A case of traumatic intrapleural foreign body with progressive supranuclear palsy removed by thoracoscopic surgery.

Traumatic intrathoracic foreign bodies are said to occur in many cases when the patient himself/herself is aware of the trauma. However, at the time of injury, the patient may sometimes be accompanied by loss of consciousness. We report a case of traumatic intrathoracic foreign body that was difficult to diagnose due to loss of consciousness at the time of injury. A 51-year-old female was brought to our emergency department with a fall trauma due to loss of consciousness while bathing. The head computed tomography and electrocardiogram showed no abnormalities, and the laceration of approximately 3 cm in length was found on the left side thorax, and it was sutured and the patient was sent home. Four days later, she returned to our hospital with a complaint of left anterior chest pain, and chest X-ray showed a left degree pneumothorax and mediastinal emphysema. She underwent semi-emergency thoracoscopic removal of the foreign body, and was discharged from the hospital on the fourth postoperative day. She had progressive supranuclear palsy, and her memory at the time of injury was not clear due to loss of consciousness caused by central autonomic neuropathy, and she also had dementia, making it difficult to interview her. She had no thoracic symptoms, and the glass fragment that had strayed into the thoracic cavity was not exposed outside the body, making the diagnosis difficult at the time of initial examination. When a patient with loss of consciousness is difficult to interview at the time of injury, it is advisable to perform an imaging examination appropriate for the site of injury, taking into consideration the presence of foreign bodies.

Poor tolerability of lenvatinib in elderly patients ≥80 years old with hepatocellular carcinoma: A multicenter observational study.

INTRODUCTION: Management of elderly patients with cancer has become a global issue. We investigated the safety and tolerability of lenvatinib in hepatocellular carcinoma (HCC) patients ≥80 years old. METHODS: We retrospectively evaluated 61 HCC patients and divided them into 2 groups: an elderly group (n = 13, ≥80 years old) and a younger group (n = 48, <80 years old). We compared the adverse events (AEs), administration period, dose intensity, objective response, and progression-free survival (PFS) between the two groups. RESULTS: The discontinuation of lenvatinib due to AEs was more frequent in the elderly group (8/13, 61.5%) than in the younger group (10/48, 20.8%) (P = 0.0043). Fatigue and appetite loss accounted for half of the cases discontinued due to AEs in the elderly group. The elderly group had a significantly lower 8-week-delivered dose intensity/body surface area ratio (147.2) and 8-week-relative dose intensity (50.0%) than those in the younger group (267.4, 67%) (P = 0.003, 0.029). The objective response rate was significantly lower in the elderly group (15.4%) than in the younger group (61.5%) (P = 0.021). The PFS in the elderly group tended to be shorter than that in the younger group (P = 0.058, hazard ratio [HR] 1.98). The modified albumin-bilirubin (mALBI) grade (hepatic function) (HR, 2.60; P = 0.01) and objective response (HR, 0.41; P = 0.011) were independently associated with the PFS in the multivariate analysis. CONCLUSION: The management of AEs is crucial for adherence and maintaining the dose intensity of lenvatinib in elderly HCC patients.

Poorly Differentiated Neuroendocrine Carcinoma of Unknown Primary with Metastasis to the Testis: A Case Report.

Neuroendocrine neoplasms are rare epithelial neoplasms with neuroendocrine differentiation. Few cases of primary testicular poorly differentiated neuroendocrine carcinomas (PD-NECs) have been reported, and secondary testicular neoplasms are rare. A 61-year-old man with a chief complaint of left testicular swelling was referred to our hospital. An orchiectomy was performed in order to determine the pathological diagnosis. Pathological examination showed diffuse sheets of highly atypical cells that were positive for neuroendocrine markers and a Ki-67 proliferation index of 80%. The patient was diagnosed with poorly differentiated small-cell NEC. Contrast-enhanced computed tomography revealed multiple metastases to the pancreas, adrenal glands, and lymph nodes. Esophagogastroduodenoscopy showed multiple gastric metastases, and biopsy revealed the same histological findings as observed for the testicular tumor. Contrast-enhanced magnetic resonance imaging of the head also revealed multiple brain metastases. The confirmed diagnosis was PD-NEC of unknown primary with metastases to the testis, stomach, pancreas, adrenal glands, brain, and lymph nodes. We started the first-line chemotherapy with etoposide and cisplatin. Stereotactic radiotherapy for the brain metastases was administered between the first and second cycles. After five cycles, a partial response was observed; however, disease progression was observed after seven cycles with recurrence of the brain metastases and enlargement of all tumors. To our knowledge, this is the first report of an unknown primary PD-NEC with metastasis to the testis.

