Pseudocirrhosis Due to Desmoplastic Response to Chemotherapy in Breast Cancer Liver Metastases.

Pseudocirrhosis can result in cirrhosis-like symptoms of portal hypertension and is observed mostly in patients with breast cancer; however, its cause is unclear. Herein, we report a case of pseudocirrhosis in a 76-year-old woman with metastatic breast cancer. The patient developed irregular contours of the liver, resembling cirrhosis, and esophageal varices during chemotherapy for breast cancer with liver metastases. Although intrahepatic metastasis was absent on imaging, a liver biopsy showed cancer cell infiltration consistent with the fibrotic area, which was similar to fibrosis seen in liver cirrhosis. Endoscopic ligation was performed for the varices; however, the patient's worsening liver function made it difficult to continue chemotherapy. Clinicians should be alert to the possibility of pseudocirrhosis developing in patients with metastatic breast cancer undergoing chemotherapy. Since pseudocirrhosis is a life-threatening complication, non-invasive markers for early diagnosis are needed.

Efficacy of oral levofloxacin monotherapy against low-risk FN in patients with malignant lymphoma who received chemotherapy using the CHOP regimen.

The safety and feasibility of oral fluoroquinolone monotherapy in patients with low-risk febrile neutropenia (FN) were demonstrated in recent studies. Levofloxacin (LVFX) is a commonly prescribed antibiotic; however, evidence for its efficacy against FN is limited. Therefore, in this study, we retrospectively investigated the efficacy of LVFX against low-risk FN in patients with malignant lymphoma at our institution. Treatment success was defined as recovery from fever and neutropenia without alteration of the initial regimen. We recruited 29 patients between January 2013 and December 2018. The median age of the cohort was 64 (range: 21-87) years; 13 (44.8%) were aged over 65 years. In total, 22 patients had diffuse large B-cell lymphoma (DLBCL). Therapy was successful in 24 (82.8%) patients, whereas 5 had treatment failure requiring a change from LVFX to intravenous broad-spectrum antibacterial agents. No deaths related to FN were observed. Two patients required FN-related chemotherapy dose reduction in subsequent cycles. Although this cohort comprised many elderly patients, our study confirmed the efficacy of LVFX in patients with low-risk FN. This may improve the treatment of low-risk FN and malignant lymphoma.

Severe Hemorrhagic Cystitis Caused by Cyclophosphamide and Capecitabine Therapy in Breast Cancer Patients: Two Case Reports and Literature Review.

Combined oral cyclophosphamide and capecitabine (XC) chemotherapy is used for metastatic breast cancer (MBC) patients. We report herein two MBC patients who developed severe hemorrhagic cystitis after XC therapy. Case 1: A 67-year-old woman with MBC had received XC therapy for 2.5 years. After a sudden onset of lower abdominal pain and gross hematuria, cystoscopy revealed a urinary bladder mucosa showing diffuse dilation of the capillaries and a large blood clot. A total dose of 60.8 g cyclophosphamide had been given and the XC regimen was discontinued immediately. The patient experienced frequent episodes of bladder tamponade over 18 months and underwent continuous bladder irrigation and cystoscopic fulguration. Hyperbaric oxygen therapy (HBOT) provided only temporary relief and the patient subsequently developed hemorrhagic shock. A bilateral ureterostomy was eventually performed. Case 2: A 65-year-old woman with MBC was given XC for 3 years, but this was discontinued after she developed new lung lesions. The patient was given a total dose of 78.4 g of cyclophosphamide. A month later, the patient complained of intermittent gross hematuria, which progressed to persistent macroscopic hematuria for 1 week. She underwent continuous bladder irrigation with saline, without an improvement in her bladder tamponade. Subsequently, the bleeding ceased completely after HBOT. Some MBC cases can be controlled for a long time with XC therapy. For those cases, we need to realize that severe hemorrhagic cystitis may occur. Even at a low dose, requires testing periodically for occult blood in the urine to detect the early stages of cystitis.

Evaluation of vascular pain in patients with colorectal cancer receiving peripheral venous chemotherapy with or without oxaliplatin.

