[A Case of Breast Cancer in the Elderly Localized in the Nipple].

An 89-year-old woman presented to our clinic with a complaint of a wound in the left nipple. The pathological diagnosis via skin biopsy revealed adenocarcinoma. A physical examination, mammography, ultrasonography, and CT scan revealed a mass in the left nipple. However, a definite diagnosis could not be established by skin biopsy. Left breast-conserving surgery and sentinel lymph node biopsy were performed for diagnosis and treatment. Histological examination revealed a scirrhous type invasive ductal carcinoma in the left nipple and areola with skin invasion and lymph node metastasis. Radiation and hormone therapy were used as adjuvant therapy. She is alive with no local recurrence for 5 months post surgery. Since ductal carcinoma of the nipple is uncommon, we present this case report along with a review of the relevant literature.

[Cancer of the Ascending Colon Diagnosed at the Same Time as Breast Cancer Following Leukemia Treatment for Which Laparoscopic Surgery Was Performed-A Case Report].

An 83-year-old woman received 8 courses of chemotherapy(mogamulizumab)for adult T cell leukemia in the hematolo- gy department of our hospital, after which she achieved complete remission and was followed up with chemotherapy(VP/ MST: sobuzoxane/etoposide)as an outpatient. Later, diarrheal symptoms appeared, and detailed examinations led to a diagnosis of cancer of the ascending colon. Although no distal metastasis was found, breast cancer was also revealed in the C area of the right breast. The general status of the patient was favorable; thus, right pectoral muscle-conserving mastectomy and concomitant sentinel lymph node biopsy were performed through laparoscope-assisted extended right hemicolectomy. The postoperative course was favorable, and she was discharged on hospital day 7. The excised tumors were pathologically diagnosed as stageⅠ breast cancer and stage Ⅲa colorectal cancer. Chemotherapy(VP/MST)was administered without adjuvant chemotherapy. Presently, 18 months after surgery, complete remission of adult T cell leukemia has been maintained, without metastasis and recurrence of cancer of the ascending colon and breast cancer.

Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

BACKGROUND & AIMS: Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. METHODS: C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. RESULTS: TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of ß-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. CONCLUSIONS: The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy.

Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma.

BACKGROUND/AIMS: Complete operative resection is the only approach to cure for intrahepatic cholangiocellular carcinoma (ICC), but the disease's prognosis is notably poor. A novel therapeutic approach is urgently required. CXC chemokine receptor 2 (CXCR2) has been associated with tumorigenesis and metastasis in human cancers. In this study, we investigated the suppressive effect of ICC growth by blocking CXCR2. MATERIAL AND METHODS: The role of CXCR2 was estimated using the human ICC cell lines, RBE and SSP25. CXCR2 small interfering RNA (siRNA) and an antagonist (SB225002) were used to block CXCR2. Proliferation assays, migration assays, and invasion assays were performed to confirm the suppressive effect of blocking CXCR2. Subcutaneous SSP25 tumors were established in athymic nude mice, and the mice were given SB225002. The expression of CXCR2 in ICC was determined by immunohistochemical staining of 34 ICC specimens. We investigated the relationship between CXCR2 expression and prognosis in ICC. RESULTS: The prognosis of patients who had higher CXCR2 expression in ICC was significantly poor (P = .004). CXCR2 siRNA treatment significantly suppressed CXCR2 expression in both RBE and SSP25. Cell proliferation, migration, and invasion were significantly suppressed by both CXCR2 siRNA and SB225002 compared with the control group. SB225002 also suppressed the growth of transplanted subcutaneous tumors (P = .02) CONCLUSION: Our results demonstrated that blocking CXCR2 clearly suppressed the development of ICC. Blocking CXCR2 may be a promising therapeutic approach for ICC.

Analysis of unique liver volume restoration after laparoscopic fenestration of liver cysts.

INTRODUCTION: Laparoscopic fenestration is a standard procedure for the treatment of non-parasitic liver cysts. After fenestration, the remnant liver often restores its volume. However, no systematic analysis of the phenomenon exists. In the present study, the pattern of liver volume restoration after laparoscopic fenestration of liver cysts was analyzed, and the mechanism for the unique restoration was investigated. METHODS: Seven patients with giant non-parasitic liver cysts underwent laparoscopic fenestration. Liver volume restoration in each section and changes in the diameter of the portal branch were analyzed after fenestration with CT or MRI. In two patients, regional liver volume restoration was assessed in detail using region-growing software, and change in portal flow distribution was estimated using computational fluid dynamics. Then, the regional liver volume restoration rate was compared with the portal hemodynamic changes. RESULTS: Liver volume restoration after fenestration was dependent on the size and position of the cysts; it not uniform throughout the remnant liver. The liver volume restoration in sections that had been compressed by giant cysts was significantly greater than in other areas after fenestration. This volume restoration was accompanied by an increase in the diameters of the portal branches in these sections. In addition, a strong correlation between the regional liver volume restoration rate and the changes in portal flow distribution existed in the computationally analyzed cases. CONCLUSION: Liver volume restoration after the fenestration of giant liver cysts non-uniformly occurs in the remnant liver. Improved portal vein circulation in the hepatic area adjacent to the excised giant liver cysts most likely regulates the greater regional volume restoration rate in the area.

Salvage treatment of laparoscopic cholecystectomy-associated bile duct stenosis combining laparoscopic and endoscopic procedures: a case report.

The incidence of laparoscopic cholecystectomy (LC)-associated bile duct injury has reached a steady state despite learning curve effect. Herein we report the case of a 74-year-old Japanese man who suffered from bile duct stenosis and stones after LC. The stenosis was due to stricture caused by surgical clips used inappropriately during LC. We planned a salvage treatment combining laparoscopic and endoscopic approaches. At laparoscopic observation, the clips had already invaded the right side of the bile duct; minimal absorbable suture was performed after all the clips were removed. The bile duct stenosis was then endoscopically dilated and the biliary stones were successfully removed. For the recurrent biliary stenosis after discharge, endoscopic balloon dilation was performed and multiple plastic stent tubes were placed. The stent tubes were removed 4 months later, and the patient has had no symptoms for 1 year. A combined laparoscopic and endoscopic approach was useful for the salvage treatment of LC-associated bile duct stenosis.

Angiogenesis is crucial for liver regeneration after partial hepatectomy.

BACKGROUND: Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. METHODS: A sFlt-1-expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti-platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. RESULTS: The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1-expressing adenoviral vector-infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1-expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. CONCLUSION: The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis.