Trends of incidence and age in adults with testicular germ cell tumors: a two-decade multicenter retrospective study.

Background: Testicular germ cell tumors (GCTs) are the most common type of cancer in adolescent boys and young adult men, but the age at onset has been increasing. However, little is known regarding the incidence and age of patients with testicular GCTs in Japan because the incidence there is low. Methods: We retrospectively reviewed the medical records of patients with GCTs in seven hospitals between 2001 and 2021. We compared the incidences of testicular GCTs, ages at onset, pathological types (seminoma or nonseminoma), and clinical stages in patients with GCTs between the periods 2001-2010 and 2011-2021. Results: We identified 193 adults (≥20 years of age) with testicular GCTs; their median age was 37 years [interquartile range (IQR), 29-47 years]. Of these patients, 87 (45.1%) were ≥40 years of age at diagnosis. The proportion of patients aged ≥40 years was significantly higher in the period 2011-2021 (54.8%) than in 2001-2010 (30.8%; P=0.001). The incidence of seminoma was significantly higher in the period 2011-2021, but clinical stage did not differ significantly between the two periods. The population-adjusted incidence among patients in their 40s was 3.4-fold higher in 2011-2021 than in 2001-2010. Conclusions: The number of patients with GCTs aged ≥40 years was significantly higher in 2011-2021, even in a population-adjusted analysis. Treatment strategies need to be adapted to older testicular germ cell tumor patients.

Artificial intelligence-based classification of peripheral blood nucleated cells using label-free imaging flow cytometry.

Label-free image identification of circulating rare cells, such as circulating tumor cells within peripheral blood nucleated cells (PBNCs), the vast majority of which are white blood cells (WBCs), remains challenging. We previously described developing label-free image cytometry for classifying live cells using computer vision technology for pattern recognition, based on the subcellular structure of the quantitative phase microscopy images. We applied our image recognition methods to cells flowing in a flow cytometer microfluidic channel, and differentiated WBCs from cancer cell lines (area under receiver operating characteristic curve = 0.957). We then applied this method to healthy volunteers' and advanced cancer patients' blood samples and found that the non-WBC fraction rates (NWBC-FRs), defined as the percentage of cells classified as non-WBCs of the total PBNCs, were significantly higher in cancer patients than in healthy volunteers. Furthermore, we monitored NWBC-FRs over the therapeutic courses in cancer patients, which revealed the potential ability in monitoring the clinical status during therapy. Our image recognition system has the potential to provide a morphological diagnostic tool for circulating rare cells as non-WBC fractions.

Significance of pelvic lymph node dissection during radical prostatectomy in high-risk prostate cancer patients receiving neoadjuvant chemohormonal therapy.

We aimed to determine the survival and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy. We retrospectively analyzed 516 patients with high-risk localized PC (< cT4N0M0) who received neoadjuvant androgen-deprivation therapy plus estramustine phosphate followed by RP between January 2010 and March 2020. Since we stopped limited PLND for such patients in October 2015, we compared the surgical outcomes and biochemical recurrence-free survival (BCR-FS) between the limited-PLND group (before October 2015, n = 283) and the non-PLND group (after November 2015, n = 233). The rate of node metastases in the limited-PLND group were 0.8% (2/283). Operation time was significantly longer (176 vs. 162 min) and the rate of surgical complications were much higher (all grades; 19 vs. 6%, grade ≥ 3; 3 vs. 0%) in the limited-PLND group. The inverse probability of treatment weighting-Cox analysis revealed limited PLND had no significant impact on BCR-FS (hazard ratio, 1.44; P = 0.469). Limited PLND during RP after neoadjuvant chemohormonal therapy showed quite low rate of positive nodes, higher rate of complications, and no significant impact on BCR-FS.

Induction of ZIP8, a ZIP transporter, via NF-κB signaling by the activation of IκBα and JNK signaling in cultured vascular endothelial cells exposed to cadmium.

