Entire Gland Research Articles

Impact on xerostomia for patients with nasopharyngeal carcinoma treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study.

6059 Background: In the intensity-modulated radiation therapy (IMRT) era, xerostomia remains one of the most common radiation-induced toxicities in nasopharyngeal carcinoma (NPC) patients. We first proposed the superficial parotid lobe–sparing IMRT (SPLS-IMRT) technique in NPC, which has been proved to significantly reduce the mean doses of bilateral entire parotid glands and superficial parotid lobes. To further validate its clinical benefits, we conducted a prospective phase II randomized controlled study to compare the incidence of xerostomia in NPC patients treated with SPLS-IMRT and conventional IMRT (C-IMRT). Methods: Patients with histologically confirmed NPC who met the eligibility criteria were randomly assigned in a 1:1 ratio to receive either SPLS-IMRT or C-IMRT. The V36 (the percentage volume receiving a dose of 36 Gy) of the entire parotid gland was constrained to be less than 40% in both groups. Additionally, V26 (the percentage volume receiving a dose of 26 Gy) of the superficial parotid lobe was constrained to be less than 30% in the SPLS-IMRT group. The primary endpoint was the incidence of xerostomia at 12 months post-IMRT. The secondary endpoints included the xerostomia questionnaire (XQ) score, unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and survival outcomes. Results: From January 2018 to September 2018, 90 patients were enrolled (45 per group). Eighty-two patients were included for xerostomia analysis (42 in the SPLS-IMRT group and 40 in the C-IMRT group). At 12 months post-IMRT, the incidence of xerostomia in the SPLS-IMRT group was significantly lower than that in the C-IMRT group (83.4% vs. 95.0%; P = 0.007), especially the grade 3 xerostomia (0% vs. 12.5%; P < 0.001). However, the median change in XQ score (XQchange) was similar between the two groups (11.9 points vs. 14.1 points; P = 0.194). Moreover, there was a significantly higher median fractional USFR (0.67 vs. 0.35; P = 0.024) and SSFR (0.66 vs. 0.32; P = 0.021) in the SPLS-IMRT group than the C-IMRT group. All 90 patients were included for survival analysis. With a median follow-up time of 37.8 months (IQR, 33.9–38.5 months), the 3-year locoregional relapse-free survival, distant metastasis-free survival, and overall survival in the SPLS-IMRT and C-IMRT groups were 92.5% vs. 90.9% (hazard ratio [HR], 1.84; P = 0.477), 83.8% vs. 81.7% (HR, 1.13; P = 0.816), and 88.9% vs. 88.2% (HR, 0.96; P = 0.949), respectively. Conclusions: SPLS-IMRT significantly reduced the incidence of xerostomia at 12 months post-IMRT in NPC by recovering parotid gland function earlier than C-IMRT, without compromising survivals. Phase III clinical trials are needed to confirm this result. Clinical trial information: NCT05020067.

Value of Whole-Thyroid CT-Based Radiomics in Predicting Benign and Malignant Thyroid Nodules.

The objective of this research is to explore the value of whole-thyroid CT-based radiomics in predicting benign (noncancerous) and malignant thyroid nodules. The imaging and clinical data of 161 patients with thyroid nodules that were confirmed by pathology were retrospectively analyzed. The entire thyroid regions of interest (ROIs) were manually sketched for all 161 cases. After extracting CT radiomic features, the patients were divided into a training group (128 cases) and a test group (33 cases) according to the 4:1 ratio with stratified random sampling (fivefold cross validation). All the data were normalized by the maximum absolute value and screened using selection operator regression analysis and K best. The data generation model was trained by logistic regression. The effectiveness of the model in differentiating between benign and malignant thyroid nodules was validated by a receiver operating characteristic (ROC) curve. After data grouping, eigenvalue screening, and data training, the logistic regression model with the maximum absolute value normalized was constructed. For the training group, the area under the ROC curve (AUC) was 94.4% (95% confidence interval: 0.941–0.977); the sensitivity and specificity were 89.7% and 86.7%, respectively; and the diagnostic accuracy was 87.6%. For the test group, the AUC was 94.2% (95% confidence interval: 0.881–0.999); the sensitivity and specificity were 89.4% and 86.8%, respectively; and the diagnostic accuracy was 87.6%. The CT radiomic model of the entire thyroid gland is highly efficient in differentiating between benign and malignant thyroid nodules.

