Ten steps for proper peripheral nerve handling during inguinal hernia surgery.

INTRODUCTION: Post-inguinal pain after a hernia surgery is prevalent and can be quite frustrating for the surgeon and patient alike. There are several sources for possible post-operative inguinal pain after a successful hernia repair; however, in the setting where a recurrent inguinal hernia is not present, it is likely related to the nerves in the inguinal canal or pelvis. Chronic inguinal groin pain after hernia repairs have been reported in a high percentage of patients following inguinal hernia surgery despite being one of the most common procedures performed annually in the USA and worldwide. MATERIALS AND METHODS: We present ten of the basic concepts utilized by peripheral nerve surgeons to limit nerve injury, which can easily be applied to open inguinal hernia surgery with or without mesh, starting with the firm understanding of the inguinal anatomy to addressing the nerves, meticulous placement of the mesh and the active revision of the surrounding structures and nerve position before closure. CONCLUSIONS: Understanding the proper handling of the inguinal nerves during hernia surgery can decrease the incidence of post-operative chronic pain by employing microsurgical concepts to day-to-day surgical procedures and prevent complications in an extensive set of patients.

Lung ultrasound and postoperative follow-up of congenital diaphragmatic hernia.

Lung ultrasound (LU) has emerged as a valuable tool for assessing pulmonary aeration noninvasively, rapidly, and reliably in different neonatal conditions. However, its role in the preoperative and postoperative evaluation in congenital diaphragmatic hernia (CDH) is still poorly analyzed. We present a cohort of 8 patients diagnosed with CDH who underwent lung ultrasound examinations at various time points before and after surgical correction. The lung ultrasound patterns were compared between two groups: mechanical ventilation ≤ 7 days (MV ≤ 7) and mechanical ventilation > 7 days (MV > 7). The ultrasound findings were also compared to CT scans and chest X-ray images to assess its diagnostic capacity for identifying postoperative complications: pneumothorax, pleural effusion, and pneumonia. Group MV ≤ 7 exhibited a normal pattern even at 48 h postsurgery, while group MV > 7 presented interstitial or alveolointerstitial pattern in both lungs for prolonged periods (2-3 weeks). Furthermore, contralateral LU pattern may be predictive of respiratory evolution.  Conclusion: Lung ultrasound is a valuable tool for evaluating the progressive reaeration of the lung following surgical correction in CDH patients. It demonstrates the ability to diagnose common postoperative complications without the need for radiation exposure while offering the advantages of quick and serial assessments. These findings highlight the potential of lung ultrasound as an effective alternative to conventional imaging methods in the management of CDH. What is Known: • Lung ultrasound evaluates lung aeration and predicts respiratory outcomes in neonatal patients. What is New: • Lung ultrasound is useful in the postsurgical management of congenital diaphragmatic hernia patients, detecting reaeration and respiratory complications.

Saving time in the radiotherapy procedures for COVID-19 pneumonia treatment. A single-institution experience.

BACKGROUND: The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities. PATIENTS AND METHODS: At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated. RESULTS: Mean age of treated patients was 83 (72-91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25-58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry. CONCLUSIONS: LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times.

Validation and comparison of Breast Graded Prognostic Assessment scores in patients with breast cancer and brain metastases.

PURPOSE: Brain metastases (BM) occur in 15-35% of patients with metastatic breast cancer, conferring poor prognosis and impairing quality of life. Clinical scores have been developed to classify patients according to their prognosis. We aimed to check the utility of the Breast Graded Prognostic Assessment (B-GPA) and its modified version (mB-GPA) and compare them in routine clinical practice. METHODS: This is an ambispective study including all patients with breast cancer BM treated in a single cancer comprehensive center. We analyzed the overall survival (OS) from BM diagnosis until death. The Kaplan-Meier method and Cox proportional hazard regression model were used in the analyses. ROC curves were performed to compare both scores. RESULTS: We included 169 patients; median age was 50 years. HER2-positive and triple negative patients were 33.7% and 20.7%, respectively. At the last follow-up, 90% of the patients had died. Median OS was 12 months (95% confidence interval 8.0-16.0 months). OS was worse in patients with > 3 BM and in patients with triple negative subtype. CONCLUSIONS: In our series, we confirm that B-GPA and mB-GPA scores correlated with prognosis. ROC curves showed that B-GPA and mB-GPA have similar prognostic capabilities, slightly in favor of mB-GPA.

