Successful re-administration of Pazopanib in a patient with metastatic renal cell carcinoma and a history of Pazopanib-induced nephrotic syndrome: a case report.

BACKGROUND: Drug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored. CASE PRESENTATION: A 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence. CONCLUSION: Pazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.

Long-Term Outcomes after Imatinib Mesylate Discontinuation in Chronic Myeloid Leukemia Patients with Undetectable Minimal Residual Disease.

BACKGROUND: Imatinib mesylate (IM) discontinuation is under active investigation in chronic myeloid leukemia-chronic phase (CML-CP) patients with undetectable minimal residual disease (UMRD). However, limited data exist on the long-term outcomes following IM discontinuation in patients treated with frontline IM therapy. METHODS: We consecutively enrolled patients with CML-CP who discontinued IM after achieving UMRD for ≥12 months between June 2009 and January 2013. RESULTS: Nineteen patients (8 male, 11 female) were included. After IM discontinuation, 14 patients (74%) lost UMRD after a median of 4.0 months. Of the 14 patients with molecular relapses, 12 (86%) relapsed within the first 9 months after IM discontinuation and 2 (14%) relapsed at 20.5 and 22.8 months, respectively. No molecular relapse was observed after 2 years of IM discontinuation. With a median follow-up of 58.1 months (range 23.0-66.5), the estimated UMRD persistence rate at 5 years was 23.7%. IM was readministered in all patients with molecular relapse, and 12 patients (86%) reachieved UMRD at a median of 5.3 months. A high-risk Sokal score, delayed UMRD achievement and short-term IM therapy were significantly associated with molecular relapse. CONCLUSION: These findings suggest that IM discontinuation in patients who achieved UMRD after frontline IM therapy resulted in favorable long-term outcomes in terms of safety and feasibility.

Glutamine protects mice from acute graft-versus-host disease (aGVHD).

Despite current immunosuppressive therapies, acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, therapeutic effects of intraperitoneal glutamine (Gln) administration (1g/kg/day) in a mouse aGVHD model were evaluated. Gln administration significantly inhibited the GVHD-induced inflammation and tissue injury in the intestine, liver, skin and spleen. Gln therapy improved the score of clinical evidence of aGVHD and prolonged the median survival of aGVHD mice. Gln administration in aGVHD mice increased the fraction of Foxp3+/CD4+/CD25+ cells in the blood measured on day 7, and decreased the serum levels of tumor necrosis factor-α measured on days 7, 14 and 21 after aGVHD induction. These results demonstrated that Gln administration may be useful in protecting the host from aGVHD.

Lymphocyte-mediated macrophage apoptosis during IL-12 stimulation.

In contrast to the well known immunostimulatory roles of IL-12, little has been known about its immunosuppressive roles. In the present study, IL-12-activated lymphocyte-mediated macrophage apoptosis was investigated by employing murine lymphocyte/macrophage cocultures. IL-12-activated lymphocytes and their culture supernatants induced an inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis in macrophages. The NO synthesis was markedly inhibited by blocking antibodies to IFN-γ and TNF-α, suggesting the key role of these lymphocyte cytokines in mediating the NO synthesis. The endogenously produced NO inhibited macrophage proliferation, and induced apoptosis in concordance with the accumulation of p53, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and DR5, and the activation of caspase-3, processes that were inhibited by N(G)-monomethyl-l-arginine, aminoguanidine (NO synthase inhibitors) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (an NO scavenger). These results were further supported by the findings obtained from the experiments employing IFN-γ-knockout and iNOS-knockout mice. Our study demonstrated a novel, non-contact-dependent mechanism of macrophage suppression by IL-12-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages due to endogenous NO synthesis induced by cytokines secreted from IL-12-activated lymphocytes.

Mode of primary cancer detection as an indicator of screening practice for second primary cancer in cancer survivors: a nationwide survey in Korea.

BACKGROUND: While knowledge and risk perception have been associated with screening for second primary cancer (SPC), there are no clinically useful indicators to identify who is at risk of not being properly screened for SPC. We investigated whether the mode of primary cancer detection (i.e. screen-detected vs. non-screen-detected) is associated with subsequent completion of all appropriate SPC screening in cancer survivors. METHODS: Data were collected from cancer patients treated at the National Cancer Center and nine regional cancer centers across Korea. A total of 512 cancer survivors older than 40, time since diagnosis more than 2 years, and whose first primary cancer was not advanced or metastasized were selected. Multivariate logistic regression was used to examine factors, including mode of primary cancer detection, associated with completion of all appropriate SPC screening according to national cancer screening guidelines. RESULTS: Being screen-detected for their first primary cancer was found to be significantly associated with completion of all appropriate SPC screening (adjusted odds ratio, 2.13; 95% confidence interval, 1.36-3.33), after controlling for demographic and clinical variables. Screen-detected cancer survivors were significantly more likely to have higher household income, have other comorbidities, and be within 5 years since diagnosis. CONCLUSIONS: The mode of primary cancer detection, a readily available clinical information, can be used as an indicator for screening practice for SPC in cancer survivors. Education about the importance of SPC screening will be helpful particularly for cancer survivors whose primary cancer was not screen-detected.

Usefulness of F-18 FDG PET/CT in subcutaneous panniculitis-like T cell lymphoma: disease extent and treatment response evaluation.

BACKGROUND.: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous lymphomas, accounting for less than 1% of cases of non-Hodgkin's lymphoma. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron-emission tomography/computed tomography (PET/CT) findings of SPTCL before and after treatment were rarely reported. CASE REPORT.: We report a case of SPTCL in which F-18 FDG PET/CT showed increased FDG accumulations in numerous subcutaneous nodules without extracutaneous disease. Contrast-enhanced CT during F-18 FDG PET/CT showed multiple minimally enhancing nodules with an infiltrative pattern in the subcutaneous layer throughout the body. Follow-up F-18 FDG PET/CT after three cycles of CHOP chemotherapy showed a complete metabolic remission of the lesions. CONCLUSIONS.: F-18 FDG PET/CT is suggested to be useful in assessing the disease activity, extent and treatment response in SPTCL.

The Positive Effects of Cancer Survivor Support Service on Distress in South Korea: A Nationwide Prospective Study.

BACKGROUND AND AIM: Cancer survivors are gradually increasing, however, they suffer from various difficulties. We aimed to investigate the characteristics of cancer survivors and the effects of the services of the Korean Cancer Survivorship Center Pilot Project launched by the South Korean government on distress. METHODS: A prospective observational cohort study was performed on cancer survivors who completed primary treatment. Cancer survivors' distress and symptoms such as fatigue, pain, depressive mood, anxiety, and insomnia were evaluated by well-trained nurses. Regarding their needs, medical and psychosocial support services were provided. RESULTS: This study included 1,921 cancer survivors, with a mean age of 57.3 years (68.7% females). Breast cancer was most common, followed by stomach and colorectal cancer. Psychosocial and medical support decreased the percentage of the high-distress group from 50.9 to 30.5% and decreased the percentage of cancer survivors with high scores in fatigue, pain, anxiety, depressive mood, and insomnia. The independent predictors of a low distress level after the use of the services were older age, the relief of fatigue, pain, and insomnia. CONCLUSION: This study showed that psychosocial and medical support is associated with the lower distress and physical and mental symptoms of cancer survivors. Psychosocial and medical support could contribute to distress relief in cancer survivors. Further management strategies for fatigue, pain and insomnia are required.

The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy.

The prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin-embedded tumor tissues. The median age was 65 years (range, 44-90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N-positive). Thirty-five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16-positive). Thirty-nine (83.0%) patients were positive for p16. After median follow-up of 51.7 months (range, 5.1-136.0 months), HPV16-positive group had significantly better 4-year progression-free survival (PFS, 63.1% vs. 15.6%, p < 0.001) and overall survival (84.6% vs. 39.8%, p = 0.008) than HPV genotype 16 negative (HPV16-negative) group. Patients with p16-positive tumor also had a better 4-year PFS (52.5% vs. 25.0%, p = 0.014) than those with p16-negative tumor. In multivariate analysis for PFS, N-positive and HPV16-negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco-regional failure was statistically superior in HPV16-positive over HPV16-negative groups (p = 0.006), but time to systemic failure was not different (p = 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted.

Sunitinib-induced hyperammonemic encephalopathy in gastrointestinal stromal tumors.

OBJECTIVE: To report 2 cases of hyperammonemic encephalopathy induced by sunitinib in patients with metastatic gastrointestinal stromal tumor (GIST). CASE SUMMARY: A 58-year-old man with imatinib-resistant metastatic GIST presented to the emergency department with confusion that developed 17 days after the initiation of sunitinib 50 mg/day. His serum ammonia level was markedly elevated (210 µg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. His neurologic status normalized within 24 hours and his serum ammonia level decreased to 64 µg/dL. A 68-year-old woman with imatinib-resistant metastatic GIST was admitted into the emergency department with confusion and irritability that developed 10 days after the start of sunitinib therapy. Her serum ammonia level was markedly elevated (389 µg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. Within 24 hours, her mental status was improved and her serum ammonia level was decreased to 116 µg/dL. Sunitinib was reintroduced, and the same symptoms occurred after day 7 of administration. Sunitinib was not prescribed afterward and the woman did not experience any further encephalopathic symptoms. DISCUSSION: Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases such as stem cell factor receptor, vascular endothelial growth factor, and platelet-derived growth factor. It is used as second-line therapy for patients with imatinib-resistant GIST. Hyperammonemic encephalopathy is an uncommon fatal complication of chemotherapy. According to the Naranjo probability scale, sunitinib was a probable cause of hyperammonemic encephalopathy in the patients described here. Although the mechanism of hyperammonemia is unclear, hyperammonemic encephalopathy might be caused by a vascular disorder related to the antiangiogenic properties of sunitinib, and it has ethnic differences associated with genetic polymorphisms. CONCLUSIONS: Sunitinib may induce hyperammonemic encephalopathy in some patients. Although further studies are warranted, clinicians should be aware of this severe adverse event when using sunitinib for treatment of GIST.

Foreign body removal using flexible bronchoscopy in terminal cancer: A case report.

RATIONALE: Pulmonary foreign body aspiration is a serious medical problem. The risk of foreign body aspiration into the airways increases considerably in patients with end stage cancer with reduced consciousness and impaired airway reflexes. However, few studies have reported on foreign body aspiration in the airways in patients with terminal cancer or receiving end-of-life care. Herein, we report the use of flexible bronchoscopy in patients with end-of-life cancer with pulmonary aspiration. PATIENT CONCERNS: A 71-year-old man with neuroendocrine carcinoma was admitted to a palliative care unit for end-of-life care. He accidentally aspirated implant teeth into the airway with decreased consciousness and death rattle. DIAGNOSIS: On chest x-ray, the foreign material was observed in the left main bronchus. INTERVENTIONS: Despite concerns regarding the use of bronchoscopy given the deterioration of the overall organ function, flexible bronchoscopy was performed. OUTCOMES: Eventually, the foreign body was removed using a basket in the nasal cavity without major complications. The patient died comfortably after 7 days. LESSONS: The possibility of patients in the palliative care unit with reduced consciousness and death rattle to aspirate foreign bodies into the airways must be carefully considered. Flexible bronchoscopy should be considered to carefully remove aspirated foreign bodies in the airway without any side effects, even in patients with terminal cancer or receiving end-of-life care.

The dosing frequency of sustained-release opioids and the prevalence of end-of-dose failure in cancer pain control: a Korean multicenter study.

BACKGROUND: End-of-dose failure is commonly observed as therapeutic levels of sustained-release opioids fall. However, little is known about using these medications for cancer pain control. To determine the dosing frequency of sustained-release opioids (morphine, oxycodone, and transdermal fentanyl) and the prevalence of end-of-dose failure in clinical practice, a patient-reported survey was performed. METHODS: A multicenter survey was conducted in 56 hospitals in Korea between June and November 2008. RESULTS: The study enrolled 1,097 cancer outpatients who were prescribed oral sustained-release opioids (morphine or oxycodone) or transdermal fentanyl. Of the oral sustained-release opioid patients, 67.0% took oral sustained-release oral opioids twice daily, while 26.2% took them more than twice daily. Of the transdermal fentanyl patients, 88.8% wore the patch for 72 h. Of the enrolled patients, 48.3% experienced worsening pain just before the next sustained-release opioid dose, and 36.8% of these patients took medication earlier than the prescribed dosing schedule. Patients felt that oral sustained-release opioids gave adequate pain control lasting an average of 9.6 h, versus an average of 62.9 h for transdermal fentanyl. CONCLUSION: This survey demonstrated that sustained-release opioids are used by patients in a manner that is inconsistent with standard recommendations. End-of-dose failure is suggested to explain increased dosing frequency, and patients reported that adequate pain relief lasted for less time than was stated in the manufacturers' prescription recommendation.

Quadruple primary malignancies of liver, bladder, lung and stomach in one patient.

Multiple primary malignancies are defined as two or more malignancies in an individual without any relationship between the tumors. Because of advances in the early detection, treatment, and supportive care for cancer, the number of cancer survivors has been gradually increasing, and this has led to an increase in the possible occurrence of subsequent malignancies. Recently, there have been reports that smoking is associated with a specific genetic mutation (the tumor suppressor gene TP53), and this genetic predisposition may be related to the development of multiple primary malignancies. Here we present a rare case of quadruple primary malignancies of the liver, bladder, lung and stomach, some of which possibly linked to smoking-related TP53 mutation. Because of its extreme rarity and the clear relationship between multiple primary malignancies and smoking-related TP53 mutation, we report this case along with a review of the relevant literature.

Primary hepatoid carcinoma of the ovary: A case report and review of the literature.

INTRODUCTION: Hepatoid carcinoma of the ovary (HCO) is a rare disease that originates from the ovarian surface epithelium. It is histologically characterized as hepatocellular carcinoma (HCC) with a hepatocyte-rich granular cytoplasm. PATIENT CONCERNS: A 65-year-old female patient was admitted with complaints of indigestion, abdominal bloating, and pain. DIAGNOSIS: The patient showed an elevated level of serum alpha-fetoprotein (AFP) with abdominal bloating and pain. After surgery and histopathology analysis, she was finally diagnosed with HCO, Figo stage IC. INTERVENTIONS: After cytoreductive surgery, she underwent adjuvant chemotherapy with carboplatin and paclitaxel. Although the disease was diagnosed at an early stage, it recurred 6 months after completion of adjuvant chemotherapy. Elevation of serum AFP level and removal of a mass from the lumbar vertebra confirmed the recurrence of this disease. Subsequently, the patient underwent radiation therapy and palliative chemotherapy. OUTCOMES: She died 31 months after the diagnosis due to disease progression. CONCLUSION: The aggressive nature of HCO was clearly observed in this case despite early diagnosis and treatment. Further studies are needed to understand the proper treatment and prognostic factors of HCO.

Primary transitional cell carcinoma of the fallopian tube: A case report and literature review.

INTRODUCTION: Primary transitional cell carcinoma (TCC) of the fallopian tube is an extremely rare tumor. PATIENT CONCERNS: A 79-year-old woman presenting with vaginal discharge. DIAGNOSIS: Pelvic magnetic resonance imaging revealed a predominantly solid mass with a lobulated contour, measuring 5.5 cm × 4.6 cm, in the left ovary. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pathological analysis revealed a high-grade TCC, measuring 7.5 cm × 4 cm, in the left fallopian tube (International Federation of Gynecology and Obstetrics stage IIB). INTERVENTION: Forty-three months postoperation, recurrence was diagnosed as peritoneal metastasis. The patient underwent 6 cycles of palliative chemotherapy consisting of cisplatin and gemcitabine, the recommended regimen for TCC of the urinary tract. OUTCOME: The patient has survived for 27 months without recurrence after palliative chemotherapy, 76 months after diagnosis. CONCLUSION: It is rare that primary TCC of the fallopian tube responds to a urinary tract treatment regimen for TCC, even when followed up for an extended period. More research is warranted to determine which treatment regimen will benefit patients the most.

Cytokines secreted by IL-2-activated lymphocytes induce endogenous nitric oxide synthesis and apoptosis in macrophages.

IL-2-activated killer (LAK) cells secrete inflammatory cytokines such as IFN-gamma and TNF-alpha, which can induce NO synthesis (NOS). In this study, we investigated IL-2-activated lymphocyte-mediated macrophage apoptosis via NOS. LAK cells and their culture supernatants induced NOS in murine macrophages. NOS was markedly inhibited by blocking antibodies to IFN-gamma and TNF-alpha, suggesting the key role of these lymphocyte cytokines in mediating NOS. Endogenous NO production inhibited macrophage proliferation and induced apoptosis in concordance with p53 accumulation and caspase-3 activation, processes that were inhibited by N(G)-monomethyl-l-arginine (a NOS inhibitor) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (a NO scavenger). Our study demonstrated a novel, noncontact-dependent mechanism of macrophage suppression by IL-2-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages as a result of endogenous NOS induced by cytokines secreted from IL-2-activated lymphocytes.

Tumor necrosis factor-alpha enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway.

The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-alpha, interleukin-4, tumor necrosis factor-alpha (TNF-alpha), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-alpha with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-alpha enhanced CD11b expression and percent of cell population in the G1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-alpha in combination with DMSO on HL-60 differentiation, but the inhibition NF-kappaB pathway did not. These results suggest that TNF-alpha synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway.

Lithotomy position-related rhabdomyolysis of gluteus maximus muscles demonstrated by bone scintigraphy.

Major urologic surgery performed in the lithotomy position sometimes results in the serious complications of rhabdomyolysis and acute renal failure. A 54-year-old man with prostate cancer (weight, 84 kg; height, 171 cm; body mass index, 28.7) underwent radical perineal prostatectomy in the lithotomy position for 7 hours. On the first postoperative day, the patient complained of numbness and pain of both thighs with oliguria. Serum creatinine kinase and myoglobin levels were elevated. Bone scintigraphy on the second day, which was confirmed by MRI, showed extraosseous increased activity in gluteus maximus muscle regions compatible with rhabdomyolysis.

Change in patients' satisfaction with pain control after using the Korean cancer pain assessment tool in Korea.

Appropriate pain assessment is very important for managing cancer pain. This study was designed to evaluate the utility of the Korean Cancer Pain Assessment Tool (KCPAT) by assessing changes in the management of cancer pain. The changes in pain intensity, the pattern of drug prescriptions, and the patients' satisfaction with pain control were analyzed after using the KCPAT. The results indicated that pain medicine prescriptions were changed in 194 (51.5%) cases after using the KCPAT, and 69.5% of these changes were affected by the KCPAT. After using the KCPAT, pain intensity as assessed by the Visual Analogue Scale (VAS, 0-10cm) decreased (4.31+/-2.35 vs. 3.60+/-2.45, P<0.0001), and the presence of associated symptoms and psychosocial items was significantly reduced. The patients' satisfaction with pain control was improved. Forty-four physicians (89.8%) thought that the KCPAT was useful. The KCPAT improved patients' satisfaction with pain control and was a useful tool for evaluating and managing cancer pain.

Expected and perceived efficacy of complementary and alternative medicine: A comparison views of patients with cancer and oncologists.

BACKGROUND & AIMS: This study sought to identify discrepancies between the expectations of patients with cancer and oncologists regarding the efficacy of complementary and alternative medicines (CAMs), and to determine how patients evaluate CAM efficacy after its use. METHODS: Data from the Cancer Patient Experience Study, a nationwide survey, were used. Seven subdivided efficacy domains were included in the survey. An oncologist-patient matching analysis was done to assess the concordance of CAM efficacies between oncologists and patients with cancer. In addition, the patients' expectations of CAM efficacies were compared before and after use. RESULTS: Out of 719 participants, 201 patients with cancer (28.0%) reported using CAMs. The patients with cancer generally tended to be more positive about CAM efficacies than the oncologists. The largest discrepancy in efficacy perception was found in the efficacy domain of survival benefit, which included complete disease remission and prolonged survival. Many patients reported that they did not experience the positive efficacy they had anticipated before use. However, a substantial proportion of patients indicated that CAMs were as effective as they had expected, even though there is little evidence supporting the CAM efficacies. CONCLUSIONS: There was a marked discrepancy and a lack of concordance in expectations of CAM efficacy between patients with cancer and oncologists. Better communication between the patients and oncologists regarding CAM efficacy would be needed to make the patients to have shared expectations, and to reduce unnecessary CAM use.