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).

Clinical characteristics of small cell carcinoma of the breast.

Primary small cell carcinoma of the breast is a rare tumor of which less than 40 cases have been reported in the literature. Because of its rarity, its biological and clinical characteristics are still not fully understood and, to date, no standard therapy has been developed. Here, we present a case and a review of the literature regarding this cancer, focusing on clinicopathological findings and treatment. Primary small cell carcinoma of the breast differs from more common types of breast cancer in its biological features. It is anticipated that an improved understanding of the clinical characteristics of this tumor will result in the development of new therapeutic modalities, which would improve its prognosis.

Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver.

BACKGROUND/AIMS: Polyurethane foam (PUF)/ spheroid-culture can improve liver-specific functions of hepatoma cell line, Hep G2. Therefore, gene expression profile in the PUF/spheroid culture is hypothesized to be different from that in the monolayer culture. The aim of this study is to clarify the characteristic gene expression in PUF/spheroid-cultured Hep G2 cells, as a cell source for bioartificial liver (BAL), using microarray analysis. METHODOLOGY: Morphological change and liver specific functions of ammonia removal rate and albumin synthesis rate of Hep G2 were compared between in a monolayer or PUF/spheroid culture. Microarray analysis was performed using cDNA microarrays made in Hitachi Software Engineering Co., Ltd., (Yokohama, Japan), which contains a total of 1,281 cDNA clones. RESULTS: The ammonia removal rate of Hep G2 spheroids increased to 369%, and the albumin synthesis rate of Hep G2 spheroids also increased 311% when compared with monolayer culture. In addition, the ammonia removal capacity of primary human hepatocytes in the PUF/spheroid culture was superior to that in the monolayer culture. The microarray analysis demonstrated that the PUF/spheroid-cultured Hep G2 cells expressed 39 up-regulated (more than 3.0-fold) and 31 down-regulated (less than 0.333-fold) genes. Among the 70 genes differentially expressed in PUF/spheroid cultured Hep G2 cells, subsets of glutathione S-transferase- and angio-tensin-related genes were drastically up-regulated, on the other hand, subsets of assigned for growth factor, glucocorticoid, and stress response, were down-regulated. CONCLUSIONS: Hepatoma cell line, Hep G2 cells in the PUF/spheroid culture is a promising hepatocyte source for BAL. Microarray analysis revealed a number of characteristic genes altered by the PUF/spheroid.

Tumor necrosis factor-a antisense transfer remarkably improves hepatic graft viability.

BACKGROUND: Cold ischemia/reperfusion injury of the hepatic graft, an unsolved problem in liver transplantations, is attributed to the release of inflammatory cytokines, especially the tumor necrosis factor- (TNF) alpha, from activated Kupffer cells (KC). Therefore, the specific inhibition of TNF-alpha could improve the viability of the hepatic graft upon reperfusion. METHODS: We assessed the efficacy of TNF-alpha antisense (TNF-AS) oligodeoxynucleotides (ODNs) delivery to KC in a rodent liver transplantation model. RESULTS: Seventy-one percent of the animals that received 6 hours preserved grafts in baths of lactated Ringer's solution (4 degrees C) and were treated with TNF-AS survived for over 14 days. Eighty percent of the animals treated with vehicle, sense ODNs, or balanced salt saline (BSS) died. Four hours after reperfusion of the liver, a significant reduction was noted in livers treated with TNF-AS in the release of cytosolic enzymes from the hepatocytes and the serum TNF-alpha (P<0.05). The expressions of TNF-alpha on KC and of intercellular adhesion molecule-1 on sinusoidal endothelial cells were completely suppressed in TNF-AS-treated livers. CONCLUSIONS: TNF-AS delivery improves the viability of the hepatic graft, and this technique may solve hepatic graft nonfunction in a clinical setting.

Extended lobectomy for procurement of the left lobe with caudate lobe for living-related liver transplantation.

Liver transplantation from living-related donors has been established for end-stage liver disease. In adult cases, the left lobe with a caudate lobe was transplanted in order to increase the graft volume. However, the procurement operation should be less invasive for the donor. In this article, we represent our technique by which the blood loss can be reduced during the harvesting operation. The technique was used to improve the extended left lobectomy for the procurement in 27 patients between May 1997 and December 1999 at Kyushu University Hospital. The groups included the following: 1) Procurement operation of the extended left lobe with caudate (n=9), 2) without caudate (n=18). The detailed record during the operation showed that the mean blood loss and the amount for the group with caudate was significantly smaller than that in the group without caudate. To reduce the blood loss during the procurement operation, we continue to use this technique in the living-related donors for adult recipients.

