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Background: Lung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion., Methods: Inbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion., Results: Histopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation., Conclusion: Hydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemia-reperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury., Methods: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 μM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation., Results: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P = .030)., Conclusion: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study was conducted to evaluate the long-term outcome of surgical treatment in patients with functional parathyroid carcinoma and to clarify factors determining prognosis., Methods: A retrospective review of 38 patients with parathyroid carcinoma was performed. The Ki-67 index was evaluated in 29 cases. Disease-free survival and cause-specific survival estimated using the Kaplan-Meier method were analyzed, and the median follow-up period was 119 months., Results: Fifteen patients developed persistent or recurrent parathyroid carcinoma, and 9 patients died of the disease. Twenty-one of 41 reoperations normalized the serum calcium level for at least 6 months. Univariate and multivariate analyses showed that locoregional tumor extension at initial operation and Ki-67 index >or=5% were significant factors affecting cause-specific survival (P = .0008, P = .05) and disease-free survival (P = .0005, P = .005), respectively. Five of 6 patients whose tumor showed a Ki-67 index >or=10% developed recurrence within 3 years after initial operation, and 4 died of the disease., Conclusions: Parathyroid carcinomas with locoregional extension at initial surgery have potential for recurrence. Our data suggest that aggressive surgical resection of recurrent parathyroid carcinoma is beneficial for palliation of hypercalcemia in selected patients. Ki-67 staining may be a valuable prognostic factor for patients with parathyroid carcinoma, especially as tumors with indices greater than 10% are more likely to recur in the early postoperative period.

Background: There have been few reports of laparoscopic adrenal-sparing surgery for bilateral adrenal tumors. We review our experience with this type of surgery with the aim of evaluating its feasibility and safety., Methods: Over a 4-year period, we treated 9 patients with bilateral benign adrenal tumors. Seven patients had bilateral pheochromocytomas (MEN 2: 5, VHL: 1, sporadic: 1), and 2 patients had Cushing's syndrome caused by bilateral adrenocortical adenomas. Laparoscopic procedures were performed by a flank approach. The mean diameter of the tumors was 3.7 cm (range, 2.0-8.5 cm)., Results: All the tumors were removed laparoscopically. Four patients with hereditary pheochromocytomas underwent bilateral total adrenalectomy because of the large tumor size and multiplicity. The other 5 patients were treated successfully with preservation of adrenocortical function. In 4 of these 5 patients, the adrenal tumors were 3 cm or less in diameter. None of the patients experienced surgical complications. At a mean follow-up of 16 months (range, 4-40 months), none of the 5 patients who were treated by adrenal-sparing surgery required corticosteroid replacement., Conclusion: Laparoscopic surgery is feasible for the treatment of bilateral adrenal tumors. Adrenal-preserving laparoscopic surgery may be practicable for the removal of these tumors, if the tumor on either side is 3 cm or less in diameter; however, our follow up is short (mean, 16 months).

Background: There have been few reports on the use of laparoscopic ultrasonography as an aid for the resection of insulinomas. In this study, we review our experience with laparoscopic ultrasonography for the intraoperative localization and resection of insulinomas., Methods: We attempted laparoscopic resection of insulinomas in 7 patients (median age, 50 years) during a 4-year period. Preoperative imaging showed that 1 of the insulinomas was located in the head of the pancreas, 2 were located in the body, and 4 were located in the tail., Results: We identified the insulinomas in all 7 patients with laparoscopic ultrasonography. In 6 of the patients, the insulinomas were laparoscopically resectable, either by enucleation (4 patients) or by resection of the pancreatic tail (2 patients). Conversion to laparotomy was necessary for the insulinomas in the head of the pancreas because they were close to the portal vein and the major pancreatic duct. All patients showed improvement in their hypoglycemia after the operations. Minor leakage of pancreatic juice occurred in 4 patients, and this was resolved with conservative treatment., Conclusions: Laparoscopic ultrasonography is useful for the intraoperative localization of insulinomas. Laparoscopy is a safe and feasible technique for resecting insulinomas located in the body or tail of the pancreas.

