A case of pseudomyxoma peritonei successfully treated with trifluridine/tipiracil (TAS-102) and bevacizumab after palliative debulking surgery.

Pseudomyxoma peritonei is a rare disease with a reported prevalence of about 1-3 per million people annually. Cytoreductive surgery and perioperative hyperthermic intraperitoneal chemotherapy are considered as treatment options improving disease control or long-term survival. However, for patients with incomplete cytoreduction or debulking surgery, outcomes are significantly poorer compared with patients who have obtained complete or optimal cytoreduction. In cases of high-grade pseudomyxoma peritonei that are considered inoperable and/or unresectable, combination chemotherapy regimen with a neo-angiogenesis inhibitor such as bevacizumab is recommended. In this report, a 62-year-old Japanese man presented with abdominal distention. Examination of ascites demonstrated a jelly-like consistency and peritoneal pseudomyxoma was suspected. To relieve progressive symptoms, palliative debulking surgery with total colectomy was performed. Postoperative pathology confirmed high-grade appendiceal mucinous neoplasm with high-grade pseudomyxoma peritonei. In our case, combination chemotherapy with trifluridine/tipiracil (TAS-102) and bevacizumab was initiated after palliative debulking surgery. As a result, carcinoembryonic antigen level was kept stable and the volume of ascites remained almost the same as at the beginning of treatment for more than 2 years. In conclusion, combination chemotherapy comprising TAS-102 and bevacizumab in patients with palliative debulking could be a useful option for patients with high-grade mucinous appendiceal neoplasm and high-grade pseudomyxoma peritonei.

[Experiences of Cardioaortic Surgery with Small Anterior Mediastinal Mass on Preoperative Computed Tomography].

Computed tomography(CT) is indispensable for diagnostic imaging. During preoperative assessment for cardioaortic surgery, a CT examination is performed not only for diagnostic purposes but also to decide the surgical strategy. In some cases, CT demonstrates a small abnormal mass in the adipose tissue of the anterior mediastinum. Sometimes radiologists diagnose the image and send the diagnostic report to cardiologists or cardiovascular surgeons. However, they tend to limit their focus to their field of specialty. Thus, they might overlook or underestimate an abnormal mass. Anterior mediastinal masses, though small, may include malignant tumors. Thus, we reviewed 12 cases in which anterior mediastinal masses were found on preoperative CT. Two of these patients were finally diagnosed with malignant tumors. We should pay attention to not only cardiovascular assessment but also mediastinal masses on preoperative CT. In some cases, concomitant surgery for cardioaortic disease and an anterior mediastinal tumor is effective.

Gastric subtype of intraductal papillary neoplasm of the bile duct: The pathologic spectrum.

BACKGROUND AND AIMS: Intraductal papillary neoplasms of bile duct (IPNBs) remain a challenging entity to manage. METHODS: The pathologic spectrum of 34 gastric subtype of IPNB (gIPNB) cases was examined in consideration of the type 1 and 2 subclassification proposed by Japan-Korea consensus and compared with gastric subtype of pancreatic intraductal papillary mucinous neoplasm (gIPMN) (44 cases). RESULTS: Type 1 gIPNBs (17 cases) showed regular papillary foveola with variable tubular pyloric glands. Eight of the type 1 gIPNBs showed low-grade dysplasia. Type 2 cases (n = 17) showed complicated papillary and tubular structures and high-grade dysplastic foveola and pyloric glands. Foveolas were predominant in 15 cases, while pyloric glands were predominant in 10 cases, and considerable areas of foveolas and pyloric glands in the remaining: these three were found similarly in type 1 and 2 gIPNB. gIPMNs showed central foveola with a peripheral pyloric gland. Such a pattern was recognizable in type 1 but vague in type 2. Type 1 was frequently found in the intrahepatic bile ducts and showed abundant mucin, as in gIPMNs, while type 2 also occurred in the extrahepatic bile ducts and were pathologically more malignant. CONCLUSION: Type 1 lesions shared features of gIPMN, while type 2 lesions differed from gIPMN and were more pathologically malignant.

Pembrolizumab-induced interstitial lung disease following thoracic surgery in a patient with non-small cell lung cancer.

The safety of treatment with immune-checkpoint inhibitors prior to thoracic surgery in patients with non-small cell lung cancer (NSCLC) remains unclear. Here, we describe the case of a 62-year-old woman with NSCLC with programmed death ligand 1 expression on 85% of tumor cells. The patient was initially considered to have unresectable stage IIIB disease and received pembrolizumab monotherapy. After 12 cycles of pembrolizumab, the primary tumor was reduced, but a small lung nodule in another lobe was unchanged. Based on the course of image findings, the nodule was considered to be an old inflammatory change. The clinical stage was changed to stage IB and partial resection was performed. Three days after thoracic surgery, the patient began to complain of coughing and shortness of breath. A CT of the chest revealed ground-glass opacity in the bilateral lung fields, suggesting interstitial lung disease (ILD) associated with pembrolizumab. Corticosteroid therapy was started and a chest X-ray showed a reduction in the opacity with improved oxygenation. This is the first case of immune-checkpoint inhibitor-related ILD triggered by thoracic surgery following long-term immune-checkpoint therapy.

