[Successful Continuation of Treatment in Advanced Colorectal Cancer by Switching to a Prior Biologic Agent after Emergence of Bevacizumab Allergy to a Biosimilar Drug-A Case Report].

Biosimilar(BS)drugs have recently been introduced owing to concerns with healthcare economics. In this report, we present a case in which a patient discontinued bevacizumab treatment following an allergic reaction to a BS formulation of bevacizumab but was able to safely continue treatment by switching to an original bevacizumab formulation in the late-line setting. The patient was a 66-year-old man diagnosed with unresectable colorectal cancer with synchronous multiple liver metastases. After primary tumor resection, chemotherapy including the original bevacizumab formulation was initiated. Allergic reactions to the BS formulation of bevacizumab occurred during the second-line treatment; however, in the late-line setting, switching back to the original bevacizumab formulation enabled the safe continuation of therapy. Overall, our case study suggests that switching of biologic agents may contribute to the ongoing management of chemotherapy.

[Long-Term Suppression with Short-Term Dose Reduction of Imatinib for Metastatic Lateral Lymph Nodes after Resection of a Rectal Gastrointestinal Stromal Tumor-A Case Report].

CASE: An 83-year-old female. At 82 years of age, the patient sought evaluation with a complaint of rectal bleeding. A 35-mm rectal gastrointestinal stromal tumor(GIST)was treated by laparoscopic ultra-low rectal resection and transanal anastomosis following trans-anal rectal dissection by perineal manipulation. Approximately 1 year later, a 20-mm metastatic lymph node within the right lateral lymph node group at the pelvic cavity was detected. The patient was diagnosed with a recurrence of rectal GIST. The patient had no symptoms and did not wish to undergo surgery. After 7 weeks of treatment with an imatinib dose reduction(200 mg), the dosage was increased and the patient was admitted to the hospital with edema of the face and lower limbs, and pleural and pericardial effusions(grade 2). After discharge from the hospital, the medication was terminated early at the patient's request. One year later, the lymph nodes had decreased in size to 7.5 mm, indicating a partial response. The treatment-free period continued, and after 5 years at 89 years of age the lymph nodes had not enlarged, thus the patient was thought to be clinically cured. We report a rare case of long-term tumor suppression using short-term low-dose imatinib therapy.

Histopathological study on the prevalence of trichosporonosis in formalin-fixed and paraffin-embedded tissue autopsy sections by in situ hybridization with peptide nucleic acid probe.

Trichosporon species are some of the most common pathogenic yeasts in Asia, and many are resistant to echinocandin antifungal drugs. Effective treatment of fungal infections requires the selection of appropriate antifungals and the accurate identification of the causal organism. However, in histopathological specimens Trichosporon spp. are often misidentified as Candida species due to morphological similarities. In situ hybridization (ISH) is a useful technique for identifying fungal species in formalin-fixed and paraffin-embedded (FFPE) tissue sections. Although many novel probes for ISH are available, the practical use of ISH for identification of fungi remains limited, in part due to the lack of adequate verifications. We conducted a two-center retrospective observational study in which the ISH technique was used to differentiate Trichosporon spp. and C. albicans in FFPE tissue from autopsy specimens. The study included 88 cases with blood stream yeast infection without Cryptococci extracted from 459 autopsy files of cases with proven invasive fungal infection (IFI). Positive signals for the Trichosporon spp. protein nucleic acid (PNA) probe and C. albicans PNA probe were seen for 7 and 35 cases, respectively, whereas the remaining 46 were negative for both. For the Trichosporon spp.- positive specimens, 5/7 were reported as candidiasis in autopsy records. Our results suggested that accurate histological identification of fungal infections remains challenging, but ISH may be a suitable approach to support histological findings. In addition, this retrospective study suggested that trichosporonosis may have high prevalence among cases of bloodstream yeast infections in Japan.

Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma.

A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.

[In two patients with economic and social issues stage I giant seminoma].

