A locally advanced pancreatic body cancer presenting common bile duct invasion resected via distal pancreatectomy after gemcitabine plus nab-paclitaxel chemotherapy: A case report.

INTRODUCTION: The locally advanced pancreatic cancer has been steadily recognized as a potentially curable disease by a combination of chemotherapy and surgery. The remarkable effect of advanced chemotherapy would help surgeons do a function-preserving operation for advanced pancreatic cancer. PRESENTATION OF CASE: A 73-year-old woman presenting with obstructive jaundice was diagnosed to have a 3-cm pancreatic body cancer invading the celiac axis (CA), superior mesenteric artery (SMA), portal/splenic vein confluence, and the common bile duct (CBD). A plastic internal stent tube was placed endoscopically. After 11 cycles (231 days) of a weekly doublet chemotherapy with 1000 mg/m2 of gemcitabine and 125 mg/m2 of albumin-bound paclitaxel, the tumor shrunk based on imaging done every four months during chemotherapy, with residual periarterial high-density area around CA and proximal SMA and the patient was referred for surgery. During the operation, the absence of cancer cells was confirmed at (1) the origin of the proper hepatic artery, gastroduodenal artery and the left gastric artery, and (2) pancreatic cut stump along the right border of the portal vein; thus, distal pancreatectomy with coeliac axis resection was done. The patient had postoperative adjuvant chemotherapy with 100 mg/day of tegafur/gimeracil/oteracil for half a year and is currently alive and well, without signs of recurrence and diabetes mellitus a year after surgery. DISCUSSION: Although surgical techniques aimed at local radicality are important, especially for conversion surgery for locally advanced pancreatic cancer, surgeons should consider the balance between radicality, safety, and functional preservation of surgery.

Distant Metastasis after Surgery for Encapsulated Papillary Carcinoma of the Breast: A Case Report.

In the absence of clear interstitial invasion, encapsulated papillary carcinoma (EPC) of the breast may be attributed to an extremely good prognosis if handled similarly to ductal carcinoma in situ (DCIS) with suitable local treatment. Here, we report our experience with a case of EPC of the breast that presented with carcinomatous pleuritis and lymphangitis carcinomatosa postoperatively, which rapidly resulted in a poor outcome. A 67-year-old woman was diagnosed with DCIS of the left breast and underwent left partial mastectomy and sentinel lymph node biopsy. EPC was diagnosed because the pathological examination showed no sign of interstitial infiltration. Postoperative radiation therapy was performed. Five years and 9 months postoperatively, the patient began experiencing cough and shortness of breath on exertion. Imaging showed right pleural effusion and consolidation of the lung field, but nothing suggesting local recurrence in the preserved left breast, local lymph nodes, or opposite breast was observed. Postoperative recurrence of breast cancer, carcinomatous pleuritis, and lymphangitis carcinomatosa were diagnosed based on the results of pleural fluid cytology. One month later, multiple brain metastases were found, and the patient died of the primary disease 5 months after recurrence. After surgery for EPC without clear interstitial infiltration, there was a small possibility of a poor outcome from distant metastasis. Therefore, although distant metastasis is uncommon, regular examination and testing should be performed.

Invasive Cancer Confined to the Nipple of the Conserved Breast: A Case Report.

Invasive breast cancer deriving from the milk duct and lobule that develops in the nipple is extremely rare, except in Paget's disease and skin cancer. This is the second reported case of the development of invasive cancer confined to the nipple after breast-conserving surgery. A 69-year-old woman visited our department due to redness, swelling, and bloody discharge of the right nipple in the last month. A needle biopsy was suggestive of invasive ductal carcinoma; we performed a removal surgery of the right residual breast tissue and a second sentinel lymph node biopsy. She underwent these procedures 10 years previously as well. Thus, we diagnosed the present lesion as a local recurrence, but it was unknown whether the lesion was a true recurrence or second cancer, namely, metachronal ipsilateral breast cancer. The present case helps promote awareness that invasive cancer rarely develops in the nipple after conserving surgery. Patients should be encouraged to visit a medical facility if experiencing skin changes and swelling of the nipple. Additionally, breast cancer patients must be carefully selected for breast-conserving surgery; failure to do so may later result in nipple-specific local recurrence.

Occlusion of multi-holed catheters used in continuous wound infusion in open gynecologic surgery: A pathological study.

