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1.  A Case of Carcinoma Showing Thymus-Like Differentiation with a Rapidly Lethal Course 
Case Reports in Oncology  2014;7(3):840-844.
A 55-year-old woman underwent a total thyroidectomy for carcinoma showing thymus-like differentiation (CASTLE). The patient was referred to our hospital after the tumor was found to have directly invaded the cervical esophagus and the entire circumference of the trachea. A total thyroidectomy was performed, followed by end-to-end anastomosis of the trachea, suprahyoid release and dissection of bilateral pulmonary ligaments. No major complications, including anastomotic dehiscence or stenosis, were observed. The patient experienced some swallowing disturbances and hoarseness during the perioperative period but fully recovered. Radiotherapy to the neck was performed as an adjuvant therapy. Eleven months after surgery, lower back pain and right leg numbness developed and led to gait inability. Multiple lung and bone recurrences were observed, but no local recurrence. Palliative radiotherapy to the bone metastasis was performed. The patient died of pleural metastasis 14 months after the initial diagnosis of CASTLE.
doi:10.1159/000370306
PMCID: PMC4307009
Carcinoma showing thymus-like differentiation; Infiltrating trachea; Reconstruction
2.  Successful Interventional Treatment for Arterioportal Fistula Caused by Radiofrequency Ablation for Hepatocellular Carcinoma 
Case Reports in Oncology  2014;7(3):833-839.
Radiofrequency ablation (RFA) is commonly used as a treatment for small hepatocellular carcinoma (HCC). Although several complications such as intraperitoneal bleeding are often observed after RFA, hepatic arterioportal fistula (APF) is a less frequently occurring complication. In this study, we describe two cases of APF caused by RFA, which was successfully occluded by an interventional approach. Case 1 involved a 68-year-old man with solitary HCC in segment VIII of the liver. Both contrast-enhanced computed tomography and color Doppler sonography indicated an APF between the anterosuperior branch of the right hepatic artery (A8) and the portal branch (P8). Concordant with these findings, digital subtraction angiography (DSA) revealed an APF in segment VIII of the liver. Subsequently, the APF was successfully occluded by transarterial embolization (TAE) using gelatin sponge particles. Case 2 involved a 67-year-old man with solitary HCC in segment VII of the liver. Although he developed obstructive jaundice because of hemobilia after RFA, it was improved by endoscopic nasobiliary drainage and the systemic administration of antibiotics. In addition, color Doppler sonography revealed a disturbed flow of the right branch of the portal vein. Similar to case 1, DSA showed an APF between A8 and P8. The APF was successfully embolized by TAE using microcoils. In conclusion, it appears that the formation of APF should be checked after RFA. It is preferable to treat RFA-induced APF promptly by an interventional approach to avoid secondary complications such as portal hypertension and liver dysfunction.
doi:10.1159/000370305
PMCID: PMC4307006
Hepatocellular carcinoma; Radiofrequency ablation; Arterioportal fistula; Transarterial embolization
3.  Multifocal Adenomatous Oncocytic Hyperplasia of the Parotid Gland 
Case Reports in Oncology  2014;7(3):819-824.
Multifocal adenomatous oncocytic hyperplasia (MAOH) is a non-neoplastic lesion that is classified as oncocytosis. MAOH is a rare entity of the parotid gland and accounts for approximately 0.1% of salivary gland lesions. Here, we report a case of MAOH of the parotid gland. The patient was a 71-year-old woman who presented with discomfort at the left side of her neck. Fine-needle aspiration cytology of the parotid gland revealed a loose sheet-like cluster of round to polygonal cells with granular cytoplasm against a hemorrhagic background. The cells had round to oval, centrally located nuclei with granular chromatin and without distinct nucleoli. Histologically, the lesion was formed of many variable-sized nodules, comprising oncocyte-like cells with small round nuclei and eosinophilic granular cytoplasm that was positive for mitochondrial antibodies. The diagnosis of MAOH is difficult to make by cytology alone, because the findings overlap with those of other oncocytic lesions. In particular, the cytological findings of MAOH have not been sufficiently reported to date. A correlation of cytology and histology was expected.
doi:10.1159/000370146
PMCID: PMC4280445  PMID: 25580104
Multifocal adenomatous oncocytic hyperplasia; Parotid gland; Oncocytes; Cytology; Histology
4.  Latency Period until the Development of Thyroid Cancer in Young Patients Submitted to Radiotherapy: Report of 10 Cases 
Case Reports in Oncology  2014;7(3):810-814.
