNA-based molecular subtypes. Next, we established predictive models for OS based on single omics, combined omics (radiomics+genomics, radiomics+transcriptomics, radiomics+proteomics) and all features (multi-omics). RESULTS: Using radiomics features, random forest algorithm showed good capacity to identify the mutations VHL (AUC=0.971), BAP1 (AUC=0.955), PBRM1 (AUC=0.972), SETD2 (AUC=0.949), and molecular subtypes m1 (AUC=0.973), m2 (AUC=0.968), m3 (AUC=0.961), m4 (AUC=0.953). The TCGA cohort was divided into training (n=104) and validation (n=103) sets. The radiomics model had promising prognostic value for OS in validation set (5-year AUC=0.775) and external validation set (5-year AUC=0.755). In the validation set, the radiomics+omics models enhanced predictive accuracy than single-omics models, and the multi-omics model made further improvement (5-year AUC=0.846). High-risk group of validation set predicted by multi-omics model showed significantly poorer OS (HR=6.20, 95%CI: 3.19-8.44, p<0.0001). CONCLUSIONS: CT radiomics might be a feasible approach to predict genetic mutations, molecular subtypes and OS in ccRCC patients. Integrative analysis of radiogenomics may improve the survival prediction of ccRCC patients.

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system, and radiomics has been adopted in tumor staging and prognostic evaluation in renal carcinomas. This study aimed to integrate image features of contrast-enhanced CT and underlying genomics features to predict the overall survival (OS) of ccRCC patients. METHOD: We extracted 107 radiomics features out of 205 patients with available CT images obtained from TCIA database and corresponding clinical and genetic information from TCGA database. LASSO-COX and SVM-RFE were employed independently as machine-learning algorithms to select prognosis-related imaging features (PRIF). Afterwards, we identified prognosis-related gene signature through WGCNA. The random forest (RF) algorithm was then applied to integrate PRIF and the genes into a combined imaging-genomics prognostic factors (IGPF) model. Furthermore, we constructed a nomogram incorporating IGPF and clinical predictors as the integrative prognostic model for ccRCC patients. RESULTS: A total of four PRIF and four genes were identified as IGPF and were represented by corresponding risk score in RF model. The integrative IGPF model presented a better prediction performance than the PRIF model alone (average AUCs for 1-, 3-, and 5-year were 0.814 vs. 0.837, 0.74 vs. 0.806, and 0.689 vs. 0.751 in test set). Clinical characteristics including gender, TNM stage and IGPF were independent risk factors. The nomogram integrating clinical predictors and IGPF provided the best net benefit among the three models. CONCLUSION: In this study we established an integrative prognosis-related nomogram model incorporating imaging-genomic features and clinical indicators. The results indicated that IGPF may contribute to a comprehensive prognosis assessment for ccRCC patients.

Safety and Efficacy of Pancreaticoduodenectomy in Octogenarians.

Backgrounds: Pancreaticoduodenectomy (PD) remains the only hope of a cure in selected patients with pancreatic adenocarcinoma (PAC). With an aging population, there will be an increasing number of very elderly patients being diagnosed with PAC of whom a selected proportion would be suitable for PD. However, the literature on outcomes of elderly patients after PD remains ambiguous. Therefore, the aim of this study was to examine the safety and efficacy of PD in octogenarians with PAC. Methods: A retrospective analysis of 304 patients with PAC undergoing PD. Patients were divided into two age groups using age of 80 years old as the cut-off. Results: Overall mortality and major morbidity rates were 0.5 and 18.5%, respectively. The octogenarian group had a higher rate of mortality (6.3%, n = 1, p < 0.001), a higher rate of major morbidity (37.5%, n = 6, p = 0.042) and a longer hospital stay (p = 0.035). However, median survival of octogenarians was 15.6 months. Multivariate analysis showed age was not identified as a prognostic factor for major morbidity and overall survival. Conclusion: Age alone should not be an exclusion criterion for consideration of PD. With careful selection, PD can be safely performed in octogenarians. Elderly patients should be referred to a specialized unit for an objective assessment to determine the suitability for this aggressive but potential curative approach.