Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms.

STEROIDOGENESIS IN HEPATIC MUCINOUS CYSTIC NEOPLASM: Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.

[Three cases of IgG4-related focal retroperitoneal fibrosis].

(Case 1) A 63-year-old man was diagnosed as retroperitoneal fibrosis by the exploratory laparotomy for the pelvic mass with high IgG4 levels. (Case 2) A 64-year-old man had past medical history of autoimmune pancreatitis which was treated by steroid use. Three years later, he was diagnosed as IgG4-related gallbladder tumor by the cholecystectomy. And, then he was diagnosed as right hydronephrosis with high IgG4 levels. (Case 3) A 71-year-old man was diagnosed as left hydronephrosis and pelvic mass by computerized tomography with high IgG4 levels. We reported three cases of IgG4-related focal retroperitoneal fibrosis. All cases had pelvic mass with high IgG4 levels and were also treated effectively with steroid use. Those symptoms of the patients occurred in close association with IgG4 levels. It is necessary to acknowledge that retroperitoneal fibrosis may have aspects of IgG4-related systemic disease and that the measurement of serum IgG4 should be considered for diagnosing and treating the conditions.

Prognostic Impact of Preoperative Assessment of Muscle Mass and Strength in Surgically Resected Lung Cancer.

BACKGROUND/AIM: The association between resected non-small cell lung cancer (NSCLC) and long-term outcomes of muscle mass depletion and muscle weakness has also not been well documented. This study evaluated whether muscle mass depletion assessed by bioelectrical impedance analysis (BIA) and low muscle strength assessed by the peak expiratory flow rate as a percentage of predicted value (%PEFR) were associated with surgical outcomes in patients with resected NSCLC. PATIENTS AND METHODS: This retrospective study included 219 patients with resected NSCLC between 2016 and 2021. The cutoff value for muscle mass depletion was according to guidelines, for low muscle strength, we defined by receiver operating characteristics analysis for recurrence-free survival (RFS). Survival analysis was performed, and postoperative outcomes were compared. RESULTS: A total of 76 patients (34.7%) had muscle mass depletion, and 114 patients (52.1%) had low muscle strength. Muscle mass depletion and low muscle strength were independent poor prognostic factors for overall survival [hazard ratio (HR)=2.631, p=0.003; HR=1.983, p=0.044] and RFS (HR=3.120, p<0.001; HR=1.857, p=0.028) in multivariate analysis. Postoperative complication was associated with low muscle strength (p=0.009). Postoperative recurrence was associated with muscle mass depletion (p=0.03). CONCLUSION: Preoperative muscle mass depletion assessed by BIA and low muscle strength determined by %PEFR are worse prognostic factors after surgical resection for NSCLC. Our results may provide some important information for preoperative management.

Effect of Postoperative Muscle Loss After Resection of Non-small Cell Lung Cancer on Surgical Outcomes.

BACKGROUND/AIM: Preoperative depletion of psoas muscle mass index (PMI) in lung cancer patients is an unfavorable prognostic factor. The relationship between post-surgical changes in PMI and survival is not clear. Therefore, we conducted a retrospective study to clarify the prognostic significance of preoperative and postoperative PMI changes. PATIENTS AND METHODS: We retrospectively reviewed lung cancer patients, who underwent curative surgical resection with lymph node dissection and computed tomography (CT) approximately six months post-surgery between 2010 and 2019. Pre- and postoperative PMI was measured from CT images at the third lumbar vertebra level. A sex-dependent PMI change ratio (postoperative PMI/preoperative PMI) was used to divide patients into two groups: high PMI loss (67 patients, ≤25th lower quartile) and low PMI loss/PMI increase (204 patients, >25th lower quartile), and clinicopathological features were compared. RESULTS: Age ≥70 years, elevated preoperative carcinoembryonic antigen levels, advanced pathological stage, lymphatic permeation, vascular invasion, performance of adjuvant platinum-doublet chemotherapy, low body mass index, and postoperative recurrence were significantly higher in the high PMI loss group. Logistic regression analysis found that Charlson comorbidity index, low body mass index, advanced pathological stage, and postoperative recurrence were associated with high PMI loss. The five-year postoperative overall survival rate was 50% in the high PMI loss group and 79% in the low PMI loss/PMI increase group (p<0.001). High PMI loss was also an unfavorable factor in a multivariable Cox's proportional hazard model (p=0.002). CONCLUSION: Postoperative muscle loss was an independent prognostic factor for poorer overall survival regardless of preoperative sarcopenia, in non-small cell lung cancer.

APAF-1 is related to an undifferentiated state in the testicular germ cell tumor pathway.

Apoptotic protease activating factor-1 (APAF-1) is a key regulator gene of apoptosis, located downstream from p53. Loss of APAF-1 expression is associated with chemorefractory malignant melanoma and neuronal cell differentiation. In order to make clear the function of APAF-1 in the carcinogenesis of germ cell tumors, we evaluated the expression levels of APAF-1 and several apoptosis and differentiation markers by immunohistochemistry in formalin-fixed paraffin-embedded samples from 43 cases of testicular germ cell tumor (TGCT) and six specimens of normal testis tissue. Expression of cleaved caspase-3, Oct-3/4, and Ki-67 were also examined by immunohistochemistry to evaluate apoptotic reactivity, tumor differentiation, and proliferation activity, respectively. APAF-1 was downregulated in two TGCT cell lines by siRNA transfection, and subsequent expression of the Ki-67 and Oct-3/4 genes and differentiation markers of three embryonic germ layers including keratin16 (KRT16) for ectoderm, vimentin (VIM) for mesoderm and GATA4 for endoderm were then tested. No significant relationship was found between APAF-1 expression and apoptotic activity in TGCTs. Expression of APAF-1, Oct-3/4, and Ki-67 was significantly higher in seminomas than in non-seminomas. In TGCTs, higher APAF-1 expression was correlated with higher proliferation (high Ki-67) and a lower degree of differentiation (high Oct-3/4). Interestingly, the expression of APAF-1 gradually decreased in accordance with tumor differentiation (seminoma and embryonal carcinoma > teratoma). Downregulation of APAF-1 in TGCT cell lines resulted in a decrease of Ki-67 and Oct-3/4 and an increase of VIM and KRT16 gene expression. These data show that higher expression of APAF-1 is related to an undifferentiated state in the TGCT pathway.

[Two cases of ileocecal carcinoid found by total colonoscopy and a review of the literature on 16 cases].

We report 2 cases of ileocecal carcinoid with review of the literature recently reported in Japan. Both cases were diagnosed as carcinoid by colonoscopic biopsy after ileocecal tumors had been pointed out by computed tomography. We performed curative operation with lymph node dissection. Since multiple lymph node metastases were shown in both cases pathologically, they were closely followed after surgery, but no recurrence has been shown. Since SSTR2a stain was strongly positive in both cases, octreotide, the effectiveness of which was verified in the PROMID study might be administered if necessary. As ileocecal carcinoid has a tendency to metastasize to other organs, careful surveillance by colonoscopy and early detection are required. Furthermore, development of effective drugs following octreotide and further investigation including biological and histopathological analysis of neuroendocrine tumors including carcinoid are necessary.

Primary Intramuscular Classic Hodgkin Lymphoma: A Rare Case Report.

Hodgkin lymphoma (HL) is a hematologic malignancy that typically presents with lymphadenopathy. We herein report a patient with HL who presented with an intramuscular mass that required differentiation from an inflammatory lesion. A 65-year-old Japanese woman was referred to our hospital with a chief complaint of chronic and expanding tumor in her left thigh. By surgical resection, she was diagnosed with primary intramuscular, Epstein-Barr virus-positive, mixed-cellularity classic HL. She received combined modality therapy, resulting in a complete response. Primary intramuscular classic HL is extremely rare. It should be listed as a differential diagnosis of intramuscular tumors.

Malignant myoepithelioma in the maxillary sinus: case report and review of the literature.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

Sarcopenia in Resected NSCLC: Effect on Postoperative Outcomes.

INTRODUCTION: Skeletal muscle depletion, referred to as sarcopenia, has recently been identified as a risk factor for poor outcomes in various malignancies. However, the prognostic significance of sarcopenia in patients with NSCLC after surgery has not been adequately determined. This study investigated the impact of sarcopenia in patients undergoing pulmonary resection for lung cancer. METHODS: This retrospective study consisted of 328 patients with pathologically confirmed NSCLC who underwent curative resection between January 2005 and April 2017. Preoperative computed tomography imaging at the third lumbar vertebrae level was assessed to measure the psoas muscle mass index (PMI, cm2/m2). Sarcopenia was defined as a cutoff value of PMI less than 6.36 cm2/m2 for males and 3.92 cm2/m2 for females, based on PMI values from "healthy" subjects. RESULTS: The median patient age was 71 years and 59% were male. Sarcopenia was present in 183 (55.8%) and was significantly related with increasing age (p < 0.001), being male (p < 0.001), smoking habit (p < 0.001), lower body mass index (p < 0.001), and postoperative major complication (Clavien-Dindo grade ≥3, p = 0.036). The prevalence of sarcopenia was higher in men than in women, and the prevalence increased with age in men, whereas the prevalence did not increase in females older than 70 years. The 5-year survival rate was 61% in patients with sarcopenia and 91% in those without. Multivariate analysis revealed that sarcopenia was an independent unfavorable prognostic factor (p = 0.019). CONCLUSIONS: Sarcopenia as determined using preoperative computed tomography could be used to predict postoperative major complication and prognosis in patients with resected NSCLC. Our results may provide some important information for preoperative management.