Large Multiple Sialoliths of Bilateral Submandibular Glands: A Case Report

Sialolithiasis is a most common disease of salivary glands most commonly occurs in submandibular gland system. Simultaneous sialolithiasis in more than one salivary gland and multiple stone formations have been reported in only 5% and 3% of cases, respectively. In this article, a rare case of bilateral presence of various stones in different sizes and shapes in the submandibular glands and its duct in a 68-year-old man has been investigated. Stones on left side were removed through an intraoral incision and on the right side; the entire salivary gland was removed with extraoral access.
 Conclusion: After precise diagnosis of sialolithiasis through various diagnostic modalities, treatment plan should be tailored based on existing condition and the decision was made to remove a salivary gland with extraoral access on one side and remove the stones by intraoral incision on the other side while preserving the salivary gland.

Targeting prostate lesions on multiparametric MRI with HDR brachytherapy: Optimal planning margins determined using whole-mount digital histology

PURPOSEMultiparametric magnetic resonance imaging (mpMRI) has demonstrated the ability to localize intraprostatic lesions. It is our goal to determine how to optimally target the underlying histopathological cancer within the setting of high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALSTen prostatectomy patients had pathologist-annotated mid-gland histology registered to pre-procedural mpMRI, which were interpreted by four different observers. Simulated HDR-BT plans with realistic catheter placements were generated by registering the mpMRI lesions and corresponding histology annotations to previously performed clinical HDR-BT implants. Inverse treatment planning was used to generate treatment plans that treated the entire gland to a single dose of 15 Gy, as well as focally targeted plans that aimed to escalate dose to the mpMRI lesions to 20.25 Gy. Three margins to the lesion were explored: 0 mm, 1 mm, and 2 mm. The analysis compared the dose that would have been delivered to the corresponding histologically-defined cancer with the different treatment planning techniques. RESULTSmpMRI-targeted plans delivered a significantly higher dose to the histologically-defined cancer (p < 0.001), in comparison to the standard treatment plans. Additionally, adding a 1 mm margin resulted in significantly higher D98, and D90 to the histologically-defined cancer in comparison to the 0 mm margin targeted plans (p = 0.019 & p = 0.0026). There was no significant difference between plans using 1 mm and 2 mm margins. CONCLUSIONSAdding a 1 mm margin to intraprostatic mpMRI lesions significantly increased the dose to histologically-defined cancer, in comparison applying no margin. No significant effect was observed by further expanding the margins.

Fully automated quantification of in vivo viscoelasticity of prostate zones using magnetic resonance elastography with Dense U-net segmentation

Magnetic resonance elastography (MRE) for measuring viscoelasticity heavily depends on proper tissue segmentation, especially in heterogeneous organs such as the prostate. Using trained network-based image segmentation, we investigated if MRE data suffice to extract anatomical and viscoelastic information for automatic tabulation of zonal mechanical properties of the prostate. Overall, 40 patients with benign prostatic hyperplasia (BPH) or prostate cancer (PCa) were examined with three magnetic resonance imaging (MRI) sequences: T2-weighted MRI (T2w), diffusion-weighted imaging (DWI), and MRE-based tomoelastography, yielding six independent sets of imaging data per patient (T2w, DWI, apparent diffusion coefficient, MRE magnitude, shear wave speed, and loss angle maps). Combinations of these data were used to train Dense U-nets with manually segmented masks of the entire prostate gland (PG), central zone (CZ), and peripheral zone (PZ) in 30 patients and to validate them in 10 patients. Dice score (DS), sensitivity, specificity, and Hausdorff distance were determined. We found that segmentation based on MRE magnitude maps alone (DS, PG: 0.93 ± 0.04, CZ: 0.95 ± 0.03, PZ: 0.77 ± 0.05) was more accurate than magnitude maps combined with T2w and DWI_b (DS, PG: 0.91 ± 0.04, CZ: 0.91 ± 0.06, PZ: 0.63 ± 0.16) or T2w alone (DS, PG: 0.92 ± 0.03, CZ: 0.91 ± 0.04, PZ: 0.65 ± 0.08). Automatically tabulated MRE values were not different from ground-truth values (P>0.05). In conclusion, MRE combined with Dense U-net segmentation allows tabulation of quantitative imaging markers without manual analysis and independent of other MRI sequences and can thus contribute to PCa detection and classification.

Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease.

Dry eye disease affects over 16 million adults in the US, and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis is not well elucidated. Here, we report that loss of Krox20, a zinc finger transcription factor involved in the development of ectoderm-derived tissues, or deletion of KROX20-expressing epithelial cells disrupted Meibomian gland formation and homeostasis, leading to dry eye disease secondary to Meibomian gland dysfunction. Ablation of Krox20-lineage cells in adult mice also resulted in dry eye disease, implicating Krox20 in homeostasis of the mature Meibomian gland. Lineage-tracing and expression analyses revealed a restricted KROX20 expression pattern in the ductal areas of the Meibomian gland, although Krox20-lineage cells generate the full, mature Meibomian gland. This suggests that KROX20 marks a stem/progenitor cell population that differentiates to generate the entire Meibomian gland. Our Krox20 mouse models provide a powerful system that delineated the identity of stem cells required for Meibomian gland development and homeostasis and can be used to investigate the factors underlying these processes. They are also robust models of Meibomian gland dysfunction–related dry eye disease, with a potential for use in preclinical therapeutic screening.

Transperineal prostate biopsy identifies locations of clinically significant prostate cancer in men considering focal therapy with PI-RADS 3-5 regions of interest.

ObjectivesTo determine the benefit of performing transperineal prostate mapping biopsy (TPMB) following multiparametric magnetic resonance imaging (mpMRI) to increase the identification of clinically significant prostate cancer (csPCa) with Gleason grade group (GG) ≥ 2 and their locations outside of the PI‐RADS v2 3–5 category lesions.MethodsmpMRI was performed in 80 men prior TPMB from two institutions. The mpMRI was considered clinically significant (csMRI) if it contained one or more PI‐RADS 3–5 category lesion. mpMRI findings were compared against csPCa diagnosed by TPMB, performed between 16 November 2010, and 13 September 2019, for the entire gland, both lobes and to the right and left anterior and right and left posterior quadrants (RA, LA, RP and LP). Sensitivity, specificity, positive and negative predictive values (PPV, NPV), accuracy and the area under curve (AUC) were determined. Thirteen men also underwent radical prostatectomy and had comparison of TPMB pathology to prostatectomy specimen grading.ResultsTPMB was positive in 60/80 (75%) of which 32 (53.3%) were csPCa. csPCa was present in the RA in 9 (11.3%), LA in 11 (13.8%), RP in 25 (31.3%) and LP in 27 (33.8%) and involved 1 quadrant in 7 (21.9%), 2 quadrants in 12 (37.5%), 3 quadrants in 11 (34.4%) and all 4 quadrants in 2 (6.3%) patients; 57/80 (71.3%) men had a mpMRIs with lesions designated as PI‐RADS 3 in 24 (30%), 4 in 25 (31.3%) and 5 in 8 (10%). A csMRI was present in the RA in 7 (8.8%), LA in 8 (10%), RP in 31 (38.8%) and in the LP in 29 (36.3%), which were limited to one quadrant in 39 (68.4%), 2 quadrants in 16 (28.1%), and 3 quadrants in 2 (3.5%). Sensitivity, specificity, PPV, and NPV were determined from the results of the TPMB and were for the entire gland 81.3%, 35.4%, 45.6% and 73.9%. There were 31 csMRIs involving the right posterior of the gland but only 25 csPCa by TPMB of which 12/31 (38.7%) were concordant for high grade disease. There were 29 men who have a csMRI in the left posterior quadrant, and 14 (48.3%) were concordant with csPCa from the TPMB.ConclusionsMpMRI should be supplemented with TPMB to correctly identify the regions of the prostate that would require ablation in men considering focal therapy.

Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer: A Double-Blind Randomized Controlled Trial

Radiation therapy for head and neck cancer frequently leads to salivary gland damage and subsequent xerostomia. The radiation response of the parotid glands of rats, mice, and patients critically depends on dose to parotid gland stem cells, mainly located in the gland's main ducts (stem cell rich [SCR] region). Therefore, this double-blind randomized controlled trial aimed to test the hypothesis that parotid gland stem cell sparing radiation therapy preserves parotid gland function better than currently used whole parotid gland sparing radiation therapy. Patients with head and neck cancer (n=102) treated with definitive radiation therapy were randomized between standard parotid-sparing and stem cell sparing (SCS) techniques. The primary endpoint was >75% reduction in parotid gland saliva production compared with pretreatment production (FLOW12M). Secondary endpoints were several aspects of xerostomia 12 months after treatment. Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only dose to the SCR regions (contralateral 16 and 11 Gy [P=.004] and ipsilateral 26 and 16 Gy [P=.001] in the standard and SCS arm, respectively) and pretreatment patient-rated daytime xerostomia (35% and 13% [P=.01] in the standard and SCS arm, respectively) differed significantly between the arms. In the SCS arm, 1 patient (2.8%) experienced FLOW12M compared with 2 (4.9%) in the standard arm (P=1.00). However, a trend toward better relative parotid gland salivary function in favor of SCS radiation therapy was shown. Moreover, multivariable analysis showed that mean contralateral SCR region dose was the strongest dosimetric predictor for moderate-to-severe patient-rated daytime xerostomia and grade ≥2 physician-rated xerostomia, the latter including reported alteration in diet. No significantly better parotid function was observed in SCS radiation therapy. However, additional multivariable analysis showed that dose to the SCR region was more predictive of the development of parotid gland function-related xerostomia endpoints than dose to the entire parotid gland.

Adrenal glands of mice and rats: A comparative morphometric study.

Mice and rats are among the most used laboratory animals. They share numerous similarities along with differences, some yet unexplored. One of them is the morphometry of their adrenal glands, whose characteristics may be related to differences in energy management, immune response, drug metabolism, behaviour and temperament. The present study tries to fill this knowledge gap with the evaluation and comparison of adrenal gland anatomical/morphometric parameters of mice and rats. In groups of 10 (n = 10) adult, male and female BALB/c mice and Wistar rats, one in every 20 sections transverse to the longitudinal axis of the gland was used for measuring entire gland area, capsule, entire cortex, cortex zones and medulla with the aid of an image analysis system and subjected to statistical analysis. Quotients of the individual areas were calculated and comparison between the resulting ratios was performed. Gland length and volume were also calculated. Statistically significant differences were revealed between the rat female and male cortex area, rat and mouse medulla/cortex, medulla/gland, zona glomerulosa/cortex and cortex/gland ratios, male and female rats' medulla/cortex, medulla/gland, capsule/gland, zona glomerulosa/cortex, zona reticularis/cortex and zona glomerulosa/zona fasciculata ratios, length and volume. The correlation evaluation revealed that in male rats and in female mice the larger medulla area was accompanied by a larger cortex area and vice versa. In general, a larger cortex area was accompanied by larger areas of cortex zones. The collected data and the revealed differences can possibly contribute to the understanding of the physiology of the two species.

