Capnocytophaga canimorsus infection led to progressively fatal septic shock in an immunocompetent patient.

BACKGROUND: Capnocytophaga canimorsus infection is rare, with a high fatality rate; however, there are few cases of death with a rapid course. This study reports a progressively fatal case of C. canimorsus. CASE PRESENTATION: A 68-year-old immunocompetent Japanese man was bitten and scratched on his right hand by a dog 6 days before emergency transportation to the emergency room with abdominal pain, back pain, and melena. The patient developed multiple-organ failure. Despite antibiotic therapy, transfusion, vasopressor therapy, and continuous renal replacement therapy, the patient died from uncontrolled metabolic acidosis 4.5 h after admission. Approximately 80 h after admission, blood cultures were positive for C. canimorsus. CONCLUSIONS: Capnocytophaga canimorsus infection can lead to rapid progression even in immunocompetent patients.

Successful diagnosis and treatment of pulmonary aspergillosis-related malignant catatonia using propofol and quetiapine: A case report.

INTRODUCTION: Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders. PATIENT CONCERNS: An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels. DIAGNOSES: At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement. INTERVENTIONS: Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely. OUTCOMES: The patient's MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital. CONCLUSION: This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment.

Transient total blindness associated with alcoholic ketoacidosis.

BACKGROUND: Methanol poisoning is often suspected in patients with high anion gap metabolic acidosis and visual deficits. Although alcoholic ketoacidosis can cause high anion gap metabolic acidosis, reports on vision loss are limited. We report the case of a patient with alcoholic ketoacidosis with transient total blindness. CASE PRESENTATION: A 56-year-old man complaining of total blindness was transferred to our hospital. Physical examination revealed a clear consciousness and mydriasis with an absence of pupillary light reflex. Blood analysis revealed high anion gap metabolic acidosis with a high ketone body concentration. Alcoholic ketoacidosis was diagnosed because the patient had a chronic alcohol abuse history and denied methanol intake. As acidemia improved because of fluid infusion and glucose and vitamin B1 supplementation, his visual acuity recovered. He was discharged after 44 days without visual deficits. CONCLUSION: Patients with alcoholic ketoacidosis may present with acute vision loss, which recovers along with treatment.

Non-surgical treatment of tetanus infection associated with breast cancer skin ulcer: a case report and literature review.

BACKGROUND: Previous studies have reported poor prognosis in cases of tetanus that develops after bacteria enters via breast cancer-related skin ulcers that are not treated with surgical debridement. Herein, we review the literature concerning this presentation and report the first case of complete remission from tetanus without surgical debridement of the skin ulcer. CASE PRESENTATION: An Asian woman aged over 60 years had a history of skin ulcer caused by breast cancer. She was diagnosed with tetanus due to trismus and opisthotonus. Based on the suspicion that the skin ulcer was the portal of entry for tetanus bacteria, we considered several debridement and thoracic surgical options for tetanus treatment. However, debridement was not performed as the surgery was considered high risk and the patient did not consent to it. The patient received treatment with anti-tetanus globulin and metronidazole; sound insulation and shielding were also performed in a dark room. Subsequently, the patient's symptoms improved, and sound insulation and deep sedation management were completed on 19th day of hospitalization. With no symptom recurrence, the patient was discharged on Day 54. To date, over 3 years after treatment, no evidence of tetanus recurrence has been observed. The case was characterized by a lack of autonomic hyperactivity. The tetanus severity was likely representative of the low amount of toxin that the patient was exposed to. CONCLUSION: This case involved moderate severity tetanus originating from a chronic skin ulcer related to breast cancer. The patient survived without undergoing extensive debridement. No evidence of tetanus relapse was observed during the follow-up period, likely due to vaccination that might have restored the patient's active immunity. Debridement is not always necessary for tetanus complicated by breast cancer skin ulcers. Furthermore, appropriate toxoid vaccination is critical for preventing the onset and recurrence of tetanus in these patients.

A System That Uses Advanced Automatic Collision Notification Technology to Dispatch Doctors to Traffic Accidents by Helicopter: The First 4 Cases.