Background
Radiotherapy increases the risk of thyroid cancer (TC); patients submitted to this treatment should undergo a long-term follow-up. Our aim is to describe the features and outcomes of young patients who developed TC after radiotherapy.
Methods
At our center, patients undergoing radiotherapy directly or indirectly involving the thyroid are regularly followed up in order to detect early dysfunction or nodules. Herein, we report the cases of 10 patients who were submitted to radiotherapy and developed TC.
Clinical Findings
Seven patients were irradiated in the neck and 3 in nearby regions. The mean age at the last radiotherapy session was 10 ± 5.5 years. The average time until the appearance of the first thyroid nodule was 14 ± 4.7 years. The mean size increment of the nodules was 2.4 ± 1.6 mm/year. On the first cytology, only 2 results were suspicious of papillary thyroid cancer (PTC). All patients presented a histology of PTC. Eight were in stage I and 2 in stage II. The median follow-up from primary diagnosis to TC and beyond was 20 and 3 years, respectively.
Conclusions
In these patients, cytologies may be difficult to interpret due to persistent benign results. The threshold for surgical indication may be anticipated, considering the increased risk of TC. We report the evolution of these nodules over time, from the end of primary oncological treatment.
doi:10.1159/000369923
PMCID: PMC4280447  PMID: 25580102
Cancer survivors; Radiotherapy; Radiation-related cancer; Thyroid cancer
5.  Primary Neuroendocrine Tumor of the Testis and Osseous, Cardiac, and Lymph Node Metastases in a Young Patient 
Case Reports in Oncology  2014;7(3):815-818.
A 19-year-old patient was diagnosed with a neuroendocrine tumor (NET) of the testis and suffered from testicular pain and swelling after orchiectomy. After a comprehensive diagnosis, this tumor was shown to be a primary, metastasizing NET of the testis. Primary NETs of the testis are very rare; in the literature, only approximately 60 patients of all ages are mentioned. Less than 20% of the patients show a metastatic spread. In our patient, lymph node, cardiac, and osseous metastases have been found. It was possible to remove the lymph node metastases through surgery, and the osseous metastases were treated by means of radiation. The exploratory thoracotomy revealed a cardiac metastatic spread; however, it was so extended that a radical resection was not possible. Thereafter, the patient received palliative antiproliferative therapy with the somatostatin analogue lanreotide in the form of monthly subcutaneous injections. This treatment resulted in a stable disease situation.
Result
It is possible to administer lanreotide autogel in order to control the growth of the tumor in a young patient with a metastasizing primary NET of the testis with an impossible curative resection of the metastases.
doi:10.1159/000369988
PMCID: PMC4280448  PMID: 25580103
Neuroendocrine tumor; Testis; Somatostatin analogue; Lanreotide; Osseus metastasis; Cardiac metastasis
6.  Port-Site Metastasis of Mucinous Borderline Ovarian Tumor after Laparoscopy 
Case Reports in Oncology  2014;7(3):804-809.
