Objective:To explore the efficient prognostic factors of cryotherapy for prostate cancer in the real-world setting.Methods:The clinical data of 105 prostate cancer patients treated at the Fudan University Shanghai Cancer center from January 2021 to December 2023 were analyzed retrospectively. The patients were divided into a non-metastatic group (62 cases, 58.7%) and a metastatic group (43 cases, 41.3%) based on the presence or absence of distant metastasis. In the non-metastatic group, the median age was 79 years (range 73 to 82), the initial PSA was 20 ng/ml (range 10 to 47), 37 cases (59.7%) received neoadjuvant endocrine therapy, and the preoperative PSA was 8 ng/ml (range 2 to 14). The ISUP grades were Grade 1 in 4 cases (6.5%), Grade 2 in 11 cases (17.7%), Grade 3 in 16 cases (25.8%), Grade 4 in 16 cases (25.8%), and Grade 5 in 15 cases (24.2%). The T-stages were T 2 in 49 cases, T 3 in 6 cases, and T 4 in 7 cases. All cases were N 0. In the metastatic group, the median age was 68 years (range 62 to 74), the initial PSA was 64 ng/ml (range 27 to 200), 42 cases (97.7%) received neoadjuvant endocrine therapy, and the preoperative PSA was 0 ng/ml (range 0 to 3). The ISUP grades were Grade 1 in 0 cases, Grade 2 in 5 cases (11.6%), Grade 3 in 3 cases (7.0%), Grade 4 in 19 cases (44.2%), and Grade 5 in 16 cases (37.2%). The T-stages were T 2 in 29 cases (67.4%), T 3 in 8 cases (18.6%), and T 4 in 6 cases (14.0%). The N-stages were N 0 in 38 cases (88.4%) and N 1 in 5 cases (11.6%). The M-stages were M 1a in 5 cases (11.6%), M 1b in 35 cases (81.4%), and M 1c in 3 cases (7.0%). The difference in T-stage between the two groups was not statistically significant ( P=0.346), while differences in other indicators were statistically significant ( P<0.05). The cryotherapy for prostate cancer was performed under general or local anesthesia, with the patients in the lithotomy position and a F20 three-lumen catheter was placed for continuous irrigation. Under transrectal ultrasound guidance, the cryoprobes were inserted parallel to the probe through the perineum, with a safe distance of 3 mm from the bladder wall. A whole-gland freezing mode was adopted, starting from the ventral side and freezing layer by layer towards the rectal side. Ultrasound was used in real-time to observe the ice ball's position and extent, adjusting it during ablation to conform to the prostate's margins while protecting surrounding structures. After ablation, the cryoprobes were removed, the puncture sites were disinfected with povidone-iodine, and gauze was applied for 20 seconds to achieve hemostasis before applying dressings. The catheter was removed 10 days postoperatively. PSA levels were rechecked on the first postoperative day and at 6 and 12 weeks postoperatively. The ratio of PSA on the first postoperative day to preoperative PSA was defined as the PSA release rate. Biochemical recurrence was defined as a PSA increase of more than 0.2 ng/ml above the postoperative nadir. The PSA progression-free survival time and the incidence of complications were compared between the two groups. Results:All procedures were successfully completed. The PSA release rates for the non-metastatic and metastatic groups were 4.2 (2.2, 6.4) and 3.9 (1.5, 6.7), respectively, with no statistical significant difference ( P=0.8272). The median PSA at 6 weeks postoperatively was 0.23 (0.01, 1.22) ng/ml, and at 12 weeks it was 0.02 (0.01, 0.49) ng/ml. The median PSA for the non-metastatic group was 0.42 (0.25, 1.00) ng/ml at 6 weeks, and it was 0.03 (0.01, 0.57) ng/ml at 12 weeks. For the metastatic group, the median PSA was 0.30 (0.14, 0.50) ng/ml at 6 weeks, and it was 0.02 (0.01, 1.17) ng/ml at 12 weeks. The median follow-up period was 339 days (range 128 to 571). No Clavien-Dindo grade ≥2 complications occurred postoperatively. One case (0.9%) experienced bladder neck stricture one month postoperatively, which improved by transurethral resection of the prostate (TURP). Two cases (1.9%) experienced urinary retention seven days postoperatively, which resolved after re-catheterization for two weeks. No urinary incontinence was reported. Two non-tumor-related deaths occurred (1.9%), one due to cardiac disease and the other due to complications from COVID-19. During follow-up, 29 cases (27.6%) experienced PSA progression, with a median PSA progression-free survival time of 808.0 days. The median PSA progression-free survival time was not reached in the non-metastatic group, while it was 764.0 days in the metastatic group. There was no statistical significant difference in PSA progression-free survival between the two groups ( P=0.422). Univariate analysis showed that preoperative PSA ( HR=1.02, 95% CI 1.00-1.03, P=0.048), T 3 stage ( HR=9.00, 95% CI 2.59-31.25, P<0.01), and T 4 stage ( HR=5.83, 95% CI 1.68-20.21, P=0.005) were prognostic factors for PSA progression-free survival. Multivariate analysis showed that T 3 stage ( HR=9.08, 95% CI 2.47-33.45, P<0.01) and T 4 stage ( HR=4.50, 95% CI 1.18-17.22, P=0.028) were independent prognostic factors for PSA progression-free survival. Conclusions:Cryotherapy for prostate cancer has a high safety profile. The efficacy of Cryotherapy is better in patients with T-stage

