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Patient: Female, 40-year-old Final Diagnosis: Squamous cell carcinoma of the breast Symptoms: A palpable tumor of the right breast Medication: — Clinical Procedure: Core needle biopsy Specialty: Oncology Objective: Unusual or unexpected effect of treatment Background: Primary squamous cell carcinoma of the breast is a rare type of metaplastic breast carcinoma, characterized by resistance to conventional chemotherapy agents. We report a case of metaplastic squamous cell carcinoma of the breast in which a pathological complete response was achieved after neoadjuvant chemotherapy with weekly paclitaxel and in which the patient remained disease free for 15 years and 7 months. Case Report: A 40-year-old woman had a palpable 5-cm-diameter tumor in the right breast that was diagnosed as meta-plastic squamous cell carcinoma of the breast based on core needle biopsy. The patient was initially treated with an adjuvant chemotherapy (AC) regimen consisting of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) as neoadjuvant chemotherapy. Because the tumor grew rapidly and the skin redness increased after 1 cycle of the AC regimen, 12 cycles of weekly paclitaxel 80 mg/m2 were subsequently administered. The tumor responded dramatically to paclitaxel. The patient underwent mastectomy with level II axillary lymph node dissection. No residual tumor cells were found, which indicated pathological complete response. The patient is currently disease free at 15 years and 7 months after the operation. Conclusions: To our knowledge, there are no previous reports of metaplastic squamous cell carcinoma of the breast in which pathological complete response was achieved by treatment with neoadjuvant chemotherapy with weekly paclitaxel (80 mg/m2).

There is little information on the risk factors for fat necrosis after breast-conserving surgery using an inframammary adipofascial flap (IAF).We conducted a retrospective cohort study from a single institution evaluating the risk factors for fat necrosis after breast-conserving surgery using an IAF (n = 41) performed from 2005 to 2020 for newly diagnosed stage 0-2 breast cancer or phyllodes tumor.Age (≥50 years of age vs.50 years of age), mammographic density (fatty vs. other) and operation period (before vs. after revision of surgical procedure and patient indication) were significantly associated with fat necrosis (p = 0.006, p = 0.04 and p = 0.02, respectively).Our study suggested that the use of an IAF with crescent dermis and selection of appropriate cases for IAF after breast-conserving surgery may be useful for the purpose of reducing fat necrosis. Further study is needed.

The purpose of this study was to evaluate the usefulness of a computer-aided diagnosis (CAD) scheme for improving the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images. The database included 97 ultrasonographic images with hypoechoic areas: 48 benign cases [benign lesion with benign mammary tissue or fibrocystic disease (n = 20), fibroadenoma (n = 11), and intraductal papilloma (n = 17)] and 49 malignant cases [ductal carcinoma in situ (n = 17) and invasive ductal carcinoma (n = 32)]. Seven clinicians, three expert breast surgeons, and four general surgeons participated in the observer study. They were asked their confidence level concerning the possibility of malignancy in all 97 cases with and without the use of the CAD scheme. Receiver operating characteristic (ROC) analysis was performed to evaluate the usefulness of the CAD scheme. The areas under the ROC curve (AUC) improved for all observers when they used the CAD scheme and increased from 0.649 to 0.783 (P = 0.0167). Notably, the AUC for the general surgeon group increased from 0.625 to 0.793 (P = 0.045). This study showed that the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images was improved by the use of a CAD scheme.

We introduce a method combining two oncoplastic techniques for breast-conserving reconstruction. The procedure is as follows: first, an extended glandular flap is made by undermining the breast from both the skin and the pectoralis fascia to the upper edge of the breast at the subclavicular area. After modeling the breast mound with the extended glandular flap, an inframammary adipofascial flap is made. The flap is reflected back to the breast area remodeled using the extended glandular flap. After reshaping the breast, the inframammary line is then re-shaped. This method is indicated for patients with breast cancer in the outer portion of the breast, who have small dense breasts, and have undergone a large excision of about 40% of their breast volume. We treated four patients, all of whom had either excellent or good cosmetic results with no fat necrosis.

