Tetsuo Nemoto

Katsuro Ichimasa, Shin-ei Kudo, Masashi Misawa, Khay Guan Yeoh, Tetsuo Nemoto, Yuta Kouyama, Yuki Takashina, Hideyuki Miyachi. Gut and Liver 2024;18:803-6. https://doi.org/10.5009/gnl240081

Aim: Previous studies have shown sex and age differences in anal sphincter function, but few morphological studies have focused on the quality and quantity of the nerves that control the sphincter muscles. The present study aimed to determine whether there are morphological and quantitative sex and age differences in the nerves in the conjoined longitudinal muscle.Methods: This was a single‐center, retrospective study using surgical specimens from 44 patients who underwent abdominoperineal resection between 2003 and 2012. Hematoxylin–eosin‐ and S‐100‐stained peripheral nerves (nerve fibers and ganglion cells) in the conjoined longitudinal muscle beneath the dentate line were observed microscopically. A qualitative examination assessed the degeneration score, which was based on the presence or absence of karyopyknosis, vacuolar degeneration, acidophilic degeneration of the cytoplasm, denucleation and adventitial neuronal changes. For quantitative examinations, each neuronal and muscular area was traced to calculate the neuronal area ratio in S‐100‐immunostained photomicrographs at the observation site.Results: Women had a significantly lower quantity of nerves than men. Older individuals (aged ≥80 years) had a significantly lower quantity of nerves than younger individuals. Furthermore, older individuals tended to show greater morphological changes that appeared to be a result of degeneration.Conclusions: The present findings suggest that anal hypofunction in women and older individuals might result from differences in the quantity and quality of the neurons controlling the anal sphincter muscle. Geriatr Gerontol Int 2018; 18: 495–500.

Aims: Extra‐ampullary duodenal adenoma (EADA) is a rare condition with poorly described clinicopathological details. In this study, we aimed to characterize EADA clinicopathologically.Methods and results: We performed a retrospective review of 44 serial cases of EADA. Each EADA was categorized as either gastric‐type (n = 5) or intestinal‐type (n = 39). All gastric‐type adenomas were located in the first portion of the duodenum and exhibited a pedunculated shape. Gastric‐type adenomas were classified into two subtypes: pyloric gland and foveolar. The former consisted of mucin 6 (MUC6)‐positive glands covered with MUC5AC‐positive cells, whereas nearly all the latter consisted of MUC5AC‐positive cells. When EADAs were categorized into high and low grades, approximately 40% (16 of 44) were high‐grade. The high‐grade adenomas were significantly larger than the low‐grade adenomas (19.4 ± 8.6 mm versus 11.8 ± 5.1 mm, P = 0.021), and all adenomas greater than 20 mm in largest diameter were categorized as high‐grade adenomas. Among 16 individuals who underwent total colonoscopy before or after duodenal mucosal resection, nine had a colorectal neoplasm, and all nine duodenal lesions were of the intestinal phenotype.Conclusions: We clarified the clinicopathological characteristics of gastric‐ and intestinal‐type EADAs. EADAs greater than 20 mm at the largest diameter were consistently high‐grade, and are thought to have the potential to progress to adenocarcinoma. These findings should be helpful for the clinical management of EADA.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins—namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)—in pulmonary arteries. We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained from 9 IPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary arterial abnormalities. Results of microscopic observation were analyzed in relation to the cellular components and size of pulmonary arteries. Varying rates of positive reactivity to Dvl-2 and Daam-1 were confirmed in all cellular components of pulmonary arteries, namely, endothelial cells, myofibroblasts, and medial smooth muscle cells. In contrast, none of these components was reactive to Wnt-11. No specific expression patterns were observed for endothelial cells or myofibroblasts under any experimental conditions. However, marked expression of Dvl-2 and Daam-1 was confirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in contrast with specimens from associated pulmonary arterial hypertension cases and controls. High Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.

