Search Results (22)

Background/Objectives: This retrospective study evaluates the predictive role of magnetic resonance imaging (MRI) in complications and recurrence in rectal cancer patients undergoing surgery and neoadjuvant therapy, highlighting the impact of structured reporting templates on MRI quality. Compared to traditional free-text reports, structured radiology reports offer a point-by-point evaluation, improving clarity and completeness by thoroughly addressing all relevant findings. MRI is critical in rectal cancer staging, guiding treatment based on tumor characteristics like T stage, sphincter involvement, vascular invasion, and lymph node status. Methods: A retrospective analysis of MRI and reports from 67 rectal cancer patients at the time of diagnosis, who were subsequently treated with neoadjuvant radiochemotherapy and surgery, was conducted. MRI report features, including tumor location, morphology, T stage, sphincter infiltration, mesorectal fascia involvement, lymph nodes, and extramural vascular invasion, were evaluated against European Society of Gastrointestinal and Abdominal Radiology (ESGAR) recommendations. Multivariate and univariate analyses were performed to correlate MRI findings with postoperative outcomes such as complications, local recurrence, bleeding, and 30-day anastomotic leaks. Results: Sphincter involvement showed a strong association with increased complications (multivariate β = 0.410, univariate r = 0.270). Extramural vascular invasion was linked to higher rates of local recurrence (multivariate β = 0.199, univariate r = 0.127). Lymph node involvement correlated with an elevated risk of postoperative bleeding (multivariate β = 0.133, univariate r = 0.293). Additionally, advanced T staging predicted a higher incidence of 30-day anastomotic leaks (multivariate β = 0.210, univariate r = 0.261). These findings may provide clinically relevant insights to support personalized surgical planning and improve preoperative risk stratification. Conclusions: Detailed MRI reporting, aligned with structured templates, significantly guides surgical and therapeutic strategies in rectal cancer management. However, the retrospective nature of the study and the limited sample size may affect the generalizability of the results. Full article

Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may provide a favorable alternative to surgery. Methods: Sixty-one patients with esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Pre-treatment staging included computed tomography, gastroscopy with biopsy, and comprehensive laboratory evaluations. Patients received preoperative CRT following the CROSS or dCRT protocols based on tumor stage. Surgical approaches included staged esophagectomy or single-stage Ivor Lewis procedures. Four patients declined surgery and were treated with dCRT. Postoperative outcomes were evaluated using pTNM classification. Follow-up included imaging and endoscopic surveillance. Statistical analyses assessed changes in staging and factors influencing treatment outcomes. Results: CRT significantly reduced T stage across the entire cohort (p = 0.0002), with complete pathological response (pT0N0M0) observed in 54.5% of patients following induction CRT (p = 0.0001). Male patients demonstrated a significant reduction in T stage (p = 0.0008), while a similar trend in females was not significant (p = 0.068). Among patients declining surgery, dCRT demonstrated acceptable oncologic control over a mean follow-up of 4 ± 0.79 years. Conclusions: Preoperative CRT effectively downstages EC and achieves high rates of response, especially in male patients. Therefore, dCRT may be a viable alternative in selected patients, emphasizing the need for individualized treatment strategies to optimize outcomes. These findings underscore the importance of refining multimodal approaches in EC care. Full article

Purpose: Multimodal approaches, including radiochemotherapy and surgical resection, are commonly used to treat rectal malignancies. Postoperative perineal hernias, though not uncommon, have shown an increasing incidence in recent years. Managing symptomatic perineal hernias presents a challenge, with a high recurrence rate after repair. This retrospective study investigates the laparoscopic placement of a non-absorbable mesh for treating pelvic floor hernias involving bowel displacement. Methods: This study included all consecutive patients requiring hernia repair due to symptomatic perineal hernias following minimally invasive abdominoperineal resection. All patients had a history of local radiation therapy. Data were collected on surgery duration, intra- and postoperative complications, and hernia recurrence rates. Results: Laparoscopic displacement of the small bowel from the pelvis was performed on eight patients, and closure of the pelvic floor hernia area was achieved using non-absorbable mesh placement. All procedures were successful, and no perioperative complications were recorded. Only one early complication occurred, classified as Clavien-Dindo II. Conclusions: The laparoscopic procedure, serving as a safe method for repositioning the small intestine and closing a perineal hernia using a mesh, has shown promising outcomes. The use of a non-absorbable mesh as an alternative to native tissue appears to be effective, with no observed recurrent hernias. However, further evaluation through long-term results or a larger cohort study is still pending. Full article