INTRODUCTION: To increase survival rates of patients with severe trauma from road traffic accidents, Japan launched the D-Call Net (DCN) system, which utilizes advanced automatic collision notification technology to dispatch doctors by helicopter. The DCN system began in November 2015 and, as of October 2019, has dispatched doctors 4 times. CASES: Case 1-Canceled because trauma was mild. Case 2-Doctor made contact with 2 patients with moderate trauma 29 minutes earlier than would have occurred conventionally. This was the first case in the world to use automotive engineering data to dispatch a doctor to a patient. Case 3-An accident involving 3 severely injured patients activated DCN, enabling doctor-patient contact 20 minutes earlier than would have been possible conventionally. Case 4-DCN was ineffective. DISCUSSION: According to 2008 data from Chiba Prefecture, in accidents where victims sustain severe trauma, the interval from accident occurrence to hospital arrival was 67 minutes, even when doctors were dispatched by air ambulance (Doctor-Heli [DH]). Use of accident information for faster doctor dispatch effectively improved survival rates. An algorithm was developed to use accident information to assess trauma severity (severity probability). DCN dispatches doctors by using data, including information on accident site and severity probability, which are sent to smartphones of doctors, thereby reducing the interval from accident to DH request by approximately 17 minutes. DCN is the first system in the world to use automotive engineering information for faster doctor dispatch to traffic accident sites. The system is crucial for improving survival rates and mitigating the aftereffects of traffic accidents.

Elderly-onset acute necrotizing encephalopathy mimicking severe heat stroke: a case report and review of the literature.

BACKGROUND: Acute necrotizing encephalopathy (ANE), known as influenza-associated encephalitis, typically affects children. CASE PRESENTATION: A 70-year-old woman was admitted to the hospital with altered consciousness, a high temperature, and severe hypotension. Computed tomography (CT) of the head showed no abnormalities; thus, a diagnosis of suspected severe heat stroke was made. On day 2, repeated head CT revealed bilateral symmetrical lesions to the thalamus, and a rapid influenza antigen test was positive. Based on the CT findings and the medical history of influenza, a differential diagnosis of ANE was made. Subsequently, brain edema spread across the whole brain, and the patient died on day 21. CONCLUSION: In elderly patients, differentiating ANE from severe heat stroke in a high-temperature environment is difficult because of the similarities in clinical symptoms due to multiple organ failure.

Effects of Oral Morphine on Dyspnea in Patients with Cancer: Response Rate, Predictive Factors, and Clinically Meaningful Change (CJLSG1101).

BACKGROUND: Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness. SUBJECTS, MATERIALS, AND METHODS: In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self-assessment questionnaire to determine whether the patients believed oral morphine was effective. RESULTS: Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty-four patients (76.1%) reported that oral morphine was effective on the self-assessment questionnaire. Among the background factors, a high score for "sense of discomfort" on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack-years were associated with greater effectiveness. CONCLUSION: Oral morphine was effective and feasible for treating cancer-related dyspnea. A higher score for "sense of discomfort" on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine. IMPLICATIONS FOR PRACTICE: This study demonstrated that oral morphine was effective in alleviating cancer-related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for "sense of discomfort" on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in "morphine-ineffective" patients.

Effectiveness of new sedation and rehabilitation methods for critically ill patients receiving mechanical ventilation.

[Purpose] The purpose of this study was to investigate the effects of new sedation management methods and cooperation between nurses and physical therapists on the duration of mechanical ventilation and hospitalization. [Subjects and Methods] Patients who had been treated at the study hospital 2 years before and after the implementation of the new methods were analyzed retrospectively and classified into a "control group" and an "intervention group", respectively. Both groups were analyzed and subsequently compared regarding the effects of the new sedation and cooperative rehabilitation. [Results] A total of 70 patients met the inclusion criteria and were divided evenly into the two groups. No significant differences were found between the groups in age, APACHE II score, or duration of stay in hospital. On the other hand, significant decreases were seen in the duration of sedation and intubation, mechanical ventilation, and stay in the emergency ward, as well as time until standing. In addition, after intervention, three patients undergoing ventilator treatment were able to be ambulated. [Conclusion] These results suggest that the new sedation and cooperative rehabilitation methods for critically ill patients were effective in the early stage of treatment and shortened the duration of stay in the ward.

Effective Treatment with Intravitreal Injection of Bevacizumab for Exudative Retinal Detachment Secondary to Choroidal Metastasis of Non-Small Cell Lung Carcinoma.