The first case was in a 39-year-old man who complained of painless, left hemiscrotal swelling. The patient's serum ß human chorionic gonadotropin (ß-hCG) was elevated. A chest X-ray and computerized tomography (CT) did not reveal any abnormal findings. The patient underwent left high orchiectomy. The tumor weighed 440 g, and was pathologically diagnosed as a seminoma. The patient chose surveillance as the management strategy. Five months after the operation, the patient stopped attending his periodic checkups. After 21 months, the patient complained of abdominal distention. A CT showed a para-aortic lymph node mass. The patient achieved a complete response following chemotherapy with etoposide and cisplatin for 4 cycles. Three months after the adjuvant chemotherapy, hospital visits stopped again due to financial difficulties. The second case was in a 36-year-old man who complained of painless, right hemiscrotal swelling and difficulty in walking. Clinical examination revealed an adult-head-sized testicular tumor with elevation of serum lactic dehydrogenase (LDH) and ß-hCG. A chest X-ray and abdominal CT did not reveal any abnormal findings. Despite a recommendation that the patient undergo immediate orchiectomy, the patient did not undergo surgery due to his unstable lifestyle. After 1 month, the patient presented with more difficulty in walking. The patient underwent right high orchiectomy. The tumor weighed 1,926 g, and was pathologically diagnosed as a seminoma. The patient chose surveillance. There has been no recurrence for 19 months postoperatively.

A Rare Case of Completely Calcified Lumber Juxta-facet Cyst: A Case Report.

Introduction: Juxta-facet cysts (JFCs) are extradural lesions. Calcification of cyst walls is often reported, although completely calcified facet cysts are extremely rare. Case Presentation: A 65-year-old man presented with a 1-year history of the right lower extremity weakness and pain, and chronic low back pain. Imaging showed hypointensity on T1- and T2-weighted magnetic resonance images which can be very well appreciated on a completely calcified computed tomography mass arising from the right L3/4 facet joint. The patient underwent a total cyst removal with a facetectomy of the right L3/4 facet, and L3 to L4 posterior fusion. Conclusion: We presented a case of a completely calcified JFC in a patient with back pain and radiculopathy who underwent cystectomy and spinal fusion. JFCs should be considered in the differential diagnosis of calcified extradural lesions.

Leiomyosarcoma with partial rhabdomyoblastic differentiation: first case report of primary cardiac origin.

BACKGROUND: Leiomyosarcoma occurring as a primary cardiac tumor has been known as an extremely rare condition. Previous studies of leiomyosarcoma with rhabdomyoblastic differentiation have conducted to those arisen from another site, and they indicated a poorer prognosis of this tumor. CASE PRESENTATION: A 69-year-old woman was referred to our hospital for an operation concerning umbilical hernia. Subsequent imaging examinations before an operation indicated the presence of primary cardiac malignant tumor due to its atypical shape. And then, it was surgically removed. Histopathologically, tumor cells consisted of two different types: spindle and polyhedral cells. Immunohistochemically, it is interesting to note that 2.1% of spindle cells and 23.1% of polyhedral cells showed positive reactivity for myogenin. Furthermore, we performed double-immunostaining for alpha-smooth muscle actin (SMA) and myogenin. The rates of alpha-SMA and myogenin double negative, alpha-SMA single positive, myogenin single positive, and alpha-SMA and myogenin double positive in spindle cells were estimated as 69.1%, 28.8%, 1.1% and 1.0%, respectively. In contrast, the rates in polyhedral cells were estimated as 76.9%, 0.0%, 23.1%, and 0.0%, respectively. CONCLUSION: Our immunohistochemical evaluation suggested that rhabdomyoblastic differentiation in leiomyosarcoma might be generated not only by de novo generation from mesenchymal cells. To the best of our knowledge, this is the first case of primary cardiac leiomyosarcoma with partial rhabdomyoblastic differentiation.

Breast implant-associated anaplastic large-cell lymphoma: first case detected in a Japanese breast cancer patient.

This paper details the first breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) case detected in Japan. The patient, a 67-year-old Japanese woman, was diagnosed with left unilateral breast cancer 17 years ago. Induration and redness presented in the left breast, which had undergone immediate breast reconstructive surgery using a tissue expander, later replaced by a silicone breast implant (SBI). Breast ultrasound showed fluid collection around the SBI. Surgery was performed to remove the left breast implant and the fragmented capsule surrounding the implant. Postoperative pathological findings did not indicate malignancy. Nine months later, a contralateral axillary lymphadenopathy was observed, and an excisional biopsy of the axillary lymph node was performed. The patient was diagnosed with BIA-ALCL and successfully underwent adjuvant CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy.