(1) Background: The sensitivity of head and neck squamous cell carcinoma (HNSCC) to ionizing radiation, among others, is determined by the number of cells with high clonogenic potential and stem-like features. These cellular characteristics are dynamically regulated in response to treatment and may lead to an enrichment of radioresistant cells with a cancer stem cell (CSC) phenotype. Epigenetic mechanisms, particularly DNA and histone methylation, are key regulators of gene-specific transcription and cellular plasticity. Therefore, we hypothesized that specific epigenetic targeting may prevent irradiation-induced plasticity and may sensitize HNSCC cells to radiotherapy. (2) Methods: We compared the DNA methylome and intracellular concentrations of tricarboxylic acid cycle metabolites in radioresistant FaDu and Cal33 cell lines with their parental controls, as well as aldehyde dehydrogenase (ALDH)-positive CSCs with negative controls. Moreover, we conducted a screen of a chemical library targeting enzymes involved in epigenetic regulation in combination with irradiation and analyzed the clonogenic potential, sphere formation, and DNA repair capacity to identify compounds with both radiosensitizing and CSC-targeting potential. (3) Results: We identified the histone demethylase inhibitor GSK-J1, which targets UTX (KDM6A) and JMJD3 (KDM6B), leading to increased H3K27 trimethylation, heterochromatin formation, and gene silencing. The clonogenic survival assay after siRNA-mediated knock-down of both genes radiosensitized Cal33 and SAS cell lines. Moreover, high KDM6A expression in tissue sections of patients with HNSCC was associated with improved locoregional control after primary (n = 137) and post-operative (n = 187) radio/chemotherapy. Conversely, high KDM6B expression was a prognostic factor for reduced overall survival. (4) Conclusions: Within this study, we investigated cellular and molecular mechanisms underlying irradiation-induced cellular plasticity, a key inducer of radioresistance, with a focus on epigenetic alterations. We identified UTX (KDM6A) as a putative prognostic and therapeutic target for HNSCC patients treated with radiotherapy. Full article

Medulloblastoma (MB) comprises four broad molecular subgroups, namely wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively, with subgroup-specific developmental origins, unique genetic profiles, distinct clinico-demographic characteristics, and diverse clinical outcomes. This is a retrospective audit of clinical outcomes in molecularly confirmed WNT-MB patients treated with maximal safe resection followed by postoperative standard-of-care risk-stratified adjuvant radio(chemo)therapy at a tertiary-care comprehensive cancer centre. Of the 74 WNT-MB patients registered in a neuro-oncology unit between 2004 to 2020, 7 patients accrued on a prospective clinical trial of treatment deintensification were excluded, leaving 67 patients that constitute the present study cohort. The median age at presentation was 12 years, with a male preponderance (2:1). The survival analysis was restricted to 61 patients and excluded 6 patients (1 postoperative mortality plus 5 without adequate details of treatment or outcomes). At a median follow-up of 72 months, Kaplan–Meier estimates of 5-year progression-free survival and overall survival were 87.7% and 91.2%, respectively. Traditional high-risk features, large residual tumour (≥1.5 cm²), and leptomeningeal metastases (M+) did not significantly impact upon survival in this molecularly characterized WNT-MB cohort treated with risk-stratified contemporary multimodality therapy. The lack of a prognostic impact of conventional high-risk features suggests the need for refined risk stratification and potential deintensification of therapy. Full article