We report a case of port-site metastasis after laparoscopic surgery for borderline mucinous ovarian tumors (mBOTs) without spillage and review the related literature. The patient was a 50-year-old nulligravida who presented with abdominal distension. Magnetic resonance imaging showed a 20 × 10-cm multilocular mass with various signal intensities. The wall and septa of the mass were neither thick nor enhanced. A laparoscopy was performed. An intact left ovarian tumor was observed. The weight of the tumor was 1,540 g. The final diagnosis was stage IA intestinal-type mBOT, so the patient did not undergo adjuvant therapy. Twenty-six months after surgery, the patient presented with a 3 × 5-cm palpable mass on the umbilicus. Biopsy of the mass revealed mucinous adenocarcinoma and computed tomography showed a 3.5 × 4.0-cm mass at the umbilicus without additional metastases. A laparotomy was performed and no metastasis in the peritoneal cavity was observed by gross examination. An umbilical mass resection, hysterectomy, right salpingo-oophorectomy, appendectomy, and partial omentectomy were performed. Hematoxylin and eosin-stained sections of the umbilical mass revealed glands of varying size infiltrating the stroma, immunohistologic staining for cytokeratin 7 was positive, and cytokeratin 20 was negative, but no other metastases were observed. The patient was diagnosed with port-site metastasis and invasive recurrence of mBOT. She underwent six cycles of adjuvant paclitaxel and carboplatin therapy. Large ovarian tumors should be carefully extracted without spillage of the tumor contents to prevent port-site metastasis, despite the low incidence.
doi:10.1159/000369994
PMCID: PMC4280454  PMID: 25566056
Borderline ovarian tumors; Port-site metastasis; Laparoscopy
7.  Long-Term Survival in a Case of Pleomorphic Carcinoma with a Brain Metastasis 
Case Reports in Oncology  2014;7(3):799-803.
Pleomorphic carcinoma (PC) is a rare malignant lung tumor with a poorer prognosis compared to other histological types of non-small cell lung cancer. However, several recent immunohistochemical studies revealed that a low MIB-1 index is a good prognostic marker in patients with PC. We report the case of a patient with PC and a single brain metastasis that achieved long-term recurrence-free survival following treatment with combined modality therapy. In this case, the MIB-1 index was reduced by gemcitabine-based chemotherapy, which may have led to long-term disease-free survival. The MIB-1 index may be a useful biomarker for the response to chemotherapy.
doi:10.1159/000368186
PMCID: PMC4280452  PMID: 25566055
Lung cancer surgery; Adjuvant/neoadjuvant therapy; Metastases
8.  18F-FDG PET/CT in Patients with Nodular Pulmonary Amyloidosis: Case Report and Literature Review 
Case Reports in Oncology  2014;7(3):789-798.
A 62-year-old woman was found to have multiple bilateral pulmonary nodules showing different 18F-fluorodeoxyglucose (FDG) uptakes on positron-emission tomography/computed tomography (PET/CT). Only the largest nodule in the left lower lobe showed an increased 18F-FDG uptake on PET/CT. Three nodules were surgically resected from different lobes of the left lung. Two lobes were benign and showed amyloid deposition. The largest nodule in the left lower lobe showed adenocarcinoma and a heavy amyloid deposition. Pulmonary amyloidosis should be added to the differential diagnosis for cases with multiple pulmonary nodules that show different 18F-FDG uptakes on PET/CT. To the best of our knowledge, this is the second reported case of a lung nodule consisting of adenocarcinoma and amyloid deposition.
doi:10.1159/000369112
PMCID: PMC4280457  PMID: 25566054
Amyloidosis; Pulmonary nodules; Lung cancer; 18F-FDG PET/CT
9.  Papillary Thyroid Cancer in Struma Testis with Malignant Transformation in the Lung Associated with Trisomy 17 Successfully Treated with Total Thyroidectomy and Radioiodine Ablation 
Case Reports in Oncology  2014;7(3):751-757.
Background
Struma testis is a rare entity, and there are only few reports on the malignant transformation of a testicular teratoma to papillary thyroid carcinoma in the literature. In this report, we describe the malignant transformation of struma testis with distant lung metastasis associated with trisomy 17 and a coexisting papillary microcarcinoma in the thyroid.
Case Report
A 56-year-old man presented after a left orchiectomy for an undescended left testicle. Pathologic examination identified a monodermal teratoma composed of thyroid parenchyma and associated with a 1.7-cm papillary thyroid carcinoma. Further evaluation showed a pulmonary mass on a chest CT scan. Total thyroidectomy revealed a 0.5-mm focus of papillary thyroid cancer, and removal of the lung mass confirmed metastatic papillary thyroid cancer. Array-comparative genomic hybridization of both tumors showed trisomy 17 in the struma testes and the lung metastasis. The patient responded well to radioactive iodine ablation and has no evidence of cancer 3 years later.