[Pathophysiology of invasive fungal infection in diabetic patients].

It has been known that diabetes mellitus impairs functioning of neutrophil, macrophage, cellular immunity, humoral immunity, and iron metabolism. In addition to them, diabetes-related angiopathy leads a patient to being at high-risk individual for several kinds of infectious diseases. Therefore, diabetes has been accepted as one of the important risk factors for invasive fungal infection. From the viewpoint of pathology, the present review describes both pathophysiology of immunosuppression induced by diabetes and histopathological characteristics of typical forms in invasive fungal infection when it occurred as an opportunistic infection; those are candidiasis, aspergillosis, and cryptococcosis. We wish to draw that pathophysiological explanation still remains obscuring of relationship between diabetes and invasive fungal infection.

A case of concomitant occurrence of struma ovarii and malignant transformation of cystic teratoma.

A 77-year-old woman received a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of a tumor in the left ovary. The surgical specimen measured 8.5x4.5x4.0 cm, and the solid lesion measured 4.0x3.5x3.5 cm. The solid lesion was diagnosed as struma ovarii. The cyst wall partially comprised squamous epithelium-like and ciliated columnar epithelium-like cells. The tumorous lesion of the cyst wall revealed a poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin7, and were negative for cytokeratin20 and thyroid transcription factor-1. The authors diagnosed that struma ovarii and other parats coexisted as a poorly differentiated adenocarcinoma that had arisen from a mature ovarian cystic teratoma. As for the identification of the origin of adenocarcinomas arising from mature ovarian cystic teratomas, more cases need to be identified and investigated.

Cellular kinetics and K-ras codon 12 mutations according to histomorphometric type of colorectal polyps with epithelial serrated proliferation.

Recent studies have examined cellular kinetics and genetic abnormalities in colorectal polyps with epithelial serrated proliferation (CP-ESP), including hyperplastic polyps, serrated adenomas, and tubulovillous adenomas. However, difficulty in histologically classifying these lesions and the lack of clear-cut diagnostic criteria have led to inconsistent findings. Some 60 cases of CP-ESP and 6 cases of CP-ESP with malignant transformation were studied. When nuclear size progressively decreased from the bottom and middle layers to the surface layer of the crypts, maturation gradient was considered positive. CP-ESP and CP-ESP adjacent to carcinoma were morphologically classified as being positive or negative for maturation gradient and inferior and lateral glandular branching. Cellular kinetics were evaluated using Ki-67 immunostaining, and polymerase chain reaction (PCR)-dependent preferential homoduplex formation assay was performed to detect the presence or absence of K-ras codon 12-point mutations. CP-ESPs were morphologically classified into five types. In CP-ESP of types 1 to 4, the proliferation zone was confined to the bottom layer of the crypts or extended from the bottom to middle layers. In contrast, the proliferation zone extended throughout the crypts in most type 5 lesions. K-ras codon 12 mutations were detected in only types 3 and 5 CP-ESP. The five histomorphologic types of CP-ESP have distinct patterns of cellular kinetics. Histomorphologically, type 3 CP-ESP is considered an atypical hyperplastic polyp, occasionally associated with an elongated proliferation zone or K-ras mutations. Preliminary evidence indicates some relation between K-ras mutations and structural atypia associated with lateral branching of the crypts.

Expression of vascular endothelial growth factor and basic fibroblast growth factor in small adenocarcinomas.

The expression of two angiogenetic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in small adenocarcinomas (

Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung.

