[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].

The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.

Effect of Intraoperative Imprint Cytology Followed by Frozen Section on Margin Assessment in Breast-Conserving Surgery.

PURPOSE: Intraoperative margin assessment can reduce positive margins in patients undergoing breast-conserving surgery. However, reports on intraoperative margin assessment have described only the use of either imprint cytology or frozen section. This study was designed to elucidate the effect of intraoperative margin assessment using imprint cytology followed by frozen section. METHODS: Overall, 522 patients were enrolled. First, the entire surgical margin was subjected to imprint cytology. Frozen section was performed only in cases with "positive" or "suspicious" imprint cytology results. An additional intraoperative excision was performed in patients with frozen section-positive lesion sites. All margins were evaluated using postoperative permanent sections after excision. RESULTS: Among 522 patients, 136 (26.1%) were imprint cytology-positive, and 386 (73.9%) were imprint cytology-negative. Among the 386 imprint cytology-negative patients not subjected to frozen section, 11 (2.1%) were permanent sections-positive (imprint cytology-false-negative). In 47 of the 136 imprint cytology-positive patients, additional intraoperative excision was unnecessary due to the frozen section-negative diagnosis. Moreover, these patients could avoid reoperation, because they were permanent section-negative. The false-positive rate of imprint cytology alone was 13.4%, but adding frozen section to imprint cytology decreased the overall false-positive rate to 2.5%. After undergoing excision, four patients still had positive margins. The overall positive margin rate in the final pathology based on permanent sections was 2.9% (15/522). CONCLUSIONS: Imprint cytology followed by frozen section led to a markedly decreased positive margin rate. This is considered the best method for intraoperative margin assessment, as it can overcome the limitations of cytology and histology performed individually.

Computed tomography-derived biomarker for predicting the treatment response to neoadjuvant chemoradiotherapy of rectal cancer.

BACKGROUND: Malignant tumor essentially implies structural heterogeneity. Analysis of medical imaging can quantify this structural heterogeneity, which can be a new biomarker. This study aimed to evaluate the usefulness of texture analysis of computed tomography (CT) imaging as a biomarker for predicting the therapeutic response of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer. METHODS: We enrolled 76 patients with rectal cancer who underwent curative surgery after nCRT. Texture analyses (Fractal analysis and Histogram analysis) were applied to contrast-enhanced CT images, and fractal dimension (FD), skewness, and kurtosis of the tumor were calculated. These CT-derived parameters were compared with the therapeutic response and prognosis. RESULTS: Forty-six of 76 patients were diagnosed as clinical responders after nCRT. Kurtosis was significantly higher in the responders group than in the non-responders group (4.17 ± 4.16 vs. 2.62 ± 3.19, p = 0.04). Nine of 76 patients were diagnosed with pathological complete response (pCR) after surgery. FD of the pCR group was significantly lower than that of the non-pCR group (0.90 ± 0.12 vs. 1.01 ± 0.12, p = 0.009). The area under the receiver-operating characteristics curve of tumor FD for predicting pCR was 0.77, and the optimal cut-off value was 0.84 (accuracy; 93.4%). Furthermore, patients with lower FD tumors tended to show better relapse-free survival and disease-specific survival than those with higher FD tumors (5-year, 80.8 vs. 66.6%, 94.4 vs. 80.2%, respectively), although it was not statistically significant (p = 0.14, 0.11). CONCLUSIONS: CT-derived texture parameters could be potential biomarkers for predicting the therapeutic response of rectal cancer.

Impact of breast cancer subtype on clinical outcomes after Gamma Knife radiosurgery for brain metastases from breast cancer: a multi-institutional retrospective study (JLGK1702).

INTRODUCTION: Brain metastasis (BM) is one of the most important issues in the management of breast cancer (BC), since BMs are associated with neurological deficits. However, the importance of BC subtypes remains unclear for BM treated with Gamma Knife radiosurgery (GKS). Thus, we conducted a multicenter retrospective study to compare clinical outcomes based on BC subtypes, with the aim of developing an optimal treatment strategy. METHODS: We studied 439 patients with breast cancer and 1-10 BM from 16 GKS facilities in Japan. Overall survival (OS) was analyzed by the Kaplan-Meier method, and cumulative incidences of systemic death (SD), neurologic death (ND), and tumor progression were estimated by competing risk analysis. RESULTS: OS differed among subtypes. The median OS time (months) after GKS was 10.4 in triple-negative (TN), 13.7 in Luminal, 31.4 in HER2, and 35.8 in Luminal-HER2 subtype BC (p < 0.0001). On multivariate analysis, poor control of the primary disease (hazard ratio [HR] = 1.84, p < 0.0001), active extracranial disease (HR = 2.76, p < 0.0001), neurological symptoms (HR 1.44, p = 0.01), and HER2 negativity (HR = 2.66, p < 0.0001) were significantly associated with worse OS. HER2 positivity was an independent risk factor for local recurrence (p = 0.03) but associated with lower rates of ND (p = 0.03). TN histology was associated with higher rates of distant brain failure (p = 0.03). CONCLUSIONS: HER2 positivity is related to the longer OS after SRS; however, we should pay attention to preventing recurrence in Luminal-HER2 patients. Also, TN patients require meticulous follow-up observation to detect distant metastases and/or LMD.

