Naldemedine is a peripherally acting μ-opioid receptor antagonist used to treat opioid-induced constipation. As this drug does not cross the blood–brain barrier, it is believed that patients without brain metastases do not experience opioid withdrawal symptoms.

Here, we experienced a case in which a cancer patient without brain metastasis presented with anxiety and restlessness that was severe enough to interfere with daily life. The patient was diagnosed with naldemedine-induced opioid withdrawal syndrome.

The patient was a 66-year-old male with liver cancer metastasizing to the chest wall, but without brain metastasis. Oxycodone was started at 10 mg/day 2 months prior to his visit to our department to treat pain related to the chest wall metastasis, and was increased to 100 mg/day 1 month later and maintained at that dose. Naldemedine was administered as a countermeasure against opioid-induced constipation. The patient developed anxiety and restlessness 10 days prior to his initial visit to our department.

After detailed examination, naldemedine-related opiod withdrawal syndrome was suspected on the basis of anxiety, agitation, and episodes of sudden onset sweating, and these symptoms disappeared within 2 days after the discontinuation of naldemedine, with no recurrence observed thereafter. In addition, head MRI revealed no brain metastasis.

Even in patients without brain metastasis, naldemedine can induce opioid withdrawal symptoms, so caution is required with patients receiving this drug. In addition, when psychiatric symptoms are pronounced, as in this case, withdrawal symptoms may be underdiagnosed.

Patients with advanced cancer present various symptoms as their disease progresses. Among these, fatigue is a frequent symptom in patients with advanced cancer and is associated with decreased quality of life (QOL). However, there are few reports regarding its association with thiamine deficiency (TD).

We report a case in which we found TD in a patient with advanced lung cancer who presented with weight loss, significant fatigue, and appeared to have a worsening general condition, for whom symptoms were dramatically improved within a short period of time by intravenous administration of thiamine.

The patient was a 76-year-old woman who had been diagnosed with lung cancer and liver metastases 6 months earlier. Due to interstitial pneumonia, she was not a candidate for chemotherapy and so palliative care was started. At 8 months after initial diagnosis, the patient complained of fatigue during a medical examination, so a blood sample was taken. A week later, she visited the hospital with a cane. She felt extremely fatigued and was unable to stand, but results from the previous blood test revealed that a TD. The fatigue disappeared 15 minutes after intravenous administration of thiamine and she was able to return home without the cane.

Fatigue is a frequent symptom in advanced cancer patients, and TD may be the underlying cause. Inclusion of TD in the differential diagnosis may contribute to improving patient QOL.

Residents who lived near the Fukushima Power Plant accident were forced to change their lifestyle after the 2011 accident. This study aimed to elucidate the association of resident lifestyle and psychological factors with onset of hepatobiliary enzyme abnormalities (HEA) after the accident.

This longitudinal study included 15705 residents who underwent a comprehensive health check, as well as a mental health and lifestyle survey between June 2011 and March 2012. Follow-up surveys were conducted between June, 2012 and March 2018. Risk factors for new HEA onset were evaluated using the Cox proportional hazards model, moreover, population attributable risks for new HEA onset were calculated.

HEA developed in 29.7% of subjects. In addition to metabolic factors such as overweight, hyperglycemia, and hyperlipidemia; there were differences in alcohol intake, evacuation, unemployment, educational background, and psychological distress between subjects with and without HEA onset. After we adjusted for potential confounding factors, an association of being overweight, hypertension, and dyslipidemia, as well as alcohol consumption, evacuation, and psychological distress with increased risk of HEA onset was realized. Among these identified risk factors, evacuation accounted for the greatest share.

Metabolic characteristics and disaster-related lifestyle aspects, including mental status, were risk factors for HAE onset after the Fukushima Power Plant accident.

Thiamine deficiency (TD) presents with various physical and psychiatric symptoms, but no cases with depression-like symptoms have been reported.

We report a patient with cancer who appeared to attempt suicide as a consequence of depressive mood likely related to TD.

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.

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.

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.

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.

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.

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.

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.

Here, we report cases of cancer patients progressing to TD within a short time period after presentation with BTC (24–28 ng/ml).