Rethinking prognostic factors in locally advanced or metastatic urothelial carcinoma in the immune checkpoint blockade era: a multicenter retrospective study.

BACKGROUND: Few studies have investigated the safety and efficacy of anti-PD-(L)1 antibodies in metastatic urothelial carcinoma (mUC) in daily clinical practice. Knowledge about the influence of baseline clinical and analytical factors on therapy outcomes is scarce. PATIENTS AND METHODS: We conducted a multicenter retrospective study involving 119 previously treated or untreated mUC patients under anti-PD-(L)1 therapy in a real-world scenario. The objectives of this study were to confirm the safety and efficacy of anti-PD-(L)1 monotherapy and to identify pretreatment factors influencing therapy outcomes. In addition, an independent prognostic model for overall survival (OS) was developed and internally validated. RESULTS: Median OS was 7.8 months [95% confidence interval (CI), 5.4-10.4], median progression-free survival (PFS) was 2.80 months (95% CI, 2.4-3.4), disease control rate (DCR) was 40% (95% CI, 31-49), and overall response rate (ORR) was 24% (95% CI, 15-31). Presence of peritoneal metastases was associated with poor OS [hazard ratio (HR) = 2.40, 95% CI, 1.08-5.33; P = 0.03]. Use of proton-pump inhibitors (PPI) was associated with poor OS (HR = 1.83, 95% CI, 1.11-3.02; P = 0.02) and PFS (HR = 1.94, 95% CI, 1.22-3.09; P = 0.005), and lower DCR (OR = 0.38, 95% CI, 0.17-0.89; P = 0.03) and ORR (OR = 0.18, 95% CI, 0.02-1.60; P = 0.002). The three risk category prognostic model developed included Eastern Cooperative Oncology Group performance status, PPI use, albumin level, presence of liver metastases, and presence of peritoneal metastases variables and was associated with higher risk of death (HR = 3.00, 95% CI, 1.97-4.56; P = 0.0001). CONCLUSIONS: This study confirms anti-PD-(L)1 monotherapy as a safe and effective treatment option in daily clinical practice for mUC patients. It also describes the presence of peritoneal metastases as an independent prognostic factor for OS and underlines the association between PPI use and worse therapeutic outcomes. Finally, it proposes a new easy-to-use risk-assessment model for OS prediction.

SEOM clinical guidelines for the treatment of advanced prostate cancer (2020).

The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.

Incidence and clinical pattern of contralateral synchronous and metachronous germ cell testicular cancer.

BACKGROUND: Incidence of a second testicular tumor is higher in patients diagnosed with testicular cancer than in the general population. As incidence of unilateral germ cell cancer is increasing worldwide and most of these patients are cured, a growing number of patients at risk of developing a contralateral testis cancer is expected. OBJECTIVE: To analyze clinical and histological characteristics, as well as the absolute and cumulative incidence of a second testicular cancer in a cohort of 3,834 patients diagnosed with germ cell testicular cancer between I/1994 and I/2018 in 18 referral hospitals of the Spanish Germ Cell Cancer Group. METHODS: Patients were treated according to stage and year of diagnoses. Contralateral testis biopsy was not routinely performed, according to European Association of Urology rules. Follow-up of the contra lateral testis consists of a physical exam only and an annual optional testicular ultrasound for 10 years. RESULTS: Median age of the patients included was 32 years (18-82). With a median follow-up of 61 months (0-240), 67/3,834 patients (1.74%) were diagnosed with a second testicular tumor. The second testicular tumor was synchronic (diagnosed within 6 months of the first orchiectomy) in 19 patients, and metachronous in 48. Pathology of the second tumor was reported as a seminomatous testis tumor in 47 patients and a nonseminomatous cancer in 20. Cumulative incidence of contralateral testicular cancer was 2% at 5 years, and 4% (IC 95% 3%-5%) at 14 years. Younger age was a risk factor for developing a second testicular tumor (P = 0.006), whereas chemotherapy reduced the risk for a metachronous testicular cancer (P = 0.046). Within our cohort, 6 families with testicular cancer aggregation (more than 2 tumors in the same family) were identified. CONCLUSIONS: Incidence of second testicular neoplasm in this cohort of 3,834 patients was similar to that which has been reported in other countries. Metachronous tumors and seminomas are more common. Follow-up of the contralateral testis is mandatory, as well as adequate information for patients to prevent a second neoplasm if feasible, and to detect and treat it as soon as possible.

