Age-dependence of semitendinosus tendon properties used for anterior cruciate ligament reconstruction differs in males and females.

BACKGROUND: The semitendinosus tendon is one of the most used autografts in anterior cruciate ligament reconstruction. Although recent evidence indicates that young patients, especially in females, may experience high rates of revision and residual instability, the reasons for the inferior outcomes in these patients remain unclear. To address this issue, we aimed to compare the mechanical properties of the semitendinosus tendon used for anterior cruciate ligament reconstruction in male and female patients of various ages. METHODS: The semitendinosus tendons harvested from 31 male and 29 female patients who underwent anterior cruciate ligament reconstruction surgery using the semitendinosus tendon autografts were used in this study. Using the distal part of the harvested semitendinosus tendon, the extent of cyclic loading-induced elongation (i.e., the extent of the increase in slack length) and the Young's modulus were measured during cyclic tensile testing. FINDINGS: Spearman correlation analyses revealed that the Young's modulus (|ρ| = 0.725, P < 0.001), but not elongation (|ρ| ≤ 0.036, P ≥ 0.351) positively correlated with the patient age in male tendon samples. In contrast, for female tendon samples, the elongation (|ρ| ≥ 0.415, P ≤ 0.025), but not the Young's modulus (|ρ| = 0.087, P = 0.655) negatively correlated with the patient age. INTERPRETATION: These results indicate that the semitendinosus tendon used for anterior cruciate ligament reconstruction in young male patients is compliant, whereas that in young female patients is susceptible to elongation induced by cyclic loading.

Ulcerated Stenosis of the Small Intestine Associated With Hepatic Portal Venous Gas After Treatment for Cytomegalovirus Enteritis: A Case Report.

Due to its rarity, cytomegalovirus (CMV) enteritis remains poorly described with regard to its endoscopic and radiological findings. A 75-year-old woman was admitted to our hospital with abdominal pain and was treated with an antiviral agent for CMV enteritis. She was readmitted to our hospital 10 days after discharge due to a recurrence of abdominal pain. Emergency computed tomography revealed hepatic portal venous gas (HPVG) and ileal dilatation involving focal stenosis of the ileum. The patient underwent laparoscopic partial resection of the small intestine and was finally diagnosed with ulcered stenosis of the small intestine after treatment for CMV enteritis. This report represents a valuable addition to the literature describing a rare case of ulcerated stenosis of the small intestine associated with HPVG after treatment for CMV enteritis.

Mixed invasive mucinous and non-mucinous adenocarcinoma of the lung with hematogenous metastases to multiple organs.

Mixed invasive mucinous and non-mucinous adenocarcinoma is a rare variant of lung adenocarcinoma. In pure invasive mucinous adenocarcinoma, multilobar and bilateral involvement are common, and extrathoracic metastasis is rare. Here, we report a case of mixed invasive mucinous and non-mucinous adenocarcinoma with distant metastasis to multiple organs without marked enlargement of the primary lung lesion. The pathological findings indicated high tumor invasiveness and the patient died 10 months after diagnosis despite chemoimmunotherapy. Further investigations are necessary to elucidate the clinical characteristics and appropriate management of mixed invasive mucinous and non-mucinous adenocarcinoma.

A Case of Duodenal Adenocarcinoma Effectively Highlighted by Linked Color Imaging and Confirmed by Histopathology.

While the differential diagnosis of duodenal adenocarcinoma versus adenoma remains the key to determining treatment strategies in patients with suspected duodenal adenocarcinoma, the role of linked color imaging (LCI) in their differential diagnosis remains insufficiently documented. In this case, esophagogastroduodenoscopy (EGD) was performed on a 67-year-old man for anemia, which revealed a 20-mm-sized, whitish, partially reddish, pedunculated lesion located in the duodenal bulb on white light imaging. Using LCI, the lesion was highlighted as a whitish, pedunculated lesion with its central and inferior areas depicted as orangish and reddish, respectively. Endoscopic mucosal resection was performed on the suspicion of an adenocarcinoma for biopsy and endoscopic diagnosis. Histological examination revealed the lesion to be an adenocarcinoma contained in an adenoma: papillary, type 0-Ip, measuring 20x20 mm, pTis (M), involving no lymphovascular invasion. This case appears to underpin the usefulness of LCI in the differential diagnosis of duodenal adenocarcinoma.

