Unilateral Tumor Research Articles

Synergistic Effects of Nanoscale CaO2 Combined with PD-1 Inhibitors in the Treatment of Hepatocellular Carcinoma: A Promising Combination.

To explore the effect of calcium peroxide nanoparticles (CaO2 NPs) combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of liver cancer and its related mechanism. Hepa1-6 cells were cultured to construct the Hepa1-6 mouse liver cancer model. In vivo mechanism study, a unilateral tumor model was established. Eighteen tumor-bearing mice were randomly divided into the control group (intra-tumoral injection of PBS solution) and the experimental group (intra-tumoral injection of CaO2 NPs). A hypoxic probe, pH probe, and micro-CT were used to evaluate the effect of CaO2 NPs on improving hypoxia, neutralizing acidity, and inducing calcium overload within the tumor. To study the effect of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors, the bilateral tumor model was established. Forty tumor-bearing mice were randomly divided into the control group (intra-tumoral/intra-peritoneal injection of PBS solution), CaO2 NPs group (intra-tumoral injection of CaO2 NPs), PD-1 group (intra-peritoneal injection of PD-1 inhibitor), and the combination group (intra-tumoral injection of CaO2 NPs and intra-peritoneal injection of PD-1 inhibitors). The administered side was recorded as the proximal tumor. Tumor volume and body weight were measured every 2 days after treatment. On day 8, serum and tumor samples were collected. The immune factors in serum (Interferon-γ (IFN-γ), Tumour necrosis factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-10 (IL-10)) and tumor tissue (IFN-γ and TNF-α) were detected by ELISA. H&E staining was used to detect tumor necrosis. Immunohistochemical staining was used to detect the amount of CD4+ and CD8+ T cells within the tumor. By analyzing the tumor volume, pathological indexes, and immune-related indexes, the effects of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors were evaluated, and they mediated immunomodulatory effects (including local and systemic immunity), and their effects on tumor burden were studied. In addition, a unilateral tumor model was established to study the effect of CaO2 NPs combined with PD-1 inhibitors on survival time. The results of in vivo mechanism study showed that CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors. The results of the study on the effect of CaO2 NPs combined with PD-1 inhibitor on proximal and distal tumors showed that, compared with the other three groups, the bilateral tumor burden of the combination group was significantly reduced, the intra-tumoral infiltration of CD8+ and CD4+ T cells were significantly increased, the secretion of anti-tumor immune factors in tumor and serum was increased, and the secretion of pro-tumor immune factors was decreased. Mice in the combination group showed the longest survival compared with the other groups. CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors, so as to reduce tumor burden and realize an immunosuppressive tumor transformation to a hot tumor, and play a synergistic role with PD-1 inhibitors in anti-liver cancer.

Efficacy and late kidney effects of nephron-sparing surgery in the management of unilateral Wilms tumor: a systematic review and meta-analysis.

To evaluate the efficiency and long-term renal function of nephron sparing surgery (NSS) in unilateral WT patients compared with radical nephrectomy (RN). The review was performed following Cochrane Handbook guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched five databases (Pubmed, Embase, Scopus, Web of Science and Cochrane) for studies reporting the efficiency and late renal function of NSS and/or RN on February 10, 2023. Comparative studies were evaluated by Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) and RoB 2.0. Assessed outcomes included survival rate, relapse rate, eGFR, renal dysfunction and hypertension. 26 studies involving 10322 unilateral WT cases underwent RN and 657 unilateral WT cases underwent NSS were enrolled. Overall effect estimates demonstrated thatNSS significantly increased eGFR at follow-up (SMD, 0.38; 95% CI 0.05-0.72; p=0.025) compared to that at diagnosis, and RN did not significantly decrease eGFR at follow-up (SMD, -0.33; 95% CI -0.77-0.11; p=0.142) compared to that at diagnosis. Moreover, no significant difference was found in outcomes of survivability (OR, 1.38; 95% CI 0.82-2.32; p =0.226), recurrence (OR, 0.62; 95% CI 0.34-1.12; p = 0.114), eGFR at follow-up (SMD, 0.16; 95% CI -0.36-0.69; p = 0.538), renal dysfunction (OR, 0.36; 95% CI 0.07-1.73; p = 0.200) and hypertension (OR, 0.17; 95% CI 0.03-1.10; p = 0.063). Current evidence suggests that NSS is safe and effective for unilateral WT patients, because it causes better renal function and similar oncological outcomes compared with RN. Future efforts to conduct more high-quality studies and explore sources of heterogeneity is recommended.