Introduction: Cervical cancer is among the most frequent types of neoplasia worldwide and remains the fourth leading cause of cancer death in women, a fact that raises the necessity for further development of therapeutic strategies. NCCN guidelines recommend radiation therapy with or without chemotherapy as the gold standard for locally advanced cervical cancer. Also, some studies claim that performing surgery after chemo-radiation therapy does not necessarily improve the therapeutic outcome. This study aims to determine the impact of the risk factors, various characteristics, and surgical treatment for patients in different stages of the disease on survival rate. Material and methods: Our study started as a retrospective, observational, unicentric one, carried out on a cohort of 96 patients diagnosed with cervical cancer from the surgical department of the Bucharest Oncological Institute, followed from 1 January 2019 for a period of 3 years. After the registration of the initial parameters, however, the study became prospective, as the patients were closely monitored through periodical check-ups. The end-point of the study is either the death of the participants or reaching the end of the follow-up period, and, therefore, we divided the cohort into two subgroups: the ones who survived after three years and the ones who did not. All 96 patients, with disease stages ranging from IA2 to IIIB, underwent radio-chemotherapy followed by adjuvant surgery. Results: Among the 96 patients, 45 (46%) presented residual tumor after radio-chemotherapy. Five patients (5%) presented positive resection margins at the post-operative histopathological examination. The presence of residual tumor, the FIGO stage post-radiotherapy, positive resection margins, and lympho-vascular and stromal invasions differed significantly between the subgroups, being more represented in the subgroup that reached the end-point. Variables correlated with the worst survival in Kaplan–Meier were the pelvic lymph node involvement—50% at three years (p—0.015)—and the positive resection margins—only 20% at three years (p < 0.001). The univariate Cox model identified as mortality-associated risk factors the same parameters as above, but also the intraoperative stage III FIGO (p < 0.001; HR 9.412; CI: 2.713 to 32.648) and the presence of post-radiotherapy adenopathy (p—0.031; HR: 3.915; CI: 1.136 to 13.487) identified through imagistic methods. The independent predictors of the overall survival rate identified were the positive resection margins (p—0.002; HR: 6.646; CI 2.0 to 22.084) and the post-radiotherapy stage III FIGO (p—0.003; HR: 13.886; CI: 2.456 to 78.506). Conclusions: The most important predictor factors of survival rate are the positive resection margins and the FIGO stage after radiotherapy. According to the NCCN guidelines in stages considered advanced (beyond stages IB3, IIA2), the standard treatment is neoadjuvant chemoradiotherapy. In our study, with radical surgery after neoadjuvant therapy, 46% of patients presented residual tumor at the intraoperative histopathological examination, a fact that makes the surgical intervention an important step in completing the treatment of these patients. In addition, based on the patient’s features/comorbidities and the clinical response to chemotherapy/radiotherapy, surgeons could carefully tailor the extent of radical surgery, thus resulting in a personalized surgical approach for each patient. However, a potential limitation can be represented by the relatively small number of patients (96) and the unicentric nature of our study. Full article

The creation of a protective stoma is considered a valid life-saving tool, significantly reducing the effects of anastomotic leakage in terms of related morbidity, mortality, and reoperation rate. The aim of this study was to evaluate the impact of a protective loop ileostomy in terms of short- and long-term postoperative morbidity, quantifying the stoma-related complications arising after stoma creation and stoma closure and the risk of permanent stoma. From January 2009 to January 2020, 149 patients with rectal cancer treated by anterior resection and protective ileostomy were enrolled in the study. A total of 113 (75.84%) patients were preoperatively treated with neoadjuvant radiochemotherapy. A clinically relevant anastomotic leak occurred in two patients (1.34%). The postoperative stoma complication rate was 6%. According to the Clavien classification, the stoma-related complication grade was I in seven patients (4.7%) and II in two patients (1.3%). A late stoma-related parastomal hernia occurred in one patient (0.67%). In 129 patients (86.57%), it was possible to close the stoma. Postoperative complications of stoma closure occurred in 12 patients (9.3%). The stoma closure complication grade was I in seven cases (5.43%), II in two cases (1.55%), and ≥3 in three cases (2.33%). Incisional hernia was the only late complication recorded in seven cases (5.42%). The permanent stoma rate was 13.43%. A protective ileostomy has a nonnegligible complication rate, but the rate of severe complications is low. Every effort should be made to clearly identify patients in whom the risk of anastomotic leakage justifies the stoma. Full article