Selection of higher molecular weight genomic DNA for molecular diagnosis from formalin-fixed material.

The patterns of DNA degradation in frozen, methanol-fixed, and formalin-fixed tissues were investigated by high-performance liquid chromatography (HPLC). The chromatograms all yielded one major peak with or without several extra minor peaks representing molecular weights of preserved genomic DNA. The most characteristic differences were in the retention times of the major peaks, with the earliest major peak occurring in the formalin-fixed tissues, and followed by the methanol-fixed, and frozen tissue samples, in that order. This means that the molecular weight of the DNA from formalin-fixed tissue is much shortened than that recovered from methanol-fixed tissue and frozen tissue. The results also indicated that a small amount of higher molecular weight DNA is still preserved in formalin-fixed tissues. To improve the amplification efficiency of polymerase chain reaction (PCR) analysis of formalin-fixed material, we isolated the higher molecular weight DNA from formalin-fixed, paraffin-embedded tissue from four different organs and compared the amplification efficiencies with those of the crude DNA extract. We used eight sets of oligonucleotide primers producing 262 to 989 base pair (bp) fragments of beta-globin. The results showed that the PCR amplification analyses were more efficient with the isolated higher molecular weight DNA than with the crude DNA extract. Our study demonstrated that not all the DNA in formalin-fixed, paraffin-embedded tissue samples is totally degraded but that a small amount of higher molecular weight DNA persists. The feasibility of molecular diagnosis using formalin-fixed material can be improved by isolating the preserved higher molecular weight DNA by HPLC.

Retroperitoneal lymphangioma with a duodenal lesion in an adult.

A multilocular-cystic and cavernous, retroperitoneal tumor was found in a 40-year-old man whose past medical history was unremarkable. On admission, he complained of a large and still growing intra-abdominal mass associated with dull pain and a low-grade fever. Laboratory findings revealed leukocytosis and C-reactive protein elevation, compatible with inflammation of the tumor. Percutaneous aspiration of the tumor was performed under transabdominal ultrasonographic guidance, and continuous drainage of fluid from within the tumor ameliorated his symptoms. From preoperative examinations, including radiological imaging, fluid aspiration, and endoscopy with biopsy, a diagnosis of retroperitoneal lymphangioma was made. Laparotomy revealed extensive adhesions between the tumor and both the duodenum and the pancreatic head. A pancreaticoduodenectomy was therefore performed. At 3-year follow-up, there was no sign of recurrence. Retroperitoneal lymphangioma is an uncommon disorder, and the cavernous type is extremely rare. The duodenal lesion was an important feature of the present case, and endoscopic biopsy of this lesion facilitated precise preoperative diagnosis of retroperitoneal lymphangioma.

Thalamic hypoperfusion in early stage of progressive supranuclear palsy (Richardson's syndrome): report of an autopsy-confirmed case.

Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is a neurodegenerative disease characterized by postural instability and vertical gaze palsy, but the clinical diagnosis of PSP-RS is often difficult in the early stage of the disease. A 64-year-old male experienced frequent falls, followed by dysarthria and dysphagia. Neurological examination at age 64 demonstrated vertical gaze palsy, dysarthria, dysphagia, and retropulsion. At that time, while brain MRI demonstrated no apparent abnormalities, SPECT showed the reduction of the cerebral blood flow in the thalamus as well as the medial frontal lobe cortices. The patient was diagnosed with probable PSP-RS, and died at age 70. On postmortem examination, there were abundant tuft-shaped astrocytes, neurofibrillary tangles, coiled bodies, and argyrophilic threads in the brain, establishing the diagnosis of PSP-RS. Our definite PSP-RS case suggests that thalamic hypoperfusion may provide helpful evidence to support a diagnosis of PSP-RS in the early stage of the disease.