Conclusion
To our knowledge, this is the first case of papillary thyroid cancer in struma testes metastatic to the lung. It highlights the difficulties in treating these patients. Surgery to remove cancer foci, followed by radioactive iodine ablation, resulted in an excellent response in our patient. Interestingly, trisomy 17, which has so far been observed only in noninvasive thyroid nodules, was associated with pulmonary metastasis in our patient.
doi:10.1159/000369202
PMCID: PMC4264490  PMID: 25520651
Trisomy 17; Struma testis; Papillary thyroid cancer; Comparative genomic hybridization
10.  Remarkable Response to Neoadjuvant Therapy with Methotrexate, Vinblastine, Adriamycin, and Cisplatin for Undifferentiated Bladder Carcinoma: A Case Report and Literature Review 
Case Reports in Oncology  2014;7(3):746-750.
We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.
doi:10.1159/000369004
PMCID: PMC4264512  PMID: 25520650
Undifferentiated bladder carcinoma; Methotrexate, vinblastine, adriamycin, and cisplatin; Neoadjuvant chemotherapy
11.  Delayed Intratumoral Hemorrhage after Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma 
Case Reports in Oncology  2014;7(3):739-745.
Transarterial chemoembolization (TACE) using a drug-eluting bead (DEB-TACE) for hepatocellular carcinoma (HCC) is a new treatment method. We report on a case of delayed intratumoral hemorrhage after DEB-TACE. An 81-year-old male with hepatitis C virus-related cirrhosis was diagnosed with a HCC of 35 mm in diameter in S5 detected by dynamic computed tomography (CT) and contrast-enhanced ultrasonography (CEUS). DEB-TACE with DC Bead® and epirubicin hydrochloride was performed because the patient declined to undergo surgical resection. The treatment was completed, and the course after DEB-TACE was favorable. However, right hypochondriac pain suddenly developed about 1 month after DEB-TACE. Unenhanced CT showed an increase of the tumor diameter and intratumoral high-intensity area, which was not enhanced in the arterial phase. CEUS performed at the time of right hypochondriac pain (5 weeks after DEB-TACE) showed nonenhancement of almost the entire tumor in the vascular phase. The cause of the symptom may have been DEB-TACE-associated intratumoral hemorrhage. Tumor hemorrhage has been reported after DEB-TACE with tumors >5 cm in diameter, and the tumor locations were subcapsular in all previous reports. There has been no case of a tumor with a diameter <5 cm distinct from the subcapsular, as was observed in our patient. Incomplete embolization might be the cause of the intratumoral hemorrhage experienced by this case presenting a few risks. To obtain the therapeutic effect of DEB-TACE while preventing the adverse events, it may be important to understand the characteristics of the beads and to apply the appropriate embolization to each individual case.
doi:10.1159/000369005
PMCID: PMC4264514  PMID: 25520649
Hepatocellular carcinoma; Intratumoral hemorrhage; Transarterial chemoembolization; Drug-eluting bead; Contrast-enhanced ultrasonography
12.  Mandibular Central Mucoepidermoid Carcinoma: A Case Report and Review of the Literature 
Case Reports in Oncology  2014;7(3):732-738.
We report the case of a patient whose main complaint was swelling on the right side of the mandible when he presented to the Ear, Nose and Throat (ENT) Service. Imaging studies revealed a large homogeneous, multilocular, expansive lesion in the body of the right mandibular ramus. The lesion was poorly enhanced following intravenous contrast injection. The patient was treated with hemimandibular surgical resection, fibula free flap reconstruction and adjuvant radiotherapy. Currently, the patient is disease free and free of posttreatment complications.
doi:10.1159/000368825
PMCID: PMC4256002  PMID: 25493087
Computed tomography; Mandible; Tumor
13.  Radiotherapy for a Phalanx Bone Metastasis of a Lung Adenocarcinoma 
Case Reports in Oncology  2014;7(3):727-731.