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.

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.

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.

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.

It is well known that the burden on the families of cancer patient extends across many aspects, but there have been no reports of family members developing delirium due to the burden of caring for a cancer patient.

We reported a caregiver who developed Wernicke encephalopathy (WE) while caring for a family member with advanced cancer.

The subject was a 71-year-old woman who had been caring for her husband, diagnosed with gastric cancer and liver metastases, for 5 months. She visited the “caregivers’ clinic” after referral by an oncologist who was worried about a deterioration in her mental condition that had appeared several weeks previously. The woman had a history of diabetes mellitus. Some giddiness was observed and, based on her inability to answer questions, her level of consciousness was checked and some disorientation was observed. She was diagnosed with delirium. A blood sample was collected to investigate the cause of the delirium, but the test data showed no hypoglycemia. Her appetite had declined since her husband was diagnosed with cancer. Thiamine deficiency was suspected as thiamine stores in the body are depleted within about 18 days and her loss of appetite had continued for 5 months. On intravenous injection of 100 mg of thiamine, her consciousness level was returned to normal in 1 h. A diagnosis of WE was supported by the patient's abnormally low serum thiamine level.

The family members of cancer patients may develop a loss of appetite due to the burden of caring, resulting in WE. When providing care for signs of distress in family members, it is necessary to pay attention not only to the psychological aspects but also to their level of consciousness and physical aspects, particularly the possibility of serious illness resulting from reduced nutritional status.

Cancer patients often want to spend their final days at home, and it is essential that general practitioners have knowledge of and technical skills related to cancer medicine and symptom relief. Recent clinical studies have revealed that Wernicke encephalopathy (WE) is quite common in cancer patients. However, there have been no reports to date on WE in cancer patients undergoing home medical care.

From a series of cancer patient undergoing home medical care, we reported a patient with lung cancer who developed WE.

An 84-year-old female with lung cancer undergoing home medical care developed an impaired mental state and an attention deficit. Her symptoms fulfilled the diagnostic criteria for delirium. WE was suspected as the patient's food intake had fallen from normal a month previously to somewhere between 50% or just a few mouthfuls. This diagnosis was supported by abnormal serum thiamine and the disappearance of delirium after thiamine administration.

When delirium occurs in cancer patients undergoing home treatment, it is necessary to suspect thiamine deficiency as a potential cause, as appropriate diagnosis and treatment can prevent irreversible brain-related sequelae.

Cognitive dysfunction has a negative effect on cancer treatment; however, in a cancer setting, specific treatments can restore cognitive function. Such conditions are known as reversible dementia, with one of these being vitamin B12 (VB12) deficiency. However, there have been no reports of VB12 deficiency identified by preoperative evaluation in cancer patients.

We studied a patient who was referred to the Department of Psycho-oncology on suspicion of cognitive decline prior to lung cancer surgery. Preoperative evaluation revealed VB12 deficiency.

The patient was an 82-year-old woman diagnosed with lung cancer. She also presented with cognitive decline and, therefore, was referred to the Department of Psycho-oncology for preoperative evaluation. The patient scored 19 points on a Mini-Mental State Examination (MMSE), which is indicative of cognitive decline. As the onset of symptoms occurred several months previously and they were subacute, the possibility of reversible dementia was considered. Extensive examination revealed VB12 deficiency, and VB12 replacement therapy normalized the MMSE score to 25 points before surgery.

When cognitive decline is observed in cancer patients, it is necessary to actively evaluate the serum levels of some B vitamins, including VB12.

The symptoms of thiamine deficiency vary considerably and asymptomatic cases; i.e., subclinical thiamine deficiency (SCTD), are known to exist. However, there is no information available on the treatment of SCTD.

We report a patient who underwent intravenous thiamine replacement therapy for about a month after being diagnosed with SCTD, but who developed SCTD again about three weeks after finishing the treatment.

