Prevention of Local Tumor Recurrence After Surgery by Thermosensitive Gel-Based Chemophotothermal Therapy in Mice.

BACKGROUND AND OBJECTIVES: Local recurrence of cancer after surgery has long been a tough problem. In the present study, thermosensitive gel-based chemophotothermal therapy was applied to prevent the recurrence of liver cancer after surgery. STUDY DESIGN/MATERIALS AND METHODS: Mesoporous silica nanoparticles (MSNs) were used as first-level carrier to co-load doxorubicin (DOX) and ICG. Then, the drug-loaded MSNs (D-I@MSN) were incorporated into poloxamer gel. A mimic model of liver cancer recurrence after surgery was prepared by subcutaneously injecting H22 cells into the armpit of mice. Then the two-level composite gel (D-I@MSN/gel) was also subcutaneously injected at the same site before the formation of tumor, followed by 808 nm laser irradiation. RESULTS: The loading efficiency and entrapment efficiency of DOX were as high as 8.85% and 96.9%, and that of ICG were 9.24% and 99.3%, respectively. The results of in vitro cytotoxicity showed that cell viability in D-I@MSN+Laser group was only 5.8% after being irradiated by 808 nm laser for 5 minutes (0.5 W/cm2 ). In animal studies, tumor formation (tumor recurrence) was greatly inhibited in D-I@MSN+Laser group. CONCLUSIONS: The thermosensitive gel-based chemophotothermal therapy showed excellent safety and efficacy when applied in the prevention of mimic local tumor replase after surgery in mice, presenting its great potential clinically. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

DIFFERENTIAL DIAGNOSTICS OF A RADIONECROSIS AND LOCAL TUMORAL RECURRENCE ACCORDING TO ARTERIAL SPIN LABELLING AFTER RADIOSURGERY TREATMENT OF MALIGNANT GLIOMAS OF A BRAIN.

OBJECTIVE: The aim: Assessment of a possibility of performing differential diagnostics of the post-beam radio necrosis (PBRN) and the local recurrence (LR) after the carried-out stereotaxic radio surgery (SRS) according to perfusion on the basis of non-contrast pulse arterial backs markings (PASL). PATIENTS AND METHODS: Materials and methods: In our research, we consider results of the stereotactic radiosurgery (SRS) which is carried out to 20 patients with the diagnosis the malignant glioma of a brain (MGB) in respect differential diagnostics of a local tumor recurrence and radionecrosis according to perfusion non-contrast MRT of a research on the basis of the sequence of PASL. The diagnosis of MGB before carrying out SRS was established to all 20 patients on the basis of a histologic research on data of a biopsy. From them the anaplastic astrocytoma (AnASTs, grade III) and at 14 - a glioblastoma was diagnosed for 6 patients (GBM, grade IV). Confirmations of the post-beam diagnosis it was carried out on the basis of a histologic research on results of a stereotactic biopsy or a surgical resection. Traditional methods of medical statistics were applied to processing of the statistical information obtained in a research at all its stages (calculation of average and relative sizes with their errors), also graphic and tabular methods were applied to rational evident statement of the received results. RESULTS: Results: The diagnosis of a local tumor recurrence according to a relative regional blood-groove on the basis of PASL was exposed to 8 patients and confirmed histologically (to 5 patients underwent surgical resection, 3 - according to biopsy data). Patients with a confirmed diagnosis of relapse according to biopsy were performed in 1 case, repeated radiosurgery and in 2 cases (with a diagnosis of multifocal continued growth of glioblastoma) - irradiation of the entire brain. Radionecrosis was diagnosed in 12 cases. In 6 cases, it was confirmed on the basis of clinical diagnostic data of dynamic observation of patients, in 3 cases - according to surgical resection, and in 3 cases - according to stereotactic biopsy. According to our data, the average rrCBF based on arterial spin labelling (PASL) rTPmean ≤ 0.8ml / 100g / minute most likely testified in favor of radionecrosis, average ≥ 1.5ml / 100g / min - in favor of tumor progression, the maximum rTPmax ≤ 1.3ml / 100g / min most likely testified in favor of radio-necrosis, the maximum indicator rTPmax≥ 1.8ml / 100g / min - in favor of tumor progression. CONCLUSION: Conclusions: According to a relative regional blood flow of rrCBF based on non-contrast PASL perfusion, it is possible to reliably carry out a differential diagnosis of radionecrosis and local tumor recurrence in patients undergoing radiosurgical treatment for malignant gliomas of the brain.

Detection of Local Tumor Recurrence After Definitive Treatment of Head and Neck Squamous Cell Carcinoma: Histogram Analysis of Dynamic Contrast-Enhanced T1-Weighted Perfusion MRI.

OBJECTIVE: This study aimed to explore the added value of histogram analysis of the ratio of initial to final 90-second time-signal intensity AUC (AUCR) for differentiating local tumor recurrence from contrast-enhancing scar on follow-up dynamic contrast-enhanced T1-weighted perfusion MRI of patients treated for head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: AUCR histogram parameters were assessed among tumor recurrence (n = 19) and contrast-enhancing scar (n = 27) at primary sites and compared using the t test. ROC analysis was used to determine the best differentiating parameters. The added value of AUCR histogram parameters was assessed when they were added to inconclusive conventional MRI results. RESULTS: Histogram analysis showed statistically significant differences in the 50th, 75th, and 90th percentiles of the AUCR values between the two groups (p < 0.05). The 90th percentile of the AUCR values (AUCR90) was the best predictor of local tumor recurrence (AUC, 0.77; 95% CI, 0.64-0.91) with an estimated cutoff of 1.02. AUCR90 increased sensitivity by 11.7% over that of conventional MRI alone when added to inconclusive results. CONCLUSION: Histogram analysis of AUCR can improve the diagnostic yield for local tumor recurrence during surveillance after treatment for HNSCC.

Radiofrequency ablation of hepatocellular carcinoma: Mono or multipolar?

BACKGROUND AND AIMS: Thermo-ablation by radiofrequency is recognized as a curative treatment for early-stage hepatocellular carcinoma. However, local recurrence may occur because of incomplete peripheral tumor destruction. Multipolar radiofrequency has been developed to increase the size of the maximal ablation zone. We aimed to compare the efficacy of monopolar and multipolar radiofrequency for the treatment of hepatocellular carcinoma and determine factors predicting failure. METHODS: A total of 171 consecutive patients with 214 hepatocellular carcinomas were retrospectively included. One hundred fifty-eight tumors were treated with an expandable monopolar electrode and 56 with a multipolar technique using several linear bipolar electrodes. Imaging studies at 6 weeks after treatment, then every 3 months, assessed local effectiveness. Radiofrequency failure was defined as persistent residual tumor after two sessions (primary radiofrequency failure) or local tumor recurrence during follow-up. This study received institutional review board approval (number 2014/77). RESULTS: Imaging showed complete tumor ablation in 207 of 214 lesions after the first session of radiofrequency. After a second session, only two cases of residual viable tumor were observed. During follow-up, there were 46 local tumor recurrences. Thus, radiofrequency failure occurred in 48/214 (22.4%) cases. By multivariate analysis, technique (P < 0.001) and tumor size (P = 0.023) were independent predictors of radiofrequency failure. Failure rate was lower with the multipolar technique for tumors < 25 mm (P = 0.023) and for tumors between 25 and 45 mm (P = 0.082). There was no difference for tumors ≥ 45 mm (P = 0.552). CONCLUSIONS: Compared to monopolar radiofrequency, multipolar radiofrequency improves tumor ablation with a subsequent lower rate of local tumor recurrence.

Conventional versus Hepatic Arteriography and C-Arm CT-Guided Ablation of Liver Tumors (HepACAGA): A Comparative Analysis.

PURPOSE: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic-arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. MATERIALS AND METHODS: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. RESULTS: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). CONCLUSIONS: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications.

Lipiodol accumulation patterns and their impact on survival outcomes in transarterial chemoembolization for hepatocellular carcinoma: a single institution retrospective analysis.

Conventional Transarterial chemoembolization (TACE) using Lipiodol is a pivotal therapeutic modality for hepatocellular carcinoma (HCC). The link between Lipiodol accumulation patterns and patient survival outcomes remains underexplored. This study assesses the impact of these patterns on the prognosis of HCC patients undergoing TACE. We evaluated HCC patients treated with selective TACE between July 2015 and March 2020, classifying post-procedure Lipiodol accumulation observed on CT scans into four distinct patterns: homogeneous, heterogeneous, defective, and deficient. We analyzed cumulative local tumor recurrence (LTR), progression-free survival (PFS), and overall survival (OS) rates across these groups. Univariate and multivariate logistic regression analyses were performed to identify potential prognostic factors influencing PFS and OS. Among 124 HCC nodules, the distribution of Lipiodol patterns was: 65 homogeneous, 24 heterogeneous, 10 defective, and 25 deficient. Median PFS was 33.2, 9.1, 1.1, and 1.0 months, respectively, while median OS spanned 54.8, 44.5, 25.0, and 29.1 months for these groups. A significant difference in survival was found only between the homogeneous and defective patterns (hazard ratio, 2.33; confidence interval 1.25-4.36). Multivariate analyses revealed nonhomogeneous patterns as significant predictors of shorter PFS (HR 6.45, p < 0.001) and OS (HR 1.73, p = 0.033). Nonhomogeneous Lipiodol patterns in HCC following TACE significantly correlate with higher recurrence and decreased survival rates, especially with defective patterns. Early detection of these patterns may guide timely intervention strategies, potentially enhancing survival outcomes for patients with HCC.