Phalanx bone metastasis as the initial presenting sign of lung cancer is a rare presentation. Lung cancer is known to metastasize to the bone, but rarely to the fingers. A 61-year-old male smoker presented with pain in the left ring finger. Severe pain discouraged the patient from using his left hand. An X-ray of the left hand showed a lytic bone lesion. The patient was treated with finger radiotherapy. Analgesics were no longer needed and the patient was able to reuse his left hand in his everyday life. Palliative radiotherapy relieved our patient and improved his quality of life.
doi:10.1159/000368345
PMCID: PMC4256000  PMID: 25493086
Acrometastasis; Phalanx; Lung adenocarcinoma; Radiotherapy; Pain relief
14.  A Near-Complete Response to Treatment with Gemcitabine plus nab®-Paclitaxel in a Patient with Metastatic Pancreatic Cancer and Poor Performance Status: A Case Report 
Case Reports in Oncology  2014;7(3):711-717.
Patients with metastatic pancreatic adenocarcinoma and poor performance status (PS) are typically excluded from clinical trials of new systemic treatments. Due to concerns that such patients cannot tolerate the greater toxicity sometimes associated with combination chemotherapy regimens, the recommended treatment for pancreatic cancer patients with poor PS is gemcitabine monotherapy. We report the case of a 79-year-old female with pancreatic adenocarcinoma metastatic to the lungs, with multiple comorbidities and an Eastern Cooperative Oncology Group PS of 3, who achieved a rapid and prolonged objective response to gemcitabine plus nab®-paclitaxel. The patient received a total of 11 cycles of treatment. Although her disease was well controlled with gemcitabine plus nab-paclitaxel, she died just over 11 months after diagnosis as a result of her comorbid conditions compounded by treatment-related hematologic toxicity. This case suggests that patients with metastatic pancreatic adenocarcinoma and poor PS may benefit from first-line combination therapy with gemcitabine plus nab-paclitaxel. Further study of this regimen in such patients is warranted.
doi:10.1159/000368346
PMCID: PMC4255998  PMID: 25493084
Gemcitabine; Metastatic; nab®-Paclitaxel; Pancreatic cancer; Poor performance status
15.  Giant Undifferentiated Oropharyngeal Sarcoma: A Case Report and Review of the Literature 
Case Reports in Oncology  2014;7(3):718-726.
We report on a patient who presented to the Ear, Nose and Throat (ENT) clinic with swelling of the neck, dysphagia, headache, dyspnea and stridor. Imaging studies revealed an expansive heterogeneous process to the left retropharyngeal region. The mass was ovoid in shape, displaying moderate enhancement after intravenous contrast administration. Subsequently, a biopsy revealed the presence of undifferentiated sarcoma. The patient was treated with chemotherapy followed by radiation therapy, but follow-up exams at 6 months posttreatment revealed that while the tumor was stable, it persisted. Consequently, the patient was enrolled in a palliative care and pain control program and is currently being followed.
doi:10.1159/000368849
PMCID: PMC4256001  PMID: 25493085
Computed tomography; Magnetic resonance imaging; Oropharynx; Sarcoma; Chemoradiation therapy
16.  The Long-Term Outcomes of Induction Chemoradiotherapy Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer 
Case Reports in Oncology  2014;7(3):700-710.
Background
Although the concept of induction therapy followed by surgical resection for locally advanced non-small cell lung cancer (LA-NSCLC) has found general acceptance, the appropriate indications and the strategy for this treatment are still controversial.
Methods
From 2000 through 2008, 36 patients received concurrent chemoradiotherapy followed by surgery. We retrospectively reviewed these cases, analyzed the outcomes and examined the prognosis.
Results
The median radiation dose given was 60 Gy. Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered to 9 cases, and a carboplatin-based chemotherapy regimen was administered to 27. A complete resection was performed in 94% of the patients. Seventeen (47.2%) patients exhibited a complete pathological response, and downstaging was induced in 26 (72%) cases. The morbidity and 30-day mortality rates were 11.1 and 0%, respectively. The 5-year overall survival rate in the patients with complete resection (n = 33) was 83.3%.