Oxaliplatin is a key chemotherapy drug in patients with colorectal cancer. Administration of oxaliplatin via a peripheral vein often causes vascular pain. However, no studies have evaluated vascular pain in patients with colorectal cancer in relation to peripheral venous administration of chemotherapy with or without oxaliplatin. We evaluated oxaliplatin-induced vascular pain using subjective and objective methods. We determined if oxaliplatin induced vascular pain in patients with colorectal cancer using a Visual Analog Scale (VAS) and a PainVision PS-2100 device. We compared VAS score between chemotherapy regimens with or without oxaliplatin, and between genders. We also examined the correlations of VAS score with pain intensity examined by the PainVision PS-2100, and with age and vessel diameter. A total of 98 patients with colorectal cancer were enrolled in this study, including 78 patients who received oxaliplatin via peripheral venous administration and 20 who received chemotherapy without oxaliplatin. The median VAS scores in patients with and without oxaliplatin were 36.5 (interquartile range 9.0-60.0) and 0 (0-4.0), respectively (P < 0.001), and the median pain intensities according to PainVision were 43.5 (14.3-98) and 36.5 (9.3-58.5), respectively (P < 0.001). There was a positive correlation between VAS and pain intensity (r = 0.584), but no correlation between VAS score and age (r = -0.174) or vessel diameter (r = -0.107). Peripheral venous administration of oxaliplatin induced vascular pain, measured both subjectively and objectively, in patients with colorectal cancer, regardless of vessel diameter.

Autoimmune Hepatitis with Concomitant Idiopathic Thrombocytopenic Purpura Diagnosed by Transjugular Liver Biopsy.

Patients with autoimmune hepatitis (AIH) may sometimes have concomitant idiopathic thrombocytopenic purpura (ITP). Severe thrombocytopenia in ITP interferes with percutaneous liver biopsy for pathological diagnosis of AIH. Here, we report a case of AIH with ITP in a 63-year-old woman. The patient presented to our hospital with liver dysfunction and thrombocytopenia. For histological examination, transjugular liver biopsy (TJLB) was performed, leading to a diagnosis of AIH. Corticosteroids treatment led to an improvement in her liver enzyme levels and platelet count. In conclusion, patients with AIH may sometimes have concomitant ITP. TJLB was effective for making the diagnosis of AIH with severe thrombocytopenia due to ITP.

Retrospective analysis of the efficacy and safety of eribulin therapy for metastatic breast cancer in daily practice.

BACKGROUND: Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented. METHODS: We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. RESULTS: The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m2 , and 75%, respectively. One patient achieved a complete response, (CR) six a partial response (PR), eight stable disease (SD) and 14 patients exhibited progressive disease. The objective response rate (ORR: CR + PR) was 24.1%, and the clinical benefit rate (CBR: CR + PR + SD) was 51.7%. The median progression-free survival was 90 days (95% confidence interval [CI] 67-126) and median overall survival was 264 days (95% CI 198-357). In patients who previously received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was administered to 20 patients (69%) after eribulin administration, and the median overall survival rate of cases that achieved greater than a PR was 1088 days. The most frequent treatment-related grade 3/4 adverse events were neutropenia (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred in 13.8% of patients, but was not exacerbated even if present before treatment. CONCLUSION: Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy.

Difference in Neutropenia due to Administration Schedule of TAS-102.

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.

Objective evaluation of oxaliplatin-induced vascular pain secondary to peripheral vein administration.

BACKGROUND: During oxaliplatin chemotherapy administration via a peripheral vein, vascular pain requires changing of the intravenous infusion route on occasion. Vascular pain induced by anticancer drugs reduces the rate of patient continuation and completion of chemotherapy. Pain is presently appraised using subjective methods, such as the visual analog scale (VAS). However, because pain evaluation can vary depending on the physical state and mood of the patient at the time of assessment, it is desirable to evaluate pain objectively. PainVision PS-2100 (PV) is a medical device that was designed to objectively and quantitatively assess patient nociception and perception. METHODS: The present study examined the correlation of subjective and objective assessment of oxaliplatin-induced vascular pain using VAS and PV, respectively. RESULTS: Vascular pain was assessed using both PV and VAS a total of 173 times for 58 colorectal cancer patients. Partial correlation analysis was performed to evaluate the relationship between PV and VAS. The mean PV and VAS scores were 44.5 (range: 0-596) and 24.8 (range: 0-100), respectively. The partial correlation coefficient was 0.408 (p < 0.0001). CONCLUSIONS: A strong correlation was not observed between the results, and a weak correlation was observed between VAS and PV scores. Objective evaluation of oxaliplatin-induced vascular pain will be required to help patients overcome vascular pain.

5-Fluorouracil Chemotherapy for Dihydropyrimidine Dehydrogenase-deficient Patients: Potential of the Dose-escalation Method.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) degrades approximately 85% of administered 5-fluorouracil (5-FU). With a reported high mortality rate, chemotherapy is generally contraindicated for patients with DPD deficiency. PATIENTS AND METHODS: Chemotherapy was initiated for a 73-year-old man with DPD deficiency. Capecitabine was administered in incrementally increasing doses, beginning with a single pill while monitoring plasma 5-FU concentration, and neutrophil and platelet counts. RESULTS: DPD protein level was 2.35 U/mg. After increasing the capecitabine dose to 1,800 mg, oxaliplatin and bevacizumab were added. Subsequent DPD protein measurement showed that the level had increased to approximately 12-fold the one before chemotherapy. Sequencing of all 23 exons of DPYD gene revealed a mutation of guanine to thymine in exon 11 (1156 G>T). CONCLUSION: This is the first report to indicate that DPD activity can be induced. These findings may provide early indications of a new method for chemotherapy for DPD-deficient patients.

Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab.

A 57-year-old male with acute-type adult T cell leukemia-lymphoma (ATL) developed persistent watery, non-bloody diarrhea at a volume of 2-3 L/day following the administration of the anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab. An extensive examination revealed the absence of any pathogenic bacteria or parasites in his stool. Biopsied specimens from the colonic mucosa contained many small nests of apoptotic bodies in the colonic glands, which mimicked acute-colonic graft-versus-host disease. Activation of the auto-reactive immune system due to the depletion of regulatory T-cells by mogamulizumab was suspected as causative. Special attention should be paid to the risk of unique immune-related adverse events induced by mogamulizumab.

Can grade 2 neutropenia predict the risk of grade 3 neutropenia in metastatic colorectal cancer patients treated with chemotherapy?

PURPOSE: Neutropenia is a major factor affecting continuation of chemotherapy for colorectal cancer. In many clinical trials, a neutrophil count of >1500 is targeted for continuation; for a count of <1500, medication is commonly discontinued. However, there is no definitive evidence supporting the need for a neutrophil count of 1500 for continuation of chemotherapy. In the clinical trials that we conducted, we discontinued chemotherapy when the neutrophil count was <1000 (grade 3); for a count of 1000-1500 (grade 2), chemotherapy was continued. Therefore, even practical treatment uses the same setting. Our aim was to examine neutrophil counts during continuation of chemotherapy in colorectal cancer patients with counts of 1000-1500 and to assess the need for discontinuation of medication for neutrophil counts in this range. Moreover, we examined neutrophil counts during the previous course of chemotherapy when they fell below 1000. METHODS: The study included 144 patients who received XELOX + bevacizumab therapy and XELOX therapy for advanced or recurrent colorectal cancer. RESULTS: Thirty (20.8 %) patients had neutrophil counts of 1000-1500. One (3.3 %) of 30 patients had a neutrophil count of <1000 during the following course of chemotherapy. Moreover, among the patients with neutrophil counts of <1000, 27.3 % had counts of 1000-1500 during the previous course of chemotherapy and 72.7 % had counts of >1500. CONCLUSIONS: Based on these results, grade 2 neutropenia cannot predict the risk of grade 3 neutropenia. Continuation of chemotherapy in patients with neutrophil counts of 1000-1500 may be appropriate, and discontinuation of therapy is not always required.

Subjective and objective assessment of oxaliplatin-induced peripheral neuropathy.

Numbness and pain are currently evaluated using subjective methods such as the visual analog scale (VAS). However, because assessment of pain can vary greatly depending on the mood and physical state of the patient at the time of assessment, it is best to evaluate pain objectively. pain vision PS-2100 (PV) is an analytical instrument that was designed to quantitatively and objectively assess sense perception and nociception in patients. The present study examined the correlation of subjective and objective assessment of oxaliplatin-induced peripheral neuropathy (PN) using VAS and PV, respectively. The mean VAS and PV scores of PN were 20.5 (range 0-100) and 27.9 (range 0-416), respectively. The partial correlation coefficient was 0.274 (p = 0.0003). No strong correlation was observed between the results and a weak correlation was observed between VAS and PV.

Administration of chemotherapy via the median cubital vein without implantable central venous access ports: port-free chemotherapy for metastatic colorectal cancer patients.

BACKGROUND: Repeated venous punctures are usually required during chemotherapy administration for cancer patients. Central venous catheters and implantable port systems have substantially facilitated vascular access, and safe, easy-to-handle port systems have become an integral part of daily clinical routines in oncology. However, several serious complications are associated with central venous ports (CV-ports), and recent developments of combined oral capecitabine and oxaliplatin (XELOX) therapies allow CV-port-free administration. In this study, the safety and efficacy of CV-port-free chemotherapy administration via the median cubital vein was assessed in metastatic colorectal cancer patients. METHODS: This study included 144 patients who received XELOX + bevacizumab (BV) or XELOX therapy for metastatic colorectal cancer without CV-port implantation. RESULTS: Eighty-five patients experienced transient vascular pain. The drip infusion route was switched to the opposite side following vascular pain in only 1 patient. No patients required CV-port implantation or delayed treatment due to adverse events associated with drug administration via the peripheral vein. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 12.5 and 17.4 % of patients, respectively. CONCLUSIONS: Port-free-chemotherapy administration via the median cubital vein is appropriate for patients with colorectal cancer, thereby avoiding complications associated with CV-ports.

Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma.