Safety and Effectiveness of Total versus Subtotal Thyroidectomy in Management of Simple Multinodular Goiter

Abstract Background: Disorders of the thyroid gland constitute the second most common endocrine disease following diabetes mellitus. The prevalence of nodular goiter and thyroid auton-omy is increased in regions with chronic Iodine Deficiency (ID). It has been documented that the thyroid gland adjusts to ID in the early stages by diffuse hyperplasia, while chronic exposure to ID results in nodular hyperplasia, increased colloid content and increased height of the follicular cells. Aim of Study: To compare between total and subtotal thyroidectomy in management of Multinodular Goiter as regard safety and effectiveness and post-operative complica-tions like: Hypocalcaemia, recurrent laryngeal nerve injury and hypoparathyroidism. Material and Methods: This prospective study was done at Ain Shams University Hospitals and Banha teaching hospital during the period between March and September 2019. This study included 40 cases of SMNG. Their age was between 30 to 45 years, consent was taken from each patient pre-operatively. Agreement of ethical committee was done. Results: Our study showed the advantages of total thy-roidectomy include adequate eradication of the disease, prevention of recurrent goiter and avoidance of the need for completion surgery in case of occult malignancy, but it is associated with higher morbidity (postoperative thyroidectomy complications: RLN palsy and hypoparathyroidism) and the need for lifelong replacement therapy (L-thyroxin supplemen-tation). Conclusion: In MNG, there are a high percentage of cases with disease involving the entire gland; many areas of appar-ently healthy tissue are found to be microscopically involved with variable grade of chronic lymphocytic thyroiditis or follicular hyperplasia or even lobular dysplasia with tendency to form nodules. These signs of disease of this organ tend to recurrence if not treated.

Perfusion analysis in parotid gland tumors using contrast-enhanced ultrasound (CEUS)

The diagnosis of parotid gland tumors is challenging due to their rarity and heterogenity. Neither conventional ultrasound nor magnetic resonance imaging (MRI) nor computed tomography (CT) allow areliable pretherapeutic diagnosis. In addition to conventional ultrasound, contrast-enhanced ultrasound (CEUS) enables amore detailed assessment of perfusion in parotid gland tumors, thereby improving evaluation of this tumor entity. Extensive studies with analysis of perfusion characteristics in different regions of interest (ROI) in parotid gland tumors are currently lacking. This study analysed and compared perfusion parameters in different intratumoral areas of malignant and benign parotid gland tumors using CEUS. A total of 100patients with tumors in the parotid gland were examined using B‑mode sonography, colour Doppler sonography and CEUS. The parameters magnitude, echogenicity, demarcation, vascularisation and in particular perfusion characteristics were measured and analysed. Analysis of quantitative CEUS parameters was performed using aspecific method for perfusion analysis with certain ROI, which were allocated in a standardized manner in the entire parotid gland tumors. The perfusion parameters were compared between intratumoral ROI in the tumors and between particular tumor entities. Qualitative CEUS analysis with an estimation of perfusion patterns was additionally performed. Histologically benign tumors were found in 92cases, and malignant tumors in eight cases. CEUS analysis of perfusion patterns revealed acentripetal perfusion pattern in malignant tumors significantly more frequently than in benign tumors. In the perfusion analysis of quantitative CEUS parameters, all tumors showed higher perfusion intensities in the peripheral ROI. In benign tumors, more differences in perfusion intensity between the intratumoral ROIs were detected compared to malignant tumors. The perfusion parameters (centripetal perfusion pattern; area under the curve) evaluated in this study have the potential to improve pretherapeutic diagnostics of parotid gland tumors in terms of differentiation of tumor entity. Further studies with larger patient cohorts are required for subsequent investigation and validation of the diagnostic accuracy of particular parameters to detect perfusion patterns potentially specific to particular tumor entities.