Emergency Endoscopic Hemostasis Using the Endoscopic Mucosal Resection Technique for Severe Bleeding From Early Gastric Cancer: A Case Report.

Bleeding from gastric cancer may lead to severe anemia and hypovolemic shock, and can be a life-threatening condition in affected patients; thus, achieving hemostasis is essential to improving their clinical course. While endoscopic hemostasis is recommended as the hemostatic modality of first choice, endoscopic hemostasis involving the endoscopic mucosal resection (EMR) technique is also being used, though under-reported. An 85-year-old man diagnosed with bleeding from gastric cancer was raced to our hospital for hemostasis. Emergency esophagogastroduodenoscopy (EGD) revealed a 45 mm-sized elevated lesion involving the coagula due to dripping bleeding from the surface of the posterior wall of the gastric lower body. EMR was performed without any technical difficulty, and hemostasis was achieved immediately. The patient was discharged without rebleeding. This case appears to support the usefulness of EMR as an emergency endoscopic hemostatic modality for severe bleeding from early gastric cancer.

Potassium-competitive acid blocker-associated gastric mucosal lesions.

Since the introduction of vonoprazan, a potassium-competitive acid blocker (P-CAB), it has been demonstrated to reversibly inhibit gastric acid secretion by engaging in potassium-competitive ionic binding to H+/K+-ATPase. In contrast, proton pump inhibitors (PPIs) achieve H+/K+-ATPase inhibition through covalent binding to cysteine residues of the proton pump. Reported cases have indicated an emerging trend of P-CAB-related gastropathies, similar to those associated with PPIs, as well as unique gastropathies specific to P-CAB use, such as the identification of web-like mucus. Pathologically, parietal cell profusions, which show a positively correlated with hypergastrinemia, have a higher incidence in P-CAB users compared to PPI users. Thus, this review aims to summarize the endoscopic and pathological findings reported to date concerning P-CAB-related gastric mucosal lesions. Additionally, it seeks to discuss the differences between the PPIs and P-CABs in terms of the formation and frequency of associated gastropathies. This review highlights the evident differences in the mechanism of action and potency of acid inhibition between P-CABs and PPIs, notably contributing to differences in the formation and frequency of associated gastropathies. It emphasizes the necessity to distinguish between P-CAB-related and PPI-related gastropathies in the clinical setting.

Invasive lobular carcinoma of the breast with colonic metastasis: a case series of three patients.

BACKGROUND: Although metastatic spread of breast cancer to the gastrointestinal tract is very rare, it is more likely to occur in invasive lobular carcinoma (ILC) than in ductal carcinoma. Colonic metastasis is particularly rare, and the treatment strategies for these cases are not clearly defined. Herein, we report three cases of ILC with various abdominal symptoms associated with colonic metastasis. CASE PRESENTATION: Case 1 A 70-year-old female patient with vomiting and melena was referred to our hospital. Endoscopic examination revealed a Dieulafoy ulcer in the rectum and an elevated lesion in the descending colon. She also had two breast nodules, and was diagnosed as ILC with colonic metastasis. Considering her general condition, the best supportive care (BSC) was offered. The patient died 4 months after confirmation of the diagnosis. Case 2 An 80-year-old female patient presented with diarrhea and vomiting. She was diagnosed with ILC with colonic metastasis, and a coloscopy revealed stenosis of the transverse colon with a metastatic lesion. Ileosigmoid bypass surgery was performed for intestinal obstruction, and systemic treatment for breast cancer was initiated. The patient developed peritoneal carcinomatosis and died 1 year and 2 months after surgery. Case 3 A 56-year-old female patient underwent left total mastectomy for ILC, and laparoscopic transverse colectomy was conducted for a colonic lesion 9 years and 2 months after. The diagnosis as colonic metastasis was not confirmed at that time. Two years and 2 months later, torose lesions were detected in the hepatic flexural and descending colon, and histopathological findings indicated that all colon tumors, including the previously resected tumor, were metastatic spread of ILC. Systemic treatment was continued, but the transverse colonic lesion penetrated the abdominal wall, and an abscess formed 2 years and 11 months after the resection. The fistula improved by continuous suction drainage following ileostomy but recurred, and the patient died 3 years and 8 months after colectomy. CONCLUSIONS: Colonic metastases from breast cancer can trigger various abdominal symptoms, and the prognosis in these cases is generally poor. In selected cases, surgical treatment for abdominal symptoms and subsequent systemic therapy can contribute to a prolonged prognosis.