The Geriatric Nutritional Risk Index Predicts Tolerability of Lenvatinib in Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: We aimed to investigate the association between The Geriatric Nutritional Risk Index (GNRI) and the tolerability of lenvatinib in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively evaluated 61 HCC patients treated with lenvatinib and compared those with low GNRI (≤98, n=26) to those with high GNRI (>98, n=35). RESULTS: The discontinuation of lenvatinib due to adverse events was more frequent in the low GNRI group (46.2%) than in the high GNRI group (17.1%) (p=0.014). Multivariate analysis revealed that low GNRI (p=0.014), hypothyroidism (model 1 p=0.021, model 2 p=0.013), and advanced age (p=0.026) were independently associated with the discontinuation of lenvatinib. The progression-free survival in the low GNRI group was significantly shorter than that in the high GNRI group (p=0.047). CONCLUSION: The GNRI might be independently associated with the tolerability of lenvatinib in patients with HCC.

[A case of advanced pancreatic cancer with oculomotor nerve palsy caused by herpes zoster after introduction of gemcitabine plus nab-paclitaxel].

A 76-year-old woman was admitted to our hospital due to diabetes and was diagnosed with advanced pancreatic cancer for which she received gemcitabine plus nab-paclitaxel. Fourteen days later, eruptions were observed in the first division of the right trigeminal nerve;she was then diagnosed with herpes zoster and was successfully treated with antiviral therapy. Seven days after the herpes zoster infection, right ophthalmoplegia appeared. Oculomotor nerve palsy secondary to herpes zoster ophthalmicus was suspected and she was treated with steroid pulse therapy. Her symptoms improved, and chemotherapy was able to be continued. Her ophthalmoplegia had almost fully resolved 41 days after the onset of herpes zoster infection.

Efficacy and safety of glecaprevir/pibrentasvir in patients with hepatitis C virus infection aged ≥75 years.

AIM: Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS: We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged <75 years). We compared the clinical characteristics, virologic response and adverse events between the two groups. The predictive factors for adverse events were also assessed. RESULTS: The presence of cirrhosis (27.9%), a history of hepatocellular carcinoma (23.3%) and comorbidities (88.4%) were more frequently observed in the elderly group than in the younger group. Six (14.0%) patients in the elderly group and 19 (21.6%) in the younger group dropped out before the sustained virologic response 12 assessment. In the intention-to-treat population, 86.0% in the elderly group and 78.4% in the younger group achieved sustained virologic response 12 (P = 0.30). In the modified intention-to-treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline <4.0 g/dL. CONCLUSION: Glecaprevir/pibrentasvir therapy was effective and well tolerated, even in elderly patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; ••: ••-••.

[Successful treatment of unresectable advanced gastric cancer with bladder metastasis using mFOLFOX6:a case report].

A 42-year-old woman was referred to our hospital for the treatment of pyloric stenosis. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) revealed the presence of type 4 advanced gastric cancer with bladder metastasis and peritoneal dissemination. Biopsy specimen examination revealed poorly differentiated adenocarcinoma with signet ring cell carcinoma. Thus, two cycles of chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin were administered. Subsequently, the gastric lesion and bladder metastasis reduced as detected using EGD and CT. Consequently, she achieved adequate oral intake. After changing the regimen to tegafur/gimeracil/oteracil and oxaliplatin, she was discharged. Currently, she continues to receive chemotherapy.

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients.

PURPOSE: To evaluate the efficacy and safety of nab paclitaxel (nab-P) plus gemcitabine (GEM) in elderly patients ≥ 75 years old with unresectable pancreatic cancer (PC) compared with younger patients. METHODS: The data of 27 unresectable PC patients treated with nab-P plus GEM as first-line chemotherapy were retrospectively analyzed. The patients were divided into two groups according to their age at inclusion: an elderly group (9 patients ≥ 75 years old) and a younger group (18 patients <75 years old). We compared the disease control rate, median overall survival (OS), and adverse events (AEs) between the two groups. Predictive factors for the OS were also evaluated. RESULTS: The clinical characteristics of patients of the two groups were not significantly different except for the age. The respective values for the disease control rate (66.7% vs. 77.8%, P = 0.542) and median OS (277 days vs. 312 days, P = 0.722) were also not significantly different between the elderly and younger group, although the relative dose intensity of GEM/nab-P in the elderly group (56.6%/53.1%) was significantly lower than that in the younger group (67.3%/63.1%) (P = 0.016/0.04). The absence of biliary drainage and CEA ≥ 6.5 were found to be poor prognostic factors in a multivariate analysis. The most common grade ≥ 3 AE was neutropenia (44% in both groups). No significant differences in the frequency of all AEs were observed between the two groups. CONCLUSIONS: Nab-P plus GEM appears effective and well-tolerated for elderly patients ≥ 75 years old with unresectable PC.

[A Case of Advanced Gastric Cancer with Bladder Metastasis].

A 61-year-old man was referred to the urology department in our hospital with gross hematuria and hydro nephrosis. Cystoscopy revealed a smooth mass lesion in his bladder, and a transurethral biopsy was performed. Signet ring cell carcinoma was found in the submucosa. Upper gastrointestinal endoscopy revealed an ulcerated lesion in his gastric body. Biopsy specimens obtained from the ulcerated lesion showed signet ring cell carcinoma. No other primary lesions were detected using colonoscopy, gallium scintigraphy, or computed tomography of the chest. He was ultimately diagnosed with advanced gastric cancer with bladder metastasis. He was prescribed combination chemotherapy of cisplatin and tegafur, gimeracil, oteracil potassium, and trastuzumab. After 2 courses of chemotherapy, there was a decrease in the size of both the gastric and bladder lesions. There was also a significant decrease in the tumor marker levels. He is currently alive after 7 courses of chemotherapy.

Endoscopic submucosal dissection in a patient with esophageal adenoid cystic carcinoma.

We report the first use of endoscopic submucosal dissection (ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus (EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution, and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor, primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion, an 8 mm submucosal tumor. Immunohistologically, tumor cells differentiating into ductal epithelium and myoepithelium were observed, and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall, vertical stump or horizontal margin invasion with pT1b-SM2 staining (1800 µm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC.

Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids.

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.

Clinical features and prognosis of elderly patients with hepatocellular carcinoma not indicated for surgical resection.

Hepatocellular carcinoma (HCC) is a major health problem worldwide. The average life expectancy during the 20th century has increased in many parts of the world, and therefore the opportunities to examine elderly HCC patients have significantly increased worldwide. Many elderly patients develop HCC with intermediate to advanced stages of disease at the initial diagnosis, and have more comorbidities and compromised liver regeneration compared with younger patients. These circumstances show that elderly patients with HCC are poorer candidates for surgical resection or transplantation. The aim of the present review was to focus on the clinical features and prognosis of elderly HCC patients not indicated for surgical resection including multimodal treatment. Although the chronological age of 60 or 65 years as the definition of an elderly person is accepted in most countries, many studies in our review article define elderly as those aged 75 years or older. Geriatr Gerontol Int 2017; 17: 189-201.

A case of adenosquamous cell carcinoma of the gallbladder with markedly elevated PTHrP and G-CSF levels.

A 76-year-old woman was referred to our hospital with anorexia. Computed tomography revealed a tumor lesion measuring 110mm in the liver at S4/5 with calcification and swelling of a paraaortic lymph node. The gallbladder was not visualized. Histological examination of a biopsy specimen from the liver tumor revealed squamous cell and undifferentiated carcinomas, and several tumor markers were elevated. Therefore, we diagnosed the patient with gallbladder adenosquamous cell carcinoma T3N2M0 stage III. Because the serum parathyroid hormone-related protein (PTHrP) and granulocyte-colony stimulating factor (G-CSF) levels were significantly elevated, we suspected that PTHrP and G-CSF production occurred because of adenosquamous cell carcinoma in the gallbladder. We initiated chemotherapy with S-1.

[A Case of Primary Cancer of the Pancreas and Colon Treated with the Combination of Gemcitabine and TS-1].

The patient was a 74-year-old man. A medical examination for diabetes revealed a hypovascular tumor in the pancreatic head. A heterogeneously enhanced tumor in the ascending colon with wall thickening was observed on enhanced CT of the abdomen. He was diagnosed with multiple primary cancers of the pancreas and colon. He received 12 courses of chemotherapy with gemcitabine (1,000 mg/m 2) and TS-1 (60 mg/m2). After 12 courses of chemotherapy, the size of the pancreatic tumor was slightly decreased and the size of the tumor in the colon was significantly decreased. The tumor marker level was also significantly decreased. The combination of gemcitabine and TS-1 is a promising treatment regimen for patients with primary cancer of the pancreas and colon.

Clinical characteristics and survival outcomes of super-elderly hepatocellular carcinoma patients not indicated for surgical resection.

AIM: Considering the dramatic increase in average life expectancy during the 20th century throughout the world, the management of elderly patients with cancer has become a global issue. We herein investigated the clinical characteristics and outcomes of super-elderly hepatocellular carcinoma (HCC) patients over 80 years old not indicated for surgical resection. METHODS: We retrospectively evaluated 206 newly diagnosed HCC patients. The patients were divided into two groups according to their age at inclusion; a super-elderly group (n = 37, ≥80 years) and a younger group (n = 169, <80 years). We compared the clinical characteristics, overall survival (OS) and disease-specific survival (DSS) rates among the two groups. Both univariate and multivariate analyses were performed to identify the factors associated with the OS and DSS. RESULTS: The proportion of women was higher in the super-elderly group than in the younger group (P = 0.017). There were no significant differences in the OS (P = 0.171) or DSS (P = 0.176) between the two groups. The multivariate analysis revealed that only the Cancer Liver Italian Program score (hazard ratio [HR], 2.972; P < 0.0001; HR, 3.694; P < 0.0001) was independently associated with the OS and DSS. Age was not found to be associated with the OS or DSS according to either the univariate or multivariate analysis. CONCLUSION: There were no significant differences in the OS and DSS rates among the super-elderly HCC patients and younger HCC patients not indicated for surgical resection. An advanced age itself does not restrict the therapeutic approach, even in super-elderly HCC patients not indicated for surgical resection.

Staging systems for hepatocellular carcinoma: Current status and future perspectives.

Hepatocellular carcinoma (HCC) is a major health concern worldwide and the third cause of cancer-related death. Despite advances in treatment as well as careful surveillance programs, the mortality rates in most countries are very high. In contrast to other cancers, the prognosis and treatment of HCC depend on the tumor burden in addition to patient's underlying liver disease and liver functional reserve. Moreover, there is considerable geographic and institutional variation in both risk factors attributable to the underlying liver diseases and the management of HCC. Therefore, although many staging and/or scoring systems have been proposed, there is currently no globally accepted system for HCC due to the extreme heterogeneity of the disease. The aim of this review is to focus on currently available staging systems as well as those newly reported in the literatures since 2012. Moreover, we describe problems with currently available staging systems and attempts to modify and/or add variables to existing staging systems.

C-Reactive Protein as a Prognostic Marker in Patients with Hepatocellular Carcinoma.