Phase 2b trial results of padeliporfin (WST11 or Tookad) vascular-targeted photodynamic therapy for partial gland ablation in men with intermediate-risk prostate cancer.

e17006 Background: Padeliporfin (WST11) vascular-targeted photodynamic therapy (VTP) has shown significant clinical benefit as a localized partial gland ablation (PGA) therapy when compared to active surveillance for low-risk prostate cancer, by curbing progression and the need for radical treatment, leading to its regulatory approval in Europe. This phase 2b trial prospectively investigated WST11-VTP for intermediate-risk cancers. Methods: Men with unilateral Grade Group 2 (GG2) cancers (Gleason 3+4), evaluated with MRI and ultrasound-guided (TRUS) biopsy, underwent up to two WST11-VTP PGA sessions. Eligibility criteria included &lt;cT2b, PSA &lt; 10, and fusion biopsy for PIRADS 3+ lesions on pretreatment MRI. Contralateral very low–risk disease was observed. The primary endpoint was prevalence of any Gleason Grade 4 or 5 (≥GG2) cancer, determined by MRI and systematic, 14-core TRUS biopsy of the entire gland (+/- fusion) at 3 and 12 months after treatment. Treatment safety and patient-reported quality of life for sexual and urinary function were assessed with validated questionnaires (IIEF-15 and IPSS, respectively). The study was powered using β = 0.2 to reject the null hypothesis (r≤70%), using a one-sided exact binomial test with 5% alpha risk. To be valid, 44 evaluable patients were required for the 12-month primary endpoint assessment. Results: Of the 50 men treated, 46 were evaluable for the 12-month primary endpoint. Before 12 months, 1 man proceeded to prostatectomy (treatment failure), 2 men refused 12-month biopsy, and 1 man died of COVID-19. At 3 months, 12/49 (24%) men underwent per protocol second WST11-VTP PGA session for GG2 tumor: 9 for residual cancer and 4 for newly identified contralateral GG2 tumors (1 bilateral). The 12-month biopsy was performed in 45 men; 38 (83%) had no Gleason grade 4 or 5 cancer, including 11/12 (92%) patients who underwent 2 PGA sessions. By 3 months, median decline in erectile function score (IIEF-5) from baseline was -1.0 (IQR -7,0). Median improvement in urinary function score (IPSS) was -1.0 (IQR -1,5), with pad-free continence observed in all patients. Median change in IIEF score by 12-months was -1.0 (IQR -5,0). Grade 3 treatment-related adverse events occurred in 6 (12%) patients. All procedure-related prostate/pelvic pain resolved by 3 weeks. Conclusions: The positive results from this trial show that WST11-VTP is effective for PGA of intermediate-risk prostate cancer, with minimal toxicity or impact on urinary and sexual function, consistent with the phase 3 trial results in low-risk disease. Based on these data, this therapy bears consideration for approval as a conservative therapeutic option for selected cases of intermediate-risk disease. Clinical trial information: NCT03315754.

Genetic hybridization of highly active exogenous functional proteins into silk-based materials using “light-clothing” strategy

Genetic hybridization of highly active exogenous functional proteins into silk-based materials using “light-clothing” strategy

Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy.

Purpose:Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on magnetic resonance imaging (MRI) is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine magnetic resonance-ultrasound fusion biopsy in the clinic.Materials and Methods:A total of 905 subjects underwent multiparametric MRI at 29 institutions, followed by magnetic resonance-ultrasound fusion biopsy at 1 institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to 2 deep learning networks (U-Net and holistically-nested edge detector) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests.Results:ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), holistically-nested edge detector (DSC=0.80, p <0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file.Conclusions:This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urological clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.

Prognostic impact of conservative surgery for pancreatic IPMNs

BackgroundThe extent of pancreatic resection for intraductal papillary mucinous neoplasms (IPMNs) remains an unresolved issue. The study aims at analyzing the prognostic impact of conservative surgery (CS) i.e. of pancreatoduodenectomy or distal pancreatectomy, versus total pancreatectomy (TP), for pancreatic IPMNs. MethodsWe retrospectively analyzed and compared data of patients who had undergone pancreatic resection for IPMNs at our center between November 2007 and April 2019. Patients were divided into two main groups based on the extent of surgery: TP-group and CS-group. Subsequently, the perioperative and the long-term outcomes were compared. Moreover, a sub-group analysis of patients with IPMN alone and patients with malignant IPMN, based on preoperative indications to surgery and post-operative histopathological findings, was also performed. ResultsFifty-three patients were included in the TP-group and 73 in the CS-group. In 50 (39.7%) cases the frozen section changed the pre-operative surgical planning, with an extension of the pancreatic resection, in 43 (34.1%) cases up to a total pancreatectomy. Twenty-six patients (20.6%) with low-grade dysplasia at the frozen section underwent CS, while twenty (15.8%) underwent TP. Comparing these two sub-groups no differences were found in surgical IPMN recurrence, nor progression. The rate of overall postoperative complications was 56.6% in the TP-group and 57.5% in the CS-group (p = 0.940). Fifteen patients (20.5%) developed diabetes in the CS-group.None of the patients treated with CS developed a surgical IPMN recurrence or progression during the follow-up period. Comparing OS and DFS of the two groups, we did not find any statistically significant difference (p = 0.619 and 0.315). ConclusionA timely CS can be considered an appropriate and valid strategy in the surgical treatment of the majority of pancreatic IPMNs, as it can avoid the serious long-term metabolic consequences of TP in patients with a long-life expectancy. On the contrary, TP remains mandatory in case of PDAC or high-risk features involving the entire gland.

Prostate Cancer Detection Using 3-D Shear Wave Elasticity Imaging

Transrectal ultrasound (TRUS) B-mode imaging provides insufficient sensitivity and specificity for prostate cancer (PCa) targeting when used for biopsy guidance. Shear wave elasticity imaging (SWEI) is an elasticity imaging technique that has been commercially implemented and is sensitive and specific for PCa. We have developed a SWEI system capable of 3-D data acquisition using a dense acoustic radiation force (ARF) push approach that leads to enhanced shear wave signal-to-noise ratio compared with that of the commercially available SWEI systems and facilitates screening of the entire gland before biopsy. Additionally, we imaged and assessed 36 patients undergoing radical prostatectomy using 3-D SWEI and determined a shear wave speed threshold separating PCa from healthy prostate tissue with sensitivities and specificities akin to those for multiparametric magnetic resonance imaging fusion biopsy. The approach measured the mean shear wave speed in each prostate region to be 4.8 m/s (Young's modulus E = 69.1 kPa) in the peripheral zone, 5.3 m/s (E = 84.3 kPa) in the central gland and 6.0 m/s (E = 108.0 kPa) for PCa with statistically significant (p < 0.0001) differences among all regions. Three-dimensional SWEI receiver operating characteristic analyses identified a threshold of 5.6 m/s (E = 94.1 kPa) to separate PCa from healthy tissue with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of 81%, 82%, 69%, 89% and 0.84, respectively. Additionally, a shear wave speed ratio was assessed to normalize for tissue compression and patient variability, which yielded a threshold of 1.11 to separate PCa from healthy prostate tissue and was accompanied by a substantial increase in specificity, PPV and AUC, where the sensitivity, specificity, PPV, NPV and AUC were 75%, 90%, 79%, 88% and 0.90, respectively. This work illustrates the feasibility of using 3-D SWEI data to detect and localize PCa and demonstrates the benefits of normalizing for applied compression during data acquisition for use in biopsy targeting studies.

Metastases or benign adrenal lesions in patients with histopathological verification of lung cancer: Can CT texture analysis distinguish?

