Objective Primary hepatobiliary neuroendocrine neoplasms (NENs) are rare tumors exhibiting several morphological and behavioral characteristics. Considering the lack of relevant data on this topic, we evaluated the clinicopathological features and treatment outcomes of patients with primary hepatobiliary NENs.

Methods/Patients We examined 43 consecutive patients treated at the National Cancer Center Hospital with pathological diagnoses of primary hepatobiliary NEN between 1980 and 2016.

Results Nine patients were diagnosed with neuroendocrine tumor (NET) G1, 9 with NET G2, and 25 with neuroendocrine carcinoma (NEC) based on the World Health Organization 2019 classification. Patients with NEC had primary sites across the hepatobiliary organs, although sites in patients with NET G1 and NET G2 only included the liver and ampulla of Vater. Patients with primary extrahepatic bile duct or ampulla of Vater NENs tended to be diagnosed earlier than patients with primary gallbladder NENs. The median survival times in the NET G1, NET G2, and NEC groups were 167.9, 97.4, and 11.1 months, respectively. A good performance status, absence of distant metastases, and low tumor grade were identified as independent predictors of a favorable prognosis.

Conclusion The NET-to-NEC ratio and tumor stage distribution at the diagnosis differed depending on the primary site. Patients with G1 and G2 NETs who underwent surgical resection had good prognoses, whereas those with NEC exhibited more advanced disease and poorer prognoses. The performance status, staging classification, and tumor grade are important factors to consider when devising an appropriate treatment strategy and predicting the prognoses of patients with primary hepatobiliary NEN.

Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer.

Metohds Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progression-free survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy.

Results In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p=0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group.

Conclusion This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.

Objective The use of a proton pump inhibitor (PPI) reduces rebleeding and mortality in patients with upper gastrointestinal bleeding (UGIB). Vonoprazan is a novel oral agent with strong and sustained acid-inhibitory activity. We clarified the effect of vonoprazan compared with oral PPIs in such patients.

Methods We analyzed the Diagnosis Procedure Combination database. The primary outcome was rebleeding, and secondary outcomes were in-hospital mortality and in-hospital mortality after rebleeding. Propensity score matching was performed to balance the comparison groups, and logistic regression analyses were used to compare the outcomes between vonoprazan and oral PPIs.

Patients Patients on vonoprazan or oral PPIs who underwent endoscopic hemostasis for UGIB between 2014 and 2019 were included.

Results We enrolled 78,964 patients, of whom 27,101 and 51,863 were prescribed vonoprazan and a PPI, respectively. After propensity score matching, the rebleeding rate of vonoprazan did not significantly differ from that of oral PPIs [6.4% vs. 6.1%; odds ratio (OR), 1.05; 95% confidence interval (CI), 0.98-1.13]; similarly, the in-hospital mortality rate (1.4% vs. 1.5%; OR, 0.91; 95% CI, 0.79-1.05) and in-hospital mortality after rebleeding (0.3% vs. 0.2%; OR, 1.09; 95% CI, 0.78-1.54) also did not significantly differ between the groups. The acquired findings were robust across dose-restricted analyses and several sensitivity analyses.

Conclusion Rebleeding and in-hospital mortality risks in patients on vonoprazan were similar to those in patients on oral PPIs. Considering the higher cost of vonoprazan, oral PPIs might be an optimal oral agent as an acid-suppressive therapy in such patients.

Objective The effect of Rikkunshito, a Japanese herbal Kampo medicine, on chemotherapy-induced nausea and vomiting (CINV) has been evaluated in several small prospective studies, with mixed results. We retrospectively evaluated the antiemetic effects of Rikkunshito in patients undergoing cisplatin-based chemotherapy using a large-scale database in Japan.