The postoperative septic complications in gastrointestinal surgery impact immediate as well as long-term outcomes, which lead to reinterventions and additional costs. The authors presented the experience of three surgery clinics in Romania regarding the specific septic complications occurring in patients operated on for rectal cancer. The study group comprised 2674 patients who underwent surgery over a 5-year period (2017–2021). Neoplasms of the middle and lower rectum (76%) were the majority. There were 85% rectal resections and 15% abdominoperineal excisions of the rectum. In total, 68.54% of patients were operated on laparoscopically, and 31.46% received open surgery. Without taking wound infections into account, 97 (3.67%) patients had abdominal-pelvic septic complications. The aim was to evaluate the causes of the complications. The percentage of suppurations after surgery of the rectum treated by radiochemotherapy was considerably higher than after surgery of the non-radiated upper rectum. The fatality rate was 5.15%. The risk of fistulas was significantly associated with the preoperative treatment, tumour position and type of intervention. Sex, age, TNM stage or grade were not significant at 0.05 the threshold. The risk of fistulas is reduced with low anterior resection, but the gravity of these complications is higher in the lower rectum compared with the superior rectum. Preoperative radiochemotherapy is a contributing factor to septic complications. Full article

In newly diagnosed IDH-wildtype glioblastoma, the frequency and prognostic relevance of tumor regrowth between resection and the initiation of adjuvant radiochemotherapy are unclear. In this retrospective single-center study we included 64 consecutive cases, for whom magnetic resonance imaging (MRI) was available for both the volumetric assessment of the extent of resection immediately after surgery as well as the volumetric target delineation before the initiation of adjuvant radiochemotherapy (time interval: 15.5 ± 1.9 days). Overall, a median new contrast-enhancement volume was seen in 21/64 individuals (33%, 1.5 ± 1.5 cm³), and new non-contrast lesion volume in 18/64 patients (28%, 5.0 ± 2.3 cm³). A multidisciplinary in-depth review revealed that new contrast-enhancement was either due to (I) the progression of contrast-enhancing tumor remnants in 6/21 patients or (II) distant contrast-enhancing foci or breakdown of the blood–brain barrier in previously non-contrast-enhancing tumor remnants in 5/21 patients, whereas it was unspecific or due to ischemia in 10/21 patients. For non-contrast-enhancing lesions, three of eighteen had progression of non-contrast-enhancing tumor remnants and fifteen of eighteen had unspecific changes or changes due to ischemia. There was no significant association between findings consistent with tumor regrowth and a less favorable outcome (overall survival: 14 vs. 19 months; p = 0.423). These findings support the rationale that analysis of the postsurgical remaining tumor-volume for prognostic stratification should be carried out on immediate postoperative MRI (<72 h), as unspecific changes are common. However, tumor regrowth including distant foci may occur in a subset of IDH-wildtype glioblastoma patients diagnosed per WHO 2021 classification. Thus, MRI imaging prior to radiotherapy should be obtained to adjust radiotherapy planning accordingly. Full article

