Follicular adenoma with a papillary architecture originating from an ectopic thyroid gland: a case report.

BACKGROUND: Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. CASE PRESENTATION: A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. CONCLUSION: This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors.

Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Clinical outcomes of first-line combination therapy with immune checkpoint inhibitor for metastatic non-clear cell renal cell carcinoma: a multi-institutional retrospective study in Japan.

BACKGROUND: In metastatic clear cell renal cell carcinoma (ccRCC), recent studies have shown promising efficacy of immune checkpoint inhibitor (ICI) combination therapy. However, there are insufficient evidences about clinical efficacy and safety of ICI combination therapy in metastatic non-ccRCC (nccRCC). METHODS: We retrospectively investigated 44 patients treated with nivolumab plus ipilimumab (ICI + ICI group) or anti-PD-1/PD-L1 inhibitor plus tyrosine kinase inhibitors (TKI) (ICI + TKI group), and assessed clinical efficacy in both groups. RESULTS: Of all patients, overall response rate and disease control rate for ICI combination treatments were 36.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 8.8 and 23.9 months, respectively. Multivariate analysis revealed that the presence of liver metastasis significantly affected worse PFS and OS (p = 0.035 and p = 0.049). Importantly, PFS and OS seemed similar in ICI + ICI group and ICI + TKI group (p = 0.778 and p = 0.559). Although the discontinuation rate of the combination therapy due to adverse effects in patients aged ≥ 75 years was significantly higher compared to that in patients aged < 75 years (45% versus 12%, p = 0.017), there were no significant differences in PFS and OS between two groups (p = 0.290 and p = 0.257, respectively). CONCLUSION: This study confirms clinical benefit of ICI combination therapy for metastatic nccRCC patients in real-world settings. Furthermore, the effectiveness of combination therapy was comparable between patients aged < 75 and those ≥75 years with respect to clinical prognosis.

3-Fr steerable microcatheter system via the upper limb artery in RADPLAT for right maxillary cancer.

BACKGROUND: To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC). MATERIAL AND METHODS: We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system. RESULTS: Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure. CONCLUSION: Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

[A Case of Prostate Cancer Diagnosed by the Bone Biopsy of the Right Iliac Metastatic Lesion].

A 73-year-old man was referred to our hospital because of a high prostate specific antigen (PSA) level. The PSA level at our hospital was 63.5 ng/ml. Pelvic magnetic resonance imaging (MRI) showed findings strongly suggestive of multiple pelvic bone metastases, but no obvious malignant findings in the prostate. A 12-core prostate biopsy was performed and no cancer was detected. Computed tomography and bone scintigraphy showed findings suspicious of bone metastases in the sternum, thoracolumbar spine, pelvic bone, and sacrum. Spine MRI revealed a mass in the vertebral body from the eighth thoracic vertebra to the first lumbar vertebra. A biopsy of the right iliac crest showed adenocarcinoma and was positive for PSA staining, leading to the diagnosis of multiple bone metastases of prostate cancer. Abiraterone acetate in combination with androgen deprivation was started. He received medication and radiation therapy to his sternum for pain relief. Spine MRI after 4 months showed decreased vertebral body weights and serum PSA levels were ＜0.003 ng/ml after 5 months. Seventeen months after treatment, PSA remains below 0.003 ng/ml, and the patient is currently pain-free.

Retrospective study of online ligation student practice incorporating flipped learning into e-learning.

PURPOSE: Flipped learning has been applied in various fields, including medical professional education. E-learning is compatible with flipped learning; however, it is considered to be unsuitable for providing training on surgical techniques. In this study, we retrospectively examined the ligation performance of online students who underwent training with flipped learning incorporated into e-learning. METHODS: We conducted a retrospective study of the ligation practices of online students at the Department of General Surgery from March 2020 to June 2021. The subjects included 134 fourth- and fifth-year medical students from Gunma University School of Medicine. We conducted mid-term checks on the 8th day of practice and an examination on the 19th day. Two instructors independently evaluated and calculated scores using the original Global Rating Scale of Gunma University. We also conducted a questionnaire survey on the ligation practice of online students. RESULTS: The total average score of the three tasks was 12.4 for Instructor 1 and 12.0 for Instructor 2. All students had a passing score. The questionnaire survey showed that 70% of the students were trained in ligation at the time of the first evaluation. CONCLUSIONS: Our online training materials and training methods enabled the acquisition of ligation skills by students who had not previously received ligation training.