Correlation between bilateral GFR in patients with localized renal cancer after partial nephrectomy.

To explore the relationship between the residual glomerular filtration rate (GFR) on the operated side and the GFR on the contralateral side following partial nephrectomy (PN) in patients with localized renal cell carcinoma (RCC). Following institutional review board approval, we conducted a retrospective analysis of clinical records from May 2018 to July 2023, involving 118 patients who underwent partial nephrectomy for unilateral localized kidney tumors (T1-T2). Glomerular filtration rate data were assessed using single photon emission computed tomography (SPECT)/computed tomography imaging [using 9mTc-DTPA (diethylenetriaminepentaacetic acid) renal dynamic imaging]. The independent determinants of postoperative renal function or renal function change were determined using linear regression analysis. In addition, the patient's demographic, clinical, and nephrometry characteristics were collected. A total of 58 patients were finally enrolled. The preoperative and postoperative GFR of bilateral kidneys showed a significant positive correlation. Postoperative GFR of the operated kidney was the independent predictor of GFR of contralateral kidney (p = 0.001). Tumor diameter (p = 0.036), age (p = 0.005), and postoperative GFR of the contralateral kidney (p = 0.001) were all independent predictors of postoperative GFR of the operated kidney. ΔGFR1 was the independent predictor of ΔGFR2. Results showed that a more pronounced postoperative decline in GFR on the operated side corresponded to a weaker compensatory capacity of the contralateral-side kidney. During the course of the surgical procedure, the active endeavor to safeguard the renal function of the operated kidney side holds paramount importance, which yields positive outcomes for postoperative kidney function on the contralateral side, consequently contributing to the overall preservation of renal function.

Associations between R.E.N.A.L. nephrometry score and survival outcomes in renal tumours.

The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P <0.001; recurrence-free survival , P <0.001), E (exophytic/endophytic) (overall survival, P =0.003; recurrence-free survival, P <0.001), N (nearness) (overall survival, P =0.063; recurrence-free survival, P <0.001), A (anterior/posterior) (overall survival, P <0.001; recurrence-free survival, P =0.005), L (location) (overall survival, P =0.008; recurrence-free survival, P <0.001) and suffix 'h' (overall survival, P =0.237; recurrence-free survival, P =0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P <0.001; recurrence-free survival, P <0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P =0.027, hazard ratio (95% confidence interval)=1.151 (1.016-1.303)] and recurrence-free survival [P <0.001, hazard ratio (95% confidence interval)=1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.

Potent induction of antitumor immunity by combining cryo-thermal ablation with immune checkpoint inhibitors in hepatocellular carcinoma.

The low response rate of immune checkpoint inhibitors (ICIs) prompts the exploration of novel combination therapies for patients with hepatocellular carcinoma (HCC). Here, we aimed to examine the efficiency and potential mechanism of cryo-thermal ablation (Cryo-A) combined with anti-programmed death protein 1 (αPD1) and/or cytotoxic T-lymphocyte antigen 4 (αCTLA4) inhibitors in a murine hepatoma model. Immunocompetent C57BL/6 mice inoculated with unilateral or bilateral H22 hepatic tumour cells were treated with Cryo-A and/or ICIs (αPD1 and/or αCTLA4). Flow cytometry, immunohistochemistry, ELISpot assay, time-of-flight cytometry, tumour rechallenging, and T-cell depletion assay were used to assess the dynamic changes of immune cell subsets following therapy. We found Cryo-A resulted in immunogenic cell death of tumour cells, activation of dendritic cells, and enhancement of antitumor immunity. Cryo-A alone was insufficient to extend survival, combining Cryo-A with αPD1 and αCTLA4 further modulated the tumour microenvironment, inducing a durable antitumor immune response by tumour-reactive CD8+ T cells and significantly prolonged survival. Time-of-flight cytometry (CyTOF) data revealed that combination therapies reshaped the tumour microenvironment by the increase of intratumoral CD8+ T cells expressed higher levels of cytotoxic markers and immune checkpoint molecules, and by downregulation of intratumoral granulocytes. The combination also resulted in the eradication of remote unablated tumours (abscopal effect). These findings suggested that Cryo-A turned HCC from "cold" tumours to "hot" tumours and the combination of Cryo-A with αPD1 and αCTLA4 may be a promising approach to improve the prognosis of HCC.