Background: Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome with tumors of many endocrine tissues. Germline MEN1 gene mutations were found in most patients with familial or sporadic MEN 1. Recently, somatic MEN1 gene mutations were also detected in sporadic non-MEN 1 endocrine tumors., Methods: We used direct sequence analysis to investigate MEN1 gene mutations in 30 parathyroid tumors obtained from 30 patients with sporadic, nonfamilial primary hyperparathyroidism., Results: Four patients had somatic mutations of the MEN1 gene, comprising 1 small insertion (1091insAGC), one missense mutation (G42S), and 2 non-sense mutations (E388X, R460X). Identical missense and non-sense mutations were found in patients with familial and non-familial MEN 1. There were no differences between clinical features of patients with and without MEN1 gene mutations., Conclusions: The incidence of somatic MEN1 gene mutations (13.3%) in Japanese patients with sporadic, nonfamilial primary hyperparathyroidism is almost equal to those of such patients in the United States and Sweden. Occasionally, the MEN1 gene mutation sites in sporadic parathyroid tumors are identical to those reported in tumors from patients with familial or sporadic MEN 1.

Background: Vascular endothelial growth factor-C (VEGF-C) is known to be related to development of lymphatic vessels. Papillary thyroid carcinoma characteristically metastasizes to regional lymph nodes, whereas follicular thyroid carcinoma commonly spreads hematogenously. The present study was designed to determine whether expression of the VEGF-C gene is related to the different metastatic features of these 2 types of thyroid carcinoma., Methods: Thyroid carcinoma specimens were obtained from 15 patients with papillary carcinoma and 4 patients with follicular carcinoma of the thyroid. VEGF-C gene expression was examined by Northern blotting and in situ hybridization. Immunohistochemistry was performed to localize the deposition of VEGF-C protein., Results: The ratios of VEGF-C gene expression determined by Northern blot analysis were significantly higher in papillary than in follicular carcinoma. Nonmalignant thyroid tissue from patients with papillary carcinoma also expressed higher levels of VEGF-C than tissue from patients with follicular carcinoma. Expression of the VEGF-C gene was observed by in situ hybridization in cells of papillary thyroid carcinoma but not in those of follicular carcinoma. Positive staining with antibody against VEGF-C was detected in papillary cancer cells., Conclusions: Concurrent overexpression of the VEGF-C gene by both tumor cells and the surrounding tissue may be related to the prevalence of intrathyroidal spread through lymphatics and regional lymph node metastasis in patients with papillary thyroid carcinoma.

Background: Anterior transabdominal exploration has traditionally been advocated as the standard procedure for pheochromocytoma. However, some authors claim that a flank extraperitoneal approach with accurate unilateral localization is justifiable., Methods: Retrospective analysis was performed on 87 patients with pheochromocytoma to determine the appropriateness of extraperitoneal exploration., Results: There were 45 men and 42 women with a mean age of 44.7 years (range, 16 to 83 years). Fifteen patients (17.5%) had pheochromocytoma as a part of multiple endocrine neoplasia (MEN) type 2A, and four had familial pheochromocytoma, von Hippel-Lindau disease, or von Recklinghausen's disease. All tumors detected by preoperative localization studies were correctly identified and were resected through flank extraperitoneal (45 patients), transabdominal (28), thoracoabdominal (13), and posterior (1) approaches. Tumors were extraadrenal in 14, multiple in 22, bilateral in 12, and unequivocally malignant in 2 patients at the initial operation. Two patients died during the immediate postoperative period, giving an operative mortality of 2.3%. Two patients had persistent disease. During follow-up within a mean period of 5 years (range, 1 month to 13.7 years) 8 patients (9.1%) experienced recurrence or metastasis. Other than the patients with MEN 2, recurrence was not attributable to the operative approach., Conclusions: If a preoperative localization study is accurate, an extraperitoneal approach is justifiable for many patients with pheochromocytomas.

Background: The aim of this study was to characterize patients with pulmonary metastasis of parathyroid carcinoma and to evaluate the long-term effect of surgical and medical therapy., Methods: Seven patients with pulmonary metastasis of parathyroid carcinoma were treated between 1980 and 1992. Six patients underwent resection of pulmonary metastases, and one patient has had long-term bisphosphonate therapy alone. Bisphosphonate was also given before or after operation to three patients., Results: Two patients underwent a unilateral thoracotomy for a single pulmonary lesion, and four other patients with multiple lesions underwent staged bilateral thoracotomies. The postoperative serum calcium level returned to normal after each thoracotomy in three patients who were alive and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted in the other three patients. In two of the patients, bisphosphonate therapy was also unable to control hypercalcemia. In one patient the serum calcium level has been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone for 3 years., Conclusions: The aggressive surgical approach to pulmonary metastasis of parathyroid carcinoma was shown to be effective for palliation in selected patients. Bisphosphonate therapy is an alternative to resection but has only a temporary calcium-lowering effect.

Background: Unilateral adrenalectomy was performed in 63 patients with primary aldosteronism. During a mean follow-up time of 4.1 years, none of the patients showed recurrence of hyperaldosteronism. However, 24 patients (38%) had persistent hypertension. The purpose of this study was to determine factors responsible for postoperative persistent hypertension., Methods: A stepwise multivariate logistic regression analysis was performed to assess the combined predictive effects of the clinicopathologic variables., Results: Age, sex, and pathologic findings were the best predictive factors of postoperative persistent hypertension. For a patient aged 50 years or more, the odds of persisting hypertension are 10.6:1, compared with those of a patient under 40 years of age. A male patient appears to have a greater chance of hypertension than a female patient; the odds ratio is 5.9:1. Persistent hypertension develops in patients with multiple adenomas or with an adenoma associated with macronodules more frequently than in those patients with a solitary adenoma; the odds ratio is 8.1., Conclusions: This study suggests that early surgical intervention at a younger age results in a more favorable outcome for patients with primary aldosteronism. The presence of macronodules in association with an adenoma is a cautious predictor of persistent hypertension after adrenalectomy.

Although the benign counterpart of medullary carcinoma of the thyroid has never been indicated in textbooks, we propose that C cell adenoma is a rare but distinct clinical entity. Two patients, a 43-year-old man and a 53-year-old woman, had similar thyroid tumors, both about 4 cm in diameter. The cut surfaces of the resected tumors were indistinguishable from a common microfollicular adenoma of the thyroid. Microscopically, the tumors were uniformly composed of fusiform cells without any follicle formation. Neither amyloid deposition nor calcification was found. Although some kind of C cell tumors were suggested, the exact nature was debatable. However, extremely high levels of calcitonin (1330 and 2065 pg/ml, respectively; normal level, less than 170 pg/ml) were found in the stored sera taken preoperatively. Serum levels of carcinoembryonic antigen (CEA) were normal in both patients. Immunohistochemically, the tumor tissues were positive for calcitonin and neuron-specific enolase but negative for CEA with a monoclonal anti-CEA antibody. No somatostatin, glucagon, or adrenocorticotropic hormone activity was found. It is highly probable that such tumors have not been closely studied and have been regarded as eccentric adenomas of the thyroid or simply as the so-called medullary carcinomas of the thyroid.

Aggressive radical resection was performed on 18 of 21 elderly patients with locally invasive-papillary carcinoma of the thyroid. Diagnostic studies, including computed tomographic and endoscopic examinations, were useful in allowing accurate determination of tumor extent. Radical resection usually consisted of total or subtotal thyroidectomy and neck dissection combined with excision of the affected organs, which in one case included a laryngotracheoesophagectomy (reconstruction of the digestive tract with a forearm free flap), a sleeve, or a window resection of the trachea in nine cases (immediate end-to-end anastomosis in all but one), a partial esophagectomy in two cases, and resection of the outer layer of the trachea or esophagus in six cases. After these operations, one patient died of rupture of the carotid artery, one died of cancer in 4 years, and one other died of unrelated disease. The other 15 patients are alive and well 1 to 5 years postoperatively, although additional exploration for nodal metastases was required in three patients. Aggressive resection therefore appears to be justified for control of locally advanced, differentiated carcinoma of the thyroid.