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Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2156
Author(s):  
Michal Grzmil ◽  
Stefan Imobersteg ◽  
Alain Blanc ◽  
Stephan Frank ◽  
Roger Schibli ◽  
...  

The inhibition of the mammalian target of rapamycin complex 1 (mTORC1) by everolimus (RAD001) was recently shown to enhance the tumor uptake of radiolabeled minigastrin. In this paper, we investigate if this finding can improve the in vivo therapeutic response to [177Lu]Lu-PP-F11N treatment. The N-terminal DOTA-conjugated gastrin analogue PP-F11N (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe) was used to evaluate treatment efficacy in the human A431/CCKBR xenograft nude mouse model in combination with RAD001. Both RAD001 and [177Lu]Lu-PP-F11N single treatments as well as their combination inhibited tumor growth and increased survival. In concomitantly treated mice, the average tumor size and median survival time were significantly reduced and extended, respectively, as compared to the monotherapies. The histological analysis of kidney and stomach dissected after treatment with RAD001 and [177Lu]Lu-PP-F11N did not indicate significant adverse effects. In conclusion, our study data demonstrate the potential of mTORC1 inhibition to substantially improve the therapeutic efficacy of radiolabeled minigastrin analogues in CCKBR-positive cancers.


Author(s):  
Irwan Barlian Immadoel Haq ◽  
Joni Wahyuhadi ◽  
Akhmad Suryonurafif ◽  
Muhammad Reza Arifianto ◽  
Rahadian Indarto Susilo ◽  
...  

Abstract Background Meningiomas arising from the petroclival area remain a challenge for neurosurgeons. Various approaches have been proposed to achieve maximum resection with minimal morbidity and mortality. Also, some articles correlated preservation of adjacent veins with less neurologic deficits. Objective To describe the experiences in using a new technique to achieve maximal resection of petroclival meningiomas and preserving the superior petrosal veins (SPVs) and the superior petrosal sinus (SPS). Methods A retrospective analysis of 26 patients harboring a true petroclival meningioma with a diameter ≥25 mm and undergoing surgery with the modified transpetrosal–transtentorial approach (MTTA) was performed. Results Fifty-four percent of 22 patients complained of severe headache at presentation. There was also complaint of cranial nerve (CN) deficit, with CN VII deficit being the most common (present in 42% of patients). The average tumor size (measured as maximum diameter) was 45.2 mm, and most of the tumors compressed the brainstem. Total resection was achieved in 12 patients (46.2%), whereas the others were excised subtotally (54.8%). Most of the patients had WHO grade I (96.1%) meningioma; only one had a grade II (3.8%) meningioma. In addition, clinical improvement and persistence of symptoms were observed in 17 (65.4%) and 8 (30.7%) patients, respectively, and postoperative permanent CN injury was observed in 3 (11.5%) patients. Conclusion Using the MTTA, maximal resection with preservation of the CNs and neurovascular SPV-SPS complex can be achieved. Therefore, further studies and improvements of the technique are required to increase the total resection rate without neglecting the complications that may develop postoperatively.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4351
Author(s):  
Graziano Ceccarelli ◽  
Gianluca Costa ◽  
Michele De Rosa ◽  
Massimo Codacci Pisanelli ◽  
Barbara Frezza ◽  
...  

Background: Gastrointestinal stromal tumors (GISTs) are most frequently located in the stomach. In the setting of a multidisciplinary approach, surgery represents the best therapeutic option, consisting mainly in a wedge gastric resection. (1) Materials and methods: Between January 2010 to September 2020, 105 patients with a primary gastrointestinal stromal tumor (GISTs) located in the stomach, underwent surgery at three surgical units. (2) Results: A multi-institutional analysis of minimally invasive series including 81 cases (36 laparoscopic and 45 robotic) from 3 referral centers was performed. Males were 35 (43.2%), the average age was 66.64 years old. ASA score ≥3 was 6 (13.3%) in the RS and 4 (11.1%) in the LS and the average tumor size was 4.4 cm. Most of the procedures were wedge resections (N = 76; 93.8%) and the main operative time was 151 min in the RS and 97 min in the LS. Conversion was necessary in five cases (6.2%). (3) Conclusions: Minimal invasive approaches for gastric GISTs performed in selected patients and experienced centers are safe. A robotic approach represents a useful option, especially for GISTs that are more than 5 cm, even located in unfavorable places.


2021 ◽  
pp. 084653712110117
Author(s):  
Tong Wu ◽  
Linda J. Warren

Purpose: We evaluated the contribution to cancer detection of supplemental breast ultrasound screening in women with dense breasts based on a single center experience by comparing our results with similar programs elsewhere. Methods: We performed a retrospective review of handheld sonographer-performed screening ultrasound exams at our academic breast imaging center, from January 1st to December 31st, 2019. Breast density, breast cancer risk factors, BI-RADS assessment, and lesion pathology were reviewed and tallied, followed by derivation of the biopsy rate, breast cancer detection rate, PPV3 and average tumor size. These values were compared to published results of breast screening programs elsewhere. Results: 695 screening breast ultrasounds for women with dense breasts and negative mammograms were performed in 2019. The biopsy rate was 1.3%, breast cancer detection rate was 7 in 1000, PPV3 was 42%, and the average tumor size was 9.0 ± 1.4 mm. Conclusions: The first-year data of the breast screening ultrasound program at our practice are promising, demonstrating comparable cancer detection rate, higher PPV3, and similar biopsy rate in those with dense breasts compared with similar programs elsewhere. Longitudinal analysis and larger sample size are required for validation. Comparison of incidence and prevalence screening data is also warranted to elucidate the true value of this program.


2021 ◽  
pp. 1-7
Author(s):  
Myeong Chan Park ◽  
Sejun Park ◽  
Seong Cheol Kim ◽  
Sungchan Park ◽  
Kyung Hyun Moon ◽  
...  

<b><i>Purpose:</i></b> This study aimed to evaluate the outcomes of large angiomyolipoma (AML) treatment by selective arterial embolization (SAE) versus nephron-sparing surgery (NSS) using a robotic surgical system. <b><i>Materials and Methods:</i></b> Between January 2011 and June 2018, we retrospectively reviewed 25 patients who underwent robot-assisted partial nephrectomy (RAPN) or SAE for large AMLs. Ten patients underwent RAPN, and 15 underwent SAE. Patient demographics, AML characteristics, and operative and postoperative clinical outcomes were recorded and analyzed. Outcomes were compared between patients who underwent RAPN and patients who underwent SAE. Specifically, changes in renal function and size were evaluated after the treatment. <b><i>Results:</i></b> The mean age of the patients was 52.9 years, and 22 of 25 patients were female. The mean maximum AML diameter on computed tomography was 8.9 cm, and 8 patients had multiple masses. Twenty-two of 25 patients had moderate to high RENAL complexity. Patients who underwent SAE had more symptoms (<i>p</i> = 0.018) and higher RENAL complexity scores (<i>p</i> = 0.013) on average. On average, tumor size decreased by 99% among RAPN patients and by 58% among SAE patients (<i>p</i> = 0.001). Although the mean pretreatment estimated glomerular filtration rate (eGFR) was higher among RAPN patients (99.8 vs. 80.0 mL/min/1.73 m<sup>2</sup>, <i>p</i> = 0.043), there were no significant changes in eGFR in either group after the treatment. One patient in the RAPN group experienced complications, but the postoperative ileus resolved without intervention. <b><i>Conclusions:</i></b> Both RAPN and SAE were effective and feasible treatment options for large AMLs. The AML characteristics and the condition of the patient might be important in determining the appropriate treatment method.


2021 ◽  
Vol 17 (3) ◽  
pp. 382-398
Author(s):  
Jin Qian ◽  
Shuo Liu ◽  
Tianshu Yang ◽  
Yi Xiao ◽  
Jiabin Sun ◽  
...  

Multidrug resistance (MDR) remains a significant impediment to chemotherapy during cancer therapy. In this study, the amphiphilic biomaterials PEI-TOS and HA-QU were synthesized to self-assemble into PEI-TOS/HA-QU core–shell micelles for the targeted codelivery of paclitaxel (PTX) and quercetin (QU) to alleviate multidrug drug resistance and enhance therapeutic efficacy. The PTX-loaded micelles possessed a uniform particle size (167.60 ± 8.185 nm), stable negative charge (–19.13 ± 0.321 mV), and pH-responsive drug release with good compatibility. The drug-loaded micelles increased the chemosensitivity of MDR tumor cells (MDA-MB-231/MDR1) to PTX and activated mitochondria-dependent apoptotic pathways (the IC50 was 2.22-fold lower than that of PTX alone). Moreover, PEI-TOS/HA-QU micelles increased the cellular uptake of lipophilic antitumor drugs by downregulating P-gp expression in MDA-MB-231/MDR1 cells. Compared with Taxol, PTX-loaded PEI-TOS/HA-QU micelles presented excellent antitumor efficacy in tumor-bearing mice, with an average tumor size that was 3.7-fold lower than that of the control group. The drug-loaded formulation showed low in vitro / in vivo toxicity and better tumor accumulation than the free drug, which led to a high tumor inhibition rate of 80.56% and considerable biocompatibility. This work describes a new platform for the codelivery of lipophilic anticancer drugs and natural active ingredients such as PTX and QU for the treatment of MDR cancer cells.


2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Thành Vinh Nguyễn ◽  
Đức Tiến Nguyễn

Tóm tắt Đặt vấn đề: Nghiên cứu đặc điểm cận lâm sàng và phân tích chỉ định phẫu thuật nội soi (PTNS) điều trị u tuyến thượng thận (TTT) lành tính không triệu chứng. Phương pháp nghiên cứu: Nghiên cứu tiến cứu 64 người bệnh (NB) u TTT lành tính không triệu chứng được điều trị bằng PTNS tại Bệnh viện Hữu nghị Việt Đức từ tháng 10/2015 đến tháng 10/2018. Kết quả: Tuổi trung bình 45,7. Nam/nữ: 3/5. Kích thước u trung bình 3,0 ± 2,1 cm. 57,8% u không hoạt động nội tiết. 73,4% u tuyến vỏ thượng thận, 17,2% u tủy thượng thận (Pheochromocytoma). Chỉ định mổ: 42,2% do u hoạt động nội tiết, 25% u thay đổi kích thước khi theo dõi, 17,2% u ≥ 4cm và 15,6% u < 4cm (Nghi ngờ Pheochromocytoma) trên cắt lớp vi tính (CLVT). Kết luận: Chỉ định PTNS cắt bỏ tuyến thượng thận nên được khuyến nghị cho những khối u có kích thước lớn hơn 4cm hoặc thay đổi chức năng nội tiết vì tăng nguy cơ ác tính, đặc biệt là ở những người bệnh trẻ tuổi. Đánh giá nội tiết nên được thực hiện ở tất cả các người bệnh để xác định tình trạng tăng tiết hormon mà chưa có biểu hiện lâm sàng. Abstract Introduction: Research of subclinical characteristics and analytical indications of the laparoscopic adrenalectomy for benign adrenal incidentaloma. Materials and Methods: Prospective research in 64 patients with adrenal incidentaloma underwent laparoscopic adrenalectomy at Viet Duc University Hospital from 10/2015 to 10/2018. Results: The average of age was 45,7 years old, male / female was 3/5. Average tumor size was 3,0 ± 2,1cm. Benign non-functional accounted for 57,8%. Adenoma is 73,4% and Pheochromocytoma in 17,2%. Indications for surgery: 42,2% of secretion tumors, 25% tumors changed in size during follow-up time, 17,2% tumors sized ≥ 4cm and 15,6% tumors sized < 4cm (suspect Pheochromocytoma) in CT scan check. Conclusion: Indications of laparoscopic adrenalectomy should be recommended for adrenal incidentaloma size over 4 cm because of the risk of malignancy, especially in young patients. Endocrine evaluation should be performed in all patients to identify silent states of hormone excess. Keywords: Adrenal adenoma, adrenal gland.


BMC Surgery ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Isamu Hoshino ◽  
Hisashi Gunji ◽  
Fumitaka Ishige ◽  
Yosuke Iwatate ◽  
Nobuhiro Takiguchi ◽  
...  

Abstract Background The number of patients with esophagogastric junction (EGJ) cancers has tended to increase. However, no clear consensus on the optimum treatment policy has yet been reached. Methods This study included patients diagnosed with adenocarcinoma of Sievert type II in whom resection was performed in our hospital. We performed a clinicopathological examination, and patients were divided into two groups by the tumor size: L group, tumor size ≥4 cm; and S group, tumor size < 4 cm. The clinical factors, such as nodal dissection and recurrence pattern, were then analyzed. Results A total of 48 patients were diagnosed with ECJ cancers. The average tumor size was 55.1 mm, and 32 cases (66.7%) had tumors ≥4 cm. Metastasis to the mediastinum was noted in 4 cases (12.5%) in the L group but none in the S group. Recurrence in the upper or middle mediastinum lymph nodes was noted in 3 cases (9.4%) in the L group. The 5-year overall survival rates were 49.7 and 83.9% in the L and S groups, respectively. Conclusions As the tumor grows large, it is difficult to accurately judge EGJ on the image, and as a result it is difficult to understand the exact esophageal invasion distance of the tumor. Therefore, lymph node dissection including the upper mediastinum is considered vital, regardless of the degree of esophageal invasion.


2019 ◽  
Vol 6 (9) ◽  
pp. 3211
Author(s):  
Udit Jaydeep Shah ◽  
Sushil D. Akruwala ◽  
Vidhyasagar M. Sharma ◽  
Manubhai V. Pipalia

Background: Gastrointestinal stromal tumors (GIST) have been recognized as a biologically distinctive tumor type, different from the smooth muscle and neural tumors of the gastrointestinal tract. They constitute majority of the gastrointestinal mesenchymal tumors of the gastrointestinal tract and are considered to be refractory to conventional chemotherapy or radiation. Surgery remains the mainstay of primary tumor management of GIST.Methods: This was a cross sectional study of the diagnosis, management and clinical outcome of cases diagnosed with GIST of the gastrointestinal tract from a teaching institute in a single year and a comparison of findings with previously published cases.­­ Study included patients newly diagnosed with GIST and managed in department of general surgery from 10 April 2018 to 31 March 2019.Results: Most patients were of age group 60-69 years with an almost equal incidence among males and females. Stomach and small bowel were found to be the commonest sites with an equal distribution of 45.45% with an average tumor size of 5 cms.Conclusions: Surgical treatment remains the main stay of management for the GIST, depending on the location, staging and metastasis. Staging laparoscopy may be done to assess respectability as peritoneal deposits can be missed by CT scan. Immunohistochemistry is mandatory in defining GIST.


2019 ◽  
Vol 161 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Solymar Torres Maldonado ◽  
James G. Naples ◽  
Ramie Fathy ◽  
Steven J. Eliades ◽  
John Y. K. Lee ◽  
...  

ObjectiveA better understanding of the natural history of vestibular schwannoma (VS) has resulted in a change in treatment paradigms. It has also been proposed that increased use of high-resolution magnetic resonance imaging has allowed for an increased identification of small tumors. The aim of this study was to evaluate recent trends in the presentation and primary management of VS in the United States.Study DesignRetrospective analysis of the National Cancer Database (NCDB).SettingNCDB database.Subjects and MethodsAll patients with a diagnosis of VS between 2004 and 2014 were included. Data were analyzed with univariable and multivariable logistic regression.ResultsIn total, 28,190 patients (mean age 55 years, 52.9% female) with VS were analyzed. Linear regression showed a small decrease in average tumor size over time (–0.06 mm/year, P = .03). Overall, 11,121 patients (40%) received surgery, 8512 (30%) radiation, and 7686 (27%) observation. Controlling for patient, tumor, and treatment center factors, the odds ratio (OR) for receiving surgery in 2014 was 0.60 (confidence interval [CI], 0.50-0.71) while the OR for receiving radiation was 0.75 (CI, 0.64-0.87) as compared to those diagnosed in 2004. The largest increases in observation rates occurred among tumors ≤2 cm ( P < .001).ConclusionThere was not a clinically significant change in the average tumor size at diagnosis. Although surgery remained the most common treatment modality in the United States, there was a strong shift in the management of VS away from primary surgery and radiation and toward a “wait-and-scan” approach.


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