Bladder cancer: do we need contrast injection for MRI assessment of muscle invasion? A prospective multi-reader VI-RADS approach.

OBJECTIVES: (1) To investigate whether a contrast-free biparametric MRI (bp-MRI) including T2-weighted images (T2W) and diffusion-weighted images (DWI) can be considered an accurate alternative to the standard multiparametric MRI (mp-MRI), consisting of T2, DWI, and dynamic contrast-enhanced (DCE) imaging for the muscle-invasiveness assessment of bladder cancer (BC), and (2) to evaluate how the diagnostic performance of differently experienced readers is affected according to the type of MRI protocol. METHODS: Thirty-eight patients who underwent a clinically indicated bladder mp-MRI on a 3-T scanner were prospectively enrolled. Trans-urethral resection of bladder was the gold standard. Two sets of images, set 1 (bp-MRI) and set 2 (mp-MRI), were independently reviewed by four readers. Descriptive statistics, including sensitivity and specificity, were calculated for each reader. Receiver operating characteristic (ROC) analysis was performed, and the areas under the curve (AUCs) were calculated for the bp-MRI and the standard mp-MRI. Pairwise comparison of the ROC curves was performed. RESULTS: The AUCs for bp- and mp-MRI were respectively 0.91-0.92 (reader 1), 0.90 (reader 2), 0.95-0.90 (reader 3), and 0.90-0.87 (reader 4). Sensitivity was 100% for both protocols and specificity ranged between 79.31 and 89.66% and between 79.31 and 83.33% for bp-MRI and mp-MRI, respectively. No significant differences were shown between the two MRI protocols (p > 0.05). No significant differences were shown accordingly to the reader's experience (p > 0.05). CONCLUSIONS: A bp-MRI protocol consisting of T2W and DWI has comparable diagnostic accuracy to the standard mp-MRI protocol for the detection of muscle-invasive bladder cancer. The experience of the reader does not significantly affect the diagnostic performance using VI-RADS. KEY POINTS: • The contrast-free MRI protocol shows a comparable accuracy to the standard multiparametric MRI protocol in the bladder cancer muscle-invasiveness assessment. • VI-RADS classification helps non-expert radiologists to assess the muscle-invasiveness of bladder cancer. • DCE should be carefully interpreted by less experienced readers due to inflammatory changes representing a potential pitfall.

Mastering bladder paraganglioma for optimal treatment: a case report of robot-assisted surgery.

Bladder paraganglioma is a rare neuroendocrine neoplasm, either functional or non-functional, arising from the urinary bladder. Functional variants present with catecholamine-related symptoms, while non-functional variants pose diagnostic challenges, mimicking urothelial carcinoma. Misdiagnosis risks underscore the importance of accurate identification for appropriate patient management. In this case, a 52-year-old man, diagnosed incidentally with hypertension and reported occasional post-micturition tachycardia, underwent abdominal ultrasound for known hepatic cyst follow-up, revealing an oval hypoechoic bladder mass. Initial consideration of bladder urothelial carcinoma prompted further investigation with contrast-enhanced CT scan and cystoscopy that confirmed extrinsic mass nature, and subsequent robotic-assisted partial cystectomy was performed. Histologically, the removed mass exhibited characteristic features of bladder paraganglioma. Postoperative recovery was uneventful, with resolution of post-micturition tachycardia at 1 month. Follow-up includes endocrinological evaluation and a 6-month CT scan. In conclusion, bladder paraganglioma should be considered in para-vesical mass differentials. This case highlights the importance of meticulous history collection, even in asymptomatic patients, the need for a multidisciplinary approach for accurate diagnosis and management of this rare condition, and the robotic approach as a viable option.

Pharmacokinetics of pegylated liposomal doxorubicin administered by intraoperative hyperthermic intraperitoneal chemotherapy to patients with advanced ovarian cancer and peritoneal carcinomatosis.

The pharmacokinetics of pegylated liposomal doxorubicin (PLD) were investigated in 17 women undergoing intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer and peritoneal carcinomatosis. HIPEC was performed immediately after completing debulking surgery, which included a number of peritonectomy procedures. PLD was injected and allowed to equilibrate in peritoneal cavity filled with 4 liters of physiological solution and stabilized at 42°C; next, the outflow line was opened and perfusion proceeded for 1 h. PLD was stable in peritoneal perfusate and plasma. During HIPEC, PLD peritoneal perfusate/plasma gradients averaged ∼600 or ≥1000 for peak concentration or area under the curve. After HIPEC, PLD plasma levels remained stable or decreased. Biopsy samples of residual normal peritoneum or ovarian carcinomatosis were collected at the end of HIPEC and were shown to contain free doxorubicin. Correlating PLD decrements in peritoneal perfusate with plasma exposure to PLD or peritoneal deposition of free doxorubicin showed that the former occurred during preperfusional equilibration of PLD in peritoneal cavity, whereas the latter occurred during 1 h of perfusion. Plasma exposure to PLD correlated negatively with the number of peritonectomy procedures performed during surgery, whereas peritoneal deposition of free doxorubicin correlated positively. Taken together, these results show that PLD administered by intraoperative HIPEC undergoes limited systemic diffusion and releases active free doxorubicin in peritoneum exposed to ovarian carcinomatosis. PLD pharmacokinetics seem to be influenced by peritonectomy procedures.

Conspicuity and muscle-invasiveness assessment for bladder cancer using VI-RADS: a multi-reader, contrast-free MRI study to determine optimal b-values for diffusion-weighted imaging.

OBJECTIVE: To (1) compare bladder cancer (BC) muscle invasiveness among three b-values using a contrast-free approach based on Vesical Imaging-Reporting and Data System (VI-RADS), to (2) determine if muscle-invasiveness assessment is affected by the reader experience, and to (3) compare BC conspicuity among three b-values, qualitatively and quantitatively. METHODS: Thirty-eight patients who underwent a bladder MRI on a 3.0-T scanner were enrolled. The gold standard was histopathology report following transurethral resection of BC. Three sets of images, including T2w and different b-values for DWI, set 1 (b = 1000 s/mm2), set 2 (b = 1500 s/mm2), and set 3 (b = 2000 s/mm2), were reviewed by three differently experienced readers. Descriptive statistics and Intraclass Correlation Coefficient (ICC) were calculated. Comparisons among readers and DWI sets were performed with the Wilcoxon test. Receiver operating characteristic (ROC) analysis was performed. Areas under the curves (AUCs) and pairwise comparison were calculated. RESULTS: AUCs of muscle-invasiveness assessment ranged from 0.896 to 0.984 (reader 1), 0.952-0.968 (reader 2), and 0.952-0.984 (reader 3) without significant differences among different sets and readers (p > 0.05). The mean conspicuity qualitative scores were higher in Set 1 (2.21-2.33), followed by Set 2 (2-2.16) and Set 3 (1.82-2.14). The quantitative conspicuity assessment showed that mean normalized intensity of tumor was significantly higher in Set 2 (4.217-4.737) than in Set 1 (3.923-4.492) and Set 3 (3.833-3.992) (p < 0.05). CONCLUSION: Muscle invasiveness can be assessed with high accuracy using a contrast-free protocol with T2W and DWI, regardless of reader's experience. b = 1500 s/mm2 showed the best tumor delineation, while b = 1000 s/mm2 allowed for better tumor-wall interface assessment.

Treatment Intensification for Locally Advanced Rectal Cancer: Impact on Pathological Complete Response and Outcomes.

AIM: Pathological complete response (pCR) and clinical outcomes [overall survival (OS), disease-free survival (DFS), locoregional control (LC)] were evaluated in a single-institution experience of different schedules of neoadjuvant chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Data for 322 patients with LARC were retrospectively analyzed. pCR was evaluated according to Mandard tumor regression grade (TRG). The Kaplan-Meier method was used to estimate OS, DFS and LC. RESULTS: Three hundred and three (94.1%) patients underwent surgery. pCR was observed in 81 patients (26.7%), with TRG1-2 rate of 41.8%. The 5- and 10-year OS, DFS and LC rates were 82.5%±2.5% and 65.5%±3.8%, 81.2%±2.4% and 79.3%±2.9%, 93.1%±1.7% and 90.5%±2.1%, respectively. CONCLUSION: Neoadjuvant CRT in LARC patients resulted in favorable long-term oncological outcomes, with a high pCR rate and acceptable toxicity.

A multidisciplinary group for prostate cancer management: A single institution experience.