[Intraoperative radiotherapy in abdominal surgery-Own experiences]. / Intraoperative Strahlentherapie in der Abdominalchirurgie ­ eigene Erfahrungen.

BACKGROUND: Intraoperative radiotherapy (IORT) can be applied for locally advanced tumors and expected or unavoidable R1 situations combined with surgical resection. The aim is to improve local tumor control and long-term survival. The indications are primary and recurrent intra-abdominal and retroperitoneal tumors. This study aimed to evaluate own data and experiences with IORT combined with surgical visceral resection. METHODS: Patients who underwent IORT combined with abdominal tumor resection in the Department of General and Visceral Surgery at the University Medical Center Freiburg between January 2008 and December 2018 were included in this study. The results were retrospectively evaluated regarding short-term and long-term outcomes. RESULTS: The most frequent indications for IORT were sarcoma followed by rectal and anal cancers. The median IORT dose used was 15 Gy (range 8-19 Gy). With a median comprehensive complication index (CCI) of 11.9, complications occurred in 24% of patients (Dindo-Clavien ≥ °III). The 90-day mortality was 0%. Especially in recurrent anal cancer the local control after 1 year was insufficient despite R0 resection. CONCLUSION: In this cohort of patients IORT could be applied with acceptable morbidity. Nevertheless, the indications and patient selection are critical factors for carrying out the treatment. The effect of IORT to improve local tumor control and long-term survival should be evaluated in further studies.

Histopathologic Patterns of Recurrent Choroidal Melanoma Following I-125 Plaque Brachytherapy.

PURPOSE: Histologic correlation of clinical patterns of recurrent choroidal melanoma following I-125 plaque brachytherapy was performed to identify pathologic mechanisms of recurrence. METHODS: We reviewed 7 cases of recurrent choroidal melanoma following I-125 plaque brachytherapy managed with enucleation. Clinical characteristics included tumor dimensions, radiation dose, time to local recurrence, and clinical pattern of recurrence. Histopathology (hematoxylin and eosin and periodic acid - Schiff) and immunohistochemistry (Ki-67, CD-163, HMB45, and SOX10) were performed. RESULTS: Mean follow-up time and time to local recurrence were 42 and 21 months after brachytherapy, respectively. Tumor recurrences were described clinically as marginal in 43%, diffuse in 29%, and extraocular extension (EOE) in 29%. Eighty-six percent were classified as mixed cell type and 14% were epithelioid type. Tumor zonation (histologic demarcation between zones of recurrent and nonrecurrent tumor cells by immunohistochemistry) was present in marginal and EOE cases (n = 6) and absent in the diffuse cases (n = 2). Ki-67 proliferative index was higher in marginal and EOE recurrences, while diffuse cases showed uniform -Ki-67 staining. CD-163 staining was found to be greater in nonrecurrent tumor. HMB45 correlated with SOX10 with a greater staining in recurrent tumor. CONCLUSION: Our observations provide a correlation between histopathologic and clinical patterns of local recurrence of choroidal melanoma after brachytherapy.

Ablation Volume Measurement After Percutaneous Cryoablation Using a Two-cryo-probe Technique for Small Hepatocellular Carcinomas.

PURPOSE: To calculate the ablation volume of percutaneous cryoablation (PCA) with a two-cryo-probe technique for small hepatocellular carcinomas (HCCs) and to assess risk factors for local tumor recurrence (LTR). MATERIALS AND METHODS: Between January 2013 and June 2017, 96 patients (mean age, 60.7 years; range, 37-83 years) with 106 small HCCs were retrospectively analyzed. The ablation volume, technical success, LTR rates, and complications were evaluated. Ablation volume was measured after the first freezing and immediately after completing PCA twice via computed tomography imaging. Prognostic factors associated with LTR were analyzed. RESULTS: Technical success was achieved in all patients. The mean final ablation volume was 19.1 ± 4.8 cm3, which was significantly higher than the first freezing ablation volume (14.7 ± 4.3 cm3, p < 0.001). During the median follow-up period of 16.7 months (range, 5-52 months), LTR-free survival rates based on Kaplan-Meier analyses at 6 months, 1 year, and 2 years were 87.7%, 84.0%, and 80.2%, respectively. Only one major complication of post-procedural arterial bleeding occurred. A final ablation volume/tumor volume < 10 was a significant risk factor for LTR (p = 0.044). CONCLUSIONS: A ratio of final ablation volume to tumor volume < 10 was a significant prognostic factor for LTR. Therefore, the measurement and prediction of the final ablation volume are important to reduce LTR.

