Fistula-Associated Anal Adenocarcinoma: A 20-Year Single-Center Experience.

BACKGROUND: Fistula-associated anal adenocarcinoma (FAAC) is a rare consequence in patients with long-standing perianal fistulas. A paucity of data are available for this patient collective, making clinical characterization and management of this disease difficult. OBJECTIVE: This study aimed to describe a single-center experience with FAAC patients, their clinical course, and histopathological and molecular pathological characterization. METHODS: All patients receiving surgery for an anal fistula in 1999-2019 at a tertiary university referral hospital were included in this retrospective analysis. Patients with FAAC were eligible for histopathological analysis, including immunohistochemistry and molecular profiling. RESULTS: This study included 1004 patients receiving surgical treatment for an anal fistula, of whom 242 had an underlying inflammatory bowel disease (IBD). Ten patients were diagnosed with a fistula-associated anal carcinoma (1.0%), and six of these patients had an FAAC (0.6%). The mean overall survival of FAAC patients was 24 ± 3 months. FAAC immunohistochemistry revealed positive staining for CK20, CDX2 and MUC2, while stainings for CK5/6 and CK7 were negative. All FAAC specimens revealed microsatellite stability. Molecular profiling detected mutations in 35 genes, with the most frequent mutations being TP53, NOTCH1, NOTCH3, ATM, PIK3R1 and SMAD4. CONCLUSION: FAAC is rare but associated with poor clinical outcome. Tissue acquisition is crucial for early diagnosis and therapy and should be performed in long-standing, non-healing, IBD-associated fistulas in particular. The immunophenotype of FAAC seems more similar to the rectal-type mucosa than the anal glands.

Added value of quantitative, multiparametric 18F-FDG PET/MRI in the locoregional staging of rectal cancer.

PURPOSE: The purpose of this study was to determine whether multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) can improve locoregional staging of rectal cancer (RC) and to assess its prognostic value after resection. METHODS: In this retrospective study, 46 patients with primary RC, who underwent multiparametric 18F-fluorodeoxyglucose (FDG) PET/MRI, followed by surgical resection without chemoradiotherapy, were included. Two readers reviewed T- and N- stage, mesorectal involvement, sphincter infiltration, tumor length, and distance from anal verge. In addition, diffusion-weighted imaging (DWI) and PET parameters were extracted from the multiparametric protocol and were compared to radiological staging as well as to the histopathological reference standard. Clinical and imaging follow-up was systematically assessed for tumor recurrence and death. RESULTS: Locally advanced rectal cancers (LARC) exhibited significantly higher metabolic tumor volume (MTV, AUC 0.74 [95% CI 0.59-0.89], p = 0.004) and total lesion glycolysis (TLG, AUC 0.70 [95% CI 0.53-0.87], p = 0.022) compared to early tumors. T-stage was associated with MTV (AUC 0.70 [95% CI 0.54-0.85], p = 0.021), while N-stage was better assessed using anatomical MRI sequences (AUC 0.72 [95% CI 0.539-0.894], p = 0.032). In the multivariate regression analysis, depending on the model, both anatomical MRI sequences and MTV/TLG were capable of detecting LARC. Combining anatomical MRI stage and MTV/TLG led to a superior diagnostic performance for detecting LARC (AUC 0.81, [95% CI 0.68-0.94], p < 0.001). In the survival analysis, MTV was independently associated with overall survival (HR 1.05 [95% CI 1.01-1.10], p = 0.044). CONCLUSION: Multiparametric PET-MRI can improve identification of locally advanced tumors and, hence, help in treatment stratification. It provides additional information on RC tumor biology and may have prognostic value.

Laparoscopic Sacral Mesh Fixation for Ventral Rectopexy: Clinical Implications From a Cadaver Study.