Increased knowledge regarding the heterogeneity of Prostate Cancer (PC) and its variable outcomes has generated controversy over the best clinical approach. Nowadays, it is well-known that patient outcomes and clinical management may be improved by an efficient organization of the national health care system. The Interdisciplinary Group for Oncological Care (GICO) for PC patients was created by our healthcare management company in September 2010. Since then, a multidisciplinary internal report was applied to PC patients. This report highlights our methodology and experience of planning a GICO, and illustrates the results obtained for the management of PC patients before and after the adopted GICO criteria in a single institution, the SS Annunziata Hospital (Chieti, Italy).

Diagnostic accuracy of biparametric vs multiparametric MRI in clinically significant prostate cancer: Comparison between readers with different experience.

BACKGROUND: MRI plays a crucial role to identify men with a high likelihood of clinically significant prostate cancer who require immediate biopsy. The added value of DCE MRI in combination with T2-weighted imaging and DWI is controversial (risks related to gadolinium administration, duration of MR exam, financial burden, effects on diagnostic performance). A comparison of a biparametric and a standard multiparametric MR imaging protocol, taking into account the different experience of the readers, may help to choose the best MR approach regarding diagnostic performance. PURPOSE: To determine the added value of dynamic contrasted-enhanced imaging (DCE) over T2-weighted imaging (T2-WI) and diffusion weighted imaging (DWI) for the detection of clinically significant prostate cancer, and to evaluate how it affects the diagnostic performance of three readers with different grade of experience in prostate imaging. MATERIALS AND METHODS: Eighty-five patients underwent prostate MR examination at 1.5 T MR scanner performed because of elevated prostate-specific antigen level and/or suspicion of prostate cancer at digital rectal examination. Two MR images sets (Set 1 = biparametric, Set 2 = multiparametric) were retrospectively and independently scored by three radiologists with 7, 3 and 1 years of experience in prostate MR imaging respectively, according to PI-RADS v2. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated by dichotomizing reader scores. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUCs) were calculated for each reader and image set. A comparison of ROC curves was performed to test the difference between the areas under the ROC curves among the three readers. RESULTS: There was no significant difference regarding the detection of clinically significant tumor among the three readers between the two image sets. The AUC for the bi-parametric and multi-parametric MR imaging protocol was respectively 0.68-0.72 (Reader 1), 0.72-0.70 (Reader 2) and 0.60-0.54 (Reader 3). ROC curve comparison revealed no statistically significant differences for each protocol among the most experienced (Reader 1) and the other readers (Readers 2-3). CONCLUSION: The diagnostic accuracy of a bi-parametric MR imaging protocol consisting of T2-weighted imaging and DWI is comparable with that of a standard multi-parametric imaging protocol for the detection of clinically significant prostate cancer. The experience of the reader does not significantly modify the diagnostic performance of both MR protocols.

Chromogenic in situ hybridization and p16/Ki67 dual staining on formalin-fixed paraffin-embedded cervical specimens: correlation with HPV-DNA test, E6/E7 mRNA test, and potential clinical applications.

Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV) infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH) technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16(INK4a)/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+). p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16(INK4a)/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16(INK4a)/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure.

Gene expression of transforming growth factor beta receptors I and II in non-small-cell lung tumors.

Transforming growth factor (TGF)beta inhibits normal epithelial cell proliferation. A decreased expression of TGFbeta receptors (TbetaR) has been associated with loss of TGFbeta sensitivity and enhanced tumor progression in many types of cancer. Although lung cancer is one of the leading causes of cancer death, a comparative analysis of TbetaR mRNA and protein expression in non-small-cell (NSC) lung tumors has not been performed. Lung tumor tissues and control non-lesional lung tissues were obtained from 17 patients undergoing thoracotomy for primary NSC lung tumors in clinical stage II. Each tissue sample was studied for TbetaRI and TbetaRII mRNA and immunoreactive protein expression, using a semi-quantitative reverse transcription-PCR method, and a quantitative immunohistochemistry method, respectively. TbetaRI protein expression was higher in tumors than in controls (p=0.0005) and a similar trend was present at the mRNA level. TbetaRII protein expression was not significantly different between tumors and controls, however an intense peri-nuclear staining for TbetaRII was observed in several tumor cells. TbetaRII mRNA levels were lower in tumors than in controls (p=0.005) and an inverse relation between TbetaRII mRNA and protein expression was detected in tumors (p=0.0013). Our findings suggest an altered function of the TbetaR system in NSC lung cancer.