Poly(d,l-lactide)/polyethylene glycol micro/nanofiber mats as paclitaxel-eluting carriers: preparation and characterization of fibers, in vitro drug release, antiangiogenic activity and tumor recurrence prevention.

Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.

Intraoperative Local Ablative Therapies Combined with Surgery for the Treatment of Bilobar Colorectal Liver Metastases.

AIM: To investigate the role of intraoperative local ablation techniques (LATs) in bilobar colorectal liver metastases (bCRLM). PATIENTS AND METHODS: Among patients who underwent LAT for CRLM between 2005 and 2015, we selected 33 patients with bilobar disease submitted to thermal ablation alone or associated to liver resection. Primary end-point was complete local response at one month (CLR). Secondary end-points were morbidity, mortality, disease-free survival (DFS), local tumor recurrence (LTR) and long-term survival. RESULTS: CLR was observed in 100% of cases, while LTR occurred in 8 cases (22%). DFS at 1, 3 and 5 years was 37%, 5% and 5%. Overall survival (OS), in the same interval, was 95%, 49% and 26%. Univariate analysis found a significant correlation between LTR and tumor size (11% ≤20 mm vs. 50% >20 mm; p=0.009). CONCLUSION: LAT is an effective adjuvant strategy in bCRLM for nodules within 20 mm diameter.

Desmoid Tumor of the Chest Wall Mimicking Recurrent Breast Cancer: Multimodality Imaging Findings.

Desmoid tumor of breast is a rare benign, locally aggressive tumor with a high recurrence rate. It has been associated with scar from previous breast surgery or trauma. Especially in breast cancer patients with previous operation history, it may simulate recurrent breast cancer clinically and radiologically. We presented multimodality imaging findings (ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography/computed tomography) of chest wall desmoid tumor mimicking recurrent breast cancer in a 38-year-old patient with a history of left modified mastectomy. The desmoid tumor is a rare benign tumor that should be considered in the differential diagnosis of malignant local tumor recurrence after breast cancer operation. Biopsy was required for accurate diagnosis and wide local excision was its appropriate surgical management.

Does Establishing a Safety Margin Reduce Local Recurrence in Subsegmental Transarterial Chemoembolization for Small Nodular Hepatocellular Carcinomas?

OBJECTIVE: To test the hypothesis that a safety margin may affect local tumor recurrence (LTR) in subsegmental chemoembolization. MATERIALS AND METHODS: In 101 patients with 128 hepatocellular carcinoma (HCC) nodules (1-3 cm in size and ≤ 3 in number), cone-beam CT-assisted subsegmental lipiodol chemoembolization was performed. Immediately thereafter, a non-contrast thin-section CT image was obtained to evaluate the presence or absence of intra-tumoral lipiodol uptake defect and safety margin. The effect of lipiodol uptake defect and safety margin on LTR was evaluated. Univariate and multivariate analyses were performed to indentify determinant factors of LTR. RESULTS: Of the 128 HCC nodules in 101 patients, 49 (38.3%) nodules in 40 patients showed LTR during follow-up period (median, 34.1 months). Cumulative 1- and 2-year LTR rates of nodules with lipiodol uptake defect (n = 27) and those without defect (n = 101) were 58.1% vs. 10.1% and 72.1% vs. 19.5%, respectively (p < 0.001). Among the 101 nodules without a defect, the 1- and 2-year cumulative LTR rates for nodules with complete safety margin (n = 52) and those with incomplete safety margin (n = 49) were 9.8% vs. 12.8% and 18.9% vs. 19.0% (p = 0.912). In multivariate analyses, ascites (p = 0.035), indistinct tumor margin on cone-beam CT (p = 0.039), heterogeneous lipiodol uptake (p = 0.023), and intra-tumoral lipiodol uptake defect (p < 0.001) were determinant factors of higher LTR. CONCLUSION: In lipiodol chemoembolization, the safety margin in completely lipiodolized nodule without defect will not affect LTR in small nodular HCCs.