BACKGROUND: Correct tack placement at the sacral promontory for mesh fixation in ventral mesh rectopexy is crucial to avoid bleeding, nerve dysfunction, and spondylodiscitis. OBJECTIVE: The present cadaver study was designed to assess the true location of tacks after mesh fixation during laparoscopic ventral mesh rectopexy in relation to vascular and nerve structures and bony landmarks. DESIGN: This was an interventional cadaver study. SETTING: This study was conducted after laparoscopic mesh fixation detailed pelvic dissection was performed following a standardized protocol. In addition, 64-row multidetector computed tomography was conducted to further define lumbosacral anatomy and tack positioning. PATIENTS: Eighteen fresh cadavers (10 female, 8 male) were included in this study. MAIN OUTCOME MEASURES: True tack position and vascular and neuronal involvement served as outcome measures. RESULTS: A total of 52 tacks were deployed (median 3, range 2-3 tacks). Median tack distance to the midsacral promontory was 16.1 mm (0.0-54.2). Only a total of 22 tacks (42.3%) were found on the right surface of the S1 vertebra, correlating with the planned deployment area. In 7 cadavers (38.8%), all tacks were deployed on the planned deployment area. The median distance to the major vessels was 10.5 mm (0.0-35.0), which was the internal iliac artery in half of the cases. Median distance of tacks to the right ureter was 32.1 mm (7.5-46.1). Neither major vessels nor the ureter was injured. Dissection of the hypogastric plexus was undertaken in 14 cadavers, and in each cadaver, tacks affected the hypogastric nerve plexus. LIMITATIONS: This study was limited by the moderate number of cadavers. CONCLUSIONS: Tack placement showed significant variation in our specimen, emphasising the need for reliable anatomic landmarks and sufficient exposure during ventral mesh rectopexy. Hypogastric nerve plexus involvement is common, thus detailed functional assessment after surgery is required. It also points out the importance of cadaver studies before implementing new surgical techniques into clinical practice. See Video Abstract at http://links.lww.com/DCR/B827. FIJACIN LAPAROSCPICA DE MALLA SACRA PARA RECTOPEXIA VENTRAL IMPLICACIONES CLNICAS DE UN ESTUDIO SOBRE CADAVERS: ANTECEDENTES:La colocación correcta de la tachuela en el promontorio sacro para la fijación de la malla en la rectopexia con malla ventral es crucial para evitar hemorragias, disfunción nerviosa y espondilodiscitis.OBJETIVO:El presente estudio en cadáveres fue diseñado para evaluar la verdadera ubicación de las tachuelas después de la fijación de la malla durante la rectopexia laparoscópica con malla ventral en relación con las estructuras vasculares y nerviosas y los puntos de referencia óseos.DISEÑO:Estudio intervencionista de cadáveres.AJUSTE:Después de la fijación laparoscópica de la malla, se realizó una disección pélvica detallada siguiendo un protocolo estandarizado. Además, se realizó una tomografía computarizada multidetector de 64 cortes para definir mejor la anatomía lumbosacra y la posición de la tachuela.PACIENTES:Se incluyeron en este estudio dieciocho cadáveres frescos (10 mujeres, 8 hombres).PRINCIPALES MEDIDAS DE RESULTADO:Posición real de tachuela y compromiso vascular y neuronal.RESULTADOS:Se utilizaron un total de 52 tachuelas (mediana 3, 2-3 tachuelas). La distancia media de tachuela al promontorio sacro medio fue de 16,1 mm (0,0-54,2). Solo se encontraron un total de 22 tachuelas (42,3%) en la superficie derecha de la vértebra S1, correlacionándose con el área planificada. En siete cadáveres (38,8%) todas las tachuelas se utilizaron en el área de planificada. La distancia media a los vasos principales fue de 10,5 mm (0,0-35,0), que era la arteria ilíaca interna en la mitad de los casos. La distancia media de las tachuelas al uréter derecho fue de 32,1 mm (7,5-46,1). No se lesionó ni los grandes vasos ni el uréter. La disección del plexo hipogástrico se realizó en 14 cadáveres y en cada cadáver, las tachuelas afectaron el plexo nervioso hipogástrico.LIMITACIONES:Número moderado de cadáveres incluidos en el estudio.CONCLUSIONES:La colocación de tachuelas mostró una variación significativa en nuestra muestra, enfatizando la necesidad de puntos de referencia anatómicos confiables y una exposición suficiente durante la rectopexia con malla ventral. La afectación del plexo nervioso hipogástrico es común, por lo que se requiere una evaluación funcional detallada después de la cirugía. También destaca la importancia de los estudios sobre cadáveres antes de implementar nuevas técnicas quirúrgicas en la práctica clínica. Consulte Video Resumen en http://links.lww.com/DCR/B827. (Traducción-Dr Yolanda Colorado).

Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium.

Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (pFDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (pFDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.