Recently, the desmoplastic reaction has been implicated as having an important function in epithelial solid tumor biology. There have been no reports showing the relativity of invasive breast cancer and the desmoplastic reaction by a quantitative analysis of the myofibroblasts that were an important player in the desmoplastic reaction. The purpose of this study was to immunohistochemically investigate the correlation between the desmoplastic reaction and the clinicopathology of invasive breast cancer. The study included 60 patients with a known prognosis of invasive breast cancer. We quantified the expression of α-SMA as a marker of myofibroblasts in the invasive breast cancer. After staining samples for α-SMA, their expression was extracted and quantified as a relative percentage by computer-assisted image analysis. There was relatively wide variation in the expression of α-SMA with the percentage of the area from 0.68 to 28.15% (mean 8.48 ± 5.40%). The metastasis group showed significantly higher α-SMA expression compared with the no metastasis group (p

An abdominal advancement flap (AAF) is a flap that pulls the elevated abdominal skin up, creating the shape of the inferior portion of the breast by making a neo-inframammary fold. We used an AAF combined with volume displacement techniques to fill the defect left after breast-conserving surgery (BCS). Forty-one small- to medium-sized breast patients whose resection area included the lower portion of the breast underwent this procedure from October 2010 to December 2014. We evaluated efficacy of this procedure. The excision volume ranged from 10 to 35 %. Complications after surgery were observed in two patients (partial necrosis of the nipple-areola complex and partial necrosis of the breast skin in one patient each). There was no fat necrosis of the flap in any of the patients. The cosmetic results were found to be excellent in 7 cases, good in 23, fair in 9 and poor in 2. In 11 cases with an unacceptable outcome, 9 cases were in the inner portion. In patients with the tumor in the inner portion, the proportion of unacceptable cases was 50 %. In the cases other than the inner portion, the proportion of unacceptable cases was 8.7 % (p

A patient presented with a 2 cm lump in the lower outer quadrant of the left breast. Mammogram and ultrasonography showed a solid mass with a microlobulated contour, partially irregular border and microcalcifications. MRI showed an irregular mass with early enhancement and high signal intensity, and the late-phase image demonstrated a partial washout pattern. These findings suggest that the tumour was a malignant invasive carcinoma. Non-invasive ductal carcinoma was diagnosed after a fine needle aspiration and core needle biopsy followed by a partial breast excision and sentinel lymph node (SLN) biopsy. A pathological examination of the lesion displayed characteristic small monomorphic cells, solid proliferation and massive distension within the lobular unit. The tumour was immunohistochemically negative for E-cadherin and pure lobular carcinoma in situ (LCIS) was diagnosed. Pure LCIS is very rare and there have been no previous reports of pure LCIS forming a solid mass.

To elucidate the possible role of pancreatic juice reflux into the biliary tract in promoting the development of biliary carcinoma, Syrian hamsters were subjected to cholecystoduodenostomy and ligation of the distal end of the common duct and then subcutaneously injected with N-nitrosobis(2-oxopropyl)amine (BOP) (experimental group). The incidences of gallbladder carcinoma and extrahepatic bile duct carcinoma in the experimental group was significantly higher than in the sham-operated group (P < 0.01, P < 0.05). The proliferating cell nuclear antigen (PCNA) labeling indices of both regions gradually increased with time, and were significantly higher in the experimental group at weeks 9 and 16 than in the sham-operated group at the same time. Trypsin and phospholipase A2 (PLA2) activities in bile and tissue levels of superoxide dismutase (SOD) in the gallbladder and extrahepatic bile ducts were higher in the experimental group than in the sham-operated group. These findings suggest that the carcinogenic effect of BOP was enhanced in biliary epithelium that had proliferated in response to and/or had been injured by activated pancreatic enzymes refluxing into the biliary tract and then increased free radical activity, leading to a high frequency of carcinoma development in the biliary tract.

The plasma lipopolysaccharide (LPS)-binding protein (LBP) plays an important role in infection caused by Gram-negative bacteria. It is markedly increased during acute-phase responses. In this study, we cloned the full length of canine LBP cDNA and determined its amino-acid sequence and its expression in several canine tissues. The isolated LBP cDNA contained a 1443-bp coding region, which encodes a 25-amino-acid signal peptide, a 456-amino-acid mature LBP and a stop codon, and a 3'-noncoding region containing a TATTTAT motif, which is probably involved in the degradation and/or suppression of mRNA translation. The amino-acid sequence of the mature canine LBP showed 78%, 66% and 67% identity with that of human, rat and rabbit LBPs, respectively. In transient expression assays, canine and human LBPs accelerated the production of tumor necrosis factor-alpha induced by LPS in human monocytes. Northern blot analysis showed that LBP mRNA is mainly expressed in the liver and kidneys of normal dogs. In situ hybridization analysis revealed that the canine LBP mRNA is mainly located in hepatocytes and in epithelial cells of the proximal urinary tubules of the kidneys. These findings suggest that LBP is produced in organs readily exposed to LPS, where it probably plays an important role in bacterial infections, particularly in those occurring after major surgery.

