Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab.

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

Thiamine deficiency as a cause of anorexia in terminally ill cancer patients: A case of possible gastrointestinal beriberi.

OBJECTIVES: Anorexia in cancer patients has a variety of causes and impairs patients' quality of life. However, there have been few reports of thiamine deficiency (TD) playing a role in anorexia during palliative care. The objective of this report was to describe such a case. METHODS: An 82-year-old woman with advanced cervical cancer was admitted for palliative care because of progressive disease. One month after admission, she developed myoclonus on the left side, difficulty speaking, slurred speech, and drooping of the left corner of the mouth, with no consciousness disturbance. She also developed nausea and complained of decreased dietary intake for more than 2 weeks. RESULTS: The patient's thiamine level, which had been measured 2 weeks earlier, was 27 ng/ml, which was below the normal range, and 100 mg of thiamine was administered intravenously. After 2 hours, the patient's neurological findings resolved, and her dietary intake improved from 30% to 40% of meals to 90% to 100%. Subsequently, the patient did not experience similar symptoms, and her clinical course was stable. Based on the patient's clinical course, gastrointestinal beriberi was diagnosed. SIGNIFICANCE OF RESULTS: This case shows that TD may cause anorexia. Many patients who receive palliative care have decreased dietary intake. Consequently, such patients may present with gastrointestinal beriberi, as in the present case. Appropriate diagnosis and treatment may contribute to increasing such patients' quality of life. It may be necessary to differentiate TD from other conditions as a cause of anorexia in patients receiving palliative care.

Utility of Combined Use of Transabdominal Ultrasonography and Fecal Immunochemical Test Examinations in Ulcerative Colitis.

This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies.

What can cause cancer patients to attempt suicide? Thiamine deficiency mimicking the symptoms of major depressive disorder.

OBJECTIVES: Thiamine deficiency (TD) presents with various physical and psychiatric symptoms, but no cases with depression-like symptoms have been reported. METHODS: We report a patient with cancer who appeared to attempt suicide as a consequence of depressive mood likely related to TD. RESULTS: The patient was a 58-year-old woman diagnosed with recurrent endometrial cancer, with lung metastasis and pelvic dissemination. The patient apparently attempted suicide was referred to the psycho-oncology department. At the time of the examination, major depressive disorder was suspected based on her mental symptoms, but when thiamine was administered intravenously in response to her poor dietary intake, her palpitations, dyspnea, anorexia, and insomnia improved, and her suicidal ideation disappeared at her reexamination 1 hour later after thiamine administration. SIGNIFICANCE OF RESULTS: It is likely that the observed palpitations, dyspnea, anorexia, and insomnia, as well as the severe depression and the attempted suicide, which were thought to be physical symptoms associated with depression, were actually related to TD. Suicidal ideation and attempted suicide are conspicuous as psychiatric symptoms. However, in such cases, rather than simply starting treatment for depression, it is necessary to consider reversible TD as a cause of these symptoms and perform differential diagnosis to confirm the physical illness.

Detection of hepatocellular carcinoma during Fontan-associated liver disease follow-up: a report of three cases.

We herein demonstrate three patients diagnosed with early hepatocellular carcinoma (HCC) during follow-up for Fontan-associated liver disease (FALD). Case 1: Twenty-one years after undergoing the Fontan procedure, a 26-year-old female was diagnosed with FALD. At the initial consultation, her serum alpha-fetoprotein (AFP) levels were markedly elevated, and dynamic enhanced computed tomography (CT) revealed HCC measuring 40 mm in diameter. She underwent partial hepatectomy. Ten months later, she underwent conventional transcatheter arterial chemoembolization (cTACE) for recurrent HCC near the resected hepatic stump as a curative treatment. Case 2: Twenty-one years after undergoing the Fontan procedure, a 25-year-old male was diagnosed with FALD and underwent HCC surveillance every 6 months. Thirteen months after the initial consultation, dynamic enhanced CT revealed HCC measuring 10 mm in diameter. He received cTACE as a curative treatment. Case 3. Twenty-eight years after undergoing the Fontan procedure, a 37-year-old male was diagnosed with FALD and underwent HCC surveillance every 3 months. Fourteen months later, abdominal ultrasonography (US) revealed HCC measuring 13 mm in diameter. He received radiofrequency ablation. These cases showed that HCC surveillance using abdominal US and AFP measurements in patients with FALD enables the detection of HCC and increases the chance of a cure.