Multiple endocrine neoplasia type 1 with Zollinger-Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple epithelial neuroendocrine tumors (NETs) and non-NETs in various organs. MEN1 encodes a 610-amino acid-long tumor suppressor protein, menin. The optimal treatment for multiple tumors, identification of the most critical tumors for patient prognosis, and menin immunohistochemistry findings remain controversial. Therefore, we aimed to elucidate these issues through a histological analysis of tumors and tumor-like lesions in a Japanese family, comprising a father and his two sons, who had MEN1 with Zollinger-Ellison syndrome (ZES). Patients and methods: All family members had a germline alteration in exon 10, c.1714-1715 del TC of MEN1, and exhibited multiple synchronous and metachronous tumors. The patients had pulmonary NETs, hyperparathyroidism, hypergastrinemia, pituitary adenomas, pancreaticoduodenal NETs, adrenocortical adenoma with myelolipoma, nodular goiter of the thyroid, lipomas, and angiofibroma. Most tumors were resected and histologically examined. We compared their clinical courses and tumor histology, and conducted menin immunohistochemistry (IHC). Results: Two patients died of pulmonary NET G2. One patient who underwent pancreaticoduodenectomy was cured of ZES; however, the two other patients who did not undergo pancreaticoduodenectomy suffered persistent ZES despite treatment with octreotide. Menin IHC revealed varying NET intensities, ranging from positive to negative stains. Conclusion: Pancreaticoduodenectomy is the most effective treatment for ZES. Long-term follow-up is essential for pulmonary NET G2 owing to the risk of distant metastasis and/or multiplicity. Moreover, the variability of menin IHC in MEN1-related tumors may indicate the pattern of tumor formation rather than the diagnostic utility of menin in MEN1.

Invasive thymoma metastases to the pancreas: A case report.

INTRODUCTION AND IMPORTANCE: Thymoma is the most common type of tumor that develops in the thymic epithelial cells. Although thymomas can invade surrounding organs in the chest cavity, extrathoracic metastasis is very rare, and little is known about the prognosis and effective treatments for such tumors. Herein, we report a case of an invasive thymoma metastasizing to the pancreas after incomplete resection. CASE PRESENTATION: A 47-year-old man presented to our hospital with an anterior mediastinal mass. Although a thymic tumor was suspected, complete resection was not achieved because the tumor had invaded the pulmonary artery trunk, superior pulmonary vein, and left brachiocephalic vein. The pathological diagnosis was a Type B3 thymoma. The patient underwent chemotherapy and radiotherapy after surgery. Three years after surgery, computed tomography indicated a pancreatic mass suggestive of pancreatic cancer. Distal pancreatectomy was performed after neoadjuvant chemotherapy and radiotherapy. The pancreatic mass was diagnosed as Type B3 thymoma metastasis. Thirteen months after surgery for the pancreatic lesion, the patient underwent resection of the bilateral lung metastases. CLINICAL DISCUSSION: To the best of our knowledge, only four cases of metastatic thymic tumors in the pancreas have been reported. All patients who underwent surgical resection for pancreatic metastasis survived for >6 months including our case. CONCLUSION: In cases of thymic tumors with metastasis to extra-thoracic organs, complete resection of the metastatic lesions can contribute to prolonged survival.

Abdominal nonfunctional paraganglioma in which succinate dehydrogenase subunit B (SDHB) immunostaining was performed: a case report.

BACKGROUND: Abdominal nonfunctional paraganglioma is rare. Malignant potential of paraganglioma is assessed by Grading of Adrenal Pheochromocytoma and Paraganglioma score and genetic testing, but genetic testing is not common. We present a case of abdominal nonfunctional paraganglioma whose malignant potential was assessed by grading of adrenal pheochromocytoma and paraganglioma score and succinate dehydrogenase subunit B staining alternative to genetic testing. CASE PRESENTATION: A 39-year-old Japanese man had a right retroperitoneal tumor without symptoms. Uptake in the tumor was shown by 123I-meta-iodobenzylguanidine scintigraphy. There were no metastases. The results of biochemical workups including blood hormones and urinary metanephrines were normal. We performed retroperitoneoscopic surgery. The tumor was positive for chromogranin A staining but negative for tyrosine hydroxylase. On the basis of the preoperative biochemical workups and pathology results, we diagnosed the tumor as nonfunctional paraganglioma. The Grading of Adrenal Pheochromocytoma and Paraganglioma score classified the tumor as moderately differentiated. Furthermore, negative succinate dehydrogenase subunit B staining suggested the patient has the SDHx (SDHA, SDHB, SDHC and SDHD) mutation. CONCLUSION: Abdominal nonfunctional PGLs are associated with SDHB mutation, and SDHB staining should be performed as a screening.

Myasthenia Gravis Associated With Pembrolizumab for Relapsed Lung Cancer After Thymoma Resection.

Immunotherapy has demonstrated clinical efficacy in patients with thymic epithelial tumors; however, there is the potential risk of serious immune-related adverse events (irAEs). Here, we report a case of myasthenia gravis (MG) associated with pembrolizumab treatment that developed after thymoma resection in a patient with lung adenocarcinoma. Symptoms of MG occurred 16 days after pembrolizumab administration and progressed rapidly, necessitating mechanical ventilation and tracheostomy. Even after tumor resection, careful monitoring is crucial for patients with thymic tumors being managed with immune checkpoint therapy, particularly regarding the development of severe irAEs.

Mixed corticomedullary tumor of the adrenal gland.

Mixed corticomedullary tumor (MCMT) of the adrenal gland is an extremely rare tumor characterized by an admixture of steroidogenic cells and chromaffin cells in a single tumor mass simultaneously producing adrenocortical hormones and catecholamines; it is associated with ectopic adrenocorticotropic hormone (ACTH) in some cases. We reviewed and summarized clinicopathological data of 28 MCMTs, including four metastatic tumors in 26 previous reports. These reports included 21 females and 7 males, and the average tumor sizes were 4.8 ± 2.5 cm and 12.6 ± 6.4 cm in the non-metastatic and metastatic groups, respectively (P<0.001). The clinical manifestations and laboratory data were as follows: Cushing or subclinical Cushing syndrome, 58% (14/24); hypertension, 71% (17/24); elevated adrenocortical hormones, 75% (18/24); elevated catecholamines, 75% (18/24); and ectopic ACTH, 71% (10/14). All four patients with metastatic MCMTs had poor prognoses and elevated adrenocortical hormone levels; however, only two patients had elevated catecholamine levels. Immunohistochemistry was essential for the pathologic diagnosis of MCMTs. In this study, using an improved technique, we detected ectopic ACTH-producing cells in the same paraffin-embedded sections reported to be negative in our previous reports. As MCMT is composed of cells with embryologically different origins, its pathogenesis has been explained by various hypotheses. We compared MCMT to the adrenal gland of birds and the early stage of human fetuses, in which nests of chromaffin cells and steroidogenic cells admix without the formation of cortex and medulla. MCMT is characterized by the immaturity of organogenesis and might be classified as an adrenal embryonal tumor.

A Case of 123I-Metaiodobenzylguanidine Scintigraphy-Negative Pheochromocytoma with a Tumor-Developing Mutation in the RET Gene.

Pheochromocytoma (PCC) is rare catecholamine-producing endocrine tumor that metastasizes in approximately 10% of cases. As a functional imaging of PCC, 123I-metaiodobenzylguanidine (MIBG) scintigraphy was established, and some cases of PCC exhibit negative accumulation on MIBG scintigraphy, indicating a high risk of metastasis. Additionally, germline genetic variants of PCC are evident in approximately 30% of cases, although the genotype-phenotype correlation in PCC, especially the association between genetic mutations and MIBG scintigraphy, remains unclear. A 33-year-old man was admitted to our hospital for further examination for hypertension. He was diagnosed with sporadic PCC, and left adrenalectomy was performed. The adrenal tumor was negative on MIBG scintigraphy. Histology of the tumor revealed a moderately differentiated PCC. Target gene testing revealed a mutation in RET (c.2071G > A). This mutation has been reported to be a tumor-developing gene involved in the pathogenesis of PCC. Moreover, the RET mutation is the only gene mutation reported in a previous study of PCC with negative results on MIBG scintigraphy, except for the SDHB gene mutation, which is a common mutation in metastatic PCC. Correctively, the present RET gene mutation may be associated to MIBG-scintigraphy negative PCC and its pathophysiology. Clinicians should follow such cases more cautiously in clinical practice.