BACKGROUND: Continuous wound infusion (CWI) with local anesthetics is useful as a method of pain management after abdominal surgery. However, there have been no studies regarding the obstruction of multi-holed catheters in this application. METHODS: We conducted from July to November 2015. In the first portion of the study, we obtained 34 catheters used postoperatively with open gynecologic surgery, and evaluated the status of each hole in vitro. Each catheter had eight holes, and we investigated the number of open holes after the removal of the catheter. In the second portion of the study, we reviewed pathological specimens from four occluded catheters. Statistical analysis was performed using the statistical software MedCalc™ (MedCalc, Ostend, Belgium), and intergroup comparisons were made with independent sample t-test. Data are expressed by mean and standard deviation. RESULTS: In each catheter, the number of remaining open holes was 0-7, and there were no catheters with all eight holes still open. Although the occlusion may be occurred after the end of infusion, 38.2% (n = 12) did not have any open holes remaining in our investigation. The composition of the emboli in the catheters was clotted blood and plasma, with a mass of fibrin and possibly some inflammation around the embolus. CONCLUSIONS: Occlusion of these catheters occurs at a very high rate, and the catheter embolus might be composed of clotted blood, plasma, and/or fibrin.

HER2-Positive Conversion in a Metastatic Liver Focus in Late Recurrent Breast Cancer.

Late recurrence of estrogen receptor (ER) positive breast cancer is common. When tissues from a recurrent or metastatic focus are available, re-evaluation of ER, progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status is recommended for treatment selection. This case report describes a 59-year-old woman who underwent surgery for left breast cancer, with a histopathological diagnosis of invasive ductal carcinoma (pathological stage T2N1aM0 Stage IIB, ER positive, PgR positive and HER2 negative). A health check-up 16 years after surgery revealed multiple hepatic mass lesions, and the patient was referred to our hospital for tests. Based on computed tomography, intrahepatic bile duct cancer or metastatic hepatic tumors were suspected, and a liver biopsy was performed. The histopathological diagnosis was a poorly differentiated adenocarcinoma (ER negative, PgR negative and HER2 positive), and the distinction from poorly differentiated intrahepatic bile duct cancer was difficult. Fluorodeoxyglucose (FDG)-positron emission tomography revealed FDG accumulation in the patient's bones and soft tissues, in addition to the hepatic tumors. The patterns and finding of metastasis were compatible with breast cancer recurrence, and the patient was diagnosed with postoperative recurrence of left breast cancer. Pertuzumab, trastuzumab, and docetaxel were started, and the therapeutic effect was assessed as a partial response. It was evident that in this case, the expression of hormone receptors and HER2 differed between the primary focus and the recurrence foci, and this contributed to the treatment strategy. Whenever possible, a biopsy should be performed for lesions that are suspected to be distal metastases.

Carcinogen-induced tumors in SFN-transgenic mice harbor a characteristic mutation spectrum of human lung adenocarcinoma.

The landscape of genetic alterations in disease models such as transgenic mice or mice with carcinogen-induced tumors has provided a huge amount of information that has shed light on the process of tumorigenesis in human non-small-cell lung cancer (NSCLC). We have previously identified stratifin (SFN) as a potent oncogene, and generated SFN-transgenic (Tg-SPC-SFN+/- ) mice, which express human SFN (hSFN) only in the lung. Here, we have found that carcinogen nicotine-derived nitrosaminoketone (NNK)-induced tumors developing in Tg-SPC-SFN+/- mice show a similar histology to human lung adenocarcinoma and exhibit high hSFN expression. In order to compare the genetic characteristics of Tg-SPC-SFN+/- tumors and human lung adenocarcinoma, the former were subjected to whole-exome sequencing. Interestingly, Tg-SPC-SFN+/- tumors showed the distinct distribution of exonic mutations and high number of mutated genes and transversion. Moreover, Tg-SPC-SFN+/- tumors showed 73 genes that were commonly detected in more than 2 tumors, mutations of which were also found in human lung adenocarcinoma. The expression levels of some of these genes were significantly associated with the clinical outcome of lung adenocarcinoma patients. Additionally, mutated genes in Tg-SPC-SFN+/- tumors were closely associated with key canonical pathways such as PI3K/AKT signaling and apoptosis signaling. These results suggest that SFN overexpression is a universal abnormality in human lung adenocarcinogenesis and Tg-SPC-SFN+/- tumors recapitulate key features of major human lung adenocarcinoma. Therefore, Tg-SPC-SFN+/- mice provide a useful model for clarifying the molecular mechanism underlying lung adenocarcinogenesis.

Bowen's Disease of the Nipple.