The effect of intraoperative goal-directed crystalloid versus colloid administration on perioperative inflammatory markers - a substudy of a randomized controlled trial.

BACKGROUND: Excessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime. METHODS: Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer's solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four. RESULTS: The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880-5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207-2116) of crystalloid and 1250 mL (750-1938) of colloid. CONCLUSION: Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT00517127 ). Registered 16th August 2007.

Plasma metabolites associated with colorectal cancer: A discovery-replication strategy.

Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.

Low anterior resection syndrome (LARS) in patients with epithelial ovarian cancer after primary debulking surgery.

OBJECTIVE: To evaluate the prevalence of low anterior resection syndrome (LARS) in patients with debulking surgery for primary advanced epithelial ovarian cancer and to identify potential risk factors for development of LARS. METHODS: We reviewed data on 552 consecutive patients with primary epithelial ovarian cancer (EOC), who underwent upfront or interval cytoreductive surgery including low anterior resection at two different academic institutions (Kliniken-Essen-Mitte, Germany, and Medical University of Vienna, Austria). Intestinal dysfunction was assessed by the validated LARS-questionnaire via telephone call. We performed descriptive statistics and a binary logistic regression model to evaluate risk factors for LARS. RESULTS: In total, 341 patients were eligible and 206 (60.4%) were successfully contacted and provided complete information. Major LARS was observed in 78 (37.9%) patients, minor LARS in 44 (21.4%) patients, and no LARS in 84 (40.8%) patients. The prevalence rate of major LARS was not influenced by time interval between surgery and LARS assessment, type of cytoreductive surgery, and recurrent disease at the time of assessment. In multivariate analyses, number of anastomosis was independently associated with an increased risk for presence of major LARS (OR 3.76 [1.95-7.24]). In the present cohort, 25.2% patients had more than one bowel anastomosis. CONCLUSIONS: LARS in general and major LARS in particular seem to be a frequent long-term complication after debulking surgery including low anterior resection in primary advanced EOC patients. Particularly EOC patients with more than one bowel anastomosis during surgery seem to be at an increased risk for major LARS.

Predictive and Prognostic Implication of Bowel Resections During Primary Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer.

OBJECTIVES: The aims of this study were to assess anastomotic leakage (AL) rate and risk factors for AL in patients with advanced epithelial ovarian cancer (EOC) undergoing cytoreductive surgery including bowel resections and to evaluate the prognostic implication of AL. METHODS: Data of 350 consecutive patients with International Federation of Gynecology and Obstetrics EOC stage IIB-IV who underwent cytoreductive surgery at the Department of General Gynecology and Gynecologic Oncology of the General Hospital of Vienna between 2003 and 2017 were collected. Within this cohort, 192 patients (54.9%) underwent at least 1 bowel resection and were further analyzed. Preoperative risk factors for AL were computed using logistic regression models. Prognostic factors for overall survival were evaluated by using log-rank tests and multivariable Cox regression model. RESULTS: Overall, the AL rate was 4.7% for patients with advanced EOC undergoing cytoreductive surgery with at least 1 bowel resection, including patients with multiple large bowel resections. The AL rate for patients with isolated rectosigmoid resection was 1.9%. In univariate analysis, the number of anastomoses per surgery (P = 0.04) was associated with the occurrence of AL. In multivariable analysis, rectosigmoid resection with additional large bowel resection was associated with a higher risk of AL compared with isolated rectosigmoid resection (P = 0.046; odds ratio, 7.23 [95% confidence interval, 1.04-50.39]). Anastomotic leakage was associated with decreased overall survival (P = 0.04) in univariate but not in multivariable survival analysis. CONCLUSIONS: Anastomotic leakage rate after rectosigmoid resection in advanced EOC is acceptably low and outweighs increased perioperative risks when performed in a high-volume institution. Nonetheless, the occurrence of AL is a severe adverse event, which even seems to negatively affect patients' overall prognosis. As no factor could be identified to clearly predict AL, extensive procedures comprising multiple bowel resections, should be avoided particularly when complete resection cannot be achieved.

Minimal-invasive approach for penetrating Crohn's disease is not associated with increased complications.