Volumetric Histogram Analysis of Apparent Diffusion Coefficient as a Biomarker to Predict Survival of Esophageal Cancer Patients.

BACKGROUND: The purpose of this study was to investigate whether histogram analysis of an apparent diffusion coefficient (ADC) can serve as a prognostic biomarker for esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled 116 patients with ESCC who received curative surgery from 2006 to 2015 (including 70 patients who received neoadjuvant chemotherapy). Diffusion-weighted magnetic resonance imaging (DWI) was performed prior to treatment. The ADC maps were generated by DWIs at b = 0 and 1000 (s/mm2), and analyzed to obtain ADC histogram-derived parameters (mean ADC, kurtosis, and skewness) of the primary tumor. Associations of these parameters with pathological features were analyzed, and Cox regression and Kaplan-Meier analyses were performed to compare these parameters with recurrence-free survival (RFS) and disease-specific survival (DSS). RESULTS: Kurtosis was significantly higher in tumors with lymphatic invasion (p = 0.005) with respect to the associations with pathological features. In univariate Cox regression analysis, tumor depth, lymph node status, mean ADC, and kurtosis were significantly correlated with RFS (p = 0.047, p < 0.001, p = 0.037, and p < 0.001, respectively), while lymph node status and kurtosis were also correlated with DSS (p = 0.002 and p = 0.017, respectively). Furthermore, multivariate analysis demonstrated that kurtosis was the independent prognostic factor for both RFS and DSS (p < 0.001 and p = 0.015, respectively). In Kaplan-Meier analysis, patients with higher kurtosis tumors (> 3.24) showed a significantly worse RFS and DFS (p < 0.001 and p = 0.006, respectively). CONCLUSIONS: Histogram analysis of ADC may serve as a useful biomarker for ESCC, reflecting pathological features and prognosis.

Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.

The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.

Conjugated bile acid-activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression.

UNLABELLED: Bile acids are important hormones during the feed/fast cycle, allowing the liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile acids activate both the ERK1/2 and AKT signaling pathways via sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes and in vivo. Here, we report that feeding mice a high-fat diet, infusion of taurocholate into the chronic bile fistula rat, or overexpression of the gene encoding S1PR2 in mouse hepatocytes significantly upregulated hepatic sphingosine kinase 2 (SphK2) but not SphK1. Key genes encoding nuclear receptors/enzymes involved in nutrient metabolism were significantly downregulated in livers of S1PR2(-/-) and SphK2(-/-) mice. In contrast, overexpression of the gene encoding S1PR2 in primary mouse hepatocytes differentially increased SphK2, but not SphK1, and mRNA levels of key genes involved in nutrient metabolism. Nuclear levels of sphingosine-1-phosphate, an endogenous inhibitor of histone deacetylases 1 and 2, as well as the acetylation of histones H3K9, H4K5, and H2BK12 were significantly decreased in hepatocytes prepared from S1PR2(-/-) and SphK2(-/-) mice. CONCLUSION: Both S1PR2(-/-) and SphK2(-/-) mice rapidly developed fatty livers on a high-fat diet, suggesting the importance of conjugated bile acids, S1PR2, and SphK2 in regulating hepatic lipid metabolism.

Development of a metastatic murine colon cancer model.