Ossification in the posterior longitudinal ligament (PLL) correlates with changes of enthesis during the early stages of development, but this issue remains controversial, as little is known regarding the details of this process. The aim of the present study was to elucidate part of the ossification mechanism. Thus, in the present study, we observed and evaluated minute ossifications in the PLL that did not exhibit symptoms of ossification of the posterior longitudinal ligament (OPLL). The subjects in the present study were derived from serial autopsy cases from January 2009 to December 2013 at Toho University Omori Medical Center, Japan. Minute ossifications in the PLL from autopsy subjects without any history of OPLL were screened as high-density areas using micro-focus X-ray CT, and the foci were histologically examined. Subsequently, we conducted both micro-focus X-ray CT image analysis and histological examination, and evaluated the correlation between these findings and putative predictive factors reported in previous studies. A total of 103 individuals among the 267 subjects involved in the present study were analyzed within the study period. There were no cases involving OPLL identification prior to death, and no subjects presented with neurological symptoms of myelopathy. The incidence of cases involving high-density areas greater than 0.1 mm2 in the PLL was 46.6 %, half of which revealed mature bone structures inside this area. Thus, the high-density areas comprised three types: a continuous posterior-annular fibrosus type (23 cases), an isolated posterior-annular fibrosus type (11 cases), and a posterior-vertebral type (29 cases). However, a positive correlation was observed between the proportion of high-density areas, age (Pearson r = 0.265, p < 0.01), and HbA1c (Pearson r = 0.294, p < 0.01). Histological examination confirmed that these high-density areas involved calcification with or without mature bone formation. We evaluated minute foci of calcification with and without ossification in the PLL from 103 cadavers, generating the following observations:

Chronic pulmonary aspergillosis (CPA) has been accepted the criteria for the diagnosis of pulmonary Aspergillus infection. Whereas, either pathophysiology or signs of CPA remains still controversial. In this study, we histopathologically investigated 25 specimens of CPA, surgically resected. 21 (84 %) of that comprised male. There were 21 cases with mild impairment of the immune system and/or a scar mostly due to old tuberculosis. There is a tendency for a negative correlation between peripheral blood white cell numbers and value level of beta-(1,3)-D-glucan. Four cases showed a granular fluorescent signal in granulation tissue surrounding the cavity without the fungal aspects itself. In conclusion, acute inflammatory exudate along the terminal respiratory tract is most significant pathophysiolocial complication of the CPA, caused to organizing pneumonia, which derives fatal respiratory failure. In addition, the viability of fungus does not concern extension of exudative inflammation at the site of erosion along terminal airway.

A 66-year-old man with postsigmoidectomy status for colon cancer received laparoscopic partial hepatectomy due to a hepatic mass with employing titanium clips were for a vascular clamp. Histological examination showed liver metastasis from sigmoid colon cancer. Twenty-nine months after the partial hepatectomy, a mass developed on the stump at the hepatic resection. Laparoscopic left lateral segmentectomy was conducted under suspicion of cancer recurrence and an automatic titanium stapling device was used. The macroscopically cut surface of the liver showed a grey-white solid nodule measuring 23 x 20 mm and involving metal clips. The nodule was consistent with granuloma microscopically. Twenty-three months after the segmentectomy, a mass reappeared on the hepatic radial margin and an open left lateral hepatic lobectomy was performed because of its growth tendency. Histopathological examination revealed granuloma similar to the previous instance. Since these nodules formed a granulomatous lesion surrounding metal staples/clips and evidence of caseous necrosis was lacking, granuloma due to surgical staples/clips was suspected. Sporadic case reports of postoperative pulmonary granuloma at the staple line have been published previously, but there are no articles detailing a case involving hepatic granuloma. We present our case as the first report of postoperative staple-line hepatic granuloma.

Gangliocytic paraganglioma (GP) is an extremely rare benign tumor that commonly arises from the second part of the duodenum. Since GP exhibit neither prominent mitotic activity nor Ki-67 immunoreactivity, this tumor is often misdiagnosed as neuroendocrine tumor (NET) G1 (carcinoid tumor). However, patients with GP may have a better prognosis than patients with NET G1. This fact emphasizes the importance of differentiating GP from NET G1, but few studies have reported the epidemiology and histopathology of GP because of its rarity. To differentiate GP from NET G1 with ease, we conducted a multi-institutional retrospective study analyzing the morphometric and immunohistochemical features of this tumor. Since only a limited number of patients with GP could be identified in our institute, we conducted a multi-institutional retrospective study of GP in Japan, which was approved by the Ethics Committee of our medical institute. The obtained tissue sections underwent detailed morphometric and immunohistochemical analyses. Additionally, to differentiate GP from NET G1 with ease, immunohistochemical findings were compared. In our examination of 12 cases of duodenal GP, we found that epithelioid cells of GP exhibited positive reactivity for progesterone receptor and pancreatic polypeptide, whereas tumor cells of NET G1 were completely negative reactivity for both. Additionally, although GP is considered to be an extremely rare NET, we found that four (40.0%) of the ten patients at our institute with duodenal NET G1 actually had GP. Although GP is regarded as a rare NET, our results suggest that it accounts for a substantial percentage of duodenal NETs. Additionally, confirmation of immunoreactivity for progesterone receptor and pancreatic polypeptide can assist in differentiating GP from NET G1.