Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.
Neuroendocrine tumors; Pancreatic; Everolimus; Octreotide long-acting repeatable
Papillary tumor of the pineal region (PTPR) is a rare brain tumor that probably arises from ependymal cells. There are no known systemic treatments for PTPR once it is refractory to surgery and radiation. We present the first case of a durable radiographic and clinical response of a PTPR to bevacizumab, an antibody against vascular endothelial growth factor, despite multiple prior treatments. Bevacizumab may be an effective treatment for PTPR.
Pineal tumor; Bevacizumab; Angiogenesis
We report the case of a 50-year-old male former smoker. He was diagnosed as having lung adenocarcinoma and treated with induction chemoradiation therapy followed by surgery and adjuvant chemotherapy. Molecular testing revealed that his tumor had an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement. Therefore, he was treated with crizotinib when his disease recurred. He achieved a partial response, which persisted for 10 months until progressive disease was confirmed. Crizotinib was continued for 1 month and the tumor size increased slightly. At that time, crizotinib was discontinued and he participated in a clinical trial of erlotinib ± Met inhibitor; however, his disease progressed rapidly after discontinuation of crizotinib, and the diagnosis of disease flare was made. Readministration of crizotinib was started immediately; however, his disease progressed rapidly, and he died 2 days after starting crizotinib retreatment. Currently, the incidence of disease flare is unknown and it is impossible to predict who will experience it. Therefore, continuing crizotinib after disease progression may be a reasonable option to avoid disease flare.
Crizotinib; Anaplastic lymphoma kinase; Disease flare; Beyond progressive disease; Non-small-cell lung cancer
We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.
Clear cell; Carcinoma; Tumor; CT; MRI; Metastases; Renal
As the literature on afferent loop obstruction (ALO) after pancreaticoduodenectomy (PD) is very limited, standardized rules for its management do not exist. Herein, we report the case of a 65-year-old male patient with chronic ALO who had undergone PD with single Roux-en-Y limb reconstruction and adjuvant chemoradiation therapy for pancreatic head adenocarcinoma 2 years earlier. The patient was brought to the operating room with the diagnosis of radiation enteritis of the afferent loop with segmental involvement and concurrent hepaticojejunostomy (HJ) and pancreaticojejunostomy (PJ) stricture. Complete mobilization of the afferent loop, removal of the affected segment and reconstruction were performed. Reconstruction of the afferent loop was a one-way option for the surgeons because the Roux-en-Y reconstruction limited endoscopic access to the afferent loop, and the segmental radiation injury of the afferent loop ruled out bypass surgery. However, mobilization of the affected segment through a field of dense adhesions and revision of the HJ and PJ were technically demanding.
Pancreaticoduodenectomy; Roux-en-Y reconstruction; Radiation enteritis; Afferent loop obstruction; Surgery
Leukopenia and selective CD4+ lymphopenia represent major adverse events associated with the use of temozolomide (TMZ), an oral alkylating agent incorporated in the treatment of glioblastoma (GBM). The increased risk of opportunistic infections, including those caused by Pneumocystis jiroveci and cytomegalovirus, has been previously described in the literature. Here we report the case, the first to our knowledge, of a patient with pulmonary invasive aspergillosis immediately after the completion of chemoradiation with TMZ for GBM. Diagnosis was confirmed through a CT-guided lung biopsy, and the patient had excellent response to systemic voriconazole. This case illustrates that TMZ can be associated with severe opportunistic infections, presumably associated with T lymphocyte immune dysfunction, and patients exposed to this agent should be carefully monitored.
Pulmonary aspergillosis; Temozolomide; Glioblastoma; Opportunistic infections
For a long time, head injury has been considered as a possible causative factor for later development of brain tumors. However, the actual role of previous head trauma in the pathogenesis of intracranial tumors is still a matter of debate, also due to the possible medico-legal implications. Some authors have suggested several criteria for establishing a possible causal relationship between the aforementioned factors. We report a case of a left posterior paraventricular high-grade glioma which developed 20 years after a posttraumatic hematoma occurring in the same area. This case is reported in detail and the relevant literature is reviewed.
Head injury; Brain tumors; MRI
This is the first paper to report the association of cancer chemotherapy with rhabdomyolysis in children. A previously healthy, 15-year-old Japanese female was diagnosed as having alveolar rhabdomyosarcoma. She received the first cycle of multi-agent chemotherapy without any adverse effects. However, she developed severe acute rhabdomyolysis shortly after the second cycle of multi-agent chemotherapy, which consisted of etoposide, ifosfamide, actinomycin-D and vincristine. Her condition deteriorated rapidly and she was treated with mechanical ventilation and fluid replacement. After further evaluation, anticancer drugs were thought to be responsible for the rhabdomyolysis.
Rhabdomyolysis; Chemotherapy; Rhabdomyosarcoma; Child; Acute renal failure
Aggressive angiomyxoma (AA) is a rare benign soft tissue tumour usually affecting the pelvis and perineum of young women. Magnetic resonance imaging (MRI) is crucial in the management of AA patients for its diagnostic contribution and for the preoperative assessment of the actual tumour extension. Given the current development of less aggressive therapeutics associated with a higher risk of recurrence, close follow-up with MRI is fundamental after treatment. In this context, diffusion-weighted (DW) imaging has already shown high efficacy in the detection of early small relapses in prostate or rectal cancer.
We report here a case of pelvic AA in a 51-year-old woman examined with dynamic contrast enhancement and DW-MRI, including apparent diffusion coefficient mapping and calculation.
To our knowledge, this is the first description of DW-MRI in AA reported in the literature. Here, knowledge about imaging features of AA will be reviewed and expanded.
Aggressive angiomyxoma; Magnetic resonance imaging; Diffusion-weighted imaging; Dynamic contast enhancement
A 64-year-old man was initially diagnosed with rectal cancer and liver metastasis. He underwent rectal amputation and partial hepatectomy. mFOLFOX6 was begun as first-line chemotherapy, but multiple pulmonary and right femoral lymph node metastases were found 1 year postoperatively. FOLFIRI plus bevacizumab was then started, but the tumors recurred after 2 years and 11 months. The regimen was changed to cetuximab with CPT-11. The lesions partially responded after 3 months, and the patient was free from progression for 1.5 years. Four years and 7 months after the adjuvant chemotherapy was started, the metastatic lesions gradually increased again, and the regimen was changed to panitumumab. After 2 months, the lesions had markedly decreased again and showed a partial response for 6 months. Although the pulmonary lesions became progressive again, the patient has been alive for 5 years and 8 months since the first operation.
Cetuximab-resistant rectal cancer; Epidermal growth factor receptor mutation; Panitumumab
To date, there are no guidelines for a rational and more favourable sequence of treatment after docetaxel. Two drugs (cabazitaxel and abiraterone) have recently been approved as second-line treatment after docetaxel failure in metastatic castration-resistant prostate cancer (mCRPC), but there are no studies comparing abiraterone versus cabazitaxel. The most suitable drug is chosen based on the physician's opinion and the patient's characteristics. In patients with a good performance status who are able to receive either treatment, it would be convenient to begin with cabazitaxel and to reserve abiraterone in case there is a worsening of the general status, in consideration of abiraterone's more favourable toxicity profile.
We describe the case of a 74-year-old male with mCRPC who presented with an interesting and uncommon tumour dissemination (pleuropulmonary) occurring after the first standard treatment with docetaxel. Intravenous treatment with cabazitaxel 25 mg/m2 and oral prednisone 10 mg continuously was initiated. The patient received a total of 8 cycles of chemotherapy. A reduction of mediastinal adenopathies and infrarenal para-aortic stable bone involvement and an absence of pleural effusion were observed. No relevant toxicity was noted. Since February 2012, a progressive PSA increase without clinical deterioration has been noted.
The selection criteria for second- and third-line systemic treatment and the excellent response obtained with cabazitaxel in an unusual disease setting are described. The results confirm the long duration and quality of response of cabazitaxel treatment. Further therapeutic options in this group of patients are suggested.
Cabazitaxel; Castration-resistant prostate cancer; Pleuropulmonary progression
An adequately sampled tumor histology that is evaluated by an experienced neuropathologist is the current international standard for the diagnosis of high-grade gliomas. We present the case of a 30-year-old female for whom clinical and radiological information dramatically changed the histological diagnosis. We suggest a new algorithm including these parameters to refine the accuracy of histological diagnosis both for standard treatment and centrally reviewed clinical trials.
Glioblastoma; Histology; MRI
Radiation therapy has a solid role in the management of breast adenocarcinoma. It significantly reduces the rates of disease recurrence. Nevertheless, radiation therapy is not without side effects and patients who have undergone breast irradiation are at increased risk for lung disease, sarcomas, acute leukemia and esophageal cancer. We present a case of radiation-induced breast osteosarcoma 29 years after radiation therapy and lumpectomy for breast adenocarcinoma. The patient had several disease recurrences after surgical resection and was found to have pulmonary metastases.
Breast osteosarcoma; Radiation therapy; Epithelial breast cancer
Alveolar soft part sarcoma (ASPS) is an unusual soft tissue malignity, occurring in less than 1% of sarcomas and typically found in the head and neck tissues in children or, in adults, in the deep soft tissues of the lower extremities. In this report, we present a 33-year-old male with primary ASPS in the right scapular bone and discuss the radiologic features of this tumor in the context of the current literature.
Alveolar soft part sarcoma; Scapula; Lung metastasis
We present a case of cystic falx meningioma. Cystic meningioma is rare and not easy to diagnose preoperatively; it is often misdiagnosed as other tumors, including glial or metastatic tumors with cystic or necrotic changes. This study showed the potential impact of 320-row computed tomography (CT) on image-based diagnostic evaluation of cystic meningioma with special attention to the novel techniques of 4-dimensional CT angiography (4D-CTA) and CT whole-brain perfusion (CTP). 4D-CTA showed the arterial supply feeding the tumor and late enhancement of the tumor nodule, similar to that seen in meningioma by conventional angiography. CTP showed that the tumor had a higher cerebral blood flow and cerebral blood volume and a longer mean transit time than adjacent brain tissue. These findings were consistent with meningioma and reinforced the other imaging findings, resulting in the correct preoperative diagnosis. The new techniques available for 320-row CT can potentially be used to improve differential diagnosis and preoperative assessment of cystic tumors with nodules.
Cystic meningioma; 320-row area detector computed tomography; 4-dimensional computed tomography angiography; Computed tomography perfusion
Myopericytoma (MPC) is a rare kind of benign neoplasm, showing derivation from perivascular myoid cells. About 115 cases have been reported in the English literature; however, most of the literature focuses on the description and classification of pathology. The case presented here is that of a 42-year-old woman with a surgical management experience of multicentric MPC in the maxillofacial region. Although small MPC can be completely and easily excised, large MPC, especially in certain anatomic sites, necessitates careful preoperative preparation.
Complication; Management; Myopericytoma
In this case study, I report on a patient with stage IV ovarian cancer and underlying pro-inflammatory comorbidities. Initially, the patient's inflammatory condition was treated with an intensive integrative anti-inflammatory protocol using a combination of oral and intravenous nutrients and botanicals along with pharmaceutical intervention. This was followed by a standard course of chemotherapy supported by an individualized integrative protocol – with excellent response. Galectin-3 levels as well as other inflammatory and tumor markers were monitored throughout the course of treatment. Correlation with other markers, the clinical course of the disease, and symptomatology are presented. Galectin-3, a novel marker with potential clinical importance in cancer progression as well as inflammation and fibrosis, has been extensively researched in multiple in vitro, in vivo, and epidemiological studies. In this paper, a case in which galectin-3 has been used to assess and monitor patient progress is presented for the first time. This case is of further interest because of its complexity, with the coexistence of acute inflammatory conditions combined with progressing metastatic cancer. Galectin-3 monitoring reflected this complexity; nevertheless, it provided useful information and correlation with other inflammatory markers. The results suggest that monitoring serum galectin-3 as a marker for both inflammatory processes and cancer progression to a higher probability of metastasis may have clinical relevance. Additional clinical research is warranted.
Galectins; Galectin-3; Carbohydrate recognition binding domain; Ovarian cancer; Inflammation; Metastasis; Integrative protocol
Current regulatory guidelines advise 5–7 days of folic acid supplementation prior to pemetrexed. Although taking folic acid during and after pemetrexed therapy is important, it remains unclear whether premedication is truly necessary, particularly as it can be inconvenient for patients, can contribute to their anxiety by delaying chemotherapy, and can create challenges in scheduling chemotherapy.
Methods and Results
We retrospectively sought to identify and evaluate outcomes among non-small cell lung cancer patients who received less than the advised folic acid premedication. Only 8 patients were identified. However, upon critical examination of first-cycle chemotherapy outcomes, we observed no major adverse events with a shortened course of folic acid premedication.
In the very rare circumstance where urgent therapy is warranted, a healthcare provider can lookto this small case series and find modest precedent for the safe administration of pemetrexed in the absence of a full week of folic acid premedication.
Folic acid; Pemetrexed; Adverse events; Premedication
Pulmonary tumor embolism rarely occurs in epithelial-derived tumors, but it has been described in different tumor entities. Microscopic pulmonary tumor embolisms are often only discovered on autopsy. Pulmonary thromboembolism, on the other hand, is a frequent complication in cancer patients, and surgery in patients with a malignant tumor is an additional risk factor. The differential diagnosis between pulmonary thromboembolism and pulmonary tumor embolism can be challenging. In this case report, we describe the rare case of a patient with primary renal synovial sarcoma and the workup for a thrombus in the left pulmonary artery.
Sarcoma; Primary renal synovial sarcoma; Tumor embolism; Thromboembolism; Endobronchial ultrasound-guided transbronchial needle aspiration
Everolimus, a potent mammalian target of rapamycin (mTOR) inhibitor, has shown anticancer activity against various types of cancer, including renal cell carcinoma (RCC); however, little information is available on the efficacy and safety of the combination of everolimus and radiotherapy. We report a case of radiation-induced esophagitis that might have been exacerbated by the sequential administration of everolimus.
A 63-year-old Japanese man with RCC complained of back pain, and magnetic resonance imaging revealed vertebral metastases. He received radiotherapy (30 Gy/10 fractions) to the T6–10 vertebrae. Everolimus was administered immediately after the completion of radiotherapy. One week later, he complained of dysphagia, nausea and vomiting. An endoscopic examination of the esophagus showed erosive esophagitis in the middle to lower portions of his thoracic esophagus, corresponding to the irradiation field.
Clinicians should be aware that everolimus might lead to the unexpected exacerbation of radiation toxicities.
Mammalian target of rapamycin; Renal cell carcinoma; Radiation recall syndrome
Non-small cell adenocarcinoma is a frequent tumour entity with a high mortality. Insight into molecular mechanisms has led to the development of promising therapeutic options, which improve the prognosis of affected patients. There are only a few reports on molecular tumour subtypes and clinical presentation of the disease. We present the case of a patient with anaplastic lymphoma kinase (ALK)-positive adenocarcinoma of the lung with an unusual metastatic pattern.
The metastatic pattern of non-small cell lung cancer with ALK translocation may be different from other lung cancers. An uncommon clinical presentation may sensitize treating physicians to perform corresponding molecular testing in order to offer the best treatment options.
Lung cancer; ALK mutation; Gastric metastasis
Oesophageal varices and gastrointestinal bleeding are common complications of liver cirrhosis. More rarely, oesophageal varices occur in patients with non-cirrhotic portal hypertension that results from thromboses of portal or splanchnic veins.
We describe 2 young men who initially presented with varices as a result of portal vein thromboses. In the clinical follow-up, both were tested positive for a JAK2 mutation and consequently diagnosed with myeloproliferative neoplasms (MPNs). In an attempt to characterise the frequency of gastrointestinal complications in patients with JAK2-positive MPNs, we retrospectively analysed all known affected patients from our clinic for the diagnosis of portal vein thromboses and oesophageal varices. Strikingly, 48% of those who had received an oesophagogastroduodenoscopy had detectable oesophageal or gastric varices, and 82% of those suffered from portal or splanchnic vein thromboses.
While the association between JAK2, myeloproliferative disease and thrombotic events is well established, patients with idiopathic oesophageal varices are not regularly tested for JAK2 mutations. However, the occurrence of oesophageal varices may be the first presenting symptom of a MPN with a JAK2 mutation, and affected patients may profit from a close haematological monitoring to assure the early detection of developing MPN.
Oesophageal varices; Variceal bleeding; Splanchnic vein thrombosis; Portal vein thrombosis; JAK2; Myeloproliferative neoplasms
Acquired arteriovenous malformations (AVMs) can develop after uterine instrumentation. The increased risks of vascular changes, including abnormal placentation, after repeated cesarean sections are well studied. Herein, we describe a patient with delayed hemorrhage from a uterine AVM, following dilation and curettage for a cesarean scar pregnancy.
A 32-year-old G3P2 presented with a cesarean scar ectopic pregnancy managed with dilation and curettage, which incurred a 1,500-ml blood loss. Within 6 weeks, she returned with 2 episodes of vaginal bleeding. Initial angiography demonstrated a high-flow arteriovenous fistula, which was coiled. Vaginal hemorrhage recurred; repeat angiography demonstrated a large AVM. Gelfoam embolization of the bilateral internal iliac arteries reduced the vascularity of the AVM. The AVM's location, starting at the left lateral apex of the cesarean scar and extending into the parametrium, necessitated a radical hysterectomy. Pathologic examination revealed a placenta percreta extending into the parametrium.
The prevalence of uterine AVMs has increased with the rise in surgical obstetrics. In patients with a failed prior interventional procedure, surgical management is necessary to prevent life-threatening hemorrhage. The location of the AVM within the abnormal uterine scar tissue requires familiarity with radical pelvic surgical techniques that are normally used in cancer surgery in order to definitively treat this delayed obstetrical complication.
Arteriovenous fistula; Arteriovenous malformation; Cesarean scar pregnancy; Hemorrhage
Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma.
We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®), a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), as second-line treatment after progression with dacarbazine, for (wild-type BRAF) metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission.
This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.
Melanoma; Ipilimumab; Complete response
Ewing's sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO) ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen.
Extraosseous Ewing's sarcoma; Surgery; Chemotherapy; Multimodality care