Hypothyroidism With ACTH Deficiency During Pembrolizumab Therapy for Lung Cancer: Case Report and Literature Review.

BACKGROUND/AIM: Immune-checkpoint inhibitors have recently shown great promise in treating various cancers, but often cause immune-related adverse events (irAEs). Simultaneous drug-induced hypothyroidism and isolated adrenocorticotropic hormone (ACTH) deficiency are rare irAEs. This combination of irAEs is associated with paradoxical endocrine dysfunction characterized by large amounts of thyroid-stimulating hormone (TSH) and small amounts of ACTH in the anterior lobe of the pituitary. We herein report a case of hypothyroidism with isolated ACTH deficiency during pembrolizumab therapy for recurrent lung cancer. CASE REPORT: Our patient was a 66-year-old man with recurrence of squamous cell lung carcinoma. Four months after chemotherapy that included pembrolizumab, the patient presented with general fatigue and laboratory tests showed high concentrations of TSH with low concentrations of free-T4. He was diagnosed with hypothyroidism and levothyroxine was prescribed. His ACTH concentration was found to be low 1 week later when he developed an acute adrenal crisis with associated hyponatraemia. We then changed his diagnosis to concurrent hypothyroidism with isolated ACTH deficiency. His condition improved after 3 weeks of administration of cortisol. CONCLUSION: It is difficult to diagnose a concurrent paradoxical endocrine disorder, such as hypothyroidism with isolated ACTH deficiency, as in the present case. Physicians should pay attention to symptoms and laboratory data to identify various types of endocrine disorders as irAEs.

Surgical treatment of Bochodalek hernia incarcerated into the extra-pleural space: A rare case report.

INTRODUCTION: Bochdalek hernias are a type of diaphragm hernia. Almost all occur in the neonatal period, only 5% of these hernias occurring in adults. We here present a rare case of adult Bochdalek hernia incarcerated in the extra-pleural space. PRESENTATION OF CASE: An asymptomatic 51-year-old man was admitted to our hospital for a detailed examination after an abnormality had been detected on a chest radiograph. Chest computed tomography (CT) examination revealed findings consistent with a left Bochdalek hernia, which we repaied surgically. Intraoperatively, retroperitoneal fatty tissue was found to be incarcerated in the extra-pleural space. Thus, surgical repair required dissection of the parietal pleura and excision of the incarcerated fatty tissues. DISCUSSION: The incarceration of the Bochdalek hernia in the extra-pleural space could not be identified on a preoperative chest CT examination. To the best of our knowledge, no reports of incarceration of a Bochdalek hernia in the extra-pleural space have been published; thus, this phenomenon is extremely rare. CONCLUSION: Surgical treatment of a Bochdalek hernia incarcerated in the extra-pleural space requires dissection of the parietal pleura and repair via a transthoracic approach.

[Analysis of Advanced or Postoperative Recurrent Non-small Lung Cancer Cases Treated with Nivolumab].

Recent developments in cancer immunotherapy are remarkable. Many reports have described the clinical effects of immune checkpoint inhibitors (ICIs), supporting their utility as a promising therapy that will achieve prominent effects even in patients resistant to cytotoxic anticancer drugs or gene-targeting therapy. ICIs may also prolong overall survival. We analyzed 10 cases of advanced lung cancer targeted with nivolumab, which is one of ICIs in our hospital and reviewed the literature regarding ICIs. We retrospectively analyzed 10 cases that consisted of 6 males and 4 females, which comprised 7 adenocarcinomas, 2 squamous cell carcinomas and one pleomorphic carcinoma. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase mutations were negative in all the adenocarcinoma cases. The 10 analyzed cases included 9 inoperable cases and 1 postoperative recurrent case, 8 second-line cases, a third-line case, and a fourth-line case. The average frequency of administrations of nivolumab was 7.4 times. The survival rate was calculated by using the Kaplan-Meier method. The clinical responses to nivolumab were partial response in 2 cases, stable disease in 4 cases, and progressive disease in 4 cases. In the 10 cases, the response rate and disease control rate were 20% and 60%, respectively. The median progression-free survival time and median survival time were 115 days and 126 days, respectively. We observed 2 cases of dermatitis and one each of pyrexia, general fatigue and drug-induced pneumonia as adverse events (AEs). One of these AEs was severe (Stevens-Johnson syndrome grade 4) but could be treated by steroid pulse therapy, steroid ointment and instillation. Among the 10 examined cases of advanced lung cancer treated with ICIs at our hospital, ICIs proved effective in 2 cases. However, we also experienced a case with Stevens-Johnson syndrome grade 4 as a severe AE. These findings suggest that while ICIs may be effective in treating patients, candidates for ICIs must be carefully selected and cautiously observed.