Unusual endoscopic findings of CMV esophagitis after liver transplantation.

Cytomegalovirus infections are associated with a high mortality rate after liver transplantation, but they are treated successfully by administration of the combination of ganciclovir plus intravenous immunoglobulin. We herein describe cytomegalovirus esophagitis in a patient having gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia after liver transplantation was detected by performing the surveillance of endoscopy. At first, the findings of endoscopy that were segmental erosive areas but no ulcerative areas on the esophageal lumen were unusual in this case of cytomegalovirus infections, but cytomegalovirus esophagitis was confirmed by cytomegalovirus immunohistochemical stain using biopsies. The patient was treated by ganciclovir at an oral dosage of 5mg/kg twice a day for 2 weeks. Our experience suggests that cytomegalovirus esophagitis should be taken into consideration when a patient has gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia and has endoscopic findings such as segmental erosions on the esophageal lumen despite having no cytomegalovirus-specific endoscopic findings such as ulcerative lesions.

Postoperative adjuvant therapy with tamoxifen, tegafur plus uracil, or both in women with node-negative breast cancer: a pooled analysis of six randomized controlled trials.

PURPOSE: This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients. PATIENTS AND METHODS: Six randomized controlled trials on node-negative breast cancer patients were conducted from 1992 through 1995 in Japan that included the three, three-arm trials (control [no adjuvant], UFT, and tamoxifen [TAM] groups) and the three, four-arm trials (control, UFT, TAM, and UFT plus TAM groups). Pooled analysis was performed on the data obtained from these six trials (involving 2,934 patients). RESULTS: Overall survival was compared between the UFT group (including both the UFT group and the TAM plus UFT group) and the non-UFT group (control group and TAM group). A significant difference (P = .04) was observed in 5-year survival rates between the UFT (95.9%) and the non-UFT (94.0%) groups. Overall survival was also compared between the TAM group (TAM group and TAM plus UFT group) and the non-TAM group (control group plus UFT group). The 5-year survival rate (95.2%) in the TAM group was not significantly different from that (93.9%) in the non-TAM group, but the subset analysis showed a significant (P = .01) improvement in the estrogen receptor-positive subset. CONCLUSION: Adjuvant UFT improves the overall survival of node-negative breast cancer patients. Given that UFT has milder adverse effects, it is suggested that UFT can be a useful alternative to doxorubicin and cyclophosphamide, or cyclophosphamide, methotrexate, and fluorouracil in the adjuvant treatment for node-negative breast cancer.

Hyperinsulinemia in patients with colorectal cancer.

BACKGROUND/AIMS: It has been reported that non-insulin dependent diabetes mellitus (NIDDM) is one of the risk factors for colorectal cancer. Usually, in the pre-NIDDM state, hyperinsulinemia is seen for 5 to 8 years. Insulin is the growth factor of epithelial and cancer cells of colon and rectum. In this study, we evaluate glucose tolerance in the patients with colorectal cancer who were never diagnosed with DM. METHODOLOGY: We studied 82 patients with colon cancer who were never diagnosed with DM. 75-g glucose tolerance test (75g GTT) was performed and we measured serum glucose (BS) and insulin (IRI) levels, and we defined them as normal glucose tolerance (NGT), impaired GT (IGT), and DM. We also defined hyperinsulinemia as highest IRI levels over 100mU/mL at 75g GTT. RESULTS: Serum glucose and insulin levels were higher in the patients with colorectal cancer than in healthy controls. In 82 colorectal cancer patients, 39 were IGT and 5 were DM. All DM patients also had hyperinsulinemia. Only 14 patients (17%) had NGT and normal IRI levels. CONCLUSIONS: Our findings suggest that hyperinsulinemia is occasionally seen in patients with colorectal cancer. Hyperinsulinemia may be one of the causes of colorectal cancer and we have to control hyperinsulinemia to prevent recurrence of colorectal cancer even after curative resection.