BACKGROUND: It has now become clear that the complex interplay of cancer and the immune responses against it plays a critical role in the tumor microenvironment during cancer progression. As new targets for cancer treatment are being discovered and investigated, murine models used for preclinical studies need to include intact immune responses to provide a closer correlation with human cancer. We have recently developed a modified syngeneic orthotopic murine colon cancer model that mimics human colon cancer progression with consistent results. MATERIALS AND METHODS: Tumors were created using the murine colon adenocarcinoma cell line, CT26, modified to overexpress the firefly luciferase gene (CT26-luc1), which allowed real-time in vivo monitoring of tumor burden when the substrate, D-luciferin, was injected intraperitoneally using the In Vivo Imaging System. Mice are Balb/c (Harlan), syngeneic with the CT26-luc1 cells. Cells are injected submucosally, suspended in Matrigel, into the cecum wall under direct visualization. RESULTS: The model has demonstrated consistent implantation in the cecum. In vivo bioluminescence allowed real-time monitoring of total tumor burden. Perioperative preparation had a significant impact on reproducibility of the model. Finally, total tumor burden quantified with bioluminescence enabled estimation of lymph node metastasis ex vivo. CONCLUSIONS: This method maintains an intact immune response and closely approximates the clinical tumor microenvironment. It is expected to provide an invaluable murine metastatic colon cancer model particularly in preclinical studies for drug development targeting those mechanisms.

[Surgical Simulation-CT Colonography for Laparoscopic Assisted Sigmoid Colectomy Preserving the Inferior Mesenteric Artery and Vein].

D2 lymph node dissection in laparoscopic surgery for early colon cancer requires selective vessel dissection, making it technically very difficult. Using surgical simulation-CT colonography (simulation-CTC), we could perform laparoscopic assisted sigmoid colectomy preserving the inferior mesenteric artery (IMA) and vein (IMV) more accurately and safely. The case described here was a type 0-Ip sigmoid colon cancer with a tumor size of 13 mm. Endoscopic mucosal resection was performed to confirm a pathological diagnosis of pT1b (4,000 mm) and v1. Sigmoid colectomy was planned, and simulation-CTC was performed, which demonstrated that the cancer was located in the proximal sigmoid colon and supplied by the first sigmoid colon artery (S1). To maintain the blood flow to the distal sigmoid colon, selective S1 resection preserving the IMA and IMV was planned. At the operation, S1, which branches off from the IMA near the bifurcation of the abdominal aorta, was dissected, and the vein accompanying S1, which branches from the IMV in the same area as S1, was dissected. The operation was performed accurately according to the plan, showing that simulation-CTC can be very useful.

Is the outcome of a salvage surgery for T4 thoracic esophageal squamous cell carcinoma really poor?

BACKGROUND: Among patients with T4 thoracic esophageal squamous cell carcinoma (TESCC), it is unclear whether the outcomes of late responders who undergo high-dose chemoradiotherapy (CRT) followed by salvage esophagectomy differs from those of early responders who undergo low-dose CRT followed by esophagectomy. METHODS: A total of 153 patients with T4 TESCC were treated with CRT. The first evaluation was performed after 40 Gy of CRT for downstaging. Of these, 28 patients could be downstaged, and underwent subsequent surgery (early responders). For the remaining patients, additional CRT was administered, and patients were re-evaluated after treatment and underwent salvage surgery. In total, 40 patients (early + late responders) were analyzed. RESULTS: The primary tumors exhibited a grade 3 response in six (21.4 %) of the early responders and two (16.7 %) of the late responders (p = 1.000). The rate of residual tumor in the primary tumor was 80 % (32/40 patients). The proportions of resected lymph nodes and positive metastatic nodes were similar between early and late responders (p = 0.406 and p = 0.859, respectively). The 5-year overall survival rates among the early and late responders were 25.9 and 36.5 %, respectively, and the median survival times were 24.8 and 24.3 months (p = 0.925), respectively. The 5-year cause-specific survival rates in the early and late responder groups were 61.5 and 72.9 % (p = 0.425), respectively. CONCLUSION: The outcomes of both early and late responders to CRT were similar, and salvage surgery for T4 TESCC outweighs the risks in patients with T4 TESCC.

Novel Advances in Qualitative Diagnostic Imaging for Decision Making in Multidisciplinary Treatment for Advanced Esophageal Cancer.

Background: Recently, neoadjuvant therapy and the succeeding surgery for advanced esophageal cancer have been evaluated. In particular, the response to the therapy has been found to affect surgical outcomes, and thus a precise evaluation of treatment effect is important for this strategy. In this study, articles on qualitative diagnostic modalities to evaluate tumor activities were reviewed, and the diagnostic indices were examined. Methods: For prediction of the effect, perfusion CT and diffusion MRI were estimated. For the histological response evaluation, perfusion CT, diffusion-MRI, and FDG-PET were estimated. For downstaging evaluation of T4, tissue-selective image reconstruction using enhanced CT was estimated and diagnostic indices were reviewed. Results: The prediction of the effect using perfusion CT with 'pre CRT blood flow' and diffusion MRI with 'pre CRT ADC value'; the estimation of the histological response using perfusion CT with 'post CRT blood flow reduction, using diffusion MRI with 'post CRT ADC increasing', and using FDG-PET with 'post CRT SUV reduction'; and the downstaging evaluation of T4 using CT image reconstruction with 'fibrous changed layer' were performed well, respectively. Conclusions: Qualitative imaging modalities for prediction or response evaluation of neoadjuvant therapy for progressive esophageal cancer were useful for the decision making of the treatment strategy of the multidisciplinary treatment.