A patient with Marchiafava-Bignami disease type A transported by ambulance with impaired consciousness and malnutrition was successfully treated after early diagnosis by MRI.

Marchiafava-Bignami disease (MBD) is a very rare disorder characterized by demyelination and necrosis of the corpus callosum. A 53-year-old male was transported to the emergency room with impaired consciousness. On his arrival, he was quite emaciated. CT examination revealed no hemorrhagic lesions whereas MR images showed hyperintense areas throughout the corpus callosum, leading to a diagnosis of MBD. His impaired consciousness improved with treatment, including parenteral thiamine administration. When examining patients with impaired consciousness because of malnutrition, MBD should be taken in consideration and the incorporation of head MR imaging into the examination protocol enables early diagnosis and treatment, and may improve the prognosis.

Delirium in patients with musculoskeletal tumours: incidence and risk factors - single-centre prospective study.

OBJECTIVES: Delirium, a neurocognitive disorder, typically occurs in older patients and those with advanced cancer. Although there have been numerous reports on delirium in patients with cancer in various conditions, there are no reports that specifically focus on patients with musculoskeletal tumours. This prospective study aimed to investigate the incidence, risk factors and prognostic implications of delirium in patients with musculoskeletal tumours. METHODS: In this single institutional study, 148 patients with musculoskeletal oncology were enrolled. The estimated risk factors included age, sex, alcohol abuse, performance status (PS), dietary status, admission route, tumour malignancy, oncological stage and blood test results. The significance of delirium in survival was also examined. RESULTS: Only 18 patients with malignant tumours had delirium (12.2%). Based on univariate analysis, older age, poor PS, dietary status, admission from another hospital, malignant tumour, carcinoma rather than sarcoma, anaemia and some laboratory abnormalities were found to be significant risk factors for delirium. Multivariate analysis showed that poor PS was significantly correlated with delirium. Additionally, delirium was significantly correlated with poor survival. CONCLUSIONS: The incidence of delirium among patients with musculoskeletal tumours was 12.2% and was observed only in patients with malignant tumours. PS is a significant risk factor for delirium. Delirium is correlated with poor prognosis.

The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab.

BACKGROUND AND AIMS: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice. METHODS: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD. RESULTS: There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001). CONCLUSIONS: The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice.

Disease Progression-Related Markers for Aged Non-Alcoholic Fatty Liver Disease Patients.

Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals. Serum levels of pro- and anti-inflammatory cytokines were measured by multiple enzyme-linked immunosorbent assay. Two standard NAFLD or fibrosis progression-related markers - the FIB-4 index and APRI score - were analyzed along with cytokine levels to define the best approach to discriminate advanced fibrosis. Ninety-eight NAFLD patients were enrolled: 59 and 39 patients with fibrosis stages 1-2 and 3-4 respectively. In addition to the FIB-4 index and APRI score, the following factors showed significant differences between stages 1-2 and stages 3-4 in a multivariate analysis: platelet counts, IP-10, and RANTES. The fibrosis stage, FIB-4, APRI, PDGF-BB, and RANTES were related to the prognosis. In aged patients, IP-10, GM-CSF, and RANTES differed between stages 1-2 and stages 3-4. FIB-4 and APRI were beneficial for their correlation with fibrosis. However, to stratify either young or elderly advanced fibrosis patients, and to identify patients likely to have a bad outcome, RANTES was the best marker.

Palliative care unit treatment and care for a terminal breast cancer patient with untreated obsessive-compulsive disorder.

OBJECTIVES: Although palliative care units treat patients with various comorbidities, there are no reports of patients with obsessive-compulsive disorder (OCD). METHODS: The treatment and care of a breast cancer patient with OCD are presented. RESULTS: A woman in her 40s was admitted to the palliative care unit for terminal breast cancer. She spent most of the day cleaning the bath and bed areas, ignoring efforts to restrain her actions by the staff. After being diagnosed with OCD, the above symptoms improved through the coordinated action of the staff and medication. SIGNIFICANCE OF RESULTS: This is the first report of the diagnosis and treatment of a patient with OCD in a palliative care unit. Early psychiatric diagnosis and subsequent staff response contributed to improvement in the patient's quality of life.

Oxidative stress-related markers as prognostic factors for patients with primary sclerosing cholangitis in Japan.

BACKGROUND/PURPOSE: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases. We investigated the clinical course and oxidative stress-related condition of PSC to determine prognostic factors. METHODS: We recruited 58 patients with PSC (mean age; 37.4 years, mean observation period; 1382 days) who visited our department from 2003 to 2021. Clinical characteristics were investigated to define prognostic factors. Oxidative stress status was evaluated using two types of markers: an oxidative stress marker (serum reactive oxygen metabolite; dROM) and an antioxidant marker (serum OXY adsorbent test; OXY). RESULTS: The revised Mayo risk, Child-Pugh, model for end-stage liver disease-sodium (MELD-Na) scores or fibrosis-related FIB-4 index significantly predicted poor overall survival. High intestinal immunoglobulin A (IgA) levels predicted poor survival. Among patients with high and intermediate revised Mayo risk scores, those with physiologically high dROM levels showed better survival than those with lower dROM levels. In this population, dROM was negatively correlated with AST and IgA, which are both correlated with survival. CONCLUSIONS: High and intermediate revised Mayo risk score group predicted a poor clinical course in PSC. Additionally, the Child-Pugh score, MELD-Na score, FIB-4 index, and serum IgA were significantly correlated with survival. In patients with high and intermediate revised Mayo risk scores, physiologically high oxidative stress status correlated with low IgA levels and a good prognosis.

The prevalence of thiamine deficiency among elderly nursing home residents: A cross-sectional study.

Background: Although thiamine deficiency (TD) can lead to Wernicke encephalopathy, the characteristics associated with TD in the elderly have not yet been clarified. We sought to clarify the frequency of TD among an institutionalized elderly population with a controlled dietary intake and to identify possible factors related to TD. Method: We undertook a cross-sectional study of residents in three nursing homes for the elderly as of June 2020. Blood thiamine concentrations were measured using a high-performance liquid chromatography method, with TD defined as a concentration of <21.3 ng/mL. Basic data (age, sex, height, weight, and BMI), dietary intake for the previous 3 weeks, degree of care (DOC), degree of independence in daily life for elderly with dementia (DIDLED), and comorbidities were analyzed using descriptive statistical methods. Results: The mean age (±SD) was 86.9 years (±8.29), with 84 residents (70.0%) being female. The DIDLED varied from total independence to long-term care level 5 (full assistance), with 89.2% suffering dementia. The mean whole blood thiamine value was 36.18 (±17.58) ng/ml, with TD confirmed in 7 (5.8%) of the 120 residents. All TD patients suffered from dementia. No TD was observed in patients with a near-normal food intake, and no related factors were observed among the other items. Conclusion: Reduced food intake may at increase the risk of TD and symptoms of TD may be overlooked in those displaying symptoms of dementia; thus, it is important for clinicians working with the elderly to remain aware of the potential for TD.

Thiamine Deficiency in a Patient With Schizophrenia: Precautions and Countermeasures for Subclinical Thiamine Deficiency.

Patients with schizophrenia often experience problems associated with ordinary exercises of life due to their mental symptoms. Those experiencing problems related to feeding behavior, in particular, are considered to be susceptible to developing Wernicke encephalopathy due to a deficiency in thiamine, the physiological stores of which are limited; however, there are few reported cases, and most of them were accompanied by the classical triad of signs. We report our experience with asymptomatic thiamine deficiency (TD) in a schizophrenia patient. A 73-year-old female was receiving medication for schizophrenia as an outpatient. No symptoms such as hallucinations or delusions were observed, the patient had a sociable personality and was able to function at a level where she could live alone. Although there were no active complaints about eating by the patient, we investigated the situation due to reports of TD in schizophrenia patients. As results revealed a significant decrease in whole blood thiamine to 19 ng/mL (reference range: 24-66 ng/mL), we administered a large dose of thiamine. No changes were observed in psychosomatic symptoms before and after administration. Patients with schizophrenia experience problems that may lead to TD, such as dietary imbalances and disturbed feeding habits. Therefore, even if patients with schizophrenia do not actively complain about their feeding behavior, it may be necessary to take medical measures such as blood sampling in consideration of the potential for developing TD.

Investigation of Whole Blood Thiamine Concentration in Independently Ambulatory Residents of a Provincial Town in Japan: A Cross-Sectional Study.

