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.

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.

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.

Opioid withdrawal syndrome developing after long-term administration of naldemedine.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE OF THE RESULTS: 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.

Wernicke encephalopathy in a caregiver: A serious physical issue resulting from stress in a family member caring for an advanced cancer patient.

OBJECTIVE: 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. METHODS: We reported a caregiver who developed Wernicke encephalopathy (WE) while caring for a family member with advanced cancer. RESULTS: 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. SIGNIFICANCE OF THE RESULTS: 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.

Naldemedine-induced opioid withdrawal syndrome with severe psychiatric symptoms in an advanced cervical cancer patient without brain metastasis.

OBJECTIVE: Naldemedine, an oral peripheral µ-opioid receptor antagonist, was developed for the treatment of constipation, a side effect of opioid use. Naldemedine is not generally recognized as causing opioid withdrawal in which associated symptoms affecting the central nervous system. METHOD: From the series of cancer patients undergoing symptom management, we report a case treated with naldemedine for constipation in relation to the use of opioids for cancer pain and who displayed severe psychological symptoms associated with withdrawal immediately after the use of naldemedine. RESULTS: The patient was a 36-year-old woman diagnosed with cervical cancer Stage IIB, PS3. When the patient, who was using oxycodone hydrochloride hydrate (80 mg/day) for ileal pain, was started on naldemedine for constipation, she complained of sweating after just 5 min and hallucinations after 1 h. The patient also displayed physical/behavioral abnormalities such as diarrhea and hyperactivity, and psychological abnormalities such as aggression toward staff.Despite the psychiatric symptoms worsening over time, there were no abnormalities in terms of blood biochemical data, and no brain metastasis was observed on MRI. Based on the Clinical Opiate Withdrawal Scale, these symptoms were judged to indicate opioid withdrawal. Naldemedine was discontinued due to naldemedine-related opioid withdrawal syndrome and, thereafter, the psychiatric symptoms diminished, with no recurrence of similar symptoms observed to date. SIGNIFICANCE OF RESULTS: If mental and behavioral abnormalities occur in patients receiving naldemedine, it is necessary to consider the possibility of opioid withdrawal syndrome as a differential diagnosis.

Wernicke encephalopathy in a lung cancer patient receiving home medical care.

OBJECTIVE: 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. METHODS: From a series of cancer patient undergoing home medical care, we reported a patient with lung cancer who developed WE. RESULTS: 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. SIGNIFICANCE OF THE RESULTS: 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.

Reversible dementia due to vitamin B12 deficiency in a lung cancer patient: Relevance of preoperative evaluation.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. SIGNIFICANCE OF THE RESULTS: When cognitive decline is observed in cancer patients, it is necessary to actively evaluate the serum levels of some B vitamins, including VB12.

[Problems Faced by the Families and Bereaved Families of Cancer Patients].

Family members of cancer patients experience major changes in their daily lives due to their loved one's illness. The associated stress spreads across all aspects of their lives, physical, emotional, psychological and social, and due to risk of physical and mental illness posed, these family members are referred to as secondary patients. With advances in cancer medicine, family participation is required in various aspects of patient decision‒making, and families must address many challenges, not just nursing. After the patient's death, the family then becomes the bereaved family. The bereaved families of patients who died of cancer have characteristic burdens such as"regret"", unhelpful communication", and"anniversary reactions", and it is necessary to take appropriate measures while paying attention to the risk of physical and mental illness among the family members. In addition, it is important to have knowledge not only of physical and mental problems but also legal problems that arise, and to ask a specialist when necessary to support patients, families, and bereaved families.

High proportion of thiamine deficiency in referred cancer patients with delirium: a retrospective descriptive study.

