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.

One of the side effects of opioid administration is opioid-induced constipation (OIC). To address this side effect, the oral peripheral μ opioid receptor antagonist naldemedine was developed. As this drug does not cross the blood–brain barrier, it is thought that it does not lead to opioid withdrawal syndrome (OWS) with central nervous system symptoms.

Here, we report a cancer patient who presented with symptoms centered round anxiety and irritation 4 months after administration of naldemedine for OIC and who was diagnosed with OWS after close investigation.

The patient was a 65-year-old female who had surgery for stage IB endometrial cancer 4 years previously, but experienced recurrence involving the pelvis 2 years later. Medical narcotics were used to control pain, but naldemedine was started to control subsequent constipation. When naldemedine-related OWS was suspected and the administration of naldemedine discontinued, the above symptoms disappeared within two days, and no recurrence was observed thereafter.

For patients receiving naldemedine, it is necessary to consider the possibility of OWS regardless of the period of administration in order to maintain patient quality of life.

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, and is sometimes overlooked because of the diversity of clinical symptoms.

From a series of WE patients with cancer, we report a lung cancer patient who developed WE, the main symptom of which was agitation.

A 50-year-old woman with lung cancer was referred to our psycho-oncology clinic because of agitation lasting for three days. No laboratory findings or drugs explaining her agitation were identified. Although the patient did not develop delirium, ophthalmoplegia, or ataxia, WE was suspected because she experienced a loss of appetite loss lasting 5 weeks. This diagnosis was supported by abnormal serum thiamine and disappearance of agitation one hour after intravenous thiamine administration.

This report emphasizes the clinical diversity of WE and indicates the limits of the ability to diagnose WE from typical clinical symptoms. The presence of a loss of appetite for more than two weeks may be the key to the accurate diagnosis of WE.

Wernicke's encephalopathy (WE) is a neuropsychiatric disorder caused by a thiamine deficiency. Although WE has been recognized in cancer patients, it can be overlooked because many patients do not exhibit symptoms that are typical of WE, such as delirium, ataxia, or ocular palsy. Furthermore, outpatients with WE who intermittently present at psycho-oncology clinics have not been described as far as we can ascertain.

This report describes two patients who did not exhibit the complete classic triad of symptoms among a series with cancer and WE, and who attended a psycho-oncology outpatient clinic.

Case 1, a 76-year-old woman with pancreatic cancer and liver metastasis, periodically attended a psycho-oncology outpatient clinic. She presented with delirium and ataxia as well as appetite loss that had persisted for 8 weeks. We suspected WE, which was confirmed by low serum thiamine levels and the disappearance of delirium after thiamine administration. Case 2, a 79-year-old man with advanced stomach cancer, was referred to a psycho-oncology outpatient clinic with depression that had persisted for about 1 month. He also had appetite loss that had persisted for several weeks. He became delirious during the first visit to the outpatient clinic. Our initial suspicion of WE was confirmed by low serum thiamine levels and the disappearance of delirium after thiamine administration. The key indicator of a diagnosis of WE in both patients was appetite loss.

This report emphasizes awareness of WE in the outpatient setting, even when patients do not exhibit the classical triad of WE. Appetite loss might be the key to a diagnosis of WE in the absence of other causes of delirium.

Thiamine is an essential coenzyme for oxidative metabolisms; however, it is not synthesized in the human body, and the average thiamine storage capacity is approximately 18 days. Therefore, thiamine deficiency (TD) can occur in any condition of unbalanced nutrition. If TD is left untreated, it causes the neuropsychiatric disorder Wernicke encephalopathy (WE). Although WE is a medical emergency, it is sometimes overlooked because most patients with WE do not exhibit all of the typical symptoms, including delirium, ataxia, and ophthalmoplegia. If all of the typical clinical symptoms of WE are absent, diagnosis of TD or WE becomes more difficult.

From a series of cancer patients, we reported three patients who developed TD without the typical clinical symptoms of WE.

A 69-year-old woman with pancreatic body cancer receiving chemotherapy with paclitaxel and gemcitabine for six months. Her performance status (PS) was 1. A detailed interview revealed that she had appetite loss for six months. Another 69-year-old woman with ovarian cancer received nedaplatin; her PS was 0. A detailed interview revealed that she had appetite loss for three months. A 67-year-old woman with colon cancer receiving ramucirumab in combination with second-line fluorouracil with folinic acid and irinotecan. Her PS was 1. A detailed interview revealed that she had appetite loss for three weeks. None exhibited typical clinical signs of WE, but they developed appetite loss for six months, three months, and three weeks, respectively. The diagnosis of TD was supported by abnormally low serum thiamine levels.