Methods The Diagnosis Procedure Combination inpatient database from July 2010 to March 2019 was used to compare adult patients with malignant tumors who had received Rikkunshito on or before the day of cisplatin administration (Rikkunshito group) and those who had not (control group). Antiemetics on days 2 and 3 and days 4 and beyond following cisplatin administration were used as surrogate outcomes for CINV. Patient backgrounds were adjusted using the stabilized inverse probability of treatment weighting, and outcomes were compared using univariable regression models.

Results We identified 669 and 123,378 patients in the Rikkunshito and control groups, respectively. There were significantly fewer patients using intravenous 5-HT₃-receptor antagonists in the Rikkunshito group (odds ratio, 0.38; 95% confidence interval, 0.16-0.87; p=0.023) on days 2 and 3 of cisplatin-based chemotherapy.

Conclusion The reduced use of antiemetics on day 2 and beyond of cisplatin administration suggested a beneficial effect of Rikkunshito in palliating the symptoms of CINV.

A 29-year-old man with severe ulcerative colitis and gastroduodenitis was initially treated with oral mesalamine and high-dose intravenous steroid therapy; however, his epigastralgia and vomiting did not improve. After initiating infliximab, the patient experienced prompt improvement in symptoms and inflammation. Although steroids were effective for the colon, they proved ineffective for gastroduodenal lesions, highlighting the necessity for molecular-targeted agents, such as infliximab, in these cases. The timing for administering such agents should be carefully considered.

A 48-year-old man developed sudden-onset haematemesis and melena after decompensated posthepatitic cirrhosis. Endoscopic variceal injectional sclerotherapy was emergently performed. However, the patient developed esophago-pleural fistula, empyema, and liver failure. He thus received symptomatic treatments and nasojejunal feedings, which failed to restore the nutrition as the gastroesophageal reflux exacerbated the hydrothorax. Percutaneous endoscopic gastro-jejunal (PEG-J) was therefore carefully performed for enteral nutrition support. The patient had recovered from the fistula at a six-month follow-up, which allowed the resumption of an oral diet. Our literature review revealed that PEG-J is a feasible approach to treating esophago-pleural fistula, a rare but lethal complication of endoscopic sclerotherapy.

A 60-year-old man with a high IgG4 level was found to have pancreatic tail enlargement on computed tomography (CT), and autoimmune pancreatitis (AIP) was confirmed by a histological diagnosis. He was treated with prednisolone for one year and seven months, at which point his treatment finished. Four months later, however, he had hematemesis from gastric varices. CT showed recurrence of pancreatic tail enlargement with obstruction of the splenic artery and vein and formation of collateral blood vessels to the gastric fornix. Endoscopic injection sclerotherapy was performed, and he underwent splenectomy. This case highlights the importance of paying attention to peripancreatic vascular abnormalities during follow-up of AIP patients.

Autoimmune pancreatitis (AIP) is considered to have a good steroid response and is recognized as a disease with a favorable prognosis. However, it has been reported that patients with AIP have malignant diseases. We herein report two cases of pancreatic cancer during the follow-up of AIP, in which both patients died of pancreatic cancer. Patients with AIP may be at a high risk of malignant diseases, including pancreatic cancer, and medium- to long-term follow-up may be necessary.

A 93-year-old man presented to our hospital with a fever, abdominal pain, and jaundice. Computed tomography revealed bilateral bile duct dilation, cystic lesions with bile duct communication, and intraluminal solid nodules arising from the bile duct wall. The patient was diagnosed with intraductal papillary neoplasm of the bile duct. Surgery was not performed, considering the patient's age. It was impossible to control cholangitis using conventional endoscopic therapy. We therefore created an access route to the bile duct using endoscopic ultrasound-guided choledochoduodenostomy and inserted a lumen-apposed metal stent. Thereafter, we performed argon plasma coagulation of the tumor in the bile duct, which successfully prevented cholangitis recurrence.