The purpose of this study was to investigate the possible association between expression of survivin, pathological findings in the tumor and survival in patients with small adenocarcinoma of the lung. Seventy-nine patients with resected tumors <2 cm in diameter were entered into the study. There were 33 males and 46 females, with a median age of 64 years (range 26-83 years). The pathological stage of the tumors was recorded as stage I, II, III and IV in 72, one, five and one case, respectively. Each patient underwent curative surgical resection for lung cancer between July 1992 and November 1999. The resected tumors were subjected to immunostaining for survivin. Thirty-eight patients had tumors with < or = 10% survivin-positive cells and 41 patients had tumors with >10% survivin-positive cells. When survivin expression and pathological findings in the resected tumors were analyzed, the frequency of venous invasion was significantly higher in the survivin-positive group (36.6% vs. 13.2%; p=0.0167). In contrast, the overall survival of survivin-positive patients (n=41) was significantly worse than that of individuals whose tumors were negative for survivin expression (n=38; log-rank test, p=0.014; Wilcoxon test, p=0.021). It can be concluded that the expression of survivin in tumor cells is a factor of poor prognosis in patients with small adenocarcinoma of the lung.

Expression of cyclin D1 but not of cyclin E is an indicator of poor prognosis in small adenocarcinomas of the lung.

We investigated the significance of cyclin D1 and cyclin E expression in resected tumors on the survival of patients with small adenocarcinomas of the lung. Seventy-two patients with resected tumors <2 cm in diameter and of pathological stage I were entered into the study. There were 29 males and 43 females, with a median age of 64 years (range 26-83 years). The patients underwent curative surgical resection for lung cancer between July 1992 and November 1999. The resected tumors were subjected to immunostaining for cyclin D1 and cyclin E expression. Twenty-six patients had tumors with >20% cyclin D1-positive cells, but only 1 patient had a tumor with >20% cyclin E-positive cells. When the survival of 72 patients was compared in relation to their oncogene expression, the overall survival of patients with positive expression of cyclin D1 was significantly worse than that of individuals whose tumors had negative expression of the gene (log-rank test p=0.0049). Increased expression of cyclin D1 but not of cyclin E is an indicator of poor prognosis in patients with small adenocarcinomas of the lung.

Increased expression of integrin beta1 is a poor prognostic factor in small-cell lung cancer.

The purpose of this study was to investigate the possible association between the expression of integrin beta1 and response to chemotherapy and survival in patients with small cell lung cancer (SCLC). One-hundred and four patients with SCLC, who had received an initial course of chemotherapy between February 1989 and July 1999, were entered into the study. There were 91 males and 13 females, with a median age of 65 years (range 40-85 years). The clinical stage of the tumors was recorded as limited disease in 43 patients and extensive disease in 61. Each patient received a full-dose of combination chemotherapy. Transbroncheal biopsy specimens of tumors obtained before chemotherapy were subjected to immunostaining for integrin beta1. Twenty-nine patients could not be evaluated for integrin beta1 immunostaining, because the tissue samples had been crushed during the biopsy procedure. Fifty-three patients had tumors with < or = 25% integrin beta1-positive cells and 22 patients had tumor with > 25% integrin beta1-positive cells. Among 75 patients whose biopsy specimens were evaluable for integrin beta1, the overall response rate to chemotherapy was 87%. When the relationship between integrin beta1 expression and tumor response to chemotherapy was considered, 17 out of 22 patients with high expression of integrin beta1 and 48 out of 53 patients with low expression of integrin beta1 showed tumor response, although the resistance rate in patients with high expression of integrin beta1 was over twice that of patients with low expression of integrin beta1 (23% vs. 9%, respectively). By comparison, the overall survival of patients with high expression of integrin beta1 (n = 22) was significantly worse than that of individuals whose tumors had low expression of integrin beta1 (n = 53; log-rank test, p=0.043; Wilcoxon test, p=0.049). The association between survival and prognostic factors was examined by multivariate regression analysis; clinical stage and integrin beta1 were found to be independent factors (p = 0.018 andp = 0.041, respectively). In conclusion, the high expression of integrin beta1 in tumor cells is a poorprognostic factor in patients with SCLC.

Therapeutic bronchoscopy followed by lobectomy for pulmonary sarcoma.

Malignant central airway obstruction is a life-threatening presentation requiring emergency palliative procedure. In selected patients, bronchoscopic intervention could be used as a bridge to curative resection. Here we report a 54-year-old male with pulmonary sarcoma of the right upper lobe, presenting with acute respiratory failure because of endobronchial extension. Emergency coring with the rigid bronchoscope and Dumon stent insertion stabilized the patient, and subsequent lobectomy resulted in occurrence-free survival over a 71-month follow-up.