BACKGROUND: Laparoscopic surgery for penetrating Crohn's disease (CD) still remains highly conflicting due to a lack of sufficient data. Therefore, the following large study was designed to compare postoperative outcomes after minimal-invasive resections for penetrating and non-penetrating CD. METHODS: Consecutive patients, who underwent laparoscopic intestinal resection for symptomatic CD at a tertiary academic referral center, were included. Patients were divided according to perioperative findings in penetrating and non-penetrating type of disease. All clinical data were obtained from an institutional database and analyzed retrospectively. RESULTS: Of 234 patients enrolled, 101 patients [females: n = 54 (53.5 %)] were operated on for non-penetrating CD and 133 patients [females: n = 50 (37.6 %)] for penetrating CD. Fistulas (p < 0.001), inflammatory mass (p < 0.001) and abscess formation (p < 0.001) were observed more frequently in the perforating group. Ileocolic resections were performed predominantly in both groups [perforating CD: n = 110 (82.7 %), non-perforating CD: n = 82 (81.2 %)], with more complex resections (>1 intestinal resection) found in perforating CD (p < 0.001). Conversion rates did not differ significantly. Notably, 30-day postoperative morbidity was comparable for both groups [perforating CD: n = 20 (15 %), non-perforating CD: n = 19 (18.8 %), p = 0.44]. Postoperative complication rates graded according to the Clavien-Dindo classification showed no difference too (p = 0.49). CONCLUSION: Laparoscopic surgery can be conducted safely in selected patients with penetrating CD without increasing the risk of postoperative complications. This finding needs to be implemented in future guidelines.

Rectal cancer surgery in older people does not increase postoperative complications--a retrospective analysis.

BACKGROUND: Rectal cancer surgery in the older population remains a highly controversial topic. The present study was designed to assess whether older patients had an increased risk for postoperative complications after rectal resection for malignancies. METHODS: Consecutive patients (n=627), who underwent rectal cancer resection at a single institution, were included in the study and analyzed retrospectively. Short-term complications were compared between patients≥80 years (n=55) and <80 years (n=572). Additionally, predictive factors for postoperative complications were analyzed. RESULTS: The older aged group showed a significantly higher rate of co-morbidities compared to controls, in terms of cardiovascular and pulmonary diseases (P=0.002, P=0.006). In older patients, a Hartmann's procedure and transanal endoscopic microsurgery (TEM) were performed most frequently (P<0.0001).The overall complication rate was 39% (n=244) (medical: n=59 (9%), surgical: n=185 (30%)), including 24 (44%) complications in the older aged group (medical: n=6 (11%), surgical: n=18 (33%)). Notably, the incidence of surgical and medical complications showed no significant difference between patients and controls (P=0.58, P=0.69).Neurological and cardiovascular disorders were associated with an increased risk for a eventful postoperative course in the older aged group (P=0.03, P=0.04). CONCLUSIONS: Rectal cancer resection can be performed safely in selected older patients. Age itself should not be considered as a risk factor for postoperative complications.

Cost-effectiveness of teduglutide in adult patients with short bowel syndrome - a European socioeconomic perspective.

BACKGROUND: Short bowel syndrome with intestinal failure (SBS-IF) is a rare but devastating medical condition. An absolute loss of bowel length forces the patients into parenteral support dependency and a variety of medical sequelae, resulting in increased morbidity and mortality. Interdisciplinary treatment may include therapy with the effective but expensive intestinotrophic peptide teduglutide. OBJECTIVES: A time-discrete Markov model was developed to simulate the treatment effect [lifetime costs, quality-adjusted life years (QALYs), and life years (LYs)] of teduglutide plus best supportive care compared with best supportive care alone in patients with SBS-IF. METHODS: The health status of the model was structured around the number of days on PS. Clinical data from 3 data sets were used: 1) an Austrian observational study (base case), 2) pooled observational cohort studies, and 3) a prospective study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects. Direct and indirect costs were derived from published sources. QALYs, LYs, and costs were discounted (3% per annum). RESULTS: Under the base case assumption, teduglutide is associated with costs of 2,296,311 € per patient and 10.78 QALYs (13.74 LYs) over a lifetime horizon. No teduglutide is associated with 1,236,816 € and 2.24 QALYs (8.57 LYs). The incremental cost-utility ratio (ICUR) amounts to 123,945 €. In case of the pooled clinical data set, the ICUR increases to 184,961 €. If clinical data based on the study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects were used, the ICUR increased to 235,612 €. CONCLUSIONS: Teduglutide in treating patients with SBS-IF meets the traditional cost-effectiveness criteria from a European societal perspective. Nevertheless, the varying concentrations of teduglutide efficacy leave a degree of uncertainty in the calculations.