A case of mucocele of the appendix associated with an increase in serum CEA level is presented. A 71-year-old man was seen at the hospital because of cough. Chest X-ray film showed no abnormal findings. However, serum CEA level was high, 14.0ng/ml. Physical examination revealed a well movable mass with smooth surface, measuring 8×4cm, in the right lower quadrant of the abdomen. Barium enema demonstrated a filling defect with smooth contour, 6×4.5cm in size, in the cecum. Colonofiberscopy showed a round submucosal tumor-like lesion. With a preoperative diagnosis of appendiceal mucocele, ileocecal resection was performed. The resected specimen showed a markedly swollen appendix, 5cm in diameter and 15cm in length. The root of the appendix was invaginated into the cecum. The appendix was histologically diagnosed as mucinous cystadenoma without any malignant changes. Immunohistochemically, the tumor cells showed a positive stain for anti-CEA antibody. The postoperative course was uneventful and the serum CEA level returned normal, 2.5ng/ml, three months after the surgery. To the best of our knowledge, a total of 40 cases of mucocele of the appendix have been reported in Japan from 1986 through 1993. Of these cases, serum CEA level was described in 19 cases. Six (31.6%) out of 19 cases showed an increase in serum CEA level.

Tenascin-C (TNC), a large hexameric extracellular glycoprotein, is a pleiotropic molecule with multiple domains binding to a variety of receptors mediating a wide range of cellular functions. We earlier reported that TNC induces epithelial-mesenchymal transition (EMT)-like change in breast cancer cells. In the present study, we clarified TNC receptor involvement in this process. Among integrins previously reported as TNC receptors, substantial expression of αv, α2, β1 and β6 subunits was detected by quantitative PCR and immunoblotting in MCF-7 cells. Integrin β6 mRNA was remarkably upregulated by transforming growth factor (TGF)-β1 treatment, and protein expression was prominently increased by additional exposure to TNC. Immunofluorescent labeling demonstrated integrin αvβ6 accumulation in focal adhesions after TNC treatment, especially in combination with TGF-β1. The α2 and β1 subunits were mainly localized at cell-cell contacts, αv being found near cell cluster surfaces. Immunoprecipitation showed increase in αvβ1 heterodimers, but not α2β1, after TNC treatment. Activated β1 subunits detected by an antibody against the Ca(2+)-dependent epitope colocalized with αv in focal adhesion complexes, associated with FAK phosphorylation at tyrosine 925. Neutralizing antibodies against αv and β1 blocked EMT-like change caused by TNC alone. In addition, anti-αv and combined treatment with anti-β1 and anti-αvβ6 inhibited TGF-β1/TNC-induced EMT, whereas either of these alone did not. Integrin subunits αv, β1 and β6, but not α2, bound to TNC immobilized on agarose beads in a divalent cation-dependent manner. Treatments with neutralizing antibodies against β1 and αvβ6 reduced αv subunit bound to the beads. Immunohistochemistry of these receptors in human breast cancer tissues demonstrated frequent expression of β6 subunits in cancer cells forming scattered nests localized in TNC-rich stroma. These findings provide direct evidence that binding of αvβ6 and αvβ1 integrins to TNC as their essential ligand induces EMT-like change in breast cancer cells.

A case of intussusception due to an invaginated Meckel's diverticulum is reported. A 51-year-old woman was admitted to the hospital because of a right lower quadrant pain which lasted for about two months and recently became colicky and intermittently. Physical examination revealed a sausage-shaped tumor of 15×8cm in size. A diagnosis of intussusception was made with ultrasonography and CT. Intraoperatively, an invaginated Meckel's diverticulum which led to intussusception was identified. Right hemicolectomy and partial resection of the ileum with an end-to-end anastomosis was performed. Histological examination of the resected specimen revealed Meckel's diverticulum containing ectopic gastric mucosa with some pylpric gland tissue. We reviewed 23 cases of Meckel's diverticulum leading to intussusception including the present case here in and discussed the clinical picture in this setting.