No reports of renal cancer in patients with Wilson's disease (WD) exist. We herein report a 37-year-old Japanese man diagnosed with WD who had been treated with d-penicillamine 9 years prior. Hepatocellular carcinoma had been diagnosed at 36 years old and treated with radiofrequency ablation therapy. One year later, renal cancer and recurrent hepatocellular carcinoma had developed. The hepatocellular carcinoma was treated after renal cancer surgical resection of a clear-cell-type renal cell carcinoma, with iron, rather than copper, deposited on the renal cancer cells. This patient harbored a novel mutation, p. Leu1395Terfs in ATP7B.

An intrahepatic portosystemic venous shunt (IPSVS) is a rare vascular abnormality, particularly in patients without cirrhosis. An 80-year-old woman without a history of chronic liver disease was admitted to our hospital with hepatic encephalopathy. Computed tomography revealed multiple IPSVSs with two large shunts in segment 6. As conservative therapies were insufficient for treating the symptoms and reducing ammonia levels, retrograde transcaval obliteration was performed. The two large shunts were successfully embolized using detachable coils. Consequently, hyperammonemia and hepatic encephalopathy dramatically improved, and the triphasic wave patterns of the electroencephalogram disappeared. Retrograde transcaval obliteration may be effective for refractory hepatic encephalopathy with IPSVS.

Staphylococcus lugdunensis, a minor species of coagulase-negative staphylococci, has attracted attention because of its formidable pathogenicity. We present a case of infective endocarditis (IE) caused by S. lugdunensis in a 72-year-old woman with a history of breast cancer and metastases who presented with fever. Two of two blood culture bottles were positive for gram-positive cocci. Transesophageal echocardiography revealed vegetation attached to the right cusp of the aortic valve and an abscess in the annulus, which was less evident on transthoracic echocardiography. This case underscores the importance of considering S. lugdunensis as a potential cause of IE.

A 50-year-old woman presented with left pleural effusion. A pleural fluid cell-block specimen and longitudinal lymph node needle biopsy suggested signet ring cell carcinoma (SRCC). Although computed tomography showed a consolidation shadow in the left lower lobe, a left lung biopsy could not be performed. Upper gastrointestinal endoscopy revealed no malignancies. We administered carboplatin, pemetrexed, ipilimumab, and nivolumab for lung cancer; however, she died due to progressive respiratory failure. Pathological autopsy revealed that the left pleura was thickened as in mesothelioma, based on which pseudomesotheliomatous carcinoma of the lung (PMCL) was diagnosed. PMCLs exhibiting an SRCC morphology are rare.

Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis (HD) is unclear. We herein report a patient with NSCLC on HD in whom nivolumab and ipilimumab were initiated. We observed general deterioration and enlarged lesions, followed by a long-term response. The patient developed secondary hypoadrenocorticism, an immune-related adverse event that was easily controlled. Nivolumab plus ipilimumab can be used safely for patients with NSCLC on HD. Long-term effectiveness can be observed after initial progression, so we should carefully assess the response.

Nontuberculous mycobacterial (NTM) infection sometimes leads to the development of pulmonary artery aneurysm (PAA), a rare but life-threatening complication. We herein report a 64-year-old woman with a history of NTM infection who presented with severe hemoptysis. Computed tomography revealed a ruptured PAA, which was treated successfully with pulmonary artery embolization. Subsequent right total pneumonectomy was performed to control infection. This case emphasizes the need to consider PAA in patients with NTM infection who present with hemoptysis. Early detection and appropriate management are critical for preventing this fatal complication.

Hodgkin lymphoma (HL) and idiopathic multicentric Castleman disease (iMCD) are markedly different conditions. However, in some cases, histological similarities caused by elevated cytokines, including interleukin-6, can lead to a misdiagnosis of HL as Castleman disease (CD). We herein report a patient with HL who had been diagnosed with CD by an expert panel and for whom an additional biopsy was useful for determining the correct diagnosis. Furthermore, we analyzed the positron emission tomography/computed tomography findings at the diagnosis and found that the maximum standardized uptake value was useful for distinguishing HL from iMCD.