Renal accumulation of prooxidant mineral elements and CKD in domestic cats.

Felids have a high incidence of chronic kidney disease (CKD), for which the most common renal lesion is chronic interstitial nephritis (CIN). CIN can be induced by tissue oxidative stress, which is determined by the cellular balance of pro- and anti-oxidant metabolites. Fish-flavoured foods are more often fed to cats than dogs, and such foods tend to have higher arsenic content. Arsenic is a pro-oxidant metallic element. We propose that renal accumulation of pro-oxidant elements such as arsenic and depletion of anti-oxidant elements such as zinc, underpin the high incidence of CIN in domestic cats. Total arsenic and other redox-reactive metal elements were measured in kidneys (after acid-digestion) and urine (both by inductively-coupled plasma-mass spectrometry) of domestic cats (kidneys, n = 56; urine, n = 21), domestic dogs (kidneys, n = 54; urine, n = 28) and non-domesticated Scottish Wildcats (kidneys, n = 17). Renal lesions were graded by severity of CIN. In our randomly sampled population, CIN was more prevalent in domestic cat versus domestic dog (51%, n = 32 of 62 cats; 15%, 11 of 70 dogs were positive for CIN, respectively). CIN was absent from all Scottish wildcats. Tissue and urinary (corrected for creatinine) arsenic content was higher in domestic cats, relative to domestic dogs and wildcats. Urine arsenic was higher in domestic cats and dogs with CIN. Arsenobetaine, an organic and relatively harmless species of arsenic, was the primary form of arsenic found in pet foods. In summary, the kidneys of domestic cats appear to have greater levels of pro-oxidant trace elements, as compared to dogs and wildcats. Since there was no difference in renal arsenic levels in cats with or without CIN, renal arsenic accumulation does not appear a primary driver of excess CIN in cats. Given clear differences in renal handling of pro vs. anti-oxidant minerals between cats and dogs, further in vivo balance studies are warranted. These may then inform species-specific guidelines for trace element incorporation into commercial diets.

Adjuvant therapy for true ampullary cancer: a systematic review.

BACKGROUND: Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes. MATERIALS AND METHODS: A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted. RESULTS: A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation. CONCLUSIONS: The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.

Treatment and Outcome of Patients with Stage IS Testicular Cancer: A Retrospective Study from the Spanish Germ Cell Cancer Group.

PURPOSE: Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or ß-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series. MATERIALS AND METHODS: We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment. RESULTS: The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, ß-human chorionic gonadotropin in 14%, and α-fetoprotein and ß-human chorionic gonadotropin in 38%. Median α-fetoprotein and ß-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85%, respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy. CONCLUSIONS: Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.

Correction to: SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016).

Due to a technical issue, the family name of the author.

Chemotherapy management for unfit patients with metastatic castration-resistant prostate cancer.

Administration of chemotherapy in prostate cancer depends on patient fitness. In unfit patients, physiological impairment determines the optimum treatment. Although no consensus on assessing patient fitness currently exists, this article proposes an algorithm combining the available information for administering chemotherapy, and in particular docetaxel, in unfit patients. It was constructed by reviewing factors that can influence treatment, such as performance status, taxane-related comorbidities and nutritional status. Geriatric scales for prostate cancer patients and alternative treatment regimens for this population are also reviewed. In summary, patients require overall assessment to optimise treatment. Use of docetaxel should be restricted in unfit patients, and other options must be evaluated, because of high toxicity and low efficacy.

SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018).

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

Prediction of transcription factor bindings sites affected by SNPs located at the osteopontin promoter.