[A Case of Boderline Resectable Pancreatic Cancer Curatively Resected after Chemotherapy with Gemcitabine and Nab-Paclitaxel].

Combination therapy containingnab -paclitaxel(nab-PTX)and gemcitabine(GEM)is widely administered for metastatic pancreatic cancer. Recently, this regimen is likely to be applied for treatment in patients with locally advanced disease or for neoadjuvant chemotherapy(NAC)in patients with borderline resectable(BR)pancreatic cancer. We report a case of BR pancreatic cancer in a patient who was eligible for comparison of the imaging findings with the microscopic findings of the resected specimen. A 72-year-old woman was admitted to our hospital with a complaint of jaundice. Enhanced CT showed a 35mm tumor at the head of the pancreas involvingthe portal vein and in contact with the superior mesenteric artery(SMA). After 4 courses of chemotherapy containinga combination of nab-PTX and GEM, the tumor reduced in size, but was still in contact with the portal vein and SMA on imaging. The level of tumor marker CA19-9 was remarkably reduced. Subtotal stomach-preservingpancreaticoduodenectomy with portal vein reconstruction was performed. Macroscopic findings of the cut surface of the resected specimen showed that a white nodule at the pancreas head involved the portal vein and was in contact with the close-cut margin from the SMA; however, microscopic findings revealed that tumor cells had disappeared in the plexus around the SMA. R0 resection was achieved. The histological treatment effect based on Evans' classification and TNM classification were GradeⅡ and pT3N1aM0(pStage ⅡB), respectively. There has been no recurrence 15 months after the surgery. Based on the abovementioned findings, chemotherapy containing a combination of nab-PTX and GEM can be an effective option of NAC for BR-A pancreatic cancer. Even if the tumor is in contact with the SMA on imaging, when the CA19- 9 level is markedly reduced, there is a possibility of achievingR0 surgery.

The Antemortem Diagnosis of Primary Malignant Pericardial Mesothelioma: A Multidisciplinary Evaluation.

A 64-year-old woman complaining of progressive dyspnea was admitted with recurrence of massive pericardial effusion. The patient had been diagnosed with radiation pericarditis based on a previous case of pericardiocentesis. To make a diagnosis and improve her symptoms, imaging examinations and pericardial fenestration were performed. Because of difficulty making a diagnosis, after some months, pericardiotomy and incision of the epicardium were performed. The patient was ultimately diagnosed with primary malignant pericardial mesothelioma of the epithelioid type. Primary malignant pericardial mesothelioma is a rare tumor that is difficult to diagnose. An antemortem diagnosis can be made by a multidisciplinary evaluation.

Rupture of Anterolateral Papillary Muscle Resulting From Small Artery Occlusion.

A 69-year-old man was admitted to our hospital for dyspnea and fever. Echocardiography showed a mobile mass on the anterolateral papillary muscle and severe mitral regurgitation. Coronary artery angiography showed no stenotic lesion. Infective endocarditis or cardiac tumor was suspected, and a mitral valve operation was performed. Intraoperative observation revealed a partially ruptured anterolateral papillary muscle and no evidence of infection or tumor. Pathologic examination of the resected papillary muscle showed atherosclerotic changes in small arteries and infarcted areas in different postinfarct time phases along the ruptured edge. It could be speculated that microvascular stenosis caused the repeated localized subendocardial infarction over time.

Metastatic Recurrence of Typical Pulmonary Carcinoid Accompanied by Carcinoid Syndrome, Successfully Treated with Octreotide LAR.

We present a case of metastatic recurrence of carcinoid tumor accompanied by carcinoid syndrome in a 68-year-old Japanese man, 12 years after resection of typical pulmonary carcinoid. Histopathologic examination from percutaneous liver biopsy revealed metastatic typical carcinoid. Clinical symptoms gradually improved after administration of octreotide LAR. Two years after starting treatment, the disease remains well controlled. This case report illustrates the possibility of antiproliferative effects of octreotide LAR on typical pulmonary carcinoid.

[A Case of Pathologically Complete Response of a Rectal Cancer after Preoperative Treatment with mFOLFOX6 and Radiation Therapy].

A 60-year-old man who had bloody stools after sigmoid colonoscopy was admitted to our hospital. A digital examination and sigmoid colonoscopy showed a type 2 circular tumor at location Rb with incomplete mobility and tumor hemorrhage, and the result of a biopsy was moderately differentiated adenocarcinoma (tub2). Computed tomography and magnetic resonance imaging suggested a possibility of invasion of the primary rectal tumor to the sacrum. The clinical stage was cT4bN0M0H0P0, cStage Ⅱ, which is generally not treatable by surgery. Sigmoid colostomy was performed, and a central venous port was implanted. After a preoperative treatment consisting of 3 courses of mFOLFOX6 and radiation therapy, the clinical stage changed to ycT2N0M0H0P0, ycStageⅠ. Super-low anterior resection and covering ileostomy were performed 46 days after the preoperative treatment. A pathological examination revealed no residual cancer cells in the primary lesion and lymph node (Grade 3, pCR). The patient has been disease-free for 4 years and 9 months after the operation.

Analytical performance of the cobas EGFR mutation assay for Japanese non-small-cell lung cancer.

INTRODUCTION: Clinical outcomes in non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have been reported to be correlated with the use of EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Therefore, it is essential to confirm the presence of EGFR mutations using highly sensitive testing methods. In this study, we compared the performance of the cobas(®) EGFR Mutation Test (cobas EGFR assay) and the therascreen(®) EGFR RGQ PCR Kit (therascreen EGFR assay) for use as an in vitro diagnostic (IVD) product. METHODS: We extracted DNA from 150 formalin-fixed, paraffin-embedded tissue samples from 150 patients diagnosed with NSCLC, and performed a comparative study of the cobas EGFR and therascreen EGFR assay methods. All discordant results were re-analyzed by direct sequencing. RESULTS: The concordance rate between the cobas EGFR assay and the therascreen EGFR assay was 98.0% (145/148). EGFR mutations were detected at a frequency of 40.9% (61/149) in NSCLC specimens using the cobas EGFR assay and 40.2% (60/149) using the therascreen EGFR assay. Three discrepant results were found in this study. Two double mutations were detected by the cobas EGFR assay but only one in the therascreen EGFR assay. No invalid results resulted from sample analysis by the cobas EGFR assay. CONCLUSIONS: Our results show a high concordance rate (98.0%) of cobas EGFR assay with an existing IVD product, the therascreen EGFR assay. Since they are IVD diagnostic products, both assays proved to be simple, validated methods in detecting the most common, clinically significant EGFR mutations and proved to be helpful for appropriate treatment guidance for NSCLC patients.

[A case of adenosquamous carcinoma of the sigmoid colon with inferior mesenteric vein thrombosis].

A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy.

[A case of sigmoid colon cancer with abdominal wall abscess].

A 63-year-old man was admitted for an abdominal mass. Computed tomography revealed an abscess (21 × 20 cm) in the abdominal wall and a tumor in the sigmoid colon. Thus, cancer of the sigmoid colon complicated by an abscess of the abdominal wall was diagnosed. The abscess was drained and transverse colostomy was performed with curative intent. After the intervention, chemotherapy (XELOX×3) was administered. Three months later, sigmoidectomy was performed and the stoma was closed. Macroscopic and microscopic examination of the resected specimen detected no remnants of cancer. In patients with advanced colon cancer and abdominal wall involvement, a two-stage operation and preoperative chemotherapy may be considered essential when curative resection is performed.

Ductal branch-oriented pancreatic resection for an intraductal papillary mucinous neoplasm in the uncinate process that caused recurrent acute pancreatitis: a case report of successful treatment.

Acute pancreatitis reportedly occurs in about 15 % of cases of branch duct (BD)-intraductal papillary mucinous neoplasms (IPMNs), with two-thirds of BD-IPMNs being located in the head or uncinate process of the pancreas. However, the surgical indications and optimal treatment methods for BD-IPMNs have not been established. A 59-year-old Japanese male with epigastralgia was admitted to our hospital. A multidetector row computed tomography (MDCT) scan disclosed grade I acute pancreatitis. Magnetic resonance cholangiopancreatography disclosed a 1.5-cm BD-IPMN in the uncinate process. Two months after discharge, the epigastralgia recurred, and MDCT again revealed grade I pancreatitis. Due to the repeated episodes of pancreatitis, we performed ductal branch-oriented pancreatic resection. To detect the inferior branch of the Wirsung duct and avoid the development of a pancreatic fistula, we injected indigo carmine into the tumor which confirmed ligation of the inferior branch. Histopathologically, the tumor proved to be an adenoma. The postoperative course was uneventful in both the short- and long-term follow-up and, to date, there has been no recurrence of pancreatitis, or diabetes mellitus during the 6 years since pancreatectomy. This procedure is one of the methods that can be used for the successful resection of a BD-IPMN in the uncinate process that caused recurrent acute pancreatitis.