Diffusion-weighted magnetic resonance imaging for predicting and detecting the early response to chemoradiotherapy of advanced esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to investigate the utility of the apparent diffusion coefficient (ADC) value in diffusion-weighted magnetic resonance imaging (DWMRI) for prediction and early detection of treatment response in advanced esophageal squamous cell carcinoma. METHOD: DWMRI was performed in 27 patients with primary cT4 esophageal carcinoma that were undergoing chemoradiotherapy before treatment and after 20 and 40 Gy. We calculated tumor ADCs and association of the treatment effect between responders and nonresponders. RESULTS: The ADC at the time of 20 Gy was significantly higher in responders compared to nonresponders (1.13 vs. 0.93; p = 0.005). The ADC cut-off value was set at 1.00 × 10(-3) mm(2)/s and the ADC predicted the responders with a sensitivity, positive predictive value and accuracy of 79, 73 and 74%, respectively. The increased rate of the ADC at the time of 20 Gy (ΔADC20) was also significantly higher in responders compared to nonresponders (35.4 vs. 1.5%; p = 0.0007). An ADC cut-off value for ΔADC20 of 15% predicted the responders with a sensitivity, positive predictive value and accuracy of 71, 100 and 85%, respectively. CONCLUSION: The ADC values predicted the prognosis of patients with advanced esophageal squamous cell carcinoma as well as the treatment response.

Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis.

OBJECTIVE: Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. METHODS: Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. RESULTS: The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). CONCLUSION: Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. KEY POINTS: • Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen • There is also negative correlation between ADCs and vascular endothelial growth factor • ADC values may contribute to the treatment of oesophageal cancer.

Apparent diffusion coefficient values measured by diffusion-weighted imaging predict chemoradiotherapeutic effect for advanced esophageal cancer.

BACKGROUND: The purpose of this study was to assess whether apparent diffusion coefficient (ADC) values of esophageal squamous cell carcinoma (ESCC) predict responses to chemoradiotherapy (CRT) and/or patient prognosis. METHODS: Magnetic resonance images were acquired to construct the diffusion-weighted images, and the ADC values were calculated before CRT in 80 patients with ESCC. A high-ADC group responded better to CRT than did a low-ADC group (p < 0.01). We divided the 80 patients into two groups based on the operating characteristic analysis: one group comprised patients with ADC values higher than the average ADC of the esophageal cancer tissue (1.10 × 10(-3) mm2/s), and the other group comprised those whose ADC values were less than the average value. A Kaplan-Meier analysis showed that the survival rate in the high-ADC group was significantly better than that in the low-ADC group (p = 0.04). CONCLUSION: Our results indicate that the ADC value may be a useful marker to predict treatment response as well as survival for patients with ESCC.

Evaluation of ulcerative colitis using diffusion-weighted imaging.

BACKGROUND/AIMS: The aims of this study were to determine the feasibility of diffusion-weighted imaging (DWI) for detecting bowel inflammation and to investigate the changes in the apparent diffusion coefficient (ADC) values in the inflamed bowel of patients with ulcerative colitis (UC). METHODOLOGY: Seven patients, who underwent DWI for UC and curative total colectomy because of insistence on conservative therapy, were enrolled in this study. The resected specimens were examined histopathologically to determine the degree of inflammation and the presence of malignancy. The ADC values of the lesions were calculated and compared among UC lesions. RESULTS: The mean ADC value of the active UC lesions was significantly (p < 0.01) lower than that of the normal colorectal tissue (1.12 +/- 0.14 x 10(-3) mm2/s vs. 1.60 +/- 0.21 x 10 (-3) mm2/s, respectively). The mean ADC value of the active lesions was significantly (p < 0.01) lower than that that of the healing lesions (1.12 +/- 0.14 x10(-3) mm2/s vs. 1.62 +/- 0.28 x 10(-3) mm2/s, respectively). CONCLUSIONS: DWI may be valuable for following patients with UC, and the stage of UC may be diagnosed easily based on the ADC values.

Volumetric histogram analysis of apparent diffusion coefficient for predicting pathological complete response and survival in esophageal cancer patients treated with chemoradiotherapy.

BACKGROUND: The purpose of the study was to evaluate whether histogram analysis of apparent diffusion coefficient (ADC) can predict pathological complete response (pCR) and survival in patients with esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy (CRT). METHODS: We retrospectively identified 58 patients with ESCC who underwent surgery after CRT between 2007 and 2016. Associations of pretreatment histogram derived ADC parameters with pathological response and survival were analyzed. RESULTS: Tumors achieved pCR (10 patients, 17.2%) showed significant lower ADC, higher kurtosis, and higher skewness than those of non-pCR (p = 0.005, 0.007, <0.001, respectively). Receiver operating characteristics analysis demonstrated skewness was the best predictor for pCR (AUC = 0.86), with a cut off value of 0.50 (accuracy, 86.2%). In Kaplan-Meier analysis, patients with higher skewness tumors (≥0.50) showed a significantly better recurrence free survival (p = 0.032, log-rank). CONCLUSIONS: Histogram analysis of ADC can enable prediction of pCR and survival in ESCC patients treated with preoperative CRT. A SHORT SUMMARY: ADC histogram analysis can be an imaging biomarker for esophageal cancer patients treated with CRT.

[Diffusion-weighted MR imaging for postoperative nodal recurrence of esophageal squamous cell cancer in comparison with FDG-PET].

We evaluated the power of DWIBS in patients with postoperative lymph node recurrence of esophageal cancer and compared with FDG-PET findings. Forty-seven suspected lesions by MDCT were enrolled. No significant difference between DWIBS and PET was observed in sensitivity (95% vs 97%), PPV (83% vs 90%) and overall accuracy rate (81% vs 87%). The ADCs (x10(-3) mm2/s) of recurrent nodes, primary cancer and normal esophagus were 1.124, 1.058 and 2.079, respectively. ADCs of recurrent nodes were significantly lower than those of normal esophagus (p<0.0001). The cut-off ADC line of 1.5 revealed 100% overall accuracy for separating the recurrent lesion from normal esophagus. Noninvasive DWIBS may become a valid modality to discriminate nodal recurrence of esophageal cancer by no means inferior to PET.

Imaging biomarkers for the treatment of esophageal cancer.

Esophageal cancer is known as one of the malignant cancers with poor prognosis. To improve the outcome, combined multimodality treatment is attempted. On the other hand, advances in genomics and other "omic" technologies are paving way to the patient-oriented treatment called "personalized" or "precision" medicine. Recent advancements of imaging techniques such as functional imaging make it possible to use imaging features as biomarker for diagnosis, treatment response, and prognosis in cancer treatment. In this review, we will discuss how we can use imaging derived tumor features as biomarker for the treatment of esophageal cancer.

Descending necrotizing mediastinitis after sequestrectomy in a patient with bisphosphonate-induced osteonecrosis of the jaw: A case report.

An 83-year-old woman underwent mastectomy for breast cancer of the right breast in 2008. In addition to hormone therapy and irradiation, zoledronate was started for bone metastasis 6 months postoperatively. Five years after the operation, the patient developed osteonecrosis of the jaw, and underwent sequestrectomy because of uncontrollable pain in the mandible. The patient visited our hospital for a 1-week history of fever and right facial swelling with pain, and was diagnosed with right mandibular cellulitis. Despite antibiotic therapy, the patient fell into shock. Follow-up computed tomography showed gas formation extending down to the posterior mediastinum, which was compatible with descending necrotizing mediastinitis (DNM). The patient succumbed to septicemia on the third hospital day. The mortality rate of DNM greatly increases in patients with advanced cancer because clinicians cannot perform radical treatment due to the impaired general condition and limited life expectancy. DNM advances by the hour; therefore, repeated computed tomography is essential when antibiotic therapy does not improve the patient's condition. Attention must be paid to detect signs of DNM in such patients. To the best of our knowledge, this is the first report in English regarding DNM caused by bisphosphonate-induced osteonecrosis of the jaw.

Pseudocirrhosis after chemotherapy in breast cancer, case reports.

Pseudocirrhosis is a rare hepatic complication of chemotherapy, which is morphological changes in hepatic contour that closely mimic cirrhosis. Like in classic cirrhosis, portal hypertension is common in patients with this condition. The mechanism of pseudocirrhosis is unknown to date. We report three cases of pseudocirrhosis arising in the setting of regression of breast cancer liver metastases. All the cases underwent systemic chemotherapy, and all had remarkable responses. Their hormone receptor statuses were all positive and Her2/neu statuses were all negative. They were all treated with cytotoxic chemotherapeutic agent and also hormone therapy. This report suggests clinicians should have pseudocirrhosis in mind when hormone therapy and cytotoxic chemotherapy are jointly administered.