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.

[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.

[A difficult case of a stent-stone complex removal with endoscopic lithotomy].

An 88-year-old patient had undergone endoscopic stenting for the treatment of acute cholangitis caused by choledocholithiasis. After a year and two months, he presented with cholangitis caused by common bile duct stones that formed a stent-stone complex. Another stent was observed adjacent to the old stent;however, the cholangitis relapsed in a short term. Thus, we planned to remove as many stones as possible. These stones were not free-floating and had affected the bile duct. Endoscopic mechanical lithotripsy was attempted;however, it failed. He was successfully treated using peroral cholangioscopy and electrohydraulic lithotripsy. After three months, he developed cholangitis because of the recurrence of choledocholithiasis. After removing as many stones as possible and performing endoscopic stenting, he was followed up as an outpatient. He had no symptoms for seven months after the procedure.

[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.

[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.

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.

[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.

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.

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.

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 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.

Elevated plasma fibrinogen levels are associated with a poor prognosis in patients with hepatocellular carcinoma.

OBJECTIVES: Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in cancer patients. We investigated the prognostic value of pretreatment plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and thirteen patients with newly diagnosed HCC were retrospectively evaluated. We investigated the correlation between pretreatment plasma fibrinogen levels, clinicopathological parameters and overall survival. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with overall survival. RESULTS: The median value of the pretreatment plasma fibrinogen level was 279 mg/dl. Elevated plasma fibrinogen levels were associated with larger tumor size, the presence of vascular invasion and higher Cancer Liver Italian Program scores. Lower plasma fibrinogen levels were associated with higher Child-Pugh grades. The overall survival rates in patients with pretreatment plasma fibrinogen levels ≥ 315 mg/dl were significantly lower than those with a pretreatment plasma fibrinogen level <315 mg/dl (p = 0.016). On multivariate analysis, the plasma fibrinogen levels (per 100 mg/dl) were found to be independently associated with overall survival (hazard ratio 1.236; p = 0.046). CONCLUSIONS: This study demonstrates that elevated pretreatment plasma fibrinogen levels are associated with tumor progression and are independently associated with a poor prognosis in patients with HCC.

The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma.

BACKGROUND: Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. METHODS: One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. RESULTS: Elevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. CONCLUSIONS: Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status.

Low geriatric nutritional risk index predicts poor prognosis in patients with cirrhosis: a retrospective study.

Aim: Malnutrition, which increases the risk of liver disease-related events and mortality, is a serious complication in cirrhosis. This study aimed to investigate whether the geriatric nutritional risk index (GNRI) could predict the long-term prognosis in patients with cirrhosis. Methods: We retrospectively evaluated 266 patients with cirrhosis and classified them into two groups based on baseline GNRI scores: risk (≤98, n = 104) and no-risk groups (>98, n = 162). The cumulative survival rates were compared between the two groups in patients with compensated and decompensated cirrhosis, respectively. Cox proportional hazards regression analysis was used to identify significant and independent factors associated with mortality. Results: The median observation period was 54.9 (33.6-61.7) months and 65 (24.4%) liver disease-related deaths occurred during the follow-up period. The GNRI scores significantly and inversely correlated with Child-Pugh score (r = -0.579), model for end-stage liver disease score (r = -0.286), and Mac-2 binding protein glycosylation isomer (r = -0.494). Multivariate analysis identified low GNRI as a significant and independent factor associated with mortality [overall cohort: hazard ratio (HR), 0.926; p < 0.001; compensated cirrhosis: HR, 0.947; p = 0.003; decompensated cirrhosis: HR, 0.923; p < 0.001]. The risk group demonstrated significantly lower cumulative survival rates than the no-risk group in overall cohort, and patients with compensated and decompensated cirrhosis (p < 0.001, <0.001, and = 0.013, respectively). Conclusion: Low GNRI was associated with poor long-term prognosis in both patients with compensated and decompensated cirrhosis. Therefore, the GNRI is a simple and useful tool for predicting prognosis and modifying the nutritional status in patients with cirrhosis.

The Geriatric Nutritional Risk Index predicts sarcopenia in patients with cirrhosis.

Patients with cirrhosis are at high risk for sarcopenia and malnutrition, which are associated with reduced quality of life and increased mortality. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and sarcopenia/gait speed and assessed the usefulness of the GNRI for predicting sarcopenia in patients with cirrhosis. We evaluated 202 patients with cirrhosis and divided them into three groups based on baseline GNRI values: low (L)-GNRI (< 94.0, n = 49), intermediate (I)-GNRI (between 94.0 and 109.5, n = 103), and high (H)-GNRI groups (> 109.5, n = 50). Sarcopenia was diagnosed according to the criteria of the Japan Society of Hepatology. The prevalence of sarcopenia and slow gait speed was the lowest in the H-GNRI group (8.0% and 26.0%, respectively) and the highest in the L-GNRI group (49.0% and 44.9%, respectively). They increased stepwise with a decline in the GNRI group (p < 0.001 and p = 0.05, respectively). The GNRI values were significantly and positively correlated with handgrip strength, skeletal muscle mass index, and gait speed. Multivariate analysis identified lower GNRI as an independent risk factor for sarcopenia. The optimal cutoff value of the GNRI for predicting sarcopenia was 102.1 (sensitivity/specificity, 0.768/0.630). The GNRI was significantly associated with sarcopenia and physical performance and could be a helpful screening tool for predicting sarcopenia in patients with cirrhosis.

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.

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.

Punctate Purpura Complicated with Immunoglobulin G4-related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition affecting multiple organs; however, the involvement of skin lesions is rare. We herein report a 65-year-old man who presented with pruritic punctate purpura on both legs and elevated liver enzyme levels. Computed tomography showed enlargement of the pancreas and thickening of the bile duct wall. Magnetic resonance cholangiopancreatography showed diffuse irregular constriction of the main pancreatic duct, stricture of the lower common bile duct, and dilation after confluent stricture. A histopathologic examination of the pancreas and his enlarged salivary gland showed infiltration of IgG4-positive plasma cells. Ultimately, the patient was diagnosed with IgG4-RD.

The Molar Ratio of Total Branched-chain Amino Acids to Tyrosine Predicts a Digit Symbol Test Abnormality in Cirrhotic Patients.

Objective We aimed to investigate the association between the digit symbol test (DST) and clinical characteristics, including the nutritional status of liver cirrhosis patients. Methods Fifty-nine cirrhotic patients without a history of overt hepatic encephalopathy were retrospectively evaluated. We examined neuropsychological abnormalities (NPAs) using the DST. We also estimated the detailed nutritional status using the Food Frequency Questionnaire (FFQ). The patients were divided into two groups according to their DST status: patients with normal DST scores (DST-Nor group, n=45) and those with abnormal DST scores (DST-Abn group, n=14). The clinical and nutritional findings of the two groups were compared. Results Overall, 14 (23.7%) patients had a DST abnormality. There were significant differences between the two groups in serum albumin (Alb; p=0.0043), valine (Val; p=0.0016), leucine (Leu; p=0.0078), isoleucine (Ile; p=0.0022), the molar ratio of total branched-chain amino acids to tyrosine (BTR; p=0.00025), total-bilirubin (T-Bil; p=0.0071), prothrombin time (%) (PT; p=0.028), and serum sodium (Na; p=0.035). A multivariate analysis found the BTR to be the only independent predictor of a DST abnormality (hazard ratio, 9.24; p<0.031). An FFQ analysis, revealed that the nutritional findings of patients with and without a DST abnormality, were similar. Conclusion The BTR was useful for predicting the risk of NPAs, as defined by a DST abnormality. The risk of NPAs may be estimated by monitoring the BTR.