Histopathological evaluation of the efficacy of antifungals for experimental Trichosporon bloodstream infection.

The efficacy of polyene macrolides to treat experimental Trichosporon bloodstream infection was evaluated by histopathological examination and viable cell counts in the kidneys of infected mice. Viable cell counts on the 5th day after infection confirmed that liposomal amphotericin B (L-AMB) is a more effective treatment than fluconazole (FLC) for mice infected with an azole-resistant strain of Trichosporon. Histological examination revealed that the administration of L-AMB induced a transformation from acute purulent inflammation caused by both azole-susceptible and -resistant strain infections to a chronic and subsiding form, whereas FLC failed to convert the acute inflammation induced by the azole-resistant strain to a subsiding form. Our results demonstrate that polyene macrolides can be used as an alternative therapy for infection of azole-resistant strains of Trichosporon and that histopathological evaluation is useful for elucidating the pathophysiology of an experimental Trichosporon infection.

Recovery of lung perfusion after sleeve resection for tuberculous bronchial stenosis.

Parenchyma-sparing main bronchial sleeve resection is a safe and effective procedure to restore impaired lung function. We present a case illustrating recovery of lung perfusion in a 24-year-old woman with dyspnea on exertion because of bronchial tuberculosis. Bronchoscopic examination revealed pin-hole stenosis of the left main bronchial orifice. 99mTc-macroaggregated albumin perfusion scanning revealed essentially absent left lung perfusion. Because of bronchomalacia in the distal portion, six rings of the left main bronchus were resected by carinoplasty. Symptoms abated and perfusion recovered to a large extent 2 months later. She became pregnant and delivered successfully 12 months postoperatively.

Pathological response and prognosis of stage III non-small cell lung cancer patients treated with induction chemoradiation.

AIM: The aim of this study was to clarify the relationship between pathological effects and the prognosis of patients with stage III non-small cell lung cancer (NSCLC) treated with induction chemoradiation. METHODS: Patients who were untreated and potentially resectable with stage III NSCLC were enrolled. They received carboplatin and docetaxel with concurrent radiotherapy (5 × 2 Gy/week with a total dose of 40 Gy) followed by surgery. We assessed the relationship between the pathological effect (Ef) (Ef 1: slight pathological response, Ef 2: moderate pathological response, Ef 3: complete pathological response) and prognosis. RESULTS: In all, 30 patients with stage III NSCLC (24 men and 6 women, mean age 60.7 years, 17 with adenocarcinomas and 13 with squamous cell carcinomas, 21 with clinical stage IIIA and nine with stage IIIB) participated in the trial and underwent induction chemoradiation. A total of 27 patients (90%) with complete response, partial response and stable disease had surgical resection. The pathological effect was Ef 1 and Ef 2 in 10 patients each, and Ef 3 in seven patients. Median survival was 10.9 months in patients with Ef 1 and 49.6 months in patients with Ef 2. Six out of seven Ef 3 patients are alive at the time of writing with a mean survival of 77.1 months (14-104 months). There was a significant difference in overall survival based on pathological effect rating (P = 0.0036). CONCLUSION: The Ef rating was well correlated with prognosis after induction chemoradiation.

First case report of acquired pure red cell aplasia associated with micafungin.

A 70-year-old Japanese man with chronic kidney disease under treatment with oral prednisolone for organizing pneumonia developed pulmonary aspergilloma. The patient was started on micafungin (MCFG), with no addition of any other new drug. About 5 weeks later, aggravation of his normocytic anemia associated with a low reticulocyte count was observed. Bone marrow puncture and biopsy revealed intense hypoplasia of the erythroblasts. As there was no evidence of malignancy, human parvovirus B19 infection, autoimmune diseases or hemorrhage, the patient was diagnosed as having acquired pure red cell aplasia (PRCA). The anemia improved along with an increase of the reticulocyte count to the normal level within 12 weeks of discontinuation of the MCFG therapy. The patient showed no evidence subsequently of any recurrence of the normocytic normochromic anemia or relapse of the PRCA. This is the first reported case of PRCA associated with MCFG.