Conclusions
Induction chemoradiotherapy followed by surgery for LA-NSCLC provided a favorable prognosis for selected patients. A complete pathological response was found in about half of cases. This strategy is feasible and was associated with low morbidity and high resectability rates, suggesting that it contributed to improving the treatment results.
doi:10.1159/000368598
PMCID: PMC4255996  PMID: 25493083
Non-small cell lung cancer; Locally advanced non-small cell lung cancer; Induction chemotherapy; Surgical resection; Prognosis
17.  Efficacy of Enteral Supplementation Enriched with Glutamine, Fiber, and Oligosaccharide on Mucosal Injury following Hematopoietic Stem Cell Transplantation 
Case Reports in Oncology  2014;7(3):692-699.
The combination of glutamine, fiber and oligosaccharides (GFO) is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO) enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT). Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3–4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days); the same was true for days of mucositis grade 3–4 (3.86 vs. 6.00 days). Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test). Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p < 0.001 and p = 0.0014, respectively). Although not significant, less gut bacterial translocation with Enterococcus species developed in the GFO group (p = 0.0728) than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.
doi:10.1159/000368714
PMCID: PMC4255989  PMID: 25493082
Glutamine; Fiber; Oligosaccharide; GFO; Mucosal injury; Hematopoietic stem cell transplantation
18.  Breast Cancer Mimic: Cutaneous B-Cell Lymphoma Presenting as an Isolated Breast Mass 
Case Reports in Oncology  2014;7(3):685-691.
Background
Primary cutaneous B-cell lymphoma typically localizes to the skin, and dissemination to internal organs is rare. Lymphomatous involvement of the breasts is also rare. We describe the clinical and radiological findings of an unusual case of primary cutaneous B-cell lymphoma presenting as an isolated breast mass without associated skin changes.
Case Presentation
The patient was a 55-year-old Caucasian female who initially presented with cutaneous B-cell lymphoma around her eyes and forehead with recurrence involving the skin between her breasts. Three years after terminating treatment due to a lack of symptoms, she presented for an annual screening mammogram that found a new mass in her upper inner right breast without imaging signs of cutaneous extension. On physical examination, there were no corresponding skin findings. Due to the suspicious imaging features of the mass that caused concern for primary breast malignancy, she underwent a core biopsy which revealed cutaneous B-cell lymphoma.
Conclusion
When evaluating patients with a systemic disease who present with findings atypical for that process, it is important to still consider the systemic disease as a potential etiology, particularly with lymphoma given its reputation as a great mimicker.
doi:10.1159/000368043
PMCID: PMC4241639  PMID: 25473394
Primary cutaneous B-cell lymphoma; Breast mass; Lymphoma
19.  Successful Crizotinib Rechallenge after Crizotinib-Induced Organizing Pneumonia in Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer 
Case Reports in Oncology  2014;7(3):681-684.
Crizotinib, a first-line anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor, has shown promising results for the treatment of locally advanced and metastatic lung cancer presenting the ALK rearrangement. On the other hand, secondary organizing pneumonia (OP) caused by anti-cancer drugs has been reported. While it is sometimes needed to rechallenge the suspected drug, the standard therapeutic strategy for secondary OP has not yet been established. We report a 60-year-old male with ALK-rearranged non-small cell lung cancer who developed crizotinib-induced OP and was successfully rechallenged with crizotinib. Six months after the rechallenge, the patient has achieved a partial response. To our knowledge, this is the first case in which crizotinib-induced OP has been successfully treated.
doi:10.1159/000366516
PMCID: PMC4224257  PMID: 25408663
Lung cancer; Crizotinib; Organizing pneumonia; EML4-ALK
20.  Long-Term Disease Control of a Pancreatic Neuroendocrine Tumor with Lanreotide Autogel®: A Case Report 
Case Reports in Oncology  2014;7(3):673-680.
The CLARINET study (ClinicalTrials.gov: NCT00353496) showed that somatostatin analogs are able to stabilize tumor growth in patients with intestinal and pancreatic neuroendocrine tumors (NETs). Here, we present a case of NET originating from the pancreatic tail that was treated with lanreotide Autogel®. A 60-year-old patient underwent resection of a pancreatic NET with splenectomy and distal pancreatectomy. Four months after surgery, there was an increase in chromogranin A levels, along with a hypercaptating lesion of approximately 3.5 cm at the residual part of the pancreatic corpus. Treatment with 30 mg monthly-administered octreotide long-acting release (LAR) was initiated. After 3 months of treatment, a control CT scan revealed diffuse metastases in the liver, although the patient presented no symptoms and liver tests were normal. Due to difficulties with the administration of octreotide LAR, treatment was switched to lanreotide Autogel® 120 mg, administered as monthly deep-subcutaneous injections. Progression-free survival, as shown by 3-monthly CT scans, was obtained for 2 years without the need to increase the lanreotide Autogel® dose, and the patient reported no side effects. After these 2 years, deterioration of the patient's clinical status and weight loss were observed, along with increased size of the liver lesions and appearance of peritoneal metastases. Chemotherapy treatment with cisplatinum-etoposide was initiated, while the lanreotide Autogel® injections were continued. After three chemotherapy cycles, a rapid decline in the patient's quality of life was noted, and she requested discontinuation of the chemotherapy and lanreotide injections. One month later, the patient died due to clinical progressive disease.
doi:10.1159/000368207
PMCID: PMC4224256  PMID: 25408662
Pancreatic neuroendocrine tumor; Somatostatin analog; Lanreotide Autogel®
21.  Variations in the Blood Phenytoin Levels during Long-Term Combined Treatment with S-1 and Phenytoin 
Case Reports in Oncology  2014;7(3):656-661.
Although combination therapy with the oral fluoropyrimidine anticancer drug S-1 and the anticonvulsant phenytoin (PHT) is known to increase blood levels of PHT and the risk of intoxication, reports on long-term monitoring of blood levels of PHT during combined S-1 and PHT treatment and a thorough understanding of their interaction are lacking. This report aims to describe interactive effects of S-1 and PHT through long-term therapeutic drug monitoring of PHT. A 72-year-old male had been prescribed oral PHT (130 mg/day) for over 20 years and started receiving S-1 therapy (80 mg/day for 4 weeks, followed by a 2-week rest) as postoperative adjuvant chemotherapy for gastric cancer. The blood PHT level was continuously monitored. Prior to receiving S-1, the patient's blood PHT concentration was 6.0 μg/ml, but it increased during S-1 therapy, reaching 22.9 μg/ml on day 84 (during a rest period of second cycle S-1 therapy). After reducing his PHT dosage to 100 mg/day, it never reached toxic levels (4.0–10.4 μg/ml). It was difficult to keep blood PHT concentrations constant because of the time lag between the period of combined use of S-1 and PHT and the timing of manifestation and disappearance of the drug interaction. The DIPS probability scale indicated a highly probable interaction between S-1 and PHT. We conclude that, when S-1 and PHT are used concurrently, occurrence and disappearance time of their interaction need to be predicted to maintain an effective and safe PHT concentration.
doi:10.1159/000368077
PMCID: PMC4299553  PMID: 25606031
S-1; Phenytoin; Drug interaction; Therapeutic drug monitoring
22.  Two Cases of Fatal Encephalopathy Related to Ifosfamide: An Adverse Role of Aprepitant? 
Case Reports in Oncology  2014;7(3):669-672.
Ifosfamide is used in the treatment of sarcomas and other tumors. It sometimes provokes encephalopathy, which is a serious complication even if it is usually reversible within 48–72 h after drug cessation. Ifosfamide is required to be activated by hepatic cytochrome P450 (CYP), especially the 3A4 subtype, leading to 4-hydroxy-ifosfamide. Ifosfamide is also converted by CYP3A4 to inactive but neurotoxic metabolites. Aprepitant is a neurokinin-1 receptor antagonist that is a potent antiemetic used in combination with 5-HT3 antagonists and corticosteroids. Aprepitant has an inhibitory effect, as well as a possible inductive effect, on CYP3A4. Since ifosfamide and aprepitant are both substrates of CYP3A4, a pharmacokinetic interaction could result in secondary effects such as the potentialization of neurological side effects. In this report, we describe 2 cases of fatal encephalopathy in patients who have received both ifosfamide and aprepitant, and we discuss the mechanisms that could be involved. Our observations draw attention to the fact that aprepitant must be avoided, or at least used with caution, in patients who are receiving ifosfamide due to the risk of severe neurological side effects.
doi:10.1159/000368184
PMCID: PMC4224236  PMID: 25408661
Aprepitant; Ifosfamide; Encephalopathy; Drug interaction
23.  Pulmonary Fibrosis Secondary to FOLFOX Chemotherapy: A Case Report 
Case Reports in Oncology  2014;7(3):662-668.