This report emphasizes the possibility of TD in cancer patients even when patients do not develop typical clinical signs of WE. The presence of appetite loss for more than two weeks may aid in diagnosing TD. Patients receiving chemotherapy may be at greater risk for developing TD.

Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency. Several reports of WE in cancer patients are known. WE is sometimes overlooked because most patients do not exhibit its typical symptoms (e.g., delirium, ataxia, ocular palsy). If delirium is not present, a diagnosis of WE is difficult because delirium is the hallmark symptom of WE.

Taken from a series on WE in cancer, we report two patients who developed WE without delirium during periodic psycho-oncology outpatient visits.

Case 1. A 61-year-old woman with non-Hodgkin lymphoma who was periodically attending a psycho-oncology outpatient clinic developed an unsteady gait. WE was suspected because she also developed appetite loss for two weeks, and we could find no other laboratory findings to explain her unsteady gait. Our diagnosis was supported by abnormal serum thiamine and disappearance of the gait disturbance after intravenous thiamine administration. Case 2. A 50-year-old woman with breast carcinoma with bone metastasis developed an unsteady gait. WE was suspected because she also developed loss of appetite for two weeks, and no other laboratory findings could explain her unsteady gait. The diagnosis was supported by abnormal serum thiamine and disappearance of the gait disturbance after administration of intravenous thiamine.

Our report emphasizes the importance of being aware of WE, even when patients do not present with delirium. The presence of loss of appetite for more than two weeks may be the key to a diagnosis of WE.

The death of a loved one is one of the most stressful events of life, and such stress affects the physical and psychological well-being of the bereaved. Dissociative amnesia is characterized by an inability to recall important autobiographical information. Dissociative amnesia in the bereaved who have lost a loved one to cancer has not been previously reported. We discuss herein the case of a patient who developed dissociative amnesia the day after the death of here beloved husband.

A 38-year-old woman was referred for psychiatric consultation because of restlessness and abnormal behavior. Her 44-year-old husband had died of pancreatic cancer the day before the consultation. On the day of the death, she looked upset and began to hyperventilate. The next day, she behaved as if the deceased were still alive, which embarrassed her family. At her initial psychiatric consultation, she talked and behaved as if her husband was still alive and in the hospital.

Her psychiatric features fulfilled the DSM–V criteria for dissociative amnesia. The death of her husband had been very traumatic for her and was considered to have been one of the causes of this dissociation.

This report adds to the list of psychiatric symptoms in the bereaved who have lost a loved one to cancer. In an oncology setting, we should consider the impact of death, the concomitant defense mechanisms, and the background of the families.

To examine the validity and reproducibility of a self-administered food-frequency questionnaire (FFQ) used for two cohort studies in Japan.

Cross-sectional study.

Two rural towns in the Miyagi Prefecture, in north-eastern Japan.

Fifty-five men and 58 women.

A 40-item FFQ was administered twice, 1 year apart. In the mean time, four 3-day diet records (DRs) were collected in four seasons within the year. We calculated daily consumption of total energy and 15 nutrients, 40 food items and nine food groups from the FFQs and the DRs. We computed Spearman correlation coefficients between the FFQs and the DRs. With adjustment for age, total energy and deattenuation for measurement error with the DRs, the correlation coefficients for nutrient intakes ranged from 0.25 to 0.58 in men and from 0.30 to 0.69 in women, with median of 0.43 and 0.43, respectively. Median (range) of the correlation coefficients was 0.35 (−0.30 to 0.72) in men and 0.34 (−0.06 to 0.75) in women for food items and 0.60 (−0.10 to 0.76) and 0.51 (0.28–0.70) for food groups, respectively. Median (range) of the correlation coefficients for the two FFQs administered 1 year apart was 0.49 (0.31–0.71) in men and 0.50 (0.40–0.64) in women for nutrients, 0.43 (0.14–0.76) and 0.45 (0.06–0.74) respectively for food items, and 0.50 (0.30–0.70) and 0.57 (0.39–0.66) respectively for food groups. Relatively higher agreement percentages for intakes of nutrients and food groups with high validity were obtained together with lower complete disagreement percentages.

The FFQ has a high reproducibility and a reasonably good validity, and is useful in assessing the usual intakes of nutrients, foods and food groups among a rural Japanese population.