BACKGROUND: Visual disturbance caused by cancer metastasis from other organs is one of the largest challenges to cancer patients' quality of life (QOL). Lung cancer is the most frequent primary site of choroidal metastasis in men, but improvement of visual disturbance has not always been emphasized in lung cancers. Recently intravitreal bevacizumab is a newer modality being tried for local control of choroidal metastases. CASE REPORT: A 68-year-old man was admitted the hospital with complaint of visual disturbance in his left eye. He was diagnosed with lung adenocarcinoma cT2N0M1b (OSS, OTH) stage IV. The ophthalmologic evaluation showed exudative fluid, which caused retinal detachment under the retina. Fluorescence angiography showed granular hyperfluorescence with leakage consistent with a tumor. He received radiotherapy for bone metastasis and systematic chemotherapy with carboplatin, pemetrexed, and bevacizumab, as well as intravitreal injection of bevacizumab 1.25 mg to improve the visual disturbance. His visual symptom and retinal detachment improved until he died. An autopsy revealed that the metastatic lesion in his left eye was totally cured macroscopically and microscopically. CONCLUSIONS: We report a case of exudative retinal detachment secondary to a metastatic choroidal tumor from lung adenocarcinoma, which was treated with chemotherapy and intravitreal injection of bevacizumab. Although he finally died of lung cancer, he maintained his visual QOL and autopsy revealed complete cure of the choroidal metastasis.

Carcinoma of unknown primary site treated with Carboplatin + Paclitaxel + bevacizumab + erlotinib and its maintenance chemotherapy.

About 3% of all cancer patients suffer from carcinoma of unknown primary site (CUP). In spite of its rarity, we will encounter them. While CUPs manifest a wide variety of clinical presentations, they have often resulted in poor prognosis. Although platinum/taxane combination chemotherapy, e.g. carboplatin (CBDCA) + paclitaxel (PTX) is widely used for patients suffering from CUP, the response rate is only about 30-40% and the median overall survival (OS) is only 9 months, which means that improvement is needed. Among the new regimens, the combination of CBDCA, PTX, bevacizumab (BEV) and erlotinib is thought to be highly promising. Herein, we report a case with CUP treated with this regimen and his maintenance therapy. Our patient was a 75-year-old man who was admitted with a left neck lump. CT revealed systemic massive lymphadenopathy. In spite of various investigations for primary origin, he was diagnosed with CUP and treated with CBDCA + PTX + BEV + erlotinib (AUC 6 + 175 mg/m(2) + 15 mg/kg + 150 mg). Since the evaluation of the efficacy indicated partial response, maintenance chemotherapy (BEV and erlotinib) was performed. Chemotherapy was continued for 9 months until the patient was in a progressive disease state with meningeal dissemination. He died 12 months after the initiation of chemotherapy, which is a longer period than the previously reported OS. Of note, according to our case, CBDCA + PTX + BEV + erlotinib and its maintenance chemotherapy are feasible and well tolerated for CUP.

Tracheal adenoid cystic carcinoma treated by repeated bronchoscopic argon plasma coagulation as a palliative therapy.

Primary tracheal tumors are uncommon, making up only 0.2% of all respiratory malignancies. Adenoid cystic carcinoma (ACC) is the most common tumor, accounting for about 30% of primary tracheal tumors. It is often difficult to manage these tumors surgically, due to its expansion and submucosal invasion, and furthermore, due to the patient's condition. Thus, it is essential to perform palliative treatment in order to maintain the airway through and to control the progress. Herein, we report a case of ACC treated by repeated bronchoscopic argon plasma coagulation (APC) as palliative therapy.A 71-year-old Japanese male was referred to our hospital's emergency department for dyspnea. Bronchoscopic examination revealed expanded intraluminal obstructive bronchial tumors from the left bronchus to right. The patient had undergone bronchoscopic APC treatment several times. The obstruction was improved, and no worsening was seen for 26 months. Repeated bronchoscopic APC as a palliative therapy is promising and useful therapy without heavy adverse reactions to control the tumor growth.

Granulocyte colony-stimulating factor-producing carcinoma of unknown primary site.

Granulocyte colony-stimulating factor (G-CSF)-producing nonhematopoietic malignancies have been reported in various organs and are associated with a poor clinical outcome. Moreover, carcinoma of unknown primary site (CUP) is an uncommon malignancy that occurs in about 2-6% of cancer patients. CUP also has a poor prognosis due to its missing profile. Since both G-CSF-producing carcinoma and CUP are rare, G-CSF-producing CUP (GCSF-CUP) is considered to have an even poorer prognosis and is seldom encountered. Herein, we report the case of a GCSF-CUP patient. A 75-year-old man was admitted to our hospital complaining of cervical lymphadenopathy. Multiple bulky lymph nodes without a primary site were revealed by image analysis. His complete blood count showed leukocytosis, and his blood chemistry panel indicated highly elevated levels of G-CSF. Although the patient was treated with combination chemotherapy of carboplatin, paclitaxel, bevacizumab and erlotinib, he died of intestinal perforation due to tumor invasion 23 days after the start of the therapy. An autopsy confirmed that the tumor was positive for anti-G-CSF antibody, but the primary site was still not detected.