Malignant cells supply their energy needs through increased glucose consumption, producing large quantities of lactic acid via glycolysis. Glucose transporters (GLUTs) and monocarboxylate transporters (MCTs) are therefore commonly up-regulated in human malignancies to mediate glucose influx and lactic acid efflux, respectively. However, their roles in malignant pleural mesothelioma (MPM) have not been fully elucidated. Here, we evaluated GLUT-1, MCT-1, and MCT-4 expression in human MPM and reactive mesothelial hyperplasia (RMH) and elucidated their biological role in vitro. GLUT-1, MCT-1, and MCT-4 expression was determined in human MPM (n = 35) and RMH (n = 20) specimens by immunohistochemistry and in frozen tissue, and MPM cell lines, by real-time reverse transcription-polymerase chain reaction and western blot analysis. GLUT-1, MCT-1, and MCT-4 functions in MPM were evaluated by transfection with small interfering RNA. Immunohistochemical analysis revealed higher levels of GLUT-1, MCT-1, and MCT-4 in MPM than in RMH. Additionally, GLUT-1, MCT-1, and MCT-4 mRNA levels were higher in MPM than in non-neoplastic mesothelial cell lines. The siRNA-mediated knockdown of GLUT-1 or MCT-1 significantly suppressed tumor cell proliferation, and MCT-1 silencing inhibited invasion and induced apoptosis. Taken together, these results indicate that combined application of GLUT-1, MCT-1, and MCT-4 immunohistochemistry might be useful in differentiating MPM from RMH and suggest that MCT-1plays an important biological role.

Pleural malignant mesothelioma with invasive micropapillary component and its association with pulmonary metastasis.

The micropapillary pattern (characterized by papillary structure with tufts lacking a central fibrovascular core) is a predictor of aggressive carcinoma. The purpose of the present study was to review 34 pleural malignant mesotheliomas (21 epithelioid, five sarcomatoid, seven biphasic and one lymphohistiocytoid), with special reference to the presence of invasive micropapillary component. Two invasive micropapillary pattern-positive tumors were identified. The invasive micropapillary pattern was seen to have a focal distribution in 15-20% of the tumor tissues. The majority of the invasive micropapillary clusters expressed MUC1 along the outer cell surface. Analysis of pleural malignant mesotheliomas with epithelioid features and with or without invasive micropapillary pattern (21 epithelioid and seven biphasic subtypes) indicated pulmonary micrometastases in only the invasive micropapillary-positive tumors (P < 0.015), and the spread was probably via the lymphatics. Lymphatic involvement (confirmed on immunohistochemistry with D2-40 antibody) and lymph node metastasis were found in both of the invasive micropapillary-positive tumor patients, whereas they were noted in only one of 10 (10%, P < 0.046) and three of nine (30%) invasive micropapillary-negative patients. To the authors' knowledge this is the first study to indicate the presence of invasive micropapillary component in pleural malignant mesothelioma. This component can predict more aggressive lymphatic spread, similar to that of carcinomas in other organs with micropapillary pattern.

Pathology of soft-tissue tumors: daily diagnosis, molecular cytogenetics and experimental approach.

This article reviews problems in diagnostic pathology and molecular cytogenetics of soft-tissue tumors. Also discussed are the origin of soft-tissue sarcomas and the molecular basis of effective target therapy for sarcomas. Molecular cytogenetic analysis of tumor-specific chromosomal translocations and associated fusion gene transcripts offers a useful adjunct to the diagnosis of soft-tissue tumors, but recent studies have indicated a growing number of fusion gene variations in each tumor type. In pleomorphic sarcoma/malignant fibrous histiocytoma, the alternative lengthening of telomeres (ALT) mechanism may result in formation of anaphase bridges and marked nuclear pleomorphism. The histogenesis of soft-tissue sarcomas has been a matter of controversy. In the present experimental model using s.c. injection of 3-methylcholanthrene in C57BL/6 mice pretreated with bone marrow-transplantation from green fluorescent protein (GFP)-positive green mice, the bone marrow-derived mesenchymal stem cells as well as the tissue-resident mesenchymal cells in the peripheral soft tissues are possible originators of sarcomagenesis. Little is known about a molecular basis of target therapy for sarcomas. Platelet-derived growth factor-BB (PDGF-BB) enhances the invasive activity of malignant peripheral nerve sheath tumor (MPNST) cells through platelet-derived growth factor receptor (PDGFR) phosphorylation, whereas imatinib mesylate inhibited such activity, suggesting that targeting PDGFR-beta may result in the establishment of novel treatment for MPNST. In addition, emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMP), playing a crucial role in tumor progression, invasion and metastasis. The MMP upregulation mechanism mediated by tumor-associated emmprin may be a potentially useful target in anti-tumor invasion therapy for sarcomas.