A case of carcinoid syndrome probably exacerbated by hemodialysis in which prochlorperazine maleate was effective.

Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy.

Ganglioside GD2 Expression Is Associated With Unfavorable Prognosis in Early Triple-negative Breast Cancer.

BACKGROUND/AIM: Gangliosides (acidic glycosphingolipids) have crucial regulatory roles in normal physiological processes, as well as in pathological conditions, including tumor onset and progression. GD2 is highly expressed in triple-negative breast cancer (TNBC), particularly in cancer stem cells. However, little is known on the clinical impact of GD2 expression on the prognosis of TNBC. Consequently, we aimed to investigate the association between GD2 expression in TNBC and the prognosis of TNBC. PATIENTS AND METHODS: We assessed GD2 expression in 76 patients with primary TNBC who had undergone surgery at our Institute between 2012 and 2015 using immunohistochemical analysis with a tissue microarray technique. We investigated the relationship between GD2 expression and clinicopathological factors in TNBC, recurrence-free survival (RFS), and overall survival (OS). RESULTS: Increased GD2 expression was observed in 45% of TNBC patients. There was no significant association between GD2 expression and clinicopathological factors in TNBC. The 5-year RFS rate among patients with GD2-positive TNBCs was significantly worse than that among patients with GD2-negative TNBCs (75.4% and 94.9%; HR=4.931; 95%CI=1.024-23.752; p=0.027). The OS in patients with GD2-positive TNBCs tended to be inferior to that of patients with GD2-negative TNBCs (HR=5.357; 95%CI=0.599-47.939; p=0.092). Interestingly, in patients with GD2-positive TNBCs, a higher grade of tumor-infiltrating lymphocytes (TILs) displayed a significantly better impact on OS (TILs-high vs. TILs-low; p=0.04). Both univariate and multivariate analyses showed that GD2 expression negatively affected RFS (p=0.027, p=0.021, respectively). CONCLUSION: GD2 expression is an independent unfavorable prognostic factor for TNBC.

A case of steatohepatitis that developed after pancreaticoduodenectomy and progressed rapidly to liver cirrhosis and hepatocellular carcinoma.

Steatohepatitis has been reported to occur after pancreaticoduodenectomy (PD). We report a case of steatohepatitis that arose after PD and led to decompensated liver cirrhosis and hepatocellular carcinoma (HCC). A 65-year-old man underwent PD for suspected intraductal papillary mucinous neoplasm. Eight years after PD, he was diagnosed with liver cirrhosis by laboratory tests and computed tomography. Histological examination of liver biopsy revealed hepatic steatosis, inflammation with ballooning of hepatocytes, and fibrosis, indicating nonalcoholic steatohepatitis as the cause of liver cirrhosis. Ten years after PD, he developed HCC and radiotherapy was performed because of impaired liver function. Intrahepatic metastasis appeared subsequently, but no further treatment could be performed due to decompensated liver cirrhosis. Survival time after PD is being prolonged by improvements in imaging studies and therapeutic strategies. Accordingly, we consider that progression to liver cirrhosis and HCC will occur increasingly in cases such as the present patient, which will become a severe problem in long-term post-PD survival. Therefore, it is necessary to clarify the precise mechanism of steatohepatitis after PD and establish appropriate therapeutic strategies.

Bullous Pemphigoid in X-linked Alport Syndrome.

Skin lesions in X-linked Alport syndrome (XLAS) are rarely observed. Bullous pemphigoid (BP) is caused by autoantibodies against BP180, also called α1 (XVII) chain, in the basement membrane zone (BMZ). A 48-year-old man with XLAS developed tense blisters. A skin biopsy showed a cleft between the basal cell layer and dermis, with the infiltration of neutrophils and eosinophils. α1 (XVII) staining was positive on the epidermal side of α2/5 (IV) staining. Oral prednisolone improved his symptoms gradually. Abundant tense blisters on the palms and soles might suggest an important role of the α5 (IV) chain in the integrity of BMZ.

Central nervous system involvement of systemic ALK-positive histiocytosis with KIF5B-ALK fusion.

ALK-positive histiocytosis is an emerging histiocytic entity that can involve a single organ or multiple organs. This disease frequently involves the central nervous system, and the importance of immunohistochemical and genetic analyses is emphasized for the accurate diagnosis of this rare entity. However, radiological findings of this disease have not been sufficiently described. Here, we report a case of a 3-year-old boy with ALK-positive histiocytosis with systemic masses that was identified to harbor KIF5B-ALK gene fusion.

Cryptococcus granuloma mimicking local progressed tumor after cryoablation of renal cell carcinoma: A case report.

Infectious granulomas arising in the kidney are rare. However, there are few reports regarding renal granulomas, such as xanthogranulomatous pyelonephritis, sarcoidosis, malakoplakia, and tuberculosis. Here, we report a case of cryptococcal granuloma resembling a locally progressed tumor after percutaneous cryotherapy for renal cell carcinoma. A male patient in his 80s with rheumatoid arthritis underwent computed tomography (CT)-guided cryoablation for biopsy-proven papillary renal cell carcinoma. Follow-up contrast-enhanced CT imaging obtained 4 months after ablation confirmed an enhanced mass on the edge of the ablation zone. There were no symptoms related to the mass. This mass was radiologically diagnosed as local tumor progression and treated with repeated cryoablation. Percutaneous biopsy of the mass was performed immediately after the second cryoablation, and the mass was pathologically diagnosed as granuloma related to Cryptococcus infection. The patient was administered antifungal fluconazole for 1 year with a good outcome.

Recurrent hepatocellular carcinoma with osteoclast-like giant cells: a case report.

BACKGROUND: Hepatocellular carcinoma with osteoclast-like giant cells is very rare and has an extremely poor prognosis. Here, we report a case of hepatocellular carcinoma with osteoclast-like giant cells that had a relatively better prognosis. CASE PRESENTATION: A 70-year-old Japanese man with hepatitis B virus-related liver cirrhosis was admitted to our hospital for the treatment of recurrent hepatocellular carcinoma. At the age of 60 years, he was first diagnosed as having hepatocellular carcinoma in the right lobe (9 cm in diameter), and liver resection of segment 7/8 was performed. Histological findings showed well-differentiated hepatocellular carcinoma. Since then, imaging studies have been performed every 3 or 4 months. One year later, hepatocellular carcinoma recurred in the lateral segment, and radiofrequency ablation was performed. Nine years after the first presentation, hepatocellular carcinoma recurrences were detected in the caudate lobe and segment 5 by imaging studies. Surgical resection of the caudate lobe was performed, and ultrasonography-guided radiofrequency ablation was subsequently performed for the segment 5 tumor. The resected tumor was simple nodular, well-differentiated HCC; it measured 21 × 21 mm and contained many osteoclast-like giant cells. As neither vascular nor bile duct invasion was found, we believe that radical resection was achieved. Since then, the hepatocellular carcinoma has not recurred for over a year and a half. CONCLUSION: Hepatocellular carcinoma with osteoclast-like giant cells is very rare and the prognosis is extremely poor, but early detection can lead to a better clinical course.

CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression.

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC. Furthermore, suppressive subsets in the local tumor microenvironment, such as tumor-associated macrophages (TAMs), which promote tumor progression, cannot be ignored to overcome immunotherapy resistance. The aims of the present study were to classify primary BC cases based on the TIL levels and PD-L1 status, and to identify suppressive immune subsets in each categorized group. A retrospective analysis of 73 patients with invasive BC was performed. The frequency of TILs was evaluated in HE-stained slides (10% cutoff), and PD-L1 levels (SP142; 1% cutoff), as well as immune subsets (CD3+, CD8+, FOXP3+, CD20+, CD68+ and CD204+ cells) were assessed using immunohistochemistry. It was revealed that 22% (16/73) of the tumors were categorized as TIL+PD-L1+, of which 69% (11/16) were TN type. By contrast, 66% (48/73) of the tumors were categorized as TIL-PD-L1-, of which 77% (37/48) were HR+ and HER2- types. The number of CD204+ M2-type macrophages was significantly associated with high histological grade (P=0.0246) and high Ki-67 (P=0.0152), whereas CD68+ macrophages were not associated with these factors. Furthermore, CD204+ macrophages and FOXP3+ Tregs accumulated in 88% (14/16) and 63% (10/16) of TIL+PD-L1+ tumors, respectively, compared with 20.8% (10/48) and 27.1% (13/48) of TIL-PD-L1- tumors. In conclusion, 22% of BC tumors were classified as TIL+PD-L1+ (69% were TN), which were enriched with suppressive immune subsets. These cell types may serve as potential novel immunotherapeutic targets.

Pharyngolaryngeal ulcers associated with the improper use of alendronate.

Bisphosphonates can cause mucosal irritation. Although esophageal ulceration is a well-recognized adverse effect of bisphosphonates, pharyngolaryngeal ulcers associated with the improper use of oral bisphosphonates have rarely been described. A previously healthy 78-year-old woman presented with refractory pharyngolaryngeal ulcers. Extensive evaluation, including biopsy, bacterial culture, and blood tests did not identify any findings that indicated a specific disease diagnosis. Antibiotics and oral prednisolone were ineffective. Ultimately, it was found that the patient regularly took a tablet of alendronate, a type of bisphosphonate, by dissolving it in the oral cavity. Within 2 weeks after withdrawal of the use of the medication, her symptoms were eliminated, and the lesions were completely healed. This case illustrates the importance of correct administration of bisphosphonates. Given the widespread use of bisphosphonates, physicians need to be aware that their improper use can cause pharyngolaryngeal ulcers.