A 54-year-old female presented with a 2-week history of increasing shortness of breath and fever. She had a history of a poorly differentiated sigmoid adenocarcinoma for which she underwent an anterior resection 6 months prior to admission, followed by 12 cycles of adjuvant FOLFOX chemotherapy. The patient was treated for a severe community-acquired pneumonia; however, she remained hypoxic. A chest CT revealed extensive right-sided fibrotic changes, tractional dilatation of the airways and ground glass density, which had developed since a staging CT scan performed 2 months previously. Although her symptoms improved with steroid therapy, repeat imaging revealed that right hydropneumothorax had developed, and this required the insertion of a chest drain. Following its successful removal, the patient continues to improve clinically and radiographically. The rapid onset and nature of these changes is consistent with a drug-induced fibrotic lung disease secondary to FOLFOX chemotherapy. The phenomenon is underreported and yet, it is relatively common: it occurs in approximately 10% of patients who are treated with antineoplastic agents, although information specifically relating to FOLFOX-induced pulmonary toxicity is limited. It is associated with significant morbidity and mortality, but is often hard to differentiate from other lung conditions, making the diagnosis a challenge. Pulmonary toxicity is an important complication associated with antineoplastic agents. It should be considered in any patient on a chemotherapeutic regimen who presents with dyspnoea and hypoxia in order to try to reduce the associated morbidity and mortality.
doi:10.1159/000368185
PMCID: PMC4224254  PMID: 25408660
Pulmonary fibrosis; Interstitial pneumonia; Chemotherapy; FOLFOX; Pneumothorax
24.  Testicular Metastasis of Prostate Cancer: A Case Report 
Case Reports in Oncology  2014;7(3):643-647.
The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA) level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b) prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.
doi:10.1159/000367779
PMCID: PMC4209256  PMID: 25408658
Prostate cancer; Testicular metastasis; Orchiectomy
25.  Intensified Neoadjuvant Chemotherapy with Nab-Paclitaxel plus Gemcitabine Followed by FOLFIRINOX in a Patient with Locally Advanced Unresectable Pancreatic Cancer 
Case Reports in Oncology  2014;7(3):648-655.
The prognosis of patients with locally advanced pancreatic cancer can be improved if secondary complete (R0) resection is possible. In patients initially staged as unresectable this may be achieved with neoadjuvant treatment which is usually chemoradiotherapy based. We report the case of a 46-year-old patient with an unresectable, locally advanced pancreatic cancer (pT4 Nx cM0 G2) who was treated with a sequential neoadjuvant chemotherapy regimen consisting of 2 cycles of nab-paclitaxel plus gemcitabine followed by 4 cycles of FOLFIRINOX. Neoadjuvant chemotherapy resulted in secondary resectability (R0 resection). After 2 cycles of nab-paclitaxel plus gemcitabine, the patient already had a complete metabolic remission as measured by integrated fludeoxyglucose (18F) positron emission tomography and computerized tomography. After a follow-up of 18 months the patient is alive without progression of disease. We propose to assess the clinical benefit of sequencing the combinations nab-paclitaxel plus gemcitabine and FOLFIRINOX as neoadjuvant therapy for patients with locally advanced and initially unresectable pancreatic cancer in a controlled clinical trial.
doi:10.1159/000367966
PMCID: PMC4209279  PMID: 25408659
Pancreatic cancer; Locally advanced disease; Neoadjuvant chemotherapy; Nab-paclitaxel; Gemcitabine; 5-Fluorouracil; Folinic acid; Oxaliplatin; Irinotecan

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