Adrenomyeloneuropathy (AMN)/adrenoleukodystrophy (ALD) is an X-linked genetic disorder caused by pathogenic variants in ABCD1. We treated a 54-year-old man with slowly progressive spastic paraparesis with later development of the cerebral form. A pathogenic splice-site variant of ABCD1 (c.1489-1G>A, p.Val497Alafs*51) and elevated levels of very long-chain fatty acids were found, leading to the diagnosis of AMN. Detailed ABCD1 mRNA expression analyses revealed decreased levels of ABCD1 mRNA accompanied by deletion of the first 31 bp in exon 6. The altered mRNA transcriptional patterns associated with splice site variants are diverse and may provide important insights into ALD pathogenesis.

We encountered a 27-year-old Japanese woman with sensorineural deafness progressing to motor and sensory neuropathy. At 16 years old, she had developed weakness in her lower extremities and hearing impairment, which gradually deteriorated. At 22 years old, combined audiological, electrophysiological, and radiological examination results were consistent with auditory neuropathy spectrum disorder (ANSD). Genetic analyses identified a previously reported missense variant in the ATP1A1 gene (NM_000701.8:c.1799C>G, p.Pro600Arg). Although sensorineural deafness has been reported as a clinical manifestation of ATP1A1-related disorders, our case suggested that ANSD may underlie the pathogenesis of deafness in ATP1A1-related disorders. This case report broadens the genotype-phenotype spectrum of ATP1A1-related disorders.

A 68-year-old man with small-cell lung cancer developed anti-collapsin response-mediator protein (CRMP)-5 antibody-related paraneoplastic neurological syndrome (PNS) presenting with ataxia and chorea during treatment with durvalumab. As a result of steroid therapy, anti-CRMP-5 antibodies became negative, hyperintense lesions on brain magnetic resonance imaging disappeared, and neurological symptoms improved. After resuming durvalumab, he became unable to walk due to neurological adverse events (nAEs). There have been no reported cases manifesting PNSs and nAEs as a result of the same immune checkpoint inhibitors (ICIs) administered at different times. Resuming ICIs in patients diagnosed with PNSs should be performed with prudence.

Mycobacterium chelonae, a rapidly growing mycobacterium found in the natural environment, is known to cause localized lesions in the skin, soft tissue, and bone through traumatic inoculation, but widespread lesions are uncommon. We herein report an immunocompromised 79-year-old man suspected of having polyangiitis granulomatosis due to weight loss, epistaxis, and nasal crusts with impending septal perforation who was subsequently diagnosed with mucocutaneous and bone disease caused by widespread M. chelonae infection. Given these findings, clinicians should be aware of the tendency to develop unusual widespread lesions in immunocompromised patients, which can present a clinical picture similar to systemic vasculitides, such as granulomatosis with polyangiitis.

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE)-related empyema is rare but can result in shock vitals, acute kidney injury, and extensive erythema. In the present case, a 92-year-old woman with empyema caused by SDSE developed STSS after pleural drainage and antibiotic therapy. Despite temporary improvement with clindamycin and pleural drainage, the patient ultimately died due to malnutrition. Autopsy findings suggested that the infection was well controlled, but infections with Streptococcus spp., including SDSE, can trigger STSS in patients with empyema.

A 42-year-old man visited our hospital due to a gradually swelling subcutaneous mass on the back of the right shoulder. The biopsy specimen was diagnosed pathologically as pleomorphic liposarcoma. Systemic computed tomography and ¹⁸F-fluorodeoxyglucose positron emission tomography revealed multiple organ metastases, including involvement of the heart, skin, liver, bone, and lung. Six cycles of doxorubicin plus ifosfamide initially controlled the disease. However, newly developed lung metastases grew rapidly during subsequent cycles of chemotherapy, and the patient died 10 months after the initial diagnosis. The initial presentation of multiple organ involvement, including the heart, is a rare clinical manifestation of pleomorphic liposarcoma.