Characterization of Propionibacterium acnes isolates from sarcoid and non-sarcoid tissues with special reference to cell invasiveness, serotype, and trigger factor gene polymorphism.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Propionibacterium acnes is the only microorganism so far isolated from sarcoid lesions. To examine whether P. acnes isolates from sarcoid tissues differ from those obtained from non-sarcoid tissues, we studied cell invasiveness, serotype, and polymorphisms of the P. acnes trigger factor protein and the two invasion-associated proteins (named PAmce and PAp60) in 35 P. acnes isolates from sarcoid lymph nodes and 127 isolates from non-sarcoid tissues. Most of the serotype I isolates (79/112; 71%), but none of the serotype II isolates (0/50) were cell-invasive. Two prominent types of trigger factors, one with and one without a 15 amino acid-residue deletion, corresponded to serotype II and serotype I, respectively. Non-invasive isolates had genomic mutations that caused more than one amino acid change in either the PAmce or PAp60 gene, with four exceptional isolates. P. acnes was finally classified into nine isotypes, and isolates obtained from sarcoid and non-sarcoid tissue did not differ. Although the finding did not link P. acnes to sarcoidosis, the present study clarified the cell invasiveness of P. acnes and the close correlation of cell invasiveness to the serotype and genotype of the two invasion-associated P. acnes genes.

Frequency and number of neuroendocrine tumor cells in prostate cancer: no difference between radical prostatectomy specimens from patients with and without neoadjuvant hormonal therapy.

BACKGROUND: Neuroendocrine tumor cells in prostate cancer are thought to increase after hormonal therapy due to neuroendocrine differentiation of tumor cells. This assumption is based on the histological analyses of limited portions of the cancerous lesions examined. METHODS: Radical prostatectomy specimens were obtained from 122 consecutive patients with prostate adenocarcinoma, 70 of whom underwent prostatectomy alone (Group A) and 52 with neoadjuvant hormonal therapy (Group B). Sections from all the 5-mm-thick slices from formalin-fixed specimens were immunostained for chromogranin-A, and the total number of choromogranin-A-positive neuroendocrine tumor cells were counted. RESULTS: No difference was found between Groups A and B in the frequency of cancer with neuroendocrine cells. The total number of neuroendocrine cells in cancer varied widely with no difference of median values in the two groups. CONCLUSIONS: These results do not support the assumption that hormonal therapy induces neuroendocrine differentiation, but suggest androgen-independent neuroendocrine cells existed before therapy.

A case of breast cancer metastatic to the tail of the pancreas.

Breast cancer metastasis to pancreas is rarely seen. There have been only 6 cases described in the literature. We present the seventh case of a 54-year-old woman with breast cancer that metastasized to the tail of the pancreas 4 years and 4 months after radical mastectomy. Although the serum levels of CA15-3 and TPA had gradually increased without symptoms, it was difficult to establish the diagnosis before contrast-enhanced abdominal CT scan was performed. Immunohistochemical staining using E-cadherin was positive, proving that the breast cancer was ductal rather than lobular in origin. CA15-3 immunohistochemically stained positive in the resected pancreas lesion. Positive monoclonal staining by GCDFP-15 (gross cystic disease fluid protein-15) in the pancreas tumor also confirmed it breast cancer origin. Investigation of chemokine/chemokine receptors may clarify a new mechanism of metastasis to the pancreas from breast cancer.

Immunoglobulin VH genes in thymic MALT lymphoma are biased toward a restricted repertoire and are frequently unmutated.

Thymic MALT lymphoma shows certain distinctive features among MALT lymphomas, such as expression of IgA isotype, consistent lack of API2-MALT1 gene fusion, and very strong association with autoimmune disease, especially Sjogren's syndrome. To help clarify the nature of the clonal lymphoid infiltrates, we analysed the usage and somatic hypermutation of the Ig heavy chain variable region (V(H)) genes in nine different cases. The V(H) rearrangement was potentially functional in all cases and was restricted to the V(H)3 family. V(H) usage was biased toward V(H)3-30 (five cases) and V(H)3-23 (three cases) segments, which have both been frequently expressed by autoimmune B cells. Somatic hypermutation was absent in five cases. Fewer than the expected replacement mutations were found in the framework regions in two cases, indicating a negative antigen selection pressure. Ongoing mutation was absent in all cases. D segment usage was varied, whereas J(H) segment usage was restricted to J(H)4. The observed patterns of V(H) usage and mutations suggested that specific antigens may play a pathologically relevant role in the genesis or progression of thymic MALT lymphoma.