The patient was a 64-year-old woman who, after starting treatment for cervical cancer, complained of anxiety and underwent an initial psychiatric examination. The psychiatric diagnosis was an adjustment disorder. Based on the possibility of SCTD complications due to her decreased appetite and weight loss, her serum thiamine concentration was measured and found to be low. Therefore, thiamine was administered intravenously for 29 days. At the end of treatment, thiamine administration was discontinued as there were no apparent neuropsychiatric symptoms or problems with appetite. Twenty-three days later, there were still no problems with appetite or neuropsychiatric symptoms, but a follow-up blood sample revealed that her serum thiamine was again below the normal range.

Currently, there is no information available regarding the diagnosis and treatment of SCTD in cancer patients. In some cases, such as this case, the deficiency recurs without any symptoms indicative of SCTD; therefore, further examination for diagnosis and treatment is necessary.

Thiamine deficiency (TD) is recognized in various kinds of disease with associated loss of appetite including cancer. However, it has not been recognized to date in bereaved partners after spousal loss from cancer.

From a series of bereaved partners who lost a spouse to cancer, we report on those who developed TD after bereavement.

Case 1 was a 57-year-old woman who sought consultation at our “bereavement clinic.” Her husband had been diagnosed with pancreatic cancer one year earlier and had died one month previously. At the first visit, she was observed to suffer depression, anxiety, and decreased appetite. Neurological, blood, and biochemical examinations did not reveal any noteworthy findings. She was diagnosed with uncomplicated bereavement. Detailed examination revealed that her appetite had been markedly decreased for approximately five weeks. The diagnosis of TD was supported by her abnormally low serum thiamine level. Case 2 was a bereaved 73-year-old male who had lost his wife to hypopharyngeal cancer one month previously after a five-year illness. He had shown a lack of energy for the month preceding his wife's death, but because there was no improvement after her death, his family recommended he seek consultation at our “bereavement clinic.” He was suffering from major depressive disorder. Detailed examination revealed that his appetite had been decreased for more than two weeks. Again, the diagnosis of TD was supported by his abnormally low serum thiamine level.

These reports demonstrate that there is a possibility that bereaved could develop TD after the loss of a loved one. TD should be considered whenever there is a loss of appetite lasting for more than 2 weeks, and medical staff should pay careful attention to the physical condition of the bereaved to prevent complications because of TD.

Thiamine deficiency (TD) is recognized in various kinds of disease with associated loss of appetite including cancer; however, TD has not been recognized in the family caregivers of cancer patients to date.

From a series of cancer patient caregivers, we reported an aged family caregiver who developed TD while caring for the cancer patient.

The caregiver was a 90-year-old male. He had been accompanying his wife, who was diagnosed with colon cancer 4 years previously, on hospital visits as the primary caregiver, but because of psychological issues, he was recommended to visit the psycho-oncology department's “caregiver's clinic” for a consultation. Detailed examination revealed that his appetite had been only about 50% of usual from about one year before, and he had lost 12 kg in weight in one year. The diagnosis of TD was supported by his abnormally low serum thiamine level.

This report demonstrates that there is a possibility that care providers could develop TD from the burdens associated with caregiving. TD should be considered whenever there is a loss of appetite lasting for more than 2 weeks, and medical staff should pay careful attention to the physical condition of care providers to prevent complications resulting from TD.

Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency. It is recognized in various stages of the cancer trajectory but has not previously been recognized during nivolumab treatment.

From a series of WE patients with cancer, we report a lung cancer patient who developed WE during treatment with nivolumab.

A 78-year-old woman with lung cancer was referred to our psycho-oncology clinic because of depressed mood. Psychiatric examination revealed disorientation to time, date, and place, which had not been recognized 1 month previously. Her symptoms fulfilled the diagnostic criteria for delirium. No laboratory findings or drugs explaining her delirium were identified. WE was suspected as she experienced a loss of appetite lasting 4 weeks. This diagnosis was supported by abnormal serum thiamine and the disappearance of delirium after intravenous thiamine administration.

We found WE in an advanced lung cancer patient receiving treatment with nivolumab. Further study revealed the association between nivolumab and thiamine deficiency. Oncologists should consider thiamine deficiency when a patient experiences a loss of appetite of more than 2 weeks regardless of the presence or absence of delirium.