Molecular Topology of the Transit Peptide during Chloroplast Protein Import.

Chloroplast protein import is directed by the interaction of the targeting signal (transit peptide) of nucleus-encoded preproteins with translocons at the outer (TOC) and inner (TIC) chloroplast envelope membranes. Studies of the energetics and determinants of transit peptide binding have led to the hypothesis that import occurs through sequential recognition of transit peptides by components of TOC and TIC during protein import. To test this hypothesis, we employed a site-specific cross-linking approach to map transit peptide topology in relation to TOC-TIC components at specific stages of import in Arabidopsis thaliana and pea (Pisum sativum). We demonstrate that the transit peptide is in contact with Tic20 at the inner envelope in addition to TOC complex components at the earliest stages of chloroplast binding. Low levels of ATP hydrolysis catalyze the commitment of the preprotein to import by promoting further penetration across the envelope membranes and stabilizing the association of the preprotein with TOC-TIC. GTP hydrolysis at the TOC receptors serves as a checkpoint to regulate the ATP-dependent commitment of the preprotein to import and is not essential to drive preprotein import. Our results demonstrate the close cooperativity of the TOC and TIC machinery at each stage of transit peptide recognition and membrane translocation during protein import.

Significant association between the preoperative erythrocyte mean corpuscular volume and infectious complications after pancreaticoduodenectomy.

PURPOSE: An organ/space surgical site infection reportedly develops in 20% of patients who undergo pancreaticoduodenectomy (PD). The present study aimed to identify the predictors for developing severe infectious complications after PD. METHODS: We retrospectively reviewed the records of 115 consecutive patients who underwent PD at Ehime University Hospital between January 2013 and January 2020. Severe infectious complications were defined as Clavien-Dindo classification grade ≥ III postoperative complications related to bacterial or fungal infections, including clinically relevant postoperative pancreatic fistula (CR-POPF). The patient characteristics, blood chemistry data, body composition data and operative data were evaluated as potential predictors of severe infectious complications. We also evaluated the erythrocyte indices, such as the mean corpuscular hemoglobin, the mean corpuscular hemoglobin concentration, and the mean corpuscular volume (MCV). RESULTS: Among 115 patients, 25 (21.7%) developed severe infectious complications, which included 20 (17.4%) cases of CR-POPF. According to multivariate analyses, MCV > 97.4fL, C-reactive protein (CRP) > 1.2 mg/dL and diameter of main pancreatic duct < 5 mm were independent predictors of severe infectious complications (odds ratio, 13.891, 7.356 and 4.676, respectively, 95% confidence interval, 3.457-55.815, 1.868-28.964 and 1.391-15.716, respectively). CONCLUSION: Preoperative high MCV/CRP values and a small main pancreatic duct are predictive factors associated with severe infectious complications after PD.

Technical details of a left-side approach to the superior mesenteric artery during pancreaticoduodenectomy.

BACKGROUND AND PURPOSE: To describe the procedure for a left-side approach to the superior mesenteric artery (SMA) during pancreaticoduodenectomy (PD) in a cadaveric study. OPERATIVE PROCEDURE: After dividing the upper jejunum, the jejunal artery (JA) is followed to its origin. At the cranial side of the JA, the mesojejunum to be dissected is detached from the ventral to the dorsal side and from the peripheral to the origin side of the SMA. The inferior pancreatoduodenal artery (IPDA), which is usually the common trunk of the IPDA and the first JA, is able to be visualized at the cranio-dorsal side of the origin of the JA. After cutting the IPDA, the mesojejunum can be detached from the SMA from the dorsal aspect to the right side. Subsequently, the pancreas head is dissected easily from the right aspect of the SMA. CONCLUSION: This left-side approach to the SMA may become a standard procedure.

[Left Essential Renal Hematuria, that Cannot Be Stopped by Ureteroscopy, Successfully Treated with the Instillation of Hydrogen Peroxide into the Renal Pelvis : A Case Report].

We report a case of left essential renal hematuria successfully treated with the instillation of hydrogen peroxide into the renal pelvis. A 68-year-old man was referred to our hospital with the chief complaint of gross hematuria. Our diagnosis was left renal essential hematuria. We could not find the bleeding point using a flexible ureteroscope. Due to prolonged gross hematuria, we performed instillation of hydrogen peroxide into the renal pelvis and the gross hematuria completely disappeared. Retrograde hydrogen peroxide instillation therapy is useful and safe for essential renal hematuria.

Serosal invasion is a strong prognostic factor for hepatocellular carcinoma after hepatectomy.

AIM: The clinical impact of serosal invasion by hepatocellular carcinoma (HCC) remains unclear. This study aimed to clarify the significance of serosal invasion as a prognostic factor for patients who underwent hepatectomy for HCC. METHODS: This retrospective study investigated patients who underwent hepatectomy for HCC between October 2003 and September 2016 in Ehime University Hospital (Toon, Japan). A total of 161 cases were enrolled after excluding cases of concomitant distant metastasis, macroscopic tumor remnant, mixed HCC, and rehepatectomy. We classified these 161 patients into groups with serosal invasion detected (S[+]) and serosal invasion undetected (S[-]). We compared patient characteristics, perioperative data, pathological findings, and prognosis between S(+) and S(-) groups. RESULTS: Serosal invasion was observed in 19 of the 161 patients (12%). The 5-year recurrence-free survival rate was lower for S(+) (13.0%) than for S(-) (28.7%, P = 0.006). The 5-year overall survival (OS) rate was lower for S(+) (24.7%) than for S(-) (63.9%, P < 0.001). Regarding OS, serosal invasion, preoperative α-fetoprotein value, presence of invasion to hepatic veins, and liver cirrhosis were independent predictors in multivariate analyses. The 3-year OS rate after recurrence was poorer in the S(+) group (22.9%) than in the S(-) group (49.7%, P = 0.001). CONCLUSIONS: Serosal invasion was a strong predictor of worse outcomes after hepatectomy for HCC. Patients showing serosal invasion need close postoperative follow-up or consideration of adjuvant treatment.

Preformed donor-specific antibodies are associated with 90-day mortality in living-donor liver transplantation.

AIM: The impact of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) on living donor liver transplantation (LDLT) is unclear. The aim of this study was to investigate the association between DSAs and short-term outcomes in LDLT recipients, and to clarify the clinical impact of DSAs. METHOD: Anti-HLA antibodies were screened in preoperative serum samples taken from 40 liver transplant recipients at Ehime University (Toon, Japan) between August 2001 and July 2015. Screening was carried out using the Flow-PRA method, and DSAs were detected in anti-HLA antibody-positive recipients using the Luminex single-antigen identification test. A mean fluorescence intensity of 1000 was used as the cut-off for positivity. We retrospectively reviewed the clinical courses of patients who were DSA-positive to elucidate early clinical manifestations in LDLT recipients. RESULTS: Fifteen (12 female and 3 male) patients (38%) had anti-HLA antibodies. Eight of the 15 anti-HLA antibody-positive patients were positive for DSAs, and all were women. The 90-day survival rate of DSA-positive patients (50%) was significantly lower than that of DSA-negative patients (84.4%) (0.0112; Wilcoxon test). On univariate analysis, the DSA-positive rate was significantly higher in the 90-day mortality group. Postoperatively, the incidence of acute cellular rejection was higher in DSA-positive than DSA-negative patients. Thrombotic microangiopathy developed only in DSA-positive patients. We found no relationship between DSA status and bile duct stricture. CONCLUSION: Preformed DSAs could be associated with elevated 90-day mortality in LDLT recipients. Further large-scale studies are required to verify the risk associated with DSAs in LDLT.

[Malignant Mesothelioma of the Tunica Vaginalis Testis : A Case Report].

A 56-year-old man presented with a painless swelling of the left scrotum. Cytologic examination of blood stained hydrocele fluid suggested malignancy. Left high orchiectomy was performed under the suspicion of malignant tumor of the tunica vaginalis testis. The final pathologic report revealed malignant mesothelioma of the tunica vaginalis testis. There is no evidence of recurrence after 114 months followup. It is important to perform en bloc resection for this disease to prevent recurrence.

Mechanism of Dual Targeting of the Phytochrome Signaling Component HEMERA/pTAC12 to Plastids and the Nucleus.

HEMERA (HMR) is a nuclear and plastidial dual-targeted protein. While it functions in the nucleus as a transcriptional coactivator in phytochrome signaling to regulate a distinct set of light-responsive, growth-relevant genes, in plastids it is known as pTAC12, which associates with the plastid-encoded RNA polymerase, and is essential for inducing the plastomic photosynthetic genes and initiating chloroplast biogenesis. However, the mechanism of targeting HMR to the nucleus and plastids is still poorly understood. Here, we show that HMR can be directly imported into chloroplasts through a transit peptide residing in the N-terminal 50 amino acids. Upon cleavage of the transit peptide and additional proteolytic processing, mature HMR, which begins from Lys-58, retains its biochemical properties in phytochrome signaling. Unexpectedly, expression of mature HMR failed to rescue not only the plastidial but also the nuclear defects of the hmr mutant. This is because the predicted nuclear localization signals of HMR are nonfunctional, and therefore mature HMR is unable to accumulate in either plastids or the nucleus. Surprisingly, fusing the transit peptide of the small subunit of Rubisco with mature HMR rescues both its plastidial and nuclear localization and functions. These results, combined with the observation that the nuclear form of HMR has the same reduced molecular mass as plastidial HMR, support a retrograde protein translocation mechanism in which HMR is targeted first to plastids, processed to the mature form, and then relocated to the nucleus.

[Early Diagnosis of Squamous Cell Carcinoma of the Urinary Bladder Reached by Routine Abdominal Ultrasonography in a Patient on Self-Catheterization : A Case Report].

A 69-year-old woman was referred to our department for refractory cystitis. Incomplete emptying of the bladder was observed, and symptoms did not improve after medication. Clean intermittent catheterization was initiated. Two years after introduction of catheterization, a mass in the bladder dome was detected by routine abdominal ultrasonography. She was diagnosed with malignant tumor of the bladder diverticulum based on cystoscopy, computed tomography, and magnetic resonance imaging. Partial cystectomy and lymph node dissection was performed following transurethral resection of the bladder tumor. Histopathology revealed squamous cell carcinoma and no signs of lymph node metastasis. She is alive and recurrence-free 28 months after surgery.

An essential role for chloroplast heat shock protein 90 (Hsp90C) in protein import into chloroplasts.

Chloroplast heat shock protein 90 (Hsp90C) represents a highly conserved subfamily of the Hsp90 family of molecular chaperones whose function has not been defined. We identified Hsp90C as a component that interacts with import intermediates of nuclear-encoded preproteins during posttranslational import into isolated chloroplasts. Hsp90C was specifically coprecipitated with a complex of protein import components, including Tic110, Tic40, Toc75, Tic22, and the stromal chaperones, Hsp93 and Hsp70. Radicicol, an inhibitor of Hsp90 ATPase activity, reversibly inhibited the import of a variety of preproteins during translocation across the inner envelope membrane, indicating that Hsp90C functions in membrane translocation into the organelle. Hsp90C is encoded by a single gene in Arabidopsis thaliana, and insertion mutations in the Hsp90C gene are embryo lethal, indicating an essential function for the chaperone in plant viability. On the basis of these results, we propose that Hsp90C functions within a chaperone complex in the chloroplast stroma to facilitate membrane translocation during protein import into the organelle.

[Outcomes of Bridge to Surgery for Obstructive Colorectal Cancer after Metallic Stent Placement in Our Hospital].

Recently, the endoscopic placement of self-expanding metallicstents (SEMSs)has become widespread for the treatment of acute malignant colorectal obstruction. This study was designed to evaluate the clinical outcomes of 22 patients with obstructive colorectal cancer who underwent SEMS placement as a bridge to surgery(BTS)from January 2012 to December 2015. The subjects comprised 15 men and 7 women with a mean age of 68.1 years. Placement and decompression were successfully achieved in all cases. No serious complications arose from the placement. After excluding 3 patients for whom preoperative chemotherapy or treatment for another disease was prioritized, the mean interval to surgery for the remaining 19 patients was 18.2 days. Operative anastomosis was performed in all patients except those who had tandem lesions. Although postoperative complications including minor leakage(n=1), surgical site infection(n=1), and ileus(n=1)were observed, the course was effective in most patients. Bridge to surgery is a relatively easy, safe, and effective method for the treatment of obstructive colorectal cancer that enables preoperative intestinal decompression and one-stage resection, preventing stoma creation.

Prostate-specific antigen measured 3 months after radical prostatectomy as a new predictor of biochemical recurrence.

BACKGROUND: This study was undertaken to investigate if the prostate-specific antigen (PSA) level measured 3 months after radical prostatectomy (RP) is a predictor of biochemical recurrence (BCR)-free survival. METHODS: We retrospectively reviewed the clinicopathologic data of 174 patients with a follow-up of at least 3 years after RP for clinically localized prostate cancer. None of the patients received neoadjuvant/adjuvant therapy. Subjects were categorized according to PSA level 3 months after RP (3M-PSA): <0.010 ng/mL (group 1; n = 119) or 0.010-0.100 ng/mL (group 2; n = 55). BCR was defined as two consecutive rises in PSA level ≥0.2 ng/mL. RESULTS: At a median follow-up of 69.5 months (range 36-113 months), 32 (18.4 %) patients experienced BCR. The median time to BCR was 16 months (range 4-98 months) after RP. The 5-year BCR-free survival rate was 92.6 and 57.4 % in groups 1 and 2, respectively. Patients in group 1 had a significantly higher BCR-free survival rate than those in group 2 (log-rank P < 0.001). According to the Cox proportional hazards model, patients with a 3M-PSA level of <0.010 ng/mL were at lower risk for BCR (P < 0.001), along with pathologic Gleason sum 6 (P = 0.028). PSA nadir level after RP was also a risk factor for BCR (log-rank P < 0.001). Area under the receiver operating characteristic curve for 3M-PSA to predict BCR was almost equivalent to that for the PSA nadir level (0.855 vs. 0.849). CONCLUSIONS: 3M-PSA is an independent predictor of BCR-free survival. Our findings might be used for a risk-adjusted follow-up protocol.

The Transmediastinal, Intrapericardial Inferior Vena Cava Approach for Hepatectomy of a Large Liver Tumor Invading the Hepatic Vein Confluence.

We report the case of a large multilocular upper liver tumor invading the hepatic vein confluence in a 41-year-old male, and the safe resection of the tumor using a transmediastinal, intrapericardial inferior vena cava (IVC) approach. Several methods for exposing suprahepatic IVCs on the cranial side of the diaphragm have been reported. However, the approach to supradiaphragmatic IVCs varies, and there are currently no reports that provide a detailed description of the anatomical landmarks during the intrapericardial IVC approach. In the case reported herein, anatomic landmarks, including the prepericardial fat in the pericardial trigone, were confirmed during the transmediastinal, intrapericardial IVC approach. We believe that such anatomic landmarks are important to ensure a safe approach to the pericardium and the intrapericardial IVC through the anterior mediastinum. We think this case report is useful in elucidating the resection of large liver tumors invading the hepatic vein confluence.

[Two Cases of Intrapelvic Schwannoma].

A 67-year-old man (case 1) and 65-year-old man (case 2) were incidentally found to have a tumor in the retrovesical region. Computed tomography and magnetic resonance imaging demonstrated a solid tumor at the right side of the rectum. 2-Deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) -positron emission tomography revealed uptake at the tumor. Both patients were cured by tumor resection. Histological diagnosis was benign schwannoma. In case 2, it was difficult to diagnose the tumor as schwannoma by imaging studies. We made a histological diagnosis by transrectal needle biopsy of the tumor before the operation. Schwannoma is located mostly in the limbs and the head and neck, but rarely in the intrapelvic cavity. We expect that the transrectal needle biopsy is valuable for diagnosing the retrovesical tumor.