Cadmium is an environmental pollutant that adversely affects various organs in the human body and is a well-known risk factor for cardiovascular diseases. These disorders are caused by the dysfunction of the vascular endothelial cells that cover the luminal surface of blood vessels. The ZIP transporter ZIP8 is one of the primary importers of cadmium, and its expression appears to be important for the sensitivity of vascular endothelial cells to cadmium. In the present study, we investigated the influence of ZIP8 on cadmium-induced cytotoxicity in vascular endothelial cells, the induction of ZIP8 expression by cadmium, and its action mechanism in vascular endothelial cells. The study revealed that: (1) cadmium cytotoxicity in vascular endothelial cells was potentiated by the overexpression of ZIP8, and the intracellular accumulation of cadmium in the cells was increased; (2) cadmium highly induced the expression of ZIP8, but not other ZIPs; (3) lead and methylmercury moderately induced ZIP8 expression, but the other tested metals did not; (4) the induction of ZIP8 expression by cadmium was mediated by both NF-κB and JNK signaling, and the accumulation of NF-κB in the nucleus was regulated by JNK signaling. Particularly, it was found that cadmium activated NF-κB to transfer it into nuclei and activated JNK to stabilize NF-κB in nuclei, resulting in the induction of ZIP8 expression. This induction appears to be crucial for cadmium cytotoxicity in vascular endothelial cells.

Induction of metallothionein isoforms in cultured bovine aortic endothelial cells exposed to cadmium.

Metallothionein (MT) is an inducible protein with cytoprotective activity against heavy metals such as cadmium, zinc, and copper. MT-1 and MT-2 are the isoforms of MT induced by and bind the heavy metals. Bovine aortic endothelial cells contain three types of MT genes, namely, MT-1A, MT-1E, and MT-2A; however, the associated protein expression of these MT isoforms has not been identified. In the present study, the expression of MT subisoform proteins in cells treated with cadmium chloride was identified using a high-performance liquid chromatography-inductively coupled plasma-mass spectrometry system. It was revealed that: (1) transcriptional induction of MT-1A by cadmium was markedly more sensitive than that of MT-1E/2A; (2) MT-1A and MT-2A proteins were the predominant MT subisoforms induced by cadmium; and (3) there might be differentiation in the functions of MT-1 and MT-2 against cadmium cytotoxicity, although the actual roles of the MT isoforms in the cells were not distinct. This is the first study to show the differential induction of isoforms of MT proteins in vascular endothelial cells by cadmium.

Rapid recurrence of primary gastric choriocarcinoma after complete resection.

INTRODUCTION: Primary gastric choriocarcinoma (PGC) is a rare and rapidly invasive tumor. We report a case of PGC diagnosed by endoscopic biopsy and treated with gastrectomy and chemotherapy. PRESENTATION OF CASE: A 78-year-old man was referred to our hospital because esophagogastroduodenoscopy showed a tumor at the fornix of the stomach. Pathologic examination of biopsy specimens revealed choriocarcinoma. Abdominal computed tomography (CT) revealed no enlarged abdominal lymph nodes or distant metastases. Robot-assisted total gastrectomy with spleen-preserving D2 lymphadenectomy was performed on the basis of a diagnosis of cT2N0M0, stage cIB PGC. The pathologic diagnosis was pT2, ly0, v1, pN0, PM0, DM0, stage pIB PGC. The postoperative course was uneventful, and the patient was followed carefully without adjuvant chemotherapy. Three months after gastrectomy, blood tests indicated that serum ß-human chorionic gonadotropin (ß-hCG) levels had increased, and CT revealed multiple liver metastases. The patient underwent a standard nongestational choriocarcinoma chemotherapy regimen with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine. Although ß-hCG levels temporarily decreased with chemotherapy, the patient experienced tumor recurrence with ascites and his serological test demonstrated an elevated level of ß-hCG (120 ng/mL). The patient died 10 months postoperatively. CONCLUSION: We report a case of stage pIB PGC with poor prognosis, recurring at only 3 months postoperatively despite curative surgery and chemotherapy.

Label-free classification of cells based on supervised machine learning of subcellular structures.

It is demonstrated that cells can be classified by pattern recognition of the subcellular structure of non-stained live cells, and the pattern recognition was performed by machine learning. Human white blood cells and five types of cancer cell lines were imaged by quantitative phase microscopy, which provides morphological information without staining quantitatively in terms of optical thickness of cells. Subcellular features were then extracted from the obtained images as training data sets for the machine learning. The built classifier successfully classified WBCs from cell lines (area under ROC curve = 0.996). This label-free, non-cytotoxic cell classification based on the subcellular structure of QPM images has the potential to serve as an automated diagnosis of single cells.

Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis.

BACKGROUND: Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. METHODS: Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays. RESULTS: Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128). CONCLUSIONS: Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.

Collateral thermal damage to the pancreas by ultrasonic instruments during lymph node dissection in laparoscopic gastrectomy.

INTRODUCTION: Laparoscopic gastrectomy (LG) with D2 or more extended lymphadenectomy for advanced gastric cancer is technically demanding. Collateral thermal damage to the pancreas secondary to energized dissection during lymphadenectomy has been reported. We retrospectively compared the pancreatic damage between LG and open gastrectomy (OG) by measuring the amylase concentration of the drainage fluid and analyzing heat conductance to the pancreas with a porcine model. METHODS: We evaluated the data of 105 consecutive patients with gastric adenocarcinoma who underwent LG or OG with lymph node dissection. Digital thermography was used to evaluate the extent of heat conductance to the pancreas during suprapancreatic lymph node dissection by either an ultrasonically activated device or electric cautery in a porcine model. RESULTS: The incidence of clinically relevant pancreatic fistula formation was not statistically significant between the LG and OG groups (3/57 vs 0/48 cases; P = 0.306). However, the median amylase concentrations of the drainage fluid on postoperative days 1 and 3 were 1355.7 and 308.8 IU/L, respectively, in the LG group and 369.0 and 125.8 IU/L, respectively, in the OG group (P < 0.001). In the experimental model, more time was required to cool the surface of the pancreas to < 40°C in the ultrasonically activated device group than in the electric cautery group (10.1 ± 5.2 vs 5.2 ± 3.0 s; P = 0.013). CONCLUSIONS: Unavoidable collateral thermal damage to the pancreas associated with electrosurgical devices might exist during LG. Heat conductance must be given more consideration in extended lymph node dissection.

Three-dimensional fusion images combining CT gastrography and CT angiography for early gastric cancer: pilot experiences of preoperative simulation prior to totally laparoscopic gastrectomy.

We herein report two cases of gastric cancer in which preoperative 3-D CT gastrography and CT angiography fusion images enabled totally laparoscopic gastrectomy. Case 1 involved a 60-year-old woman with a superficial depressed lesion on the greater curvature of the middle gastric body. Case 2 involved a 64-year-old woman with a superficial depressed lesion on the posterior wall of the upper gastric body. In both cases, 3-D fusion images were prepared from enhanced CT scans after the area near the lesions was clipped under preoperative gastroendoscopy. Based on the relative position between the clips and nearby vessels, a resection line was preoperatively determined in each case. Totally laparoscopic distal gastrectomy and totally laparoscopic proximal gastrectomy were performed in cases 1 and 2, respectively, with safe surgical margins. Three-dimensional fusion images can help in preoperative simulation of totally laparoscopic gastrectomy.

Successful coil embolization for life-threatening hemorrhage in childhood leukemia induction therapy.

An 11-year-old boy was experienced severe life-threatening hemorrhage from a branch of the superior mesenteric artery (SMA) after acute lymphoblastic leukemia induction therapy. The patient had a history of attention deficit hyperactivity disorder (ADHD), diagnosed at 3 years of age. Subsequent to discontinuing his psychotropic medication, the patient's mental status deteriorated and treatment with midazolam for 3 weeks was necessary to allow the completion of the leukemia induction regimen. On day 51, although there was no indication of thrombocytopenia or a coagulation disorder, the patient began to hemorrhage suddenly from anal with resulting hypovolemic shock, and large-volume blood transfusion was initiated. Although upper and lower endoscopy failed to determine the location of the hemorrhage, angiography enabled us to determine that it was a branch of the SMA (the middle colic artery #6), and selective arterial embolization was used to arrest the bleeding. There could have been underlying causes, such as, a probable malformation or aneurysm in that area, although there was no indication before or after the event. This is a rare case of arterial hemorrhage from a branch of the SMA that occurred in a pediatric patient idiopathically during the induction therapy of leukemia.