A Rare Case of Sinonasal Seromucinous Hamartoma Developing from the Nasal Septum.

A 45-year-old man presented with a history of chronic left nasal congestion. Nasal endoscopy revealed a pedunculated polypoid mass with glandular epithelium surface on the posterior nasal septum. Computed tomography revealed a 25-mm mass-like growth in the left posterior nasal cavity attached to the nasal septum with a stalk. The patient underwent transnasal endoscopic surgery, and the tumor was removed under a block with safety margin. The final pathological diagnosis was sinonasal seromucinous hamartoma (SH). Sinonasal SH is a rare tumor with only 31 reported cases. Transnasal endoscopic surgery is currently the first-line treatment for sinonasal SH. Differential diagnoses of this lesion include inflammatory polyps, respiratory epithelial adenomatoid hamartoma, and adenocarcinoma. Although SH is a benign tumor, its progression to adenocarcinoma has been reported. Therefore, unilateral posterior nasal tumors must be diagnosed precisely.

Prognostic impact of pre-referral tumor resection in unilateral Wilms tumor: A single-institute experience from a lower middle-income country.

The objectives of this study were to evaluate the prognostic impact of pre-referral surgical resection of Wilms tumor (WT) performed at non-oncology centers, and to strategize an improved care plan for this very curable pediatric tumor. In this study conducted in a large pediatric cancer center in Pakistan, we retrospectively reviewed the electronic medical records (EMR) of 149 patients with unilateral WT from September 2008 to August 2017. Based on treatment approach, patients were categorized into two groups: (i) pre-referral tumor resection (PTR: n=75), and (ii) post-neoadjuvant chemo nephrectomy (PCN: n=74). The proportion of metastatic disease in PTR and PCN groups was 33.3% and 35.1%, respectively. In the PTR subset, median time to admission after PTR was 5weeks (mean 11, SEM 2.8, range: 2-202) weeks, with 53.3% (n=40) presenting more than 4weeks after PTR. Twenty patients had no cross-sectional imaging prior to PTR and underwent surgery after abdominal ultrasound only. On baseline imaging at our center, 58.7% (n=44) of the PTR group had radiologically evaluable disease (four metastases only, 19 local residual tumor only, 21 both localized tumor and visible metastases). Disease staging was uncertain in 23 patients because of no or inadequate histology specimens and/or lymph node sampling in patients with no evaluable disease. Statistically significant differences were recorded for the two subsets regarding tumor volume, extent and nodularity, renal vein and renal sinus involvement, lymph node status, tumor rupture and histopathologic features, and tumor stage, with a 10-year event-free survival (EFS) for PCN and PTR of 74.3% and 50.7%, respectively (p<.001). In the PTR group, EFS for those presenting within 4weeks and later was 91.4% versus 15.0%, respectively (p<.0001). Suboptimal pre-referral surgical intervention results in poor survival outcomes in unilateral WT. Our findings highlight the need for a comprehensive action plan for educating healthcare professionals engaged in WT diagnosis and referral process. PCN in a multidisciplinary team approach can reduce surgical morbidity and seems to be a better strategy to improve the survival rates in low-resource settings.

Nephrectomy for Pediatric Renal Tumors: A Modified Surgical Approach to Minimize Post-operative Intestinal Obstruction

BackgroundThe authors present a modified surgical technique during tumor nephrectomy in children with a conservative approach towards small bowel manipulation and cutting of the peritoneal reflections. We aimed to evaluate this modified surgical approach regarding the incidence of post-operative small bowel obstruction (SBO), and its technical utility. MethodsThe study includes all children with unilateral renal tumors who underwent radical nephrectomy and lymph nodes sampling at our tertiary center from 2010 to 2022. The modified technique was performed via the usual transverse incision. We cut the peritoneal reflections short of the cecum or short of the sigmoid colon. The colon is reflected over SB packing it, proceeding to nephrectomy and lymph nodes sampling. Data included demographics, clinical characteristics, treatment strategy, operative details, post-operative SBO, and overall outcomes. ResultsThe study included 890 patients with a median age of 3.2 years. The median tumor largest diameter was 13 cm (range: 9–18 cm). The modified surgical technique was adopted in 287 patients (32.3 %). Forty-three patients (43/890, 4.8 %) had post-operative SBO. Out of them, only 4 cases were operated on using the modified surgical technique (p-value<0.001). There were no significant differences between both techniques regarding timing of surgery, tumor rupture, lymph nodes sampling, and tumor size (p-value = 0.775, 0.328, 0.216, and 0.563, respectively). ConclusionsThe modified surgical approach is significantly correlated with lower incidence of post-operative SBO with no increased risk of tumor rupture or incomplete lymph nodes sampling. The timing of surgery or tumor characteristics had no significant impact on the technical utility of the modified surgical approach. Level of EvidenceLevel IV.

Our Experience in Managing Carotid Body Tumors in Tertiary Care Center

Abstract Introduction: Carotid body tumors (CBTs), also known as paragangliomas or chemodectomas, are rare neuroendocrine neoplasms that arise near the carotid bifurcation within glomus cells derived from the embryonic neural crest. The reported incidence of CBTs is 1–2 cases per 1 lakh cases. Surgery is the mainstay of treatment. Objectives: The objective of this study was to report our experience and describe the presentation, surgical approach, postoperative complications, and outcomes of surgical treatment. Materials and Methods: It is a single-institution experience where a retrospective analysis of 6 cases with CBTs of patients who were candidates for surgery from June 2018 to June 2021 with a mean follow-up period of 24 months was done. Results: The mean age was 37 years, with a female predominance of 66%. The mean size of the tumor was 4.4 ± 1 cm. Four (66%) cases were presented with pain and pulsating neck swelling, and 2 (33%) cases were incidentally detected. All the cases were unilateral tumors. Neck ultrasound was done in all cases as a primary investigation. Magnetic resonance imaging was performed in 5 (87.5%) cases, which revealed tumors having near circumferentially encasing the internal carotid artery (ICA). No cases were malignant. All cases were surgically approached through transcervical vertical incision. Four cases (66%) and 2 (33%) cases were classified as Shamblin’s type II and III, respectively. Two (33%) cases needed special maneuvers such as division of the posterior belly of digastric and nasal intubation for the extra length of ICA. No major complications occurred. One patient (16.6%), as the tumor could not be dissected from the adventitia of ICA so, had to resect it, and primary end-to-end anastomosis was done. External carotid artery ligation was performed in 1 (16.6%) case. Minor postoperative complications such as hoarseness of voice occurred in 2 (33%) patients. No operative mortality occurred. Conclusion: We found a predominance of women and pain as the most common presenting complaint. Resection of CBTs by surgeons with experience in vascular reconstruction is recommended. Early surgical management is recommended to avoid neurological deficit or vascular reconstruction due to a Shamblin’s class III tumor. Preferred approach was caudo–cranial during dissection. Cranial nerve injury continues to be the most common complication.

Critical elements of radical nephroureterectomy for pediatric unilateral renal tumor

Children with renal masses require surgical management to provide accurate surgical staging and skilled resection of the tumor. This document includes evidence-based recommendations for pediatric surgeons regarding the resection, staging, and proper nodal basin evaluation.

Genotype-specific precision tumor therapy using mitochondrial DNA mutation-induced drug release system.