Bowen's disease is a type of intraepidermal squamous cell carcinoma that commonly develops in areas of the skin exposed to sunlight, such as the scalp, trunk, and limbs. Although development of Bowen's disease in other sites, such as the nipple, is extremely rare, we herein report our experience with one such case. A 76-year-old female presented to our hospital with complaints of right nipple pruritus. We diagnosed Bowen's disease via nipple skin biopsy, and the patient underwent right nipple resection. The deep tissue margin was positive for malignancy; therefore, the patient subsequently underwent right partial mastectomy. Histopathology revealed tumor cells inside the lactiferous ducts, but the resection margin was negative for malignancy. Bowen's disease of the nipple may progress from the skin to the lactiferous ducts. Clinical findings can be used to evaluate lesion progression and determine the necessary extent of skin and mammary gland resection.

Central Nervous System Lymphoma Harboring the JAK2 V617F Mutation That Developed after a 20-year History of Polycythemia Vera.

A 78-year-old man who had a 20-year history of polycythemia vera (PV) with a JAK2 V617F mutation presented with gradually progressive disturbance of consciousness. Hyper-intense lesions in the peri-lateral ventricular area and left cerebellar hemisphere were observed by T2-weighted and fluid-attenuated inversion recovery magnetic resonance imaging. Cytologic and genetic analyses of the lymphoma cells obtained from his cerebrospinal fluid established the diagnosis of B-cell lymphoma. No lesions outside of the brain were recognized. Because of his poor general condition, he was not treated actively. A postmortem analysis revealed a JAK2 V617F mutation in the lymphoma cells, suggesting their origin was a PV clone.

Intramammary Metastasis in a Patient with a History of Renal Cell Carcinoma: A Case Report.

Intramammary metastasis of renal cell carcinoma (RCC) is extremely rare, accounting for only 1.5% of all intramammary metastases. Distinguishing intramammary metastases from benign tumors and breast cancer is clinically problematic. Some patients undergo excessive surgery after a misdiagnosis of breast cancer instead of a mammary tumor. We performed a core needle biopsy (CNB) of a breast mass that developed in a 71-year-old woman after surgeries for bilateral RCC and breast cancer, leading to a diagnosis of intramammary metastasis of RCC. In this case, the CNB and immunohistochemical examination were critical for reaching a definitive diagnosis. We conclude that, when examining patients with mammary tumors, establishing their history of malignant tumors may help diagnose intramammary metastasis and select the best treatment strategy.

Endogenous reference RNAs for microRNA quantitation in formalin-fixed, paraffin-embedded lymph node tissue.

Lymph node metastasis is one of the most important factors for tumor dissemination. Quantifying microRNA (miRNA) expression using real-time PCR in formalin-fixed, paraffin-embedded (FFPE) lymph node can provide valuable information regarding the biological research for cancer metastasis. However, a universal endogenous reference gene has not been identified in FFPE lymph node. This study aimed to identify suitable endogenous reference genes for miRNA expression analysis in FFPE lymph node. FFPE lymph nodes were obtained from 41 metastatic cancer and from 16 non-cancerous tissues. We selected 10 miRNAs as endogenous reference gene candidates using the global mean method. The stability of candidate genes was assessed by the following four statistical tools: BestKeeper, geNorm, NormFinder, and the comparative ΔCt method. miR-103a was the most stable gene among candidate genes. However, the use of a single miR-103a was not recommended because its stability value exceeded the reference value. Thus, we combined stable genes and investigated the stability and the effect of gene normalization. The combination of miR-24, miR-103a, and let-7a was identified as one of the most stable sets of endogenous reference genes for normalization in FFPE lymph node. This study may provide a basis for miRNA expression analysis in FFPE lymph node tissue.

Lymphoplasmacytic Lymphoma Presenting with Diarrhea and Joint Pain Which was Successfully Diagnosed by an MYD88 Mutation Analysis.

A 55-year-old man presented to our department with diarrhea, weight loss, fatigability, and polyarthralgia. Blood tests revealed elevated soluble interleukin-2 receptor levels and IgG-type M protein positivity, without any findings that were suggestive of collagen disease. After computed tomography (CT) detected enlarged lymph nodes in the abdominal para-aortic region, lymphoma was suspected. CT-guided needle biopsy of the lymph node did not help to achieve a definitive diagnosis; however, a bone marrow test showed the pathological features of B-cell lymphoma. A genetic examination detected a MYD88 L265P mutation; the mutation analysis was valuable in diagnosing lymphoplasmacytic lymphoma in a IgM-type M protein-negative patient.

miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma.

Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941) were also included among those selected by TargetScan analysis. Real-time reverse transcription PCR (real-time RT-PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1-). Among these microRNAs, only miR-34b and miR-3941 depressed luciferase activity by targeting 3'UTR-IGBP1 in the luciferase vector. We transfected miR-34b and miR-3941 into lung adenocarcinoma cell lines (A549, PC-9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR-34b and miR-3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR-34b, we found that miR-3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR-3941 has an important role in the progression of lung adenocarcinoma at an early stage.