Background Thiamine deficiency (TD) is an important public health problem in nutrition, occurring in 2-6% of the population in Europe and the US, whereas thiamine levels are reported to be significantly reduced by 36.6-40% in some populations of East Asia. However, there is little information available at present, regarding factors such as age, despite the continued aging of society. Further, studies such as those mentioned above have not yet been undertaken in Japan, the country in which population aging is most advanced. Objective To investigate TD in the Japanese community-dwelling individuals who are independently ambulatory. Methods We undertook an examination of TD in blood samples obtained from 270 citizens in a provincial town, aged 25-97 years, who were able to walk to the venue and provide informed consent for inclusion in this research and of whom 8.9% had a history of cancer. We summarized the demographic characteristics of the subjects. The whole-blood thiamine concentrations were measured using the high-performance liquid chromatography method. A value of 21.3 ng/ml or less was taken as low and a borderline value was set as less than 28 ng/ml. Results The mean (±SD) whole blood thiamine concentration was 47.6 ± 8.7 ng/ml. No TD was observed to exist participating in this study, with no subjects even showing show borderline values. Further, there was no significant difference in thiamine level between those aged 65 or older and those aged less than 65. Conclusions No cases of TD were observed among the subjects in this study, nor was the concentration of thiamine found to be related to age. It is possible that the frequency of TD might be very low in citizens who have a certain level of activity. In the future, it is necessary to expand the prevalence of TD to a wider range of subjects.

Naldemedine-induced opioid withdrawal with restlessness as the predominant symptom in a palliative care setting.

OBJECTIVES: Opioid analgesics play a central role in cancer pain treatment; however, it has been reported that opioid-induced constipation (OIC) develops in 80% of patients using opioid analgesics and leads to a decrease in quality of life. Naldemedine improves constipation without affecting the analgesic action of opioid analgesics via peripheral µ-opioid receptors. METHODS: We report a terminally ill cancer patient who was diagnosed with opioid withdrawal syndrome (OWS) based on symptoms centered around restlessness and sweating that developed 43 days after administration of naldemedine for OIC. RESULTS: The patient was a 78-year-old woman who was diagnosed with stage IVB uterine sarcoma in October, 1 year prior to her visit to our clinic,  and underwent chemotherapy after surgery, but the disease became progressive. Thereafter, metastasis to the fourth thoracic vertebrae (Th4) was identified, and loxoprofen and acetaminophen were started for pain at the metastatic site. Oxycodone hydrochloride hydrate 10 mg/day was additionally administered on postoperative day 11, followed by naldemedine 0.2 mg/day for OIC. On the 43rd day after administration, the patient began to wander the hospital ward in a wheelchair and became noticeably restless. OWS due to naldemedine administration was suspected, and naldemedine was discontinued. The symptoms improved 7 days later, and no similar symptoms were observed thereafter. SIGNIFICANCE OF RESULTS: Patients receiving palliative care often exhibit psychiatric symptoms such as anxiety and depression, but OWS due to naldemedine should also be considered as a potential cause.

Can depressed cancer patients with a borderline thiamine concentration develop deficiency within a short time period?

BACKGROUND: Despite increasing reports of thiamine deficiency (TD) among cancer patients, there remain some patients with borderline thiamine concentrations (BTC). However, it is unclear whether such patients subsequently develop TD. METHODS: Here, we report cases of cancer patients progressing to TD within a short time period after presentation with BTC (24-28 ng/ml). CASE 1: A 49-year-old female with lung cancer. During treatment for depression, the patient showed a decreased appetite, and a blood sample revealed BTC (25 ng/ml). Fourteen days later, she reported a continued loss of appetite, and despite the absence of the 3 classical signs of Wernicke encephalopathy (WE), additional testing showed a thiamine level of 23 ng/ml, leading to a diagnosis of TD. CASE 2: A 65-year-old female developed depression during chemotherapy for angiosarcoma. Her blood sample revealed BTC (25 ng/ml). Seven days later, despite the absence of the classical signs of WE, a further testing revealed a thiamine level of 20 ng/ml. CASE 3: A 41-year-old female developed depression during chemotherapy for ovarian cancer. No loss of appetite was observed, but a blood sample revealed BTC (25 ng/ml). Seven days later, despite the absence of the classical signs of WE or decreased appetite, further testing revealed a thiamine level of 19 ng/ml. SIGNIFICANCE OF RESULTS: Depressed cancer patients with BTC may develop TD within a short time frame. To prevent TD, health-care professionals should maintain an awareness of its potential and the need for regular testing of thiamine level or prophylactic replacement therapy.

History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients.

This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC.