Venous thromboembolism in hospitalized patients receiving chemotherapy for malignancies at Japanese community hospital: prospective observational study.

BACKGROUND: Although Asian population was recognized to have a lower risk of venous thromboembolism (VTE), its increasing prevalence and incidence remain unclear in patients with malignancies. We attempted to predict VTE development using activation markers of coagulation and fibrinolysis. METHODS: We enrolled patients with malignancy admitted to Tonan Hospital between April and December 2014 to receive a new-for-them chemotherapy regimen. All patients were examined for VTE by computed tomography and whole-leg compression ultrasonography before chemotherapy and three months later. We also examined plasma levels of thrombin-antithrombin complex (TAT) and plasmin α2-plasmin inhibitor complex (PIC) before chemotherapy. The cut off values of TAT and PIC were set at 2.1 ng/mL and 1.8 µg/mL, respectively. RESULTS: Of 97 patients, the majority (67%) had distant metastases. The most common malignancies were colorectal (26%), breast (23%), and stomach (19%) cancer. VTE was detected in 29 patients (31%); all were asymptomatic. VTE was newly developed in 12 patients in the three-month observation period, which means the incidence was 49 per 1000 person-years. Non-increased PIC with increased TAT was the only significant risk factor for both VTE prevalence and incidence in multivariate analysis, and the odds ratios were 3.0 (95% confidence interval, 1.1-8.2; P = 0.034) and 9.4 (95% confidence interval, 1.7-51.9; P = 0.011), respectively. CONCLUSIONS: The prevalence and incidence of VTE were high in hospitalized Japanese patients receiving chemotherapy for malignancies. Non-increased PIC with increased levels of TAT may be an independent risk factor for VTE development.

High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients.

BACKGROUND: Trastuzumab following anthracycline causes cardiotoxicity in up to 28% of patients. Although the cardiotoxicity is often irreversible once cardiac dysfunction is detected, the early predictor has not been established yet. METHODS: We prospectively observed breast cancer patients treated with anthracycline or trastuzumab at Tonan Hospital. All patients underwent echocardiography and blood sampling at baseline, and every three months during chemotherapy. Cardiotoxicity was defined as a decline in left ventricular ejection fraction >10% points. RESULTS: Of 40 patients, 34 patients (85%) were treated with anthracycline (epirubicin), 18 (45%) with trastuzumab, and 12 (30%) with both agents. Cardiotoxicity was observed in four patients (10%), who were all treated with both agents. The absolute levels of high-sensitive troponin T (hs-TnT) were increased in all four patients with cardiotoxicity, and all the highest points were observed before or at the time of detection of cardiotoxicity. The highest level of hs-TnT was not significantly different in patients with and without cardiotoxicity. "Hs-TnT increment from baseline to the highest value" and "hs-TnT integration value above baseline" were significantly greater in patients with cardiotoxicity (0.039 vs. 0.007 ng/mL, P = 0.046, 0.113 vs. 0.022 ng months/mL, P = 0.013, respectively). The integration value had 100% sensitivity and specificity with a cutoff level at 0.070 ng months/mL. CONCLUSIONS: Hs-TnT assay may be able to predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients, and the hs-TnT increment or hs-TnT integration value above baseline was more reliable than the absolute value.

Shoulder Pain after Fall, Septic Shock, and Pyomyositis Associated with Breast Cancer Chemotherapy and Lymphedema.

BACKGROUND: As a symptom of pyomyositis, sepsis usually follows local inflammation signs. Here, we report pyomyositis with lymphedema of upper extremity in which septic shock and poor local findings initially presented during chemotherapy for breast cancer. CASE REPORT: An 80-year-old woman presented with chronic right shoulder pain during chemotherapy for the recurrent disease. She had a history of postmastectomy lymphedema, diabetes mellitus, and repeated hyaluronic acid injections to the shoulder joint. The pain suddenly worsened with septic shock and no apparent local signs. Magnetic resonance imaging revealed myonecrosis, and no pus was yielded by ultrasound-guided needle aspiration. After 2 weeks of recovery by conservative medical management, surgical drainage was performed. Late formulated massive intramuscular pus showed severe neutrophil infiltration and myonecrosis. CONCLUSION: Pyomyositis can develop into septic shock with poor local signs. Myelosuppression after chemotherapy can cause myonecrosis without macroabscess, and magnetic resonance imaging was useful for the diagnosis of this condition. When unspecified local pain appears during cancer chemotherapy we should consider this disease, too.

Unusual Development of Pulmonary Tumor Embolism from Controlled Liver Metastases of Transitional Cell Carcinoma: An Autopsy Case.

Clinicians generally suspect pulmonary tumor embolism (PTE) with uncontrolled carcinomas which often spread to lungs. We, however, experienced an autopsy case of diffuse microscopic PTE despite controlled liver metastases of transitional cell carcinoma (TCC). A 66-year-old man with progressing respiratory symptoms showed almost normal chest findings on computed tomography. Although liver metastases were successfully shrunk by chemotherapy, the patient died from aggressive respiratory failure. An autopsy revealed small pulmonary vessels showing diffuse tumor emboli. TCC can cause PTE even if liver metastases are controlled. We must therefore be aware that PTE can manifest as respiratory symptoms without any computed tomography findings.

Paraneoplastic Erythrocytosis of Colon Cancer, with Serum Erythropoietin within the Normal Reference Range.

BACKGROUND: Paraneoplastic erythrocytosis can be brought on by ectopic erythropoietin production usually in kidney, brain, and liver tumor with increase of serum erythropoietin level. We report here a paraneoplastic erythrocytosis of colon cancer with serum erythropoietin within the normal reference, which required an immunohistologic test for erythropoietin-antibody to be diagnosed. CASE REPORT: Our case report was of a 75-year-old woman with erythrocytosis. Her hemoglobin and serum erythropoietin levels were 191 g/dL and 12.6 IU/L (reference range, 9.1-32.8), respectively. Colonoscopy revealed an advanced sigmoid colon tumor 20 mm in diameter. She underwent colectomy, and immunohistochemical examination showed the colon adenocarcinoma was focally positive for erythropoietin-antibody. One month after the surgery, her hemoglobin level decreased to 117 g/L. CONCLUSIONS: Colon cancer can cause paraneoplastic erythrocytosis, and it is important to consider not simply the absolute serum erythropoietin level but also the serum erythropoietin level relative to simultaneously measured hemoglobin level. We should include paraneoplastic erythrocytosis as a differential diagnosis in cases of high hemoglobin level unexplained by other diseases.

Conversion therapy of gastric cancer with massive malignant ascites and ovarian metastases by systemic and intraperitoneal chemotherapy.

Intravenous and intraperitoneal paclitaxel with S-1 is showing promising results in gastric cancer with peritoneal metastases. We herein report a successful conversion of unresectable to resectable disease using combination chemotherapy with trastuzumab. The patient was a 39-year-old woman with human epidermal growth factor receptor 2-positive gastric cancer with peritoneal, pulmonary and bilateral ovarian metastases. After 6 cycles of S-1 plus cisplatin with trastuzumab, followed by 15 cycles of intravenous and intraperitoneal paclitaxel with S-1 and trastuzumab, the pulmonary and peritoneal metastases exhibited complete response and no evidence of malignancy was found on diagnostic laparoscopy. We performed metastasectomy of the bilateral sizeable ovaries, followed by total gastrectomy. The patient had no recurrence for 16 months after the gastrectomy. Therefore, satisfactory response to systemic and intraperitoneal chemotherapy may convert unresectable to resectable disease, and primary tumor resection with ovarian metastasectomy may prolong survival. This combination chemotherapy has the potential of becoming a conversion therapy for gastric cancer with peritoneal metastases, even if ascites and ovarian metastases are extensive.

Conversion therapy for pancreatic cancer with peritoneal metastases using intravenous and intraperitoneal paclitaxel with S-1.

Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body. The patient underwent abdominal surgery, but no excision was performed, as two peritoneal metastases in the bursa omentalis were detected. Combination therapy was initiated, consisting of intravenous and intraperitoneal paclitaxel with S-1 as a single-center clinical trial. The regimen consisted with 2-week administration of S-1 (80 mg per day) followed by 1 week of rest, intravenous paclitaxel 50 mg/m2, and intraperitoneal paclitaxel 20 mg/m2 by a peritoneal access device on days 1 and 8. Over the seven cycles of the chemotherapy, the primary lesion did not change in size, and peritoneal lavage cytology remained negative. After confirming the disappearance of the peritoneal lesions by exploratory laparoscopy, the patient underwent distal pancreatectomy combined with resection of the transverse mesocolon and stomach wall. Thus, the 2-way chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was well-tolerated and was able to convert pancreatic cancer with peritoneal metastases to resectable disease.

Efficacy of palonosetron and 1-day dexamethasone in moderately emetogenic chemotherapy compared with fosaprepitant, granisetron, and dexamethasone: a prospective randomized crossover study.

BACKGROUND: Although palonosetron (PALO) and NK1 receptor antagonist both reduce chemotherapy-induced nausea and vomiting, no comparison trial in moderately emetogenic chemotherapy (MEC) had been reported. The purpose of this study was to find out which drug combinations are preferable for patients receiving MEC. METHODS: Chemotherapy-naive patients receiving MEC were randomized to two groups; group A first received PALO therapy [PALO plus 1-day dexamethasone (DEX)], and group B first received fosaprepitant (FAPR) therapy [FAPR, granisetron (GRAN), and DEX]. Patients were re-allocated to the other therapy, respectively, for the second cycle of chemotherapy. We administered intravenous PALO (0.75 mg) and DEX (9.9 mg) to the PALO therapy group, and FAPR (150 mg), DEX (4.95 mg), and GRAN (3 mg) to the FAPR therapy group, on Day 1. Complete response (CR) was the primary endpoint; complete control (CC), total control (CT), and the therapy chosen by the patients for their third and following cycles of antiemetic therapy were the secondary endpoints. We evaluated CR, CC, and TC in the acute phase, in the delayed phase, and over the whole period. RESULTS: A total of 35 patients and 70 cycles of therapy was evaluable for analysis. No significant difference was found at all evaluation points. Overall CR rates for PALO and FAPR therapy were 74 vs 69 % (P = 0.567), CC rates 66 vs 69 % (P = 0.521), and TC rates 46 vs 60 % (P = 0.235), respectively. Patients also showed no clear preference for their third and following cycles of chemotherapy, choosing both regimens almost equally often (PALO 10 vs FAPR 13). CONCLUSIONS: PALO and 1-day DEX is almost equivalent to FAPR, GRAN, and DEX for MEC.

[A Case of Delayed Vascular Injury as a Complication Related to Implanted Central Venous Port Catheter].

A 74-year-old woman with advanced gastric cancer was admitted to our hospital. A central venous (CV) port catheter was implanted into the right subclavian vein for preoperative chemotherapy and parenteral nutritional management. On the 35th day after implantation, she complained of diarrhea, fever and dyspnea. The chest radiograph showed a right-sided massive pleural effusion. As the patient progressively fell into severe respiratory distress, endotracheal intubation was performed for management of respiration by mechanical ventilation. Initially, given the patient's symptoms, she was diagnosed with septic shock. Therefore, after placement of a CV catheter through the right femoral vein, in consideration of the possibility of a port infection, she was treated with thoracentesis and infusion of antibiotics. The patient gradually recovered, and again received parenteral nutrition through the CV port catheter. After the infusion was administered, she complained of dyspnea. A CT scan of the chest revealed a right pleural effusion and displacement of the tip of the CV port catheter out of the wall of the superior vena cava. We diagnosed delayed vascular injury (DVI), and the CV port catheter was removed. She soon recovered with conservative treatment. We speculated that the initial respiratory symptoms such as the pleural effusion were caused by DVI. DVI should therefore be recognized as a complication related to implanted CV port catheters.