Fulminant hepatic failure and hepatomegaly caused by diffuse liver metastases from small cell lung carcinoma: 2 autopsy cases.

Fulminant hepatic failure (FHF) is defined as a liver disease that causes encephalopathy within 8 weeks of onset in the absence of pre-existing liver disease. Although liver metastases are commonly found in cancer patients, FHF secondary to diffuse liver infiltration is rare. Here, we report the rare autopsy cases of patients with small cell lung carcinoma (SCLC) and secondary FHF. These patients presented with remarkable hepatomegaly and a near complete replacement of the liver parenchyma with metastatic tumor. Neoplastic involvement of the liver should be considered in the differential diagnosis of FHF.

CBDCA + Pemetrexed + Bevacizumab and Its Maintenance Chemotherapy in a Case of Solitary Breast Metastasis from a Lung Adenocarcinoma Resistant to Gefitinib.

Based on the AVAPERL trial (36th ESMO 2011), CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy with pemetrexed + bevacizumab is a new promising regimen for the treatment of advanced non-small-cell lung adenocarcinoma. Herein, we report the rare case of a patient with solitary breast metastasis from a lung adenocarcinoma, which was effectively treated using CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy. A 57-year-old female was admitted to the hospital due to pleural effusion and cardiac tamponade caused by a lung adenocarcinoma possessing a mutation of the epidermal growth factor receptor (EGFR) gene (deletion of exon 19). The patient was treated by first-line chemotherapy (gefitinib 250 mg/body/day) which resulted in complete response. After 12 months, carcinoembryonic antigen was gradually increasing and she complained of a right breast mass. With a core-needle biopsy, the breast tumor was pathologically diagnosed as recurrence and solitary metastasis of a lung adenocarcinoma. Further study of the second mutation of EGFR revealed a T790M mutation. The patient was treated by second-line chemotherapy [CBDCA + pemetrexed + bevacizumab (AUC 6 + 500 mg/m(2) + 15 mg/kg)] and its maintenance chemotherapy (pemetrexed + bevacizumab). The cases of patients with breast metastasis from other organs are very rare. Immunohistopathological analysis is very useful to diagnose whether the malignancy is primary or not. In the case of a breast tumor with present or previous malignancy, a metastatic breast tumor should be considered. Furthermore, the biopsy of the breast metastasis also revealed the second mutation of resistance to gefitinib, T790M. Of note, according to our case, CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy is feasible and well tolerated for breast metastasis from a lung adenocarcinoma which is resistant to gefitinib and possesses the T790M mutation in the EGFR gene.

Successful treatment of severe accidental hypothermia with cardiac arrest for a long time using cardiopulmonary bypass - report of a case.

Accidental hypothermia is defined as an unintentional decrease in body temperature to below 35°C, and cases in which temperatures drop below 28°C are considered severe and have a high mortality rate. This study presents the case of a 57-year-old man discovered drifting at sea who was admitted to our hospital suffering from cardiac arrest. Upon admittance, an electrocardiogram indicated asystole, and the patient's temperature was 22°C. Thirty minutes of standard CPR and external rewarming were ineffective in raising his temperature. However, although he had been in cardiac arrest for nearly 2 h, it was decided to continue resuscitation, and a cardiopulmonary bypass (CPB) was initiated. CPB was successful in gradually rewarming the patient and restoring spontaneous circulation. After approximately 1 month of rehabilitation, the patient was subsequently discharged, displaying no neurological deficits. The successful recovery in this case suggests that CPB can be considered a useful way to treat severe hypothermia, particularly in those suffering from cardiac arrest.

Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells.