C-reactive protein (CRP) is an acute phase reactant synthesized by hepatocytes that is regulated by pro-inflammatory cytokines, particulary interleukin-6 (IL-6). Over the last decade, CRP has been reported to be associated with a poor prognosis in patients with various types of cancer. Although the mechanisms by which the systemic inflammatory response reflected by an elevated serum CRP level influences survival in patients with cancer have not been fully elucidated, several possibilities involving the activation of IL-6, thereby elevating the CRP level, in cancer patients have been proposed. With regard to hepatocellular carcinoma (HCC), since Hashimoto et al. first demonstrated that the preoperative serum CRP level is an independent and significant factor predictive of a poor prognosis in patients undergoing surgical resection, several investigators have identified an elevated serum CRP level to be an indicator of poor outcomes in HCC patients undergoing transplantation, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection and best supportive care. Recently, the CRP level has been reported to be clinically applicable as a marker of treatment outcomes in HCC patients. However, large-scale, prospective validation studies are needed to confirm these results.

The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma.

BACKGROUND: The C-reactive protein/albumin (CRP/Alb) ratio is associated with outcomes in septic patients. We investigated the prognostic value of the CRP/Alb ratio in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated 186 newly diagnosed HCC patients and investigated the correlations among the pretreatment CRP/Alb ratio, clinicopathological parameters, and overall survival (OS). Multivariate analyses were performed to identify the clinicopathological parameters associated with OS. Subsequently, we evaluated the prognostic value of the CRP/Alb ratio compared with other inflammation-based prognostic scores [Glasgow Prognostic Score (GPS), modified GPS (mGPS), and neutrophil lymphocyte ratio (NLR)] using the area under the curve (AUC). RESULTS: The optimal cutoff level for the CRP/Alb ratio was 0.037. An elevated CRP/Alb ratio (≥0.037) was associated with tumor progression and reduced liver functional reserve. In the multivariate analysis, the CRP/Alb ratio [hazard ratio (HR) 3.394; p < 0.0001], Cancer Liver Italian Program score (HR 2.686; 95% CI 2.122-3.401; p < 0.0001), and vascular invasion (HR 3.376; 95% CI 1.594-7.151; p = 0.001) were independently associated with OS (HR 3.394; p < 0.0001). The CRP/Alb ratio had higher AUC values at 6 months (0.844), 12 months (0.863), and 24 months (0.82) compared with the GPS, mGPS, and NLR. CONCLUSION: The CRP/Alb ratio might be an independent prognostic marker in patients with HCC, and may have comparable prognostic ability to other established inflammation-based prognostic scores. The prognostic value of this novel inflammation-based prognostic score needs to be verified in patients with other types of cancer.

The addition of C-reactive protein to validated staging systems improves their prognostic ability in patients with hepatocellular carcinoma.

OBJECTIVES: C-reactive protein (CRP) is a practical prognostic marker in patients with hepatocellular carcinoma (HCC). We investigated the prognostic value of adding the CRP level to other validated staging systems (Cancer Liver Italian Program, Japan Integrated Staging, Barcelona Clinic Liver Cancer classification system, Tokyo score and tumor node metastasis classification) in HCC patients. METHODS: One hundred and eighty-six newly diagnosed HCC patients were retrospectively evaluated. A multivariate analysis identified the clinicopathological variables associated with overall survival; the variables identified were then added to each staging system and compared to those without the additional variable. RESULTS: In multivariate analysis, an elevated serum CRP level was independently associated with a poor prognosis (hazard ratio 3.792, p < 0.0001). The addition of the CRP level to each of the established staging systems provided a higher linear χ(2) value and a lower -2 log likelihood than those without the addition of the term. Moreover, the area under the receiver-operating characteristic curve (AUC) analysis showed that the addition of CRP improved the AUC of each staging system. CONCLUSIONS: This study demonstrates that an elevated serum CRP level is independently associated with a poor prognosis in HCC patients, and the addition of the CRP level to the validated staging systems could improve the prognostic ability of each staging system.