Repeat intestinal resections increase the risk of recurrence of Crohn's disease.

BACKGROUND: Which factors predict recurrence in patients with Crohn's disease in the era of immunosuppressive medications is still under debate. OBJECTIVE: The current study was conducted to assess long-term outcome after ileocolic resection for Crohn's disease and to define predictive factors for surgical relapse. DESIGN: This is a retrospective study. SETTINGS: The study was conducted in a tertiary referral center. PATIENTS: A consecutive cohort of patients (n = 203) with Crohn's disease who underwent ileocolic resection between 1997 and 2006 were analyzed. The mean follow-up time was 8.4 (±2.4) years. MAIN OUTCOME MEASURES: The cumulative probability for repeated intestinal resection for recurrent Crohn's disease was described by Kaplan-Meier curves. Predictors of surgical recurrence were analyzed by univariate tests. RESULTS: One hundred five patients (51.7%) were exposed to azathioprine/6-mercaptopurine, and 28 patients (13.8%) were exposed to tumor necrosis factor-α blockers after operation. During the follow-up period, 32 patients (15.8%) were reoperated on for disease recurrence. At 5 and 10 years after index surgery, 95.5% and 81.3% of the patients had reoperation-free survival. Previous resections for Crohn's disease (HR, 2.981; 95% CI, 1.411-6.29; p = 0.003) and urgent indication for surgery (HR, 2.729; 95% CI, 1.047-7.116; p = 0.03) were significant risk factors for reoperation. In addition, patients with postoperative complications following ileocolonic resection were more likely to require reoperation (HR, 1.712; 95% CI, 041-2.817; p = 0.03). In a multiple Cox regression model, previous intestinal resection for Crohn's disease remained significant (p = 0.0114) with a HR of 2.654 (95% CI, 1.246-5.654). LIMITATIONS: The limitation is the retrospective design of the study, with its potential selection bias. CONCLUSION: In the present analysis, previous intestinal resection for Crohn's disease was found to be an independent risk factor for surgical recurrence. Consequently, shorter surveillance intervals in this group of patients should be considered.

Anastomotic leakage after low anterior resection for rectal cancer: comparison of stapled versus compression anastomosis.

PURPOSE: Surgical technique and perioperative management in rectal cancer surgery have been substantially improved and standardized during the last decades. However, anastomotic leakage following low anterior resection still is a significant problem. Based on animal experimental data of improved healing of compression anastomosis, we hypothesized that a compression anastomotic device might improve healing rates of the highest-risk anastomoses. METHODS: All low anterior resections for rectal cancer performed or directly supervised by the senior author between January 2004 and June 2012 were analyzed. Only patients with a stapled or compression anastomosis located within 6 cm from the anal verge were included. Until December 2008, circular staplers were employed, while since January 2009, a novel compression anastomotic device was used for rectal reconstruction exclusively. RESULTS: Out of 197 patients operated for rectal cancer, a total of 96 (34 females, 35.4 %) fulfilled inclusion criteria. Fifty-eight (60.4 %) were reconstructed with circular staplers and 38 (39.6 %) using a compression anastomotic device. Significantly, more laparoscopic procedures were recorded in the compression anastomosis group, but distribution of gender, age, body mass index, American Society of Anaesthesiologists score, rate of preoperative radiotherapy, tumor staging, or stoma diversion rate were similar. Anastomotic leakage was observed in seven cases (7/58, 12.1 %) in the stapled and twice (2/38, 5.3 %) in the compression anastomosis group (p = 0.26). CONCLUSIONS: In this series, rectal reconstruction following low anterior resection using a novel compression anastomotic device was safe and (at least) equally effective compared to traditional circular staplers concerning leak rate.

Identifying risk factors for allogenic blood transfusion in oral and oropharyngeal cancer surgery with free flap reconstruction.

PURPOSE: Several observational studies in head and neck cancer have reported that allogenic blood transfusion is associated with increased postoperative complications, increased risk of tumor recurrence, and worse prognosis. The aim of this study was to identify preoperative and intraoperative factors predicting blood transfusion in patients undergoing surgery for oral and oropharyngeal cancer. PATIENTS AND METHODS: We conducted a retrospective cohort study of patients undergoing tumor resection and free flap reconstruction for locally advanced oral and oropharyngeal squamous cell carcinoma between 2000 and 2008. The primary outcome variable was perioperative exposure to allogenic blood transfusion. Univariate and multivariate logistic regression models were used to determine predictors of blood transfusion. RESULTS: A cohort of 142 participants was found eligible. In a multivariate model, Charlson score ≥ 1 (OR, 5.2; 95% CI, 1.4 to 19.3; P = .01), preoperative hemoglobin levels ≤ 12 g/dl (OR, 4.4; 95% CI, 1.2 to 16.2; P = .03), bone resection (OR, 5.1; 95% CI, 1.5 to 17.8; P = .01), and osseous free tissue transfer (OR, 8.8; 95% CI, 1.0 to 74.8; P = .046) were independently associated with an increased risk of blood transfusion. CONCLUSION: Our study identified patient- and surgery-related factors predicting a higher risk of exposure to allogenic blood transfusion. This readily available preoperative information could be used to better stratify patients according to their transfusion risk and may thereby guide blood conservation strategies in high-risk patients.

Postoperative failure of platelet recovery is an independent risk factor for poor survival in patients with oral and oropharyngeal cancer.

OBJECTIVE: The aim of this study was to evaluate the postoperative platelet count changes in patients with oral and oropharyngeal squamous cell carcinoma undergoing preoperative chemoradiotherapy in order to test the hypothesis that the failure of platelets to recover to normal range within 7 days after surgery represents a significant risk factor for poor survival. MATERIALS AND METHODS: A cohort of 102 patients with primary locally advanced oral and oropharyngeal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery was retrospectively analyzed. For each patient, platelet counts were evaluated prior to neoadjuvant treatment, prior to surgery and throughout postoperative days 1 to 7. The Kaplan-Meier method and Cox regression models were used to assess the impact of platelet count changes on survival. RESULTS: Overall survival rate at 5 years was 28% for patients whose platelets did not recover by day 7, with 52% for patients whose platelets remained within a normal level or recovered to this by day 7 (p = 0.005). In multivariate analysis, failure of platelet recovery by day 7 was independently associated with shorter overall survival (p = 0.03). CONCLUSIONS: We demonstrated that the failure of platelets to recover to normal range by the seventh postoperative day is an independent adverse prognostic factor in patients with oral and oropharyngeal cancer undergoing neoadjuvant treatment and surgery. CLINICAL RELEVANCE: Our results indicate that physicians should pay closer attention to monitoring the postoperative platelet count course, as it may predict the clinical outcome of patients with oral and oropharyngeal cancer.

Teduglutide in amyloidosis-associated intestinal failure.

Amyloidosis is a heterogeneous disease characterized by tissue deposition of abnormally folded fibrillary proteins that can manifest itself by a wide variety of symptoms depending on the affected organs. GI involvement among amyloidosis patients is common. Its clinical manifestation often presents with nonspecific symptoms such as weight loss, diarrhea, and malabsorption. With no specific treatment existing for GI amyloidosis, therapy focuses on impeding amyloid deposition and managing the patients' symptoms with supportive measures. Here, we present an AL-amyloidosis patient with GI involvement and intestinal failure (IF) who was successfully treated with the glucagon-like peptide-2 (GLP-2) analogue teduglutide. Over the course of treatment with teduglutide, the patient was able to achieve independence from parenteral nutrition and experienced a significant improvement in quality of life (QoL) as stool frequency and consistency improved, urinary output was stabilized and body weight as well as body composition improved over the course of teduglutide therapy. With no longer being exposed to the burden and associated risks of parenteral nutrition, we were able to reduce the potential morbidity and mortality rate as well as to improve the patient's overall QoL. Intestinal tissue biopsy workup revealed a histopathological correlate for the clinical response; Congo-Red-positive intestinal depositions almost completely disappeared within 6 months of teduglutide therapy. Implementing intestinotrophic GLP-2 analogue teduglutide may enrich the spectrum of treatment options for amyloidosis patients with IF who are dependent on parenteral support.