Overexpression of Dickkopf 3 in hepatoblastomas and hepatocellular carcinomas.

Dickkopf 3 (Dkk3) is a protein expressed at a very early stage of hepatogenesis. In this study, we examined whether Dkk3 was related to a premature or dedifferentiated nature in hepatoblastomas (HBLs) and hepatocellular carcinomas (HCCs). It was demonstrated that Dkk3 was overexpressed in HBLs and HCCs and that its expression was more frequent in the former than in the latter, being consistent with the fact that most HBLs show an embryonal or fetal hepatic histology, whereas there was no distinct relationship between Dkk3 expression and clinical data or histology. All of the HBLs expressed Dkk3, alpha-fetoprotein (AFP), or both proteins, suggesting that, similar to AFP, Dkk3 is another potentially useful biomarker detecting a wide range of HBLs. Furthermore, Dkk3 and AFP were expressed reciprocally in the tumors. These results suggest that Dkk3 may be related to the premature or dedifferentiated nature of HBLs and HCCs, whereas AFP may be related to a more differentiated nature. Thus, assessment of Dkk3 and AFP may be useful in the diagnosis of hepatic tumors.

Transtracheal endoluminal resection of a pleomorphic adenoma occluding subglottis.

A 71-year-old male was treated for suspected bronchial asthma because of dyspnea and stridor for 3 months before presenting at our hospital. Chest computed tomogram and a laryngotracheoscopy revealed a mass occupying the subglottic cavity. Instead of a laryngotracheal resection, the tumor was extirpated from the posterior wall of the subglottis and the first two tracheal rings successfully through a vertical tracheotomy just above the life-saving trachestomy tube, and was diagnosed as pleomorphic adenoma. The patient is alive and well with no recurrent tumor 12 years after surgery, without any effect on the function of the voice or swallowing.

Neuronatin expression and its clinicopathological significance in pulmonary non-small cell carcinoma.

INTRODUCTION: Neuronatin is a protein that is specifically expressed in the nervous system in the course of embryonal brain development, and its expression is limited to the pituitary gland in normal human adults. Neuronatin expression has been reported in some types of tumor. The purpose of this study was to clarify the significance of neuronatin expression in pulmonary non-small cell carcinoma. METHODS: We determined the frequency of neuronatin expression in surgically resected samples from non-small cell lung carcinoma (51 adenocarcinoma and 41 squamous cell carcinoma) by immunohistochemical staining, and investigated the correlations between expression level and various clinicopathological features. RESULTS: Expression of neuronatin was observed more frequently in squamous cell carcinoma (63%) than in adenocarcinoma (25%). In most cases, nontumorous lung tissue did not react with the antibody against neuronatin. In both adenocarcinoma and squamous cell carcinoma, less differentiated tumors expressed neuronatin more frequently than did differentiated tumors. In adenocarcinoma, but not squamous cell carcinoma, the prognosis of neuronatin-positive cases was significantly worse than that of neuronatin-negative cases. CONCLUSION: Neuronatin expression is specific for tumor tissue and was detected in both pulmonary adenocarcinoma and squamous cell carcinoma at high frequency, particularly in less differentiated tumors. Neuronatin expression is associated with poor prognosis in patients with adenocarcinoma, and may be useful as a prognostic marker for lung adenocarcinoma.

Effectiveness of steroid treatment for hoarseness caused by idiopathic fibrosing mediastinitis: report of a case.

A 65-year-old woman was referred to our department for investigation and treatment of hoarseness. A chest computed tomography (CT) scan showed a mediastinal mass spreading into the aortopulmonary window. This finding and that of flexible laryngoscopy suggested that the hoarseness was being caused by left recurrent nerve involvement resulting in left vocal cord paralysis. Thus, we performed a mediastinoscopic biopsy via a parasternal incision. Pathological examination revealed dense fibrous tissue infiltrated with varied inflammatory cells. Because no etiological pathogen or neoplastic lesion was identified, we diagnosed idiopathic fibrosing mediastinitis and began treating the patient with prednisolone. After a course of treatment, the mediastinal lesion showed a remarkable response. The hoarseness resolved as the lesion became smaller. Laryngoscopy confirmed recuperation of vocal cord function. This report shows that steroid therapy is a treatment option for hoarseness caused by recurrent laryngeal nerve involvement of fibrosing mediastinitis, if administered under close observation.