BACKGROUND/OBJECTIVES: Recent studies have revealed thiamine deficiency (TD) as a cause of delirium in cancer patients. However, the extent to which Wernicke encephalopathy is present and in what patients is not well understood. SUBJECTS/METHODS: In this retrospective descriptive study, we investigated referred cancer patients who were diagnosed with delirium by a psycho-oncologist to clarify the proportion of TD, the therapeutic effect of thiamine administration, and the factors involved in its onset. RESULTS: Among 71 patients diagnosed with delirium by a psycho-oncologist, TD was found in 45% of the patients. Intravenous administration of thiamine led to a recovery in about 60% of these patients. We explored the factors associated with TD using a multivariable regression model with a Markov chain Monte Carlo imputation procedure. We found an association between TD and chemotherapy (adjusted odds ratio, 1.98 [95% confidence interval, 1.04-3.77]); however, there were no significant associations between TD and the other factors we considered. CONCLUSIONS: TD is not particularly rare in delirium patients undergoing psychiatric consultation. The delirium was resolved in more than half of these patients by intravenous administration of thiamine. Oncologists should consider TD as a cause of delirium in cancer patients. Further prospective study is needed to clarify the relationship between TD and delirium in cancer patients.

Subclinical thiamine deficiency identified by pretreatment evaluation in an esophageal cancer patient.

Despite the fact that both thiamine deficiency (TD) and Wernicke encephalopathy (WE) have been observed to some degree in cancer patients, such cases of TD and/or WE reported to date have all been diagnosed after the initiation of treatment. We here report a case of TD that presented without the commonly accepted triad of WE symptoms based on a total nutritional evaluation prior to the onset of treatment for cancer. The patient was a 71-year-old man with esophageal cancer who was referred to the oncology outpatient clinic for evaluation to determine the treatment plan. Although he did not present with delirium, cerebellar signs, or ocular symptoms, TD was suspected based on a reduction in appetite lasting 2 months as thiamine stores in the body are depleted in as few as 18 days. Blood findings showed a marked decline in serum thiamine level supported, which the diagnosis of TD. This case revealed the existence of a cancer patient with subclinical TD prior to the onset of treatment for cancer. Due to the fact that TD can occur without the characteristic symptoms as in this case, we believe it is important that total nutritional evaluation of cancer patients always be considered.

Subclinical thiamine deficiency: What is the most appropriate method of diagnosis and treatment?

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE OF RESULTS: 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.

Validating the efficacy of interval appendectomy for acute appendicitis: representative three cases with different etiologies.

BACKGROUND: Appendectomy for acute appendicitis (AA) is considered one of the most common emergency surgeries. However, emergency appendectomy accompanied with complex lesions such as extensive abscess formation is not recommended in most cases. Therefore, non-operative management followed by interval appendectomy (IA) for AA has been tried. Herein, we present three AA cases with specific etiology that underwent interval appendectomy. CASE PRESENTATION: Case 1: A 68-year-old man was diagnosed AA with intestinal malrotation and intra-abdominal abscesses. He initially treated with conservative therapy and underwent laparoscopic IA after detailed preoperative examination. Case 2: A 22-year-old man had been under treatment for pancolitis-type ulcerative colitis (UC), also bothered by right-lower abdominal pain several times a year. The appendix always appeared swollen on every CT taken during symptoms. He underwent laparoscopic IA; pathological finding revealed typical UC histological features in the resected appendix. After the surgery, he never suffered from terrible right lower abdominal pain. Case 3: A 69-year-old woman complaining a right lower abdominal pain had undergone CT examination, which revealed AA with appendiceal mass, irregular wall thickness of the cecum, and mediastinal and para-aortic lymph node swelling. The operation was carried out after conservative therapy. The pathological diagnosis revealed BRAF mutated colorectal carcinoma. She had received systematic chemotherapy after the surgery, and all metastatic lesions have completely disappeared. CONCLUSION: Interval appendectomy provided us with much clearer anatomical information and precise therapeutic strategies, avoiding technical and general operative complications, and also induced fast recovery and short length of hospital stay. Interval appendectomy is a reasonable procedure and could be recommended in case of AA with some different etiology.

Neuroleptic malignant syndrome in patients with cancer: a systematic review.

BACKGROUND: Antipsychotics potentially cause a low incidence of the side effect called neuroleptic malignant syndrome (NMS), which has a high mortality rate. However, few studies on NMS among patients with cancer exist. AIMS: We aimed to examine the characteristics of antipsychotic-induced NMS among patients with cancer. METHODS: We conducted a systematic review of published reports on NMS described during the treatment of patients with any type of cancer. Articles were identified by a comprehensive search of PubMed, Web of Science, the Cochrane Library and reference lists from relevant articles published until 25 December 2019. Original articles or case reports on humans published in English were included. This review summarises the symptoms, characteristics, treatment course and prognosis of patients with cancer with NMS. RESULTS: Eleven patients with various cancer types from ten case reports published from 1988 to 2013 met the eligibility criteria. Mean age of the 11 patients was 52.5 (range, 32-83) years. NMS developed mostly during the postoperative period, and haloperidol and D2 receptor antagonists were determined as the common causative drugs. Ten patients survived following treatment that mostly involved discontinuing the causative drugs and administering dantrolene, if necessary. CONCLUSION: Although NMS intrinsically has a low incidence and high mortality, only few reports were available, with most patients surviving after early detection and appropriate treatment. Healthcare providers should consider NMS development while prescribing antipsychotics to ensure prompt recognition of the condition and rapid treatment for preventing unnecessary deaths.

"Phantom akathisia" in an amputated leg of a sarcoma patient: a case report.

BACKGROUND: Akathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to the diversity of symptoms, it is often overlooked. We hereby report a case with akathisia that mainly appeared in an amputated leg. CASE PRESENTATIONS: A 60-year-old woman, who had undergone external hemipelvectomy for a recurrent soft tissue sarcoma, was referred to the Department of Psycho-Oncology due to worsening anxiety and restlessness. She was not unconscious or disoriented. Her chief complains included restlessness, an itching sensation in the area corresponding to the amputated left leg, and a feeling as if the lost left leg were raising itself. Detailed examination revealed that she had been administered 10 mg per day of oral prochlorperazine maleate for nausea induced by the oxycodone that had been prescribed to control post-operative pain. Akathisia was suspected and prochlorperazine maleate treatment was discontinued. All the symptoms were alleviated on the next day, and disappeared in 3 days. Eventually, she was diagnosed with akathisia. CONCLUSIONS: This case indicates that the symptoms associated with akathisia can occur in an amputated extremity. Considering two previous reports of "phantom dyskinesia", extrapyramidal syndromes may result in unusual presentations if occurring in an amputated extremity. Not only should the use of antipsychotic drugs and antidepressants be carefully considered, but also closer observation of psychological symptoms is required after prescription of these drugs because the clinical presentation of akathisia can be various and confusing due to modifications caused by other factors as in this case.

Thiamine deficiency in a patient with recurrent renal cell carcinoma who developed weight loss with normal appetite and loss of energy soon after nivolumab treatment.

BACKGROUND: Nivolumab has become an effective treatment option for cancer in various sites; however, this drug may cause immune-related adverse effects due to its mechanism of action. Furthermore, little has been reported on thiamine deficiency (TD) in patients receiving nivolumab treatment. METHOD: From a series of cancer patients, we reported a patient with recurrent renal cell carcinoma who developed TD after the start of nivolumab treatment. RESULTS: A 74-year-old man with recurrent renal cell carcinoma was referred to the psycho-oncology department as he had lost about 4 kg and displayed a loss of energy after four cycles of nivolumab treatment. Psychiatric interviews revealed a decrease in energy. Neurological examination did not reveal any impairment in consciousness, ataxia, or ocular symptoms. He did not develop appetite loss. The malabsorption or overconsumption of some nutrients is thought to occur due to the rapid loss of weight; thus, a reduction in vitamin B1, which has a short storage period in the body and is often deficient in cancer patients, was suspected. The diagnosis of TD was supported by the patient's abnormally low serum thiamine level. SIGNIFICANCE OF RESULTS: In patients treated with nivolumab, it is necessary to pay careful attention to TD when proceeding with the treatment. It is hoped that future research may reveal the link between nivolumab administration and TD.