Background: Locally advanced gastroesophageal junction adenocarcinoma (GEJ) is treated with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. The aim of this study was to compare pathologic response and long-term outcomes in junction adenocarcinoma treated with neoadjuvant RCT versus CT. Methods: All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 were retrospectively analyzed. Results: A total of 94 patients were included, 67 (71.2%) RCT and 27 (28.8%) CT. Complete pathologic response was more frequent in RCT patients (13.4% vs. 7.4%, p = 0.009) with a trend to better lymph node control (ypN0) (55.2% vs. 33.3%; p = 0.057). RCT offered no benefit in R0 resection (66.7% vs. 72.1% CT, p = 0.628) and was related to higher postoperative cardiovascular complications (35.8% vs. 11.1%; p = 0.017). Long-term overall and disease-free survival were similar (5-year OS 61.1% RCT vs. 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs. 22.8% CT; p = 0.763). NAT type was neither independently associated with pathologic response nor long-term survival. Discussion: Patients with locally advanced GEJ adenocarcinoma treated with RCT had more postoperative cardiovascular complications but higher rates of complete pathologic response and a trend to superior locoregional lymph node control. This did not translate in a survival or recurrence benefit. Full article

Objective: To investigate oncological and functional outcomes in patients treated with salvage partial laryngectomy (SPL) after failed radio/chemotherapy. Study design: Retrospective multicenter chart review. Methods: Medical records of patients treated with SPL from January 1998 to January 2018 in two University Medical centers were retrieved. The SPL included horizontal supraglottic laryngectomy, hemi-laryngectomy and crico-hyoido-epiglottopexy. The following outcomes were investigated: histopathological features; overall survival (OS); recurrence-free survival (RFS) local and regional controls; post-operative speech recovery; and the oral diet restart and decannulation. Results: The data of 20 patients with cT1–cT3 laryngeal cancer were collected. The mean follow-up of patients was 69.7 months. The mean hospital stay was 43.0 days (16–111). The following complications occurred in the immediate post-operative follow-up: neck fistula (N = 6), aspiration pneumonia (N = 5), and chondronecrosis (N = 2). Early or late total laryngectomy was carried out over the follow-up period for the following reasons: positive margins and local recurrence/progression (N = 7), chondronecrosis (N = 2) and non-functional larynx (N = 1). The restart of the oral diet was carried out in 12/15 (80%) SPL patients (five patients being excluded for totalization). All patients recovered speech, and decannulation was performed in 14 patients (93%). The 5-year OS and RFS were 50% and 56%, respectively. The 5-year local and regional control rates were 56% and 56%, respectively. Conclusions: Partial laryngectomy is an alternative therapeutic approach to total laryngectomy in patients with a history of failed radiation. Full article

When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2–5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5–79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8–86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1–86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors. Full article

(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy. Full article

Most patients with head and neck squamous cell carcinomas (HNSCC) are diagnosed at a locally advanced stage and show heterogeneous treatment responses. Low SLC3A2 (solute carrier family 3 member 2) mRNA and protein (CD98hc) expression levels are associated with higher locoregional control in HNSCC patients treated with primary radiochemotherapy or postoperative radiochemotherapy, suggesting that CD98hc could be a target for HNSCC radiosensitization. One of the targeted strategies for tumor radiosensitization is precision immunotherapy, e.g., the use of chimeric antigen receptor (CAR) T cells. This study aimed to define the potential clinical value of new treatment approaches combining conventional radiotherapy with CD98hc-targeted immunotherapy. To address this question, we analyzed the antitumor activity of the combination of fractionated irradiation and switchable universal CAR (UniCAR) system against radioresistant HNSCC cells in 3D culture. CD98hc-redirected UniCAR T cells showed the ability to destroy radioresistant HNSCC spheroids. Also, the infiltration rate of the UniCAR T cells was enhanced in the presence of the CD98hc target module. Furthermore, sequential treatment with fractionated irradiation followed by CD98hc-redirected UniCAR T treatment showed a synergistic effect. Taken together, our obtained data underline the improved antitumor effect of the combination of radiotherapy with CD98hc-targeted immunotherapy. Such a combination presents an attractive approach for the treatment of high-risk HNSCC patients. Full article

Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm³), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients. Full article