Precise killing of tumor cells without affecting surrounding normal cells is a challenge. Mitochondrial DNA (mtDNA) mutations, a common genetic variant in cancer, can directly affect metabolic homeostasis, serving as an ideal regulatory switch for precise tumor therapy. Here, we designed a mutation-induced drug release system (MIDRS), using the single-nucleotide variation (SNV) recognition ability and trans-cleavage activity of Cas12a to convert tumor-specific mtDNA mutations into a regulatory switch for intracellular drug release, realizing precise tumor cell killing. Using Ce6 as a model drug, MIDRS enabled organelle-level photodynamic therapy, triggering innate and adaptive immunity simultaneously. In vivo evaluation showed that MIDRSMT could identify tumor tissue carrying SNVs in mtDNA in unilateral, bilateral, and heterogeneous tumor models, producing an excellent antitumor effect (~82.6%) without affecting normal cells and thus resulting in a stronger systemic antitumor immune response. Additionally, MIDRS was suitable for genotype-specific precision drug release of chemotherapeutic drugs. This strategy holds promise for mutation-specific personalized tumor treatment approaches.

Survival prognosis model for elderly women with epithelial ovarian cancer based on the SEER database.

We aimed to analyze the risk factors of elderly women with epithelial ovarian cancer (EOC) using data on the SEER database, and to generate a nomogram model their 1-, 3-, and 5-year prognoses. The resulting nomogram model should be useful for clinical diagnoses and treatment. We collected clinical data of women older than 70 years with epithelial ovarian cancer (diagnosed on the basis of surgical pathology) from the SEER database including datasets between 2010 and 2019. We randomly grouped the data into two groups (7:3 ratio) using the R language software. We divided the independent prognostic factors obtained by univariate and multi-factor Cox regression analyses into training and validation sets, and we plotted the same independent prognostic factors in a nomogram model of overall survival (OS) at 1, 3, and 5 years. We used the C-index, calibration curve, and area under the curve to validate the nomograms. We further evaluated the model and its clinical applicability using decision curve analyses. We identified age, race, marital status, histological type, AJCC staging, differentiation degree, unilateral and bilateral tumor involvement, number of positive lymph nodes, chemotherapy, surgery, sequence of systemic treatment versus surgery, and time from diagnosis to treatment as independent prognostic factors for elderly women with EOC (P < 0.5). The C-indexes were 0.749 and 0.735 in the training and validation sets, respectively; the ROC curves showed that the AUC of each prognostic factor was greater than 0.7; and, the AUC values predicted by the line plot were similar in the training and validation sets. The decision curves suggest that this line plot model has a high clinical value for predicting overall survivals at 1, 3, and 5 years in elderly women with EOC. The nomogram model in this study can provide an accurate assessment of the overall survival of women older than 70 years with EOC at the time of the first treatment, and it provides a basis for individualized clinical treatment.

Enhanced Peroxide Fluxes and Radiosensitization in Colorectal Tumors but Not Normal Enterocytes from the Combination of Superoxide Dismutase Mimetics and Pharmacological Ascorbate

Selective superoxide dismutase mimetics (DMs), including GC4419 and GC4711, are radiation (RT) modulators which induce opposite effects in tumors and normal tissues and may be ideally suited for locally advanced rectal cancer. However, their tumor radiosensitization effect is limited at RT doses relevant to rectal cancer (2-5 Gy). Over this dose range, they protect normal mucosal tissues, but we and others have shown they do not reliably enhance tumor radiosensitization at doses < 8-15 Gy. We hypothesize that combining DMs and other therapies which also target redox metabolism may effectively sensitize tumors to clinically relevant RT doses for rectal cancer while maintaining their normal tissue sparing effects. Like DMs, pharmacological ascorbate (P-AscH) selectively increases lethal hydrogen peroxide (H2O2) fluxes in tumors, but it does so through distinct mechanisms which are potentially complimentary with DMs (particularly at low RT doses). Human HCT116, SW480, and HT29 colorectal tumor models and non-malignant FHs74 intestinal epithelial cells were used. Clonogenic survival was assessed following single-fraction RT (2-5 Gy) +/- P-AscH (5 pmol/cell) +/- GC4711 (20 µM). Dependency on H202 fluxes was tested by adding bovine catalase with drug and RT treatments. Oxygen consumption in culture media was measured using a Clark electrode. Rectal toxicity was assessed in vivo using IHC in fixed rectal tissues following fractionated, image-guided rectal RT (5-9 Gy x 3). Tumor growth delay was assessed following RT (5 Gy x 3) +/- P-AscH (4 g/kg) +/- GC4419 (10 mg/kg) in animals with unilateral HCT116 flank tumors. Combination therapy with P-AscH and GC4711 potently radiosensitized all tumor lines in vitro whereas neither agent significantly decreased clonogenic survival as a monotherapy. Neither drug nor combination treatment sensitized FHs74 epithelial cells. P-AscH increased oxygen consumption and H2O2 production in culture media and the addition of GC4711 significantly increased both more than P-AscH alone. Co-treatment with exogenous catalase inhibited cancer cell killing with combination therapy +/- RT. In vivo, combination therapy significantly enhanced tumor growth delay and survival. Both agents significantly decreased markers of acute rectal RT injury as monotherapies. Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H202 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors.

Discordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers.

Oncotype DX, a 21-gene expression profiling test, has become standard of care in the management of estrogen receptor (ER)-positive breast cancer. In multifocal tumors, it is unclear whether testing of the different foci is necessary. We evaluated the concordance of Oncotype DX recurrence scores (RS) between 2 tumor foci in synchronous bilateral or unilateral multifocal tumors and characterized pathological predictors of discordance. We reviewed 713 ER+, HER2- primary invasive breast cancer patients with Oncotype RS and identified 17 bilateral synchronous patients (34 tumors) and 13 unilateral multifocal patients (26 tumors) with available Oncotype RS on all foci. Discordance in Oncotype RS between synchronous tumors was recorded and associations with clinicopathologic features including tumor size, histology, Nottingham histologic grade, progesterone receptor staining, and Ki67 index were analyzed. Bilateral synchronous tumors were present in older patients (median age 59years) and had larger tumor (median size 17mm) and more discordant histology (10/17, 59%) as compared to unilateral multifocal tumors (median age 49years, p < 0.01; median tumor size 12mm, p = 0.01; discordant histology 2/13, 15%, p = 0.03). Oncotype RS were discordant in 47% (8/17) of bilateral and 54% (7/13) of unilateral multifocal tumors. Concordant Oncotype RS was associated with similar histologic grade and Ki67 index in 78% (7/9) of bilateral and 100% (6/6) of multifocal tumors. In contrast, only 25% (2/8) of bilateral (p = 0.06) and 14% (1/7) of unilateral multifocal (p < 0.01) cases with discordant Oncotype RS had concordant histology grades and Ki67 levels. In synchronous tumors with discordant Oncotype RS and Ki67 index, all (4/4) foci with higher RS had higher Ki67 index. Discordance of Oncotype RS is common in both bilateral and unilateral multifocal breast cancer and is likely associated with discordant histologic grade or Ki67.

Extended partial laryngectomy with functional preservation using the rotational crico-thyrotracheopexy.

Glottic tumors with infiltration of the anterior/posterior commissure, and lesions with subglottic, cricoid, or cricoarytenoid joint infiltration have been highly controversial in the past, from the perspective of oncological safety. Although conservation laryngeal resection options exist, most are limited by the extent of resection proscribed by the technique and the postoperative functional results. Oncologically speaking, extended vertical hemilaryngectomy is often the optimal solution. However, limited reconstruction methods often compel total laryngectomy. Eight patients with vocal fold malignancy, which infiltrated the anterior and sometimes the posterior commissure and with subglottic extension and resultant uni/bilateral vocal fold motion impairment, were treated by single stage extended vertical partial laryngectomy with rotational crico-thyrotracheopexy as a functional reconstruction of the laryngeal framework. Patients were evaluated with objective and subjective function tests. Histologic examination demonstrated tumor-free margins in every case. Definitive decannulation was successful in all cases within 2 weeks. All patients had a stable and adequate airway during follow-up and reported socially acceptable voice. Oral feeding was possible in seven patients. Rotational crico-thyrotracheopexy, as a single stage reconstruction technique, is based on well-vascularized, readily available, appropriately shaped local tissues, without significant donor site morbidity or need for long-term stenting to reconstruct large laryngeal defects after extended vertical hemilaryngectomy for advanced unilateral glottic tumors and is applicable even with supra/subglottic invasion or infiltration of the contralateral vocal fold. An adequate airway can be achieved with socially acceptable voice and safe swallowing without compromising oncologic reliability. 4 (retrospective case series review).