Primary Duodenal Adenocarcinoma Expressing Carbonic Anhydrase IX.

Primary duodenal adenocarcinoma is a rare malignancy whose carbonic anhydrase IX (CA9) expression remains poorly understood. A 73-year-old man visited our hospital for a medical checkup. Transnasal endoscopy revealed a submucosal, tumor-like lesion with a central depression located in the descending part of the duodenum on white light imaging. On texture and color enhancement imaging mode 1, the lesion was highlighted as a reddish, elevated lesion with an irregular mucosa in its central depressed area. Pancreaticoduodenectomy was performed on the suspicion of duodenal adenocarcinoma for biopsy and endoscopic diagnosis, which led to the lesion being diagnosed as tubular adenocarcinoma, pT1b (SM). Immunohistological staining revealed an adenocarcinomatous component positive for CA9, as well as a normal duodenal mucosa. To our knowledge, this report is among the first to describe CA9-expressing primary duodenal adenocarcinoma.

Colonic Intramural Hematoma.

Colonic intramural hematoma is a rare condition and its endoscopic and radiological findings remain poorly described. An 82-year-old woman was hospitalized with a diagnosis of acute cerebral infarction. She immediately received anticoagulant therapy with argatroban for 1 week. With the appearance 4 days later of hematochezia, she was found to have severe anemia. Following insertion of the colonoscope, a large submucosal hematoma was shown to be present in the descending colon, with the mucosa shown to be necrotic and the residual mucosa around the hematoma shown to be yellowish. Computed tomography revealed a hyperdense mass in the descending colon. Laparoscopic colectomy was performed for the lesion diagnosed as intramural hematoma. Pathologically, it was a hematoma located in the subserosal layer involving full-thickness hemorrhage. To our knowledge, this report represents a valuable addition to the literature describing a case of colonic intramural hematoma whose diagnosis was effectively established by the combined use of CS and CT.

Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report.

BACKGROUND: Ectopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases. CASE PRESENTATION: We present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient's death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-ß-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation. CONCLUSIONS: We experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.

Genetic Analysis of Pheochromocytoma and Paraganglioma Complicating Cyanotic Congenital Heart Disease.

CONTEXT: Pheochromocytoma and paraganglioma (PPGL) may appear as a complication of cyanotic congenital heart disease (CCHD-PPGL) with frequent EPAS1 mutations, suggesting a close link between EPAS1 mutations and tissue hypoxia in CCHD-PPGL pathogenesis. OBJECTIVE: Our aim is to further investigate the role of EPAS1 mutations in the hypoxia-driven mechanism of CCHD-PPGL pathogenesis, particularly focusing on metachronous and/or multifocal CCHD-PPGL tumors. METHODS: We performed whole-exome sequencing (WES) for somatic and germline mutations in 15 PPGL samples from 7 CCHD patients, including 3 patients with metachronous and/or multifocal tumors, together with an adrenal medullary hyperplasia (AMH) sample. RESULTS: We detected EPAS1 mutations in 15 out of 16 PPGL/AMH samples from 7 cases. Conspicuously, all EPAS1 mutations in each of 3 cases with multifocal or metachronous tumors were mutually independent and typical examples of parallel evolution, which is suggestive of strong positive selection of EPAS1-mutated clones. Compared to 165 The Cancer Genome Atlas non-CCHD-PPGL samples, CCHD-PPGL/AMH samples were enriched for 11p deletions (13/16) and 2p amplifications (4/16). Of particular note, the multiple metachronous PPGL tumors with additional copy number abnormalities developed 18 to 23 years after the resolution of hypoxemia, suggesting that CCHD-induced hypoxic environments are critical for positive selection of EPAS1 mutants in early life, but may no longer be required for development of PPGL in later life. CONCLUSION: Our results highlight a key role of activated hypoxia-inducible factor 2α due to mutated EPAS1 in positive selection under hypoxic environments, although hypoxemia itself may not necessarily be required for the EPAS1-mutated clones to progress to PPGL.