A rare anomaly of the right superior pulmonary vein: Report of a case.

INTRODUCTION: Although there are a lot of variations of pulmonary veins (PVs) including dangerous type that could cause serous complications during the surgery, limited information has been reported about these variations. We have experienced an extremely rare anomaly of the right superior PV. PRESENTATION OF CASE: A 74-year-old man patient with right lung cancer visited our hospital. Chest computed tomography (CT) revealed a pulmonary nodule in the right lower lobe. Contrast-enhanced three-dimensional CT (3D-CT) showed that the right superior PV ran abnormally between the right main pulmonary artery (PA) and the right main bronchus. We performed right lower lobectomy and systematic nodal dissection. The operative findings confirmed that the right superior PV ran abnormally same as 3D-CT. DISCUSSION: In most reported cases, anomalous PVs pass behind the right bronchi or into the roof of the left atrium. The anomaly reported in the present case has been reported in only one case report. This case suggests that the space between the right main PA and the right main bronchus is not always safe for dissection. CONCLUSION: Preoperative 3D-CT is useful for avoiding unexpected bleeding.

Solitary fibrous tumor of the lung: a case report.

Solitary fibrous tumors (SFTs) are relatively rare neoplasms that commonly occur in the pleura. The pathological feature of SFTs is a proliferation of spindle-shaped cells in interlacing or storiform fascicles. SFTs appear to derived from pluripotential submesothelial cells, but not the covering mesothelium. SFTs distinctively show diffuse staining for CD34 but lack staining for smooth muscle markers. We herein report a relatively rare case of a 68-year-old male patient without symptoms, who underwent resection for what was considered to be SFT.

A primary cellular fibrohistiocytoma of the lung: Report of a case.

INTRODUCTION: Cellular fibrohistiocytoma (CFH) is a type of fibrohistiocytic tumor that commonly occurs in the dermis and superficial subcutis. The designation is used for lesions that show increased cellularity with a fascicular growth pattern and frequent extension. Our search of literature only revealed one case of a primary CFH of the lung. We experienced a rare patient with a primary CFH of the lung. PRESENTATION OF CASE: We herein present a rare case of a 77-year-old female patient without a cutaneous lesion, who underwent resection for what was considered to be a primary CFH of the lung. There has been no recurrence including a cutaneous lesion in a year after surgery. DISCUSSION: CFH is considered to be benign, but rare cases showing multiple recurrences and involving metastasis to the lymph nodes and internal organs have been reported. At present, it is not possible to predict this aggressive biological behavior based on the tumor histology. CONCLUSION: It is essential to perform resection with an adequate margin with close clinical follow-up.

A rare pulmonary hamartoma: fibroleiomyomatous hamartoma.

Pulmonary hamartomas are more common than expected because they are usually asymptomatic and are either discovered on routine chest radiography or when they are noted incidentally in approximately 0.25 % of autopsies. In contrast, pulmonary fibroleiomyomatous hamartoma, which consists of interlacing bundles of smooth muscle cells admixed with fibrous tissue and numerous tubular or cleft-like epithelial inclusions, is a rare type of hamartoma. Controversy exists regarding the pathogenesis of this tumor. We herein present a rare case of a 68-year-old male patient without a pre-existing smooth muscle tumor, who underwent resection for a tumor that was considered to be a true pulmonary fibroleiomyomatous hamartoma.

[Placement of An Expandable Metallic Stent for Malignant Tracheal Stenosis: A Case Report].

The utility of stent placements has been widely reported. We performed a thought-provoking stent placement for malignant tracheal stenosis recently. A 90-year-old woman who was admitted to our hospital because of a urinary tract infection was treated with a course of antibiotics, but she demonstrated a rapidly progressive course with dyspnea. Chest computed tomography showed severe tracheal stenosis due to an upper mediastinal mass. She was put on noninvasive positive pressure ventilation (NPPV) because of severe respiratory failure. Bronchoscopy showed severe tracheal stenosis due to direct invasion by the upper mediastinal mass. An expandable metallic stent (EMS) was placed in the trachea, after which a bronchoscopy showed a widely patent airway, and she got off NPPV. Then she did not need supplemental oxygen. She could seat herself, and have an enough meal, independently. However, takotsubo cardiomyopathy occurred and she died 11 days after the placement of the EMS. Since a malignant airway complication can be fatal, tracheal stent placement is a useful treatment in the management of malignancy with airway stenosis. In this case, it was thought that an early intervention of airway stenosis would have reduced the risk of takotsubo cardiomyopathy in a patient with severe symptoms of airway stenosis and stress.

Thoracoscopic plication for idiopathic eventration of the bilateral diaphragm: Report of a case.

INTRODUCTION: Diaphragmatic eventration, defined as permanent elevation of the diaphragm without defects, is a rare anomaly in adults. Trauma, neoplasms, infection, and degenerative disease are the most common causes of this condition, whereas idiopathic eventration of the diaphragm is relatively infrequent. PRESENTATION OF CASE: We herein present the rare case of an 85-year-old female with idiopathic eventration of the bilateral diaphragm. The patient demonstrated a rapidly progressive course with dyspnea; therefore, thoracoscopic surgery of the unilateral diaphragm was performed. She subsequently withdrew from home oxygen therapy, which had introduced preoperatively, and exhibited a significant improvement in her pulmonary function for one year after the operation. DISCUSSION: Various approaches for diaphragmatic plication have been reported, including open (transthoracic or transabdominal) and minimally invasive methods, such as thoracoscopic or laparoscopic plication. We consider thoracoscopic plication to be an effective minimally invasive method, although single-lung ventilation is required. CONCLUSION: We experienced a case in which thoracoscopic plication of the unilateral diaphragm resulted in adequate objective improvements in the pulmonary function in a patient with idiopathic eventration of the bilateral diaphragm.

Surgical management of pulmonary arteriovenous fistula in a female patient.

INTRODUCTION: We herein describe a rare case of a pulmonary arteriovenous fistula (PAVF). PRESENTATION OF CASE: The patient was a 20-year-old asymptomatic female, admitted to our hospital because of an abnormal shadow in the right lung field on chest X-rays. Chest computed tomography (CT) revealed two nodules with well-defined margins in the right upper and lower lobes. Contrast-enhanced three-dimensional CT (3D-CT) revealed two enhanced solitary lung nodules which were connected with linear structures suggestive of feeding arteries and drainage veins, respectively. Based on these findings, we made a preoperative diagnosis of PAVF. We performed partial pulmonary resection of the right upper and lower lobes by video-assisted thoracoscopic surgery (VATS). The histopathological findings revealed small and medium-sized vascular channels composed of arteries with mild and irregularly thickened muscle walls and juxtaposed or seemingly anastomosing dilated veins. Based on these findings, a diagnosis of PAVF was confirmed. The patient had an uneventful postoperative course. DISCUSSION: A PAVF is often associated with various complications, and pregnancy could be a risk factor for these complications because of the increase in the shunt fraction. Females with known PAVF should be maximally treated prior to becoming pregnant as complications of PAVF during pregnancy can have devastating consequences. Therefore, we thought that treatment should be recommended in this case in the event she might later choose to become pregnant. CONCLUSION: Surgical resection using VATS for a limited number of ipsilateral isolated pulmonary arteriovenous fistulae is recommended due to its safety, low recurrence and low mortality rate.

Lung granuloma mimicking pulmonary arteriovenous malformation: Report of a case.

INTRODUCTION: While hypervascular lesions in the lung are known to mimic pulmonary arteriovenous malformation (PAVM), here we report a rare case of lung granuloma mimicking PAVM, on which video-assisted thoracic surgery (VATS) was performed. PRESENTATION OF CASE: A 76-year-old woman without any symptom was admitted to our hospital because of abnormal shadow in the left lung field on chest X-ray. A 20mm×14mm nodule with well-defined margins and smooth contours in the left upper segment was detected in her chest computed tomography (CT). Contrast-enhanced three-dimensional CT (3D-CT) revealed an enhanced solitary lung nodule, which was connected with linear structures suggestive of feeding artery and drainage vein. Thus, we made a preoperative diagnosis of PAVM by performing partial pulmonary resection by VATS. Intraoperatively, elastic hard nodule was palpable in the left upper segment and bruit was not convincing. Histopathological findings revealed multiple foci of coagulative necrosis surrounded by epithelioid cell granuloma containing Langhans-type multinucleated giant cells, involving the medium-sized blood vessels in the pulmonary parenchyma. Abnormal vascular structures, such as PAVM were not convincing. Based on these findings, a diagnosis of left lung granuloma was made. DISCUSSION: Preoperatively, it was difficult to distinguish the left lung granuloma from PAVM, because hypervascular lesion, such as inflammatory changes can present as strongly enhanced nodules after injection of contrast material. CONCLUSION: Surgical approach seems appropriate, not only for the purpose of diagnosis, but also for the safety in treatment of a PAVM.

An idiopathic azygos vein aneurysm mimicking a mediastinal mass.

Azygos vein aneurysms are very rare causes of mediastinal masses and are usually accidental findings on chest roentgenography. Most are detected in patients with portal hypertension or venous malformations. An idiopathic azygos vein aneurysm is assumed to be congenital and is much more exceptional. We present the case of a 76-year-old man who underwent excision of an idiopathic azygos vein aneurysm by video-assisted thoracoscopic surgery (VATS).

Differential expression of insulin-like growth factor 1 in human primary liver cancer.

Insulin-like Growth Factor 1 (IGF-1) antigen was immunohistochemically examined in 28 patients of the primary hepatocellular carcinoma with hepatectomy. IGF-1 was expressed in 93% (26/28) of the primary lesion and 100% (28/28) of the normal liver. Compared with expression in normal liver, decreased expressions in primary lesions were noted in 36% (10/28) for IGF-1. Histological examination revealed that there were significant correlations between patients with decreased expressions of IGF-1 in primary lesions and poor differentiated hepatocellular carcinoma, and portal vein infiltration. These results indicate that expression of IGF-1 has the relationship with the differentiation in human primary hepatocellular carcinoma.

Gastrointestinal bleeding and blood transfusion in the elderly in Japan.

BACKGROUND/AIMS: The incidence of gastrointestinal bleeding (GIB) increases with age and blood transfusion is frequently given for the management of GIB. In this report, we summarized our data of the patients with GIB and discussed the relationship between blood transfusion and age in patients with GIB. METHODOLOGY: The patients were divided into two groups according to age, following elderly (≥75 years old) and younger (<75 years old) group. The causes and clinical outcome (blood transfusions, management) of each group were compared. RESULTS: One-hundred and twenty patients with GIB were hospitalized (59 men, 61 women) with a mean age of 72.0±15.8 years (range 16-96 years old). Thirty-one patients (25.8%) received blood transfusion. The mean pre-transfusion hemoglobin was 6.4±1.2g/dL (elderly 6.3±1.4, younger 6.6±1.0g/dL) and the mean amount of blood transfusion was 2.8±1.6U (elderly 3.2±1.8, younger 2.3±0.9U). The elderly patients using antithrombotic drugs need greater amounts of blood transfusion than younger patients using antithrombotic drugs. The hemoglobin level of the elder patients without antithrombotic drugs was significantly lower than that of younger patients without antithrombotic drugs. CONCLUSIONS: Our data suggest that our blood transfusion strategy seems to be in tolerance level with restrictive blood transfusion strategy.

Gastrointestinal bleeding associated with antithrombotic therapy in the elderly in Japan.

BACKGROUND/AIMS: We summarize data of patients with gastrointestinal bleeding (GIB) and discuss the relationship between antithrombotic drug use and age in patients with GIB. METHODOLOGY: One-hundred and twenty patients with GIB were divided into two groups according to age (=75 years old and <75 years old). The causes and clinical outcome of each group were compared. RESULTS: Forty-two patients received antithrombotic therapy. The main antithrombotic drugs were low dose aspirin (38 patients), ticlopidine (5 patients) and warfarin (3 patients). Compared with younger GIB patients, elderly patients had more coexisting illness and antithrombotic drugs. In patients taking antithrombotic drugs, upper GIB is more frequent than those not taking antithrombotic drugs (p<0.05) and antithrombotic drugs were the risk for GIB from erosive lesions of the esophagus or stomach. In the lower gastrointestinal tract, there was no difference of incidence related to antithrombotic use. The initial endoscopic hemostasis was performed in 14 patients. Eight varices patients received endoscopic vanding and 6 of 43 gastroduodenal ulcer patients had mechanical clip hemostasis. CONCLUSIONS: From our findings, antithrombotic drugs were considered to be a risk for GIB. It might be important to prevent or minimize GIB in elderly patients prescribed antithrombotic drugs.

Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats.

AIM: To investigate the effects of hyperbaric oxygenation (HBO) on regeneration of the biliary ductal system and postoperative cholestasis in hepatectomized rats. METHODS: HBO was performed in Wistar rats daily starting 12 h after a 70% partial hepatectomy. Regenerated liver weight, serum parameters and the proliferating cell nuclear antigen labeling index of hepatocytes and biliary ductal cells were measured. Hepatocyte growth factor (HGF), c-Met and transforming growth factor (TGF) ß-1 mRNA expression levels were analyzed by quantitative reverse transcription polymerase chain reaction. RESULTS: HBO improved the postoperative serum levels of total bile acid but not transaminase levels. HBO promoted hepatocyte and biliary ductal cell proliferation. The hematoxylin and eosin-stained specimens revealed fewer ballooned hepatocytes and higher cell densities in the HBO group compared to the control group. HBO suppressed c-Met mRNA levels at 15 h but did not modulate HGF or TGF ß-1 mRNA expression levels. CONCLUSION: HBO promoted regeneration of biliary ductal cells and improved postoperative cholestasis after a partial hepatectomy.

Immunohistochemical Examination of a Resected Advanced Hilar Cholangiocarcinoma Arising in a 29-Year-Old Male without Primary Sclerosing Cholangitis.

A 29-year-old man with advanced hilar cholangiocarcinoma was successfully treated with an extended right lobectomy. The carbohydrate antigen 19-9 (CA19-9) level was elevated to 939 IU/l, and the pathological findings revealed moderately differentiated tubular adenocarcinoma which involved almost the entire thickness of the hepatic duct and the adjacent liver tissue (T3) and which was associated with lymph node metastasis (N1). It was a stage IIB (T3N1M0) tubular adenocarcinoma according to UICC pathological staging. Immunohistochemical examination revealed that Ki-67, cyclin D1, and MMP-7 were positive, and 14-3-3sigma and p27 were negative. The pathological and immunohistochemical findings indicated high malignant potential indicating poor prognosis. We administrated the postoperative adjunct gemcitabine combined with S-1 chemotherapy. The patient is alive without recurrence and doing well two years after surgery. We also review other reports of cholangiocarcinoma patients aged less than 30 years.

Gastric bleeding from a penetrating pancreatic pseudocyst with pseudoaneurysm of the splenic artery.

The successful management of gastric bleeding from a pseudocyst with a pseudoaneurysm of the splenic artery is reported here. A 62-year-old male patient was referred to our hospital with a complaint of hematomesis. On a computed tomography and an abdominal angiography, it was evident that he was actively bleeding from a splenic pseudoaneurysm caused by a pancreatic pseudocyst. A transcathetheral arterial embolization (TAE) was performed on the splenic pseudoaneurysm to control bleeding. After the TAE, we resected the pancreatic pseudocyst by distal pancreatectomy with partial gastrectomy. Gastrointestinal bleeding from a pseudoaneurysm caused by a pancreatic pseudocyst is a rare, but sometimes lethal, complication. As only conservative therapy or TAE often results in lethal re-bleeding, we propose to perform elective surgery after TAE.

Time-course changes in the liver of biliary atresia patients on magnetic resonance imaging.

BACKGROUND: Using magnetic resonance imaging (MRI), changes in the livers of postoperative biliary atresia (BA) patients were investigated. METHODS: Periodic MRI was performed in 32 postoperative BA patients. The findings were evaluated by calculating the near-normal liver tissue area that corresponded with normal- or high-signal regions on T1-weighted imaging. The patients were divided into three groups based on the extent of near-normal liver tissue on the final MRI: group A, n = 14; group B, n = 13; and group C, n = 5, included patients with >40%, 20-40%, and <20% area of near-normal liver tissue, respectively. The relationship among the macroscopic and histological findings in the liver at orthotopic living donor liver transplantation (OLDLT), patient outcomes, and MRI findings were investigated. RESULTS: In group A, 11 patients had no evidence of liver dysfunction. In group B, six patients either had undergone or were awaiting OLDLT. In group C, all patients had undergone OLDLT. All patients had either adequate or impaired bile drainage in each liver segment. The segmental changes corresponded with the liver architecture at OLDLT. The changes could be evaluated on MRI at 1-2 years after surgery. CONCLUSIONS: Adequate and restricted areas of liver tissue with near-normal structure were indicative of good and poor prognoses, respectively. Shortly after portoenterostomy, these segmental changes occurred and/or developed in each liver segment and could be detected on MRI. It is emphasized that patients with >40% area of near-normal liver architecture at the initial stages did not require OLDLT, while those with <20% area did require OLDLT.

Laparoscopic cholecystectomy using a novel two-port technique for surgical residency training.

For the cosmetic benefits of patients, many institutions attempted to perform laparoscopic cholecystectomy (LC) with a minimum port. It has not yet been discussed whether the number of ports used in LC affect an outcome in a residency training program. We enrolled 101 patients consecutively. Eight freshmen (PGY1) performed 32 operations (13 cases with two-port, 23 cases with four-port). Clinical data were compared with the data by the senior staff. In the freshman group, the duration of surgery was longer in the two-port group than in the four-port group (P = 0.0297); however, there were no complications. In the two-port group, the freshman group took longer than the senior group (P = 0.0266). As for the volume of intraoperative bleeding, there was no statistical significance. Our two-port technique seems to be a feasible, effective, and safe technique for performing LC in the residency training program on selected patients.