BACKGROUND: The role of ZEB1, a master epithelial-to-mesenchymal transition gene, in malignant pleural mesothelioma (MPM) is unclear. METHODS: The expression of ZEB1, E-cadherin, vimentin, and epithelial cell adhesion molecule (EpCAM) in 18 MPM cell lines and a normal pleural mesothelial cell line MeT-5A was determined by quantitative real-time polymerase chain reaction and Western blot testing. RNA interference-mediated transient and/or stable knockdown of ZEB1 and EpCAM was performed. Microarray expression analysis was performed with a TORAY-3D gene chip. Growth was evaluated by colorimetric proliferation and colony formation assays. Luciferase reporter assay was performed to access the effects of ZEB1 knockdown on EpCAM promoter activity. RESULTS: Most MPM cell lines exhibited mesenchymal phenotype and expressed ZEB1. Transient ZEB1 knockdown suppressed growth in all four cell lines studied (ACC-MESO-1, H2052, Y-MESO-8A, Y-MESO-29) while stable ZEB1 knockdown suppressed growth only in Y-MESO-29. Genome-wide gene expression analysis revealed that EpCAM was the most prominently up-regulated gene by both transient and stable ZEB1 knockdown in ACC-MESO-1, with more marked up-regulation in stable knockdown. We hypothesized that EpCAM up-regulation counteracts the stable ZEB1 knockdown-induced growth inhibition in ACC-MESO-1. Transient EpCAM knockdown suppressed growth dramatically in ACC-MESO-1 cells expressing shZEB1 but only modestly in those expressing shGFP, supporting our hypothesis. Luciferase reporter assay showed that ZEB1 knockdown resulted in increased EpCAM promoter activity. EpCAM was also up-regulated in Y-MESO-29 expressing shZEB1, but this EpCAM up-regulation did not counteract ZEB1knockdown-induced growth suppression, suggesting that the counteracting effects of EpCAM may be cellular context dependent. CONCLUSIONS: RNA interference-mediated ZEB1 knockdown may be a promising therapeutic strategy for MPM, but one has to consider the possibility of diminished growth inhibitory effects of long-term ZEB1 knockdown, possibly as a result of EpCAM up-regulation and/or other gene expression changes resulting from ZEB1 knockdown.

Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells.

Epithelial-mesenchymal transition (EMT), which involves the persistent loss of epithelial markers and expression of mesenchymal markers, is assumed to have a critical role in not only tissue development during embryogenesis but also central mechanisms that enhance the invasive and metastatic ability of cancer cells. Twist has been identified to play an essential role in EMT-mediated tumor invasion and metastasis. Although recent studies suggest that twist expression levels in tissue specimens of lung cancer might be associated with prognosis, the expression of twist in lung cancer cells itself and its effect have not been fully evaluated. Here, we evaluated twist expression and its effect on phenotype alteration in lung cancer cell lines. Twist expression varied among human lung cancer cell lines. The lung cancer cell lines with high twist expression also tended to show a high vimentin/E-cadherin ratio, which was supported by a migration assay, in which high twist expression gave rise to high cell motility. Furthermore, in comparison to control cells, the lung cancer cells with ectopic expression of twist showed a significant phenotype alteration through EMT and an increasing ability to migrate in vitro, in part, due to a tenfold increase in matrix metalloproteinases activity and almost a 60% increase in modulation of focal adhesion kinase activity, although a contribution of microRNA appeared unlikely in our study. Our present analysis of twist expression in lung cancer provide clues to comprehensive understanding of the mechanisms, by which metastasis often develops in lung cancer.

Pivotal role of epithelial cell adhesion molecule in the survival of lung cancer cells.

Epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of human cancers including lung cancer, and its contribution to increased proliferation through upregulation of cell cycle accelerators such as cyclins A and E has been well established in breast and gastric cancers. Nevertheless, very little is known about its role in supporting the survival of cancer cells. In addition, the functional role of EpCAM in the pathogenesis of lung cancer remains to be explored. In this study, we show that RNAi-mediated knockdown of EpCAM suppresses proliferation and clonogenic growth of three EpCAM-expressing lung cancer cell lines (H3255, H358, and HCC827), but does not induce cell cycle arrest in any of these. In addition, EpCAM knockdown inhibits invasion in the highly invasive H358 but not in less invasive H3255 cells in a Transwell assay. Of note, the EpCAM knockdown induces massive apoptosis in the three cell lines as well as in another EpCAM-expressing lung cancer cell line, HCC2279, but to a much lesser extent in a cdk4/hTERT immortalized normal human bronchial epithelial cell line, HBEC4, suggesting that EpCAM could be a therapeutic target for lung cancer. Finally, EpCAM knockdown partially restores contact inhibition in HCC827, in association with p27(Kip1) upregulation. These results indicate that EpCAM could contribute substantially to the pathogenesis of lung cancer, especially cancer cell survival, and suggest that EpCAM targeted therapy for lung cancer may have potential.