OBJECTIVES: This study investigate the clinical and imaging features of Ewing sarcoma (ES) of the jaw. METHODS: Eight cases of pathologically diagnosed ES of the jaw from January 2010 to June 2022 were included in the study. Clinical and radiological features were retrospectively analyzed. RESULTS: Among the eight cases, the mean age at onset was 29.4 years, and the male to female ratio was 7∶1. The predilecting site was the posterior part of mandible, accounting for 75% of the cases. The lesions often exhibited early numbness of the lower lip and lymphadenopathy. The main radiographic manifestation of mandibular lesions was ill-defined radiolucency, mixed with fibrous or brush-like tumor matrix, and soft tissue mass. The maxillary ES lesions mainly presented as lytic bone destruction accompanied by adjacent soft tissue mass. Periosteal ossification was rarely seen. CONCLUSIONS The clinical and imaging characteristics of ES in the jaw are helpful for its diagnosis.
Male ; Humans ; Female ; Sarcoma, Ewing/pathology* ; Retrospective Studies ; Radiography ; Mandible/pathology* ; Lip ; Bone Neoplasms

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.

Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective:To explore the clinical value of cryoablation technology in the treatment of patients with primary tumor recurrence after radical radiotherapy for prostate cancer.Methods:The clinical data of 21 patients with prostate cancer recurrence after radical radiotherapy in the Fudan University Affiliated Cancer Hospital from August 2017 to February 2021 was retrospectively analyzed. The average age was 73.1 (57.3-85.0) years old, and the Gleason score was 6 in 5 cases, 7 in 8 cases, and ≥8 in 8 cases. The clinical stage of the first diagnosis: 13 cases of cT 2 stage; 8 cases of cT 3 stage. The baseline PSA before radiotherapy was 35.3 (6.4-78.5) ng/ml, and the lowest PSA after radiotherapy was 1.8 ng/ml. After a median follow-up of 8 (3-12) months, all patients were detected with persistently elevated PSA. Pelvic MRI and PSMA SPECT showed that the primary prostate lesion had recurred. PSA before cryoablation was 4.1 (1.8-14.4) ng/ml. Comprehensive assessment of preoperative examination showed that the patient only had a recurrence of the primary tumor, and no lymph node or distant metastasis was seen. An argon-helium cryogenic surgical treatment system was used to place 1 to 3 cryo-needles for recurring lesions, and cryoablation was performed using two cold and hot cycles. Observation indicators include prognostic indicators such as PSA, recurrence and metastasis, and the occurrence of adverse reactions. Results:Complications after cryoablation include: 2 cases of urinary retention, 1 case of urinary tract infection, and 2 cases of urination with tissue shedding. The PSA of 11 cases decreased rapidly 2 to 3 months after operation, and dropped to the lowest median value of 0.4 (0.003 to 2.8) ng/ml. After cryoablation, the median follow-up was 18 (6-51) months. Imaging examinations in 1 case showed that the prostate still had limited diffusion or increased PSMA uptake, and 4 cases had PSA progression but no recurrence or metastasis. The median recurrence time for advanced patients was 13 (4-36) months. Larger prostate volume ( P<0.001) and higher blood PSA before ablation( P=0.021) were related to biochemical recurrence. Conclusions:Prostate cryoablation could delay the progression of the primary tumor after radical radiotherapy for prostate cancer. The incidence of complications such as urinary retention and urinary tract infection is not high, and it is generally safe and controllable.

Objective:To observe the clinical effect and safety of regional lymph node dissection in metastatic castration resistant prostate cancer(mCRPC).Methods:The clinical data of 22 patients with mCRPC who underwent regional lymph node dissection in our hospital from August 2015 to May 2021 were retrospectively analyzed. All patients had undergone radical prostatectomy and entered mCRPC, metastatic lymph nodes limited to pelvic or retroperitoneal without other metastasis were determined by PSMA-PET in 5 cases and PSMA-SPECT in 17 cases. The median time from radical surgery to mCRPC was 32 (4-96) months, and the median time from discovery of mCRPC to regional lymph node dissection was 4 (1-43) months. The median PSA before regional lymph node dissection was 4.44 (2.00-22.15) ng/ml. Image of local examination showed pelvic lymph node metastasis in 16 cases, retroperitoneal lymph node metastasis in 3 cases, pelvic together with retroperitoneal lymph node metastasis in 3 cases. Before regional lymph node dissection, 18 patients were treated with drug castration combined with first-generation antiandrogens, and 4 patients were treated with drug castration combined with abiraterone. The lymph node dissection range was determined according to the location of metastatic lymph nodes. Obturator lymph nodes and lymph node metastasis around external iliac and internal iliac vessels: the range of dissection includes fibrous adipose tissue around external iliac vein and internal iliac vein, and obturator lymph adipose tissue. Common iliac and pelvic floor lymph node metastasis: dissect lymphoid adipose tissue around common iliac vessels on the basis of the original dissection range as far as the aortic bifurcation. Retroperitoneal lymph node metastasis: remove all lymph node adipose tissue located between the bifurcation of renal artery and aorta. The PSA remission rate, PSA remission time, surgical complications and other relevant clinicopathological features were analyzed.Results:Among the 22 cases, 6 cases underwent unilateral pelvic lymph node dissection, 10 cases underwent bilateral pelvic lymph node dissection, 3 cases underwent retroperitoneal lymph node dissection, and 3 cases underwent pelvic and retroperitoneal lymph node dissection at the same time. 19 cases (86.3%) showed positive lymph nodes by pathology. An average of 9.8 (3-29) lymph nodes were dissected in each patient, with an average of 4.1 (0-12) positive lymph nodes. All 22 cases continued to use the previous anti-androgen therapy after lymph node dissection. 17 cases (77.3%) achieved PSA remission after operation, of which 9 cases developed PSA progression, and the median PSA progression time was 12 (2-36) months. Univariate analysis showed that PSA value during radical operation ( P=0.029), N stage during radical operation ( P=0.057), the number of positive lymph nodes during regional lymph node dissection ( P=0.069) and the location of lymph node metastasis during regional lymph node dissection ( P =0.005) were related to the progression time of PSA. Postoperative complications: lymphatic leakage in 7 cases; 5 cases of postoperative fever, of which 1 case was confirmed to have pelvic bacterial infection. One patient suffered from massive intra-operative bleeding due to the invasion of blood vessels by metastatic lymph nodes. After timely hemostasis during the operation, the patient returned to the ward and was discharged 6 days later. One case of intestinal obstruction, and 1 case of body surface wound infection. 6 cases of lymphatic leakage healed within 1 month after operation, and 1 case of lymphatic leakage healed within 3 months after operation. Conclusions:For mCRPC patients with lymph node metastasis which could be surgically removed, regional lymph node dissection may further delay the starting time of posterior drugs, and the complications are relatively controllable.

Retrospectively analyze the clinicopathological data of a patient with metastatic hormone sensitive prostate cancer, and review relevant literature. The patient was male, 68 years old. Complaints of dysuria and urgency for half a year. Blood PSA>100 ng/ml, magnetic resonance showed that the prostate was occupying space, the boundary with the seminal vesicle gland was not clear, and the pelvic cavity had multiple bone lesions. Bone scan revealed multiple bone metastases. The prostate biopsy showed adenocarcinoma, Gleason score 5+ 5. The clinical stage was T 3N 0M 1b.A palliative transurethral resection of the prostate was performed due to urination obstruction, and endocrine therapy with medical castration combined with abiraterone and prednisone. PSA was continuously controlled at <0.006 ng/ml. After half a year of treatment, the prostate-specific membrane antigen single-photon emission computerized tomography and magnetic resonance examination revealed sternal and parasternal soft tissue lesions. Local radiotherapy and continuous endocrine therapy were given. The disease was under long-term control.There are various treatment options for metastatic hormone sensitive prostate cancer. Medical castration treatment combined with abiraterone and prednisone can effectively control the disease with mild adverse reactions. Palliative transurethral resection of the prostate can improve the symptoms of urinary obstruction and may also improve the prognosis of patients.

Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q_R)) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m² intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) μg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 μg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 μg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.