Assessment of the kidney functional state prior and after partial nephrectomy for a unilateral tumor using mathematical processing of computed tomography data with contrast enhancement

Background. According to the contemporary data available contrast-enhanced computed tomography can be used to assess total and split kidney function. The Urology Clinic of the I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University) utilizes mathematical processing of computed tomography data for the assessment of split kidney function.Aim. To evaluate the effect of main renal artery clamping (warm ischemia time) during partial nephrectomy for a unilateral tumor on the kidney function.Materials and methods. 33 patients of both sexes who underwent partial nephrectomy for unilateral kidney tumor were enrolled in the study. Prior to and 3–6 months after the surgery, 3D glomerular filtration rate (GFR), 3D perfusion, 3D volume of the renal parenchyma were evaluated by mathematical processing of computed tomography data with contrast enhancement. As well as that the dynamics of the total GFR (CKD-EPI equation) and total volume of the kidneys were assessed.Results. No significant changes were registered for both general functional renal parameters (creatinine level, total GFR, total volume of functioning renal parenchyma) and split 3D GFR. There were significant differences in 3D perfusion and kidney parenchyma volume prior and after partial nephrectomy.Conclusion. The results of the research highlight good reserve capacity the kidneys after partial nephrectomy with main renal artery clamping. The evidence that the non-operated kidney takes over the function of the resected kidney is based on the fact that there is an increase in its perfusion and volume of the kidney in the postoperative period. This state can also be regarded as a redistribution of functional loads between the kidneys, which is an adaptive mechanism in the postoperative period.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

The rationale for nephron-sparing surgery in unilateral non-syndromic Wilms tumour.

The central question of nephron-sparing surgery in unilateral non-syndromic Wilms tumour sits at a crossroads between surgery, oncology, and nephrology. There has been a significant paradigm shift in paediatric oncology towards reducing toxicity and addressing long-term treatment-related sequalae amongst childhood cancer survivors. After paediatric nephrectomy and 30-50years of follow-up, 40% of patients will have chronic kidney disease, including 22% with hypertension and 23% with albuminuria. It is difficult to predict which patients will progress to develop hypertension, reduced glomerular filtration rate, albuminuria, and a higher cardiovascular risk. For these reasons, nephron-sparing surgery when it is technically feasible must be considered. To decrease the incidence of positive surgical margins (viable tumour present at a resection margin), incomplete lymph node sampling, and complications, these procedures should be performed at specialist and experienced reference centres. Based on the impacts of individual treatment pathways, survivors of childhood WT need to be followed through adulthood for early detection of chronic kidney disease, hypertension, and prevention of cardiovascular events.

Robot-assisted Simple Enucleation Versus Standard Robot-assisted Partial Nephrectomy for Low- or Intermediate-complexity, Clinical T1 Renal Tumors: A Randomized Controlled Noninferiority Trial

BackgroundAlthough partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. ObjectiveTo compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. Design, setting, and participantsThis is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18–80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). Outcome measurements and statistical analysisWe defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. Results and limitationsA cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference −0.7%, 95% CI −4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). ConclusionsRASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. Patient summaryWe carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.

Correlation between 3D morphometric characteristics of kidney tumors and their histological structure

Aim. To assess the correlation between clinical characteristics (sex, age, and maximum tumor size), 3D morphometric characteristics of renal lesions obtained through processing of multispiral computed tomography data, and renal tumor histology.Materials and methods. Evaluation of kidney tumor malignancy on the basis of comparative analysis of primarily morphometric characteristics of the lesion obtained through processing of multispiral computed tomography data and histological tumor structure is presented. Data of 308 patients (175 (56.8 %) males and 133 (43.2 %) females) with unilateral renal tumors were analyzed.Results. Multivariable analysis showed that malignancy of kidney tumor is associated with sex (male), location in the middle segment, tumor size, tumor shape (spherical with conical base) (24.8 %), while mushroom-like lesion shape was more common in benign tumors (35.2 %). In univariate models, only two variables were statistically significant predictors: patient sex and tumor shape.Conclusion. The developed logistic model based on analysis of such predictors as sex and kidney tumor shape has a high percentage (87.6 %) of correct predictions of tumor histological structure.