This data contains information related to the research article entitled "Osteopontin splice variants and polymorphisms in Cancer Progression and Prognosis" [1]. Here, we describe an in silico analysis of transcription factors that could have altered binding to their DNA target sequence as a result of SNPs in the osteopontin gene promoter. We concentrated on SNPs associated with cancer risk and development. The analysis was performed with PROMO v3.0.2 software which incorporates TRANSFACT v6.4 of. We also present a figure depicting the putative transcription factor binding according to genotype.

Nutritional changes in patients with locally advanced head and neck cancer during treatment.

OBJECTIVE: The purpose of the study is to evaluate changes in body composition and nutritional status that occur throughout the oncological treatment in head and neck cancer patients. METHODS: A prospective cohort observational study in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) that underwent treatment with induction chemotherapy (iCT) followed by chemoradiotherapy or bioradiotherapy were invited to participate. All patients had dietetic counseling from the diagnosis and a close monitoring throughout the treatment implementing nutritional support as needed. RESULTS: From June 2011 until October 2012, 20 patients were included. Nutritional and anthropometric parameters were collected at diagnosis, post iCT, after radiotherapy, 1 and 3months post radiotherapy. According to Patient Generated Subjective Global Assessment, 30% of patients were malnourished at diagnosis. After iCT there was an increase in weight, body mass index (BMI) and fat free mass (FFM) with almost complete improvement in dysphagia and odynophagia. Nevertheless a significant nutritional deterioration (p=0.0022) occurred at the end of radiotherapy with 95% of patients becoming severe or moderate malnourished. Nutritional parameters such as weight, BMI and hand grip strength also decrease significantly during treatment. CONCLUSIONS: Despite an intensive nutritional support from the diagnosis throughout the oncological treatment in advanced HNSCC cancer patients, nutritional status deteriorates during radiotherapy. Our findings suggest that iCT may help improve nutritional status by ameliorating the symptoms that limit the oral intake. This improvement in the nutritional status could contribute to minimize further deterioration. Further investigations are needed involving novel approaches to avoid nutritional deterioration.

Skeletal anomalies in reared Senegalese sole Solea senegalensis juveniles: a radiographic approach.

Reared Senegalese sole Solea senegalensis Kaup show a high incidence of vertebral anomalies; however, little is known about its skeletal anomaly profile in the later farming phases. The purpose of this study was to provide a detailed description and quantification of the most common skeletal anomalies in reared Senegalese sole in the juvenile stage by means of computed radiography. A total of 374 Senegalese sole were classified according to the external morphology of the fish as normal or altered and then radiographed in latero-lateral and in dorso-ventral projections. Radiographic evaluation of anomalies focused especially on vertebral body anomalies (VBA) and vertebral column deviations (VCD). The 2 orthogonal projections provided a more complete visualization of the skeleton. Approximately 75% of the individuals showed at least 1 anomaly, while VBA and/or VCD were detected in 48.9% of the specimens. Regarding external morphology, 88% of the fish were categorized as normal, although about 72% of these normal fish displayed abnormalities in radiographies. The most frequent anomalies consisted of deformations of the caudal complex plates (hypurals, parhypural and epural), preurals and caudal vertebrae. Scoliosis was the most prevalent among VCD, affecting the caudal area in almost 15% of the individuals. The anomaly profile at the juvenile stages showed some differences compared to what has been reported previously in earlier stages of development. In light of these results, further investigation into the progression of skeletal anomalies over time and the causative factors at later stages is required.

Osteopontin splice variants and polymorphisms in cancer progression and prognosis.

Osteopontin (OPN) is an extracellular matrix protein that is overexpressed in various cancers and promotes oncogenic features including cell proliferation, survival, migration, and angiogenesis, among others. OPN can participate in the regulation of the tumor microenvironment, affecting both cancer and neighboring cells. Here, we review the roles of OPN splice variants (a, b, c) in cancer development, progression, and prognosis, and also discuss the identities of isoforms 4 and 5. We also discussed how single-nucleotide polymorphisms (SNPs) of the OPN gene are an additional factor influencing the level of OPN in individuals, modulating the risks of cancer development and outcome.

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.