This paper reports a case of Crohn's disease of the colon, complicated with free perforation with a review of the Japanese literature. A 23-year-old man has been followed with the diagnosis of Crohn's disease of the entire colon in another hospital. He was admitted to the hospital because of sudden onset of abdominal pain. Plain X-ray and CT scan disclosed a free air. Emergency operation was performed with a diagnosis of free perforation of G. I. tract. A free perforation was observed in the ascending colon. Right hemicolectomy with primary anastomosis was carried out. Pathological examination revealed transmural inflammation with noncaseous granulomas and the diagnosis of Crohn's disease of the colon was confirmed. During the early postoperative course, inflammatory reactions such as spike fever and elevated CRP, persisted for 4 days, which subsided with steroid administration. The patient was discharged one and half month after the surgery without any serious complication. Free perforation of the colon is a rare complication in Crohn's disease and 16 cases have been reported so far in Japan.

Objectives A computer-aided diagnosis (CAD) scheme for determining histological classifications of breast masses is expected to be useful for clinicians in making a differential diagnosis. The purpose of this study was to evaluate the usefulness of using the CAD scheme on ultrasonographic images. Methods The database consisted of 390 breast ultrasonographic images with masses. Three experienced clinicians independently provided subjective ratings on the likelihood of malignancy for each of the 390 masses. Fifty benign masses (25 cysts and 25 fibroadenomas) and 50 malignant masses (25 noninvasive ductal carcinomas and 25 invasive ductal carcinomas) were selected as unknown cases for an observer study based on a stratified randomization method with the ratings. The likelihood of the histological classification in each unknown case was evaluated by the CAD scheme with image features that clinicians commonly use for describing masses. In the observer study, seven observers provided their confidence levels regarding the malignancy of the unknown case before and after viewing the likelihood of the histological classification. The usefulness of the CAD scheme was evaluated with a multireader multicase receiver operating characteristic (ROC) analysis. Results The areas under the ROC curves (AUCs) for all observers were improved by use of the CAD scheme. The average AUC increased from 0.716 without to 0.864 with the CAD scheme (P = .006). Conclusion The presentation of the likelihood of the histological classification evaluated by the CAD scheme improved the clinicians' performance and therefore would be useful in making a differential diagnosis of masses on ultrasonographic images.

Tenascin C (TNC) is an extracellular matrix glycoprotein up-regulated in solid tumors. Higher TNC expression is shown in invading fronts of breast cancer, which correlates with poorer patient outcome. We examined whether TNC induces epithelial-mesenchymal transition (EMT) in breast cancer. Immunohistochemical analysis of invasive ductal carcinomas showed that TNC deposition was frequent in stroma with scattered cancer cells in peripheral margins of tumors. The addition of TNC to the medium of the MCF-7 breast cancer cells caused EMT-like change and delocalization of E-cadherin and β-catenin from cell-cell contact. Although amounts of E-cadherin and β-catenin were not changed after EMT in total lysates, they were increased in the Triton X-100-soluble fractions, indicating movement from the membrane into the cytosol. In wound healing assay, cells were scattered from wound edges and showed faster migration after TNC treatment. The EMT phenotype was correlated with SRC activation through phosphorylation at Y418 and phosphorylation of focal adhesion kinase (FAK) at Y861 and Y925 of SRC substrate sites. These phosphorylated proteins colocalized with αv integrin-positive adhesion plaques. A neutralizing antibody against αv or a SRC kinase inhibitor blocked EMT. TNC could induce EMT-like change showing loss of intercellular adhesion and enhanced migration in breast cancer cells, associated with FAK phosphorylation by SRC; this may be responsible for the observed promotion of TNC in breast cancer invasion.

We defined the glandular flap including fat in the subclavicular area as an extended glandular flap, which has been used for breast-conserving reconstruction in the upper portion of the breast. Indication. The excision volume was 20% to 40% of the breast volume, and the breast density was dense. Surgical Technique. The upper edge of the breast at the subclavicular area was drawn in the standing position before surgery. After partial mastectomy, an extended glandular flap was made by freeing the breast from both the skin and the pectoralis fascia up to the preoperative marking in the subclavicular area. It is important to keep the perforators of the internal mammary artery and/or the branches of the lateral thoracic artery intact while making the flap. Results. Seventeen patients underwent remodeling using an extended glandular flap. The cosmetic results at 1 year after the operation: excellent in 11, good in 1, fair in 3, and poor in 2. All cases of unacceptable outcome except one were cases with complications, and more than 30% resection of moderate or large size breasts did not obtain an excellent result for long-term followup. Conclusion. This technique is useful for performing the breast-conserving reconstruction of small dense breasts.

We have used an inframammary adipofascial flap for breast-conserving reconstruction in the inferior portion of the breast since 2005. The aim herein is to report this oncoplastic procedure in detail, including the long-term results. The surgical procedure was as follows: A skin incision is made at the inframammary line. After partial resection of the breast, a tongue-shaped flap of the fat and the anterior sheath of the rectus abdominis muscle are pulled up in the inframammary area. The flap is then inserted into the breast area where the tumor was removed, and it is secured with absorbable sutures to the surrounding breast tissue. When making the flap, it is very important to preserve several intercostal perforators around the inframammary line. Cosmetic results at more than 5 years after the operation in the 5 patients were assessed using photographs. The results were found to be good in 4 cases (80%) and poor in 1 case. The poor outcome was a case with 100% fat necrosis of the flap. This surgical procedure is easy to perform, and the long-term cosmetic outcomes were good, without complications. We consider this procedure to be useful for breast-conserving reconstruction after breast cancer occurring in the inferior portion of the breast.

In breast-conservative therapy (BCT), it is difficult to repair defects in the inferior portion of the breast. We performed an immediate reconstruction using an inframammary adipofascial flap after breast conservation in 4 patients with breast cancer in the inferior portion of their breasts and evaluated the usefulness of the procedure. A skin incision is made at the inframammary line. Immediately following BCT, a tongue-shaped flap of the fat and the anterior sheath of the rectus abdominis muscle are pulled up and inserted to reconstruct the breast mound. The cosmetic outcomes of all patients were good, and this surgical procedure can be easily performed by general surgeons without the need of assistance by plastic surgeons. We believe this to be a useful surgical modality for the reconstruction of BCT in the inferior portion breast cancer.

To understand the mechanisms of tissue remodeling during cancer progression, it is important to know the type of cells that actively express extracellular matrix (ECM) proteins. Twenty-nine adenocarcinomas, 5 adenomas and non-neoplastic mucosa samples were therefore investigated to determine their fibronectin (FN) and tenascin-C (TN-C) expression using in situ hybridization (ISH) and immunohistochemical staining. In the non-neoplastic mucosa, no mRNA signals were found. Two of the adenomas demonstrated positive signals in peri-cryptal cells and the vessels. In the cancers, TN-C and FN mRNAs were found in 86% and 96% of the total cases, respectively. The signals were mainly detected in myofibroblasts, labeled with α-smooth muscle actin, in the cancer stroma. TN-C mRNA-positive cells were often observed in localized areas, such as in cancer stroma associated with invading edges and/or in host tissues surrounding the invading cancer front, but rarely in the center of the tumors. FN mRNA-positive cells were more widely spread throughout the cancer stroma, although they were also frequently observed at invading edges. Vascular cells in cancer tissues were also labeled. In 10 specimens, cancer cells themselves expressed FN and/or TN-C mRNA. Comparison with histo-pathological findings revealed positive relationships between the degree of mRNA expression of FN and TN-C and the depth of invasion as well as the frequency of metastasis to lymph nodes. The expression of FN and TN-C by myofibroblasts, vascular cells and cancer cells could be important for the remodeling process of neoplastic tissues during cancer development and progression. Int. J. Cancer 73:10–15, 1997. © 1997 Wiley-Liss, Inc.

Tenascin (TN)-C and fibronectin (FN), which are glycoproteins of the extracellular matrix (ECM), are up-regulated in cancer tissues, including breast cancer. For assessment of their involvement in cancer invasion, it is important to know which cells are responsible for their production and secretion. The distribution of cells expressing TN and FN mRNAs in benign and malignant human breast tissues was therefore analysed by in situ hybridization, using digoxigenin-labelled cRNA probes, in addition to demonstrating the proteins immunohistochemically. Both mRNAs were expressed in epithelial cancer as well as in stromal cells in a large fraction of the tumours, with co-expression in individual cells. In cancers with intraductal components and/or those consisting of large nests, the mRNAs were more often expressed in the cancer than in the stromal cells. In scirrhous carcinomas, in contrast, the stromal cells were almost always positive for TN and FN mRNAs, while the cancer cells only rarely exhibited TN or FN expression. In benign lesions including adenosis, fibroadenoma and intraductal papilloma, the expression patterns also varied. These findings indicate that TN and FN co-expressed by cancer cells and stromal cells are probably involved in the intraductal extension and early invasion of cancer cells and in the remodelling of cancer stroma.