Excision of the urachal remnant using the abdominal wall-lift laparoscopy: A case report.

INTRODUCTION: Here, we report the surgical excision of the urachal remnant using the abdominal wall-lift laparoscopy with a camera port in the umbilicus, combined with a small Pfannenstiel incision to optimally treat the bladder apex. PRESENTATION OF CASE: A 21-year-old woman presented with periumbilical discharge and pain on urination. Contrast enhanced CT and MRI showed an abscess in the umbilical region that was connected to the bladder via a long tube-like structure. It was diagnosed as an infected urachal sinus. Partial excision of the umbilical fossa followed by dissection of the urachal remnant was easily performed using the abdominal wall-lift laparoscopy from the umbilicus down to the bladder without pneumoperitoneum or additional trocar placement. A Pfannenstiel incision was made above the pubis to get access to the junction between the urachal remnant and the bladder. Under direct vision, we succeeded in accurately dividing the remnant tract, and we adequately closed the bladder opening with absorbable sutures. This method has the advantage of easily closing peritoneal defects after excision of the urachal remnant with direct sutures under a laparoscopic view from the umbilicus. Cosmetic satisfaction was obtained postoperatively. DISCUSSION AND CONCLUSION: Urachal sinus excision using the abdominal wall-lift laparoscopy seems to surpass the previously reported methods in term of safety, cosmetics, and adequacy of surgical procedures.

Epithelioid hemangioendothelioma originating from the chest wall with rib metastases.

An asymptomatic 39-year-old woman was referred to us for an abnormal nodular opacity detected on the chest X-ray. Histopathological and further examinations revealed findings consistent with epithelioid hemangioendothelioma (EHE) originating from the chest wall with metastases to the ribs. Complete excision was performed; however, adjuvant chemotherapy was not administered because of the patient's mental disorder. There are very few reports of EHE arising from the chest wall; therefore, we present this case report with the clinicopathological features of EHE and discuss the therapeutic aspects.

Life-threatening acute heart failure due to primary cardiac undifferentiated pleomorphic sarcoma.

A 41-year-old man was admitted with acute heart failure and shock status. An echocardiogram showed a mobile tumor obstructing blood flow through the mitral valve with a stalk on the posterior left atrium (LA) wall. Emergent open-heart surgery was performed to resect the tumor (77×36×30 mm). Histological examination confirmed that it was an undifferentiated pleomorphic sarcoma. Unfortunately, positron emission tomography performed five months after surgery demonstrated a local recurrence around the right pulmonary vein and LA. We performed proton beam radiotherapy to treat the local recurrence, and it was effective. The patient has survived more than one year since the first life-threatening heart failure episode.

ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma.

Genetic abnormality in early-stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array-comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real-time genomic PCR and immunohistochemistry. The results were then verified using another set of early-stage adenocarcinomas. Array-comparative genomic hybridization indicated frequent amplification at chromosome 3q26. Of the seven genes located in this region, we focused on the epithelial cell transforming sequence 2 (ECT2) oncogene, as ECT2 amplification was detected only in invasive adenocarcinoma, and not in in situ carcinoma. Quantitative PCR and immunohistochemistry analyses also detected overexpression of ECT2 in invasive adenocarcinoma, and this was correlated with both the Ki-67 labeling index and mitotic index. In addition, it was associated with disease-free survival and overall survival of patients with lung adenocarcinoma. These results were verified using another set of early-stage adenocarcinomas resected at another hospital. Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma.

Possibility of molecular targeting therapy for the treatment of cancer of unknown primary origin by analysis of intracellular signaling molecules.

Recently, antibody-mediated epidermal growth factor receptor (EGFR) blockade has become a major research focus, and a number of clinical studies on this new treatment have been started in the field of clinical oncology. This retrospective study investigated the role of KRAS gene mutations and clinical features for possibilities for new therapies in patients with cancer of unknown primary (CUP). We investigated the role of KRAS, PIK3CA and BRAF gene mutations and clinical features for possibilities for new therapies in patients with CUP. Nine patients with metastases from an unknown primary tumor were included in this retrospective study. The KRAS, BRAF and PI3KCA mutational analyses were carried out by means of PCR using genomic DNA for each PCR reaction. The mutation rate in CUP for codon 12 or 13 of the KRAS gene and for PIK3CA was lower than that in colorectal cancer, while the same mutation rate for BRAF was almost the same in the two; this means that the EGFR antibodies can possibly treat CUP.