IntroductionDistant metastases are found in the many of patients with lung cancer at time of diagnosis. Several diagnostic tools are available to distinguish between metastatic spread and benign lesions in the adrenal gland. However, all require additional diagnostic steps after the initial CT. The purpose of this study was to evaluate if texture analysis of CT-abnormal adrenal glands on the initial CT correctly differentiates between malignant and benign lesions in patients with confirmed lung cancer. Materials and methodsIn this retrospective study 160 patients with endoscopic ultrasound-guided biopsy from the left adrenal gland and a contrast-enhanced CT in portal venous phase were assessed with texture analysis. A region of interest encircling the entire adrenal gland was used and from this dataset the slice with the largest cross section of the lesion was analyzed individually. ResultsSeveral texture parameters showed statistically significantly difference between metastatic and benign lesions but with considerable between-groups overlaps in confidence intervals. Sensitivity and specificity were assessed using ROC-curves, and in univariate binary logistic regression the area under the curve ranged from 36 % (Kurtosis 0.5) to 69 % (Entropy 2.5) compared to 73 % in the best fitting model using multivariate binary logistic regression. ConclusionIn lung cancer patients with abnormal adrenal gland at imaging, adrenal gland texture analyses appear not to have any role in discriminating benign from malignant lesions.

The tubercle of Zuckerkandl, the ligament of Berry - importance for thyroid surgery.

The anatomical structures of the tubercle of Zuckerkandl (TZ) and the ligament of Berry (LB) have been known since the turn of the 20th century. The importance of the relationship between these structures and the thyroid gland was pointed out in the first half of the last century; nevertheless, it was neglected by most of the then surgeons. An increased interest of surgeons in detailed knowledge of these structures could only be observed from the 80´sof the last century in connection with guidelines for radical surgical treatments of the gland (both for benign and malignant diseases) and with the need to enhance the safety of these treatments. The knowledge of these two important structures and the skill of an exact surgical technique are necessary for the protection of the recurrent laryngeal nerve and the parathyroid glands, and also for the actual removal of the entire thyroid gland. Thyroid surgeons must keep in mind the existence of many anatomical and pathological variations in these regions, which makes the preparation of the gland so delicate.

Mist1+ gastric isthmus stem cells are regulated by Wnt5a and expand in response to injury and inflammation in mice

Background and aimsThe gastric epithelium undergoes continuous turnover. Corpus epithelial stem cells located in the gastric isthmus serve as a source of tissue self-renewal. We recently identified the transcription factor...

Intravital microscopy of dynamic single-cell behavior in mouse mammary tissue.

Multiphoton intravital imaging is essential for understanding cellular behavior and function in vivo. The adipose-rich environment of the mammary gland poses a unique challenge to in vivo microscopy due to light scattering that impedes high-resolution imaging. Here we provide a protocol for high-quality, six-color 3D intravital imaging of regions across the entire mouse mammary gland and associated tissues for several hours while maintaining tissue access for microdissection and labeling. An incision at the ventral midline and along the right hind leg creates a skin flap that is then secured to a raised platform skin side down. This allows for fluorescence-guided microdissection of connective tissue to provide unimpeded imaging of mammary ducts. A sealed imaging chamber over the skin flap creates a stable environment while maintaining access to large tissue regions for imaging with an upright microscope. We provide a strategy for imaging single cells and the tissue microenvironment utilizing multicolor Confetti lineage-tracing and additional dyes using custom-designed filters and sequential excitation with dual multiphoton lasers. Furthermore, we describe a strategy for simultaneous imaging and photomanipulation of single cells using the Olympus SIM scanner and provide steps for 3D video processing, visualization and high-dimensional analysis of single-cell behavior. We then provide steps for multiplexing intravital imaging with fixation, immunostaining, tissue clearing and 3D confocal imaging to associate cell behavior with protein expression. The skin-flap surgery and chamber preparation take 1.5 h, followed by up to 12 h of imaging. Applications range from basic filming in 1 d to 5 d for multiplexing and complex analysis.