Meeting actual benchmarks for short- and long-term outcomes after cytoreductive surgery for peritoneal surface malignancy at a newly established academic treatment center.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a curative treatment for selected patients with peritoneal surface malignancy. Reaching actual outcomes benchmarks is challenging given the complex nature of peritoneal surface malignancy surgery. The aim of this study was to assess how the benchmarks for morbidity and oncologic outcome can be reached at a newly established program for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Building on existing institutional experience in complex abdominal surgery and interdisciplinary ovarian cancer treatment, a peritoneal surface malignancy center for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was established at the Medical University of Vienna using a structured mentoring process. This is a retrospective analysis of the first 100 consecutive patients. Morbidity and mortality were assessed using the Clavien-Dindo classification, and oncologic outcomes using overall survival. RESULTS: Major morbidity and mortality were 26% and 3%, and median overall survival was 49.0 months. In patients with colorectal peritoneal metastases, the median overall survival was 35.1 months (all colorectal peritoneal metastases patients) and 48.8 months in the subgroup with Peritoneal Surface Disease Severity Score ≤3. No median overall survival could be calculated in patients with low-grade appendiceal mucinous neoplasms, appendiceal adenocarcinoma, or peritoneal mesothelioma due to >50% of patients being alive at the end of follow-up. CONCLUSION: We show that the current morbidity and oncological outcomes benchmarks can be reached within the first 100 cases of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a newly established peritoneal surface malignancy center. Previous institutional experience in complex abdominal surgery and a structured mentoring process are key factors in achieving this goal.

The predictive value of comorbidities on postoperative complication rates and overall survival in left-sided oncological colorectal resections: a multicentre cohort study.

INTRODUCTION: Surgical- and nonsurgical complications significantly worsen postoperative outcomes, and identification of patients at risk is crucial to improve care. This study investigated whether comorbidities, graded by the Charlson Comorbidity Index (CCI), impact complication rates and impair long-term outcome in a cohort of left-sided colorectal resections. METHODS: Retrospective analysis of patients undergoing oncological left-sided colorectal resections due to colorectal cancer between 01/2015 and 12/2020 in two referral centers in Austria using electronic medical records and national statistical bureau survival data. Patients with recurrent disease, peritoneal carcinomatosis, and emergency surgeries were excluded. Comorbidities were assessed using the CCI, and complication severity was defined by the Clavien-Dindo classification (CDC). Logistic regression analysis was performed to identify factors influencing the risk for postoperative complications, and overall survival was assessed using data from the national statistics bureau. RESULTS: A total of 471 patients were analyzed. Multinominal logistic regression analysis identified a CCI greater than or equal to 6 ( P =0.049; OR 1.59, 95% CI: 1.10-2.54) and male sex ( P =0.022; OR 1.47, 95% CI: 1.21-2.98) as independent risk factors for major complications. While patients with a high CCI had the worst postoperative survival rates, perioperative complications only impacted on overall survival in patients with low CCIs, but not in patients with high CCIs. CONCLUSION: Although a high CCI is a risk factor for major postoperative complications, the presence of comorbidities should not result in withholding surgery.

Efficacy of cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn's disease-A prospective nationwide multicenter cohort study.

BACKGROUND: The use of mesenchymal stem cells is considered a novel and promising therapeutic option for patients with perianal fistulizing Crohn's disease; however, data on its clinical application remain scarce. This multicenter nationwide study aimed to assess the clinical efficacy of mesenchymal stem cells in closing complex anal fistulas. METHODS: In this study 14 Crohn's disease patients (3 males, 11 females) with complex anal fistulas treated in 3 tertiary hospitals in Austria were included between October 2018 and April 2021. Injection of 120 million allogeneic expanded adipose-derived mesenchymal stem cells (Cx601-darvadstrocel) was performed in each patient. Closure of the external fistula opening without secretion by external manual compression was defined as treatment success. RESULTS: The median age of the patient population at the time of surgery was 32 years (range 26-53 years) with a median body mass index of 21.7 kg/m2 (range 16.7-26.6 kg/m2). Of the patients 12 (86%) received monoclonal antibodies (infliximab, adalimumab, ustekinumab, vedolizumab) at the time of surgery. The median number of complex fistulas was 1.4 (range 1-2), The median operative time was 20 min (range 6-50 min) with no perioperative complications. After a median follow-up of 92 weeks, we found successful fistula closure in 57.1% (n = 8) of treated patients. The perianal disease activity index did not improve significantly from initially 7 to a median of 6 after 52 weeks (p = 0.495). CONCLUSION: Darvadstrocel is a safe, minimally invasive surgical technique without significant perioperative complications. Clinical success can be expected in about half of the treated patients.