Simin Schadmand-Fischer

Gemcitabine in combination with EGF-Receptor antibody (Cetuximab) as a treatment of cholangiocarcinoma: a case report

BackgroundExtensive disease of cholangiocarcinoma (CC) determines the overall outcome and limits curative resection. Despite chemotherapy, which has been introduced to improve the outcome of biliary tract malignancies, the benefit in survival is still marginal.Case presentationWe report a 69-year-old patient with non-resectable CC showing hepatic metastasis and peritoneal carcinomatosis. Diagnosis was based on computed tomography, mini-laparoscopy and bioptic specimens. Histology revealed an adenocarcinoma of the biliary tract with expression of epithelial growth factor receptor. After informed consent the patient received experimental gemcitabine (1000 mg/m2) every other week and cetuximab (250 mg/m2) weekly for palliative chemotherapy. During the reported follow up (since time of first presentation) 20 cycles of chemotherapy were administered. Relevant chemotherapy-related toxicity was limited on gemcitabine-associated side effects. Predominantly, haematological toxicity (CTC, grade 3) and neutropenic fever (CTC, grade 3) promoted by catheter-related sepsis were observed. Cetuximab caused only mild skin toxicity (CTC, grade 1).Chemotherapy led to a partial response (> 30% reduction, according to RECIST) of the target lesions and disappearance of the peritoneal carcinomatosis as shown by computed tomography. Partial response occurred after 17 weeks of treatment and remained stable during the entire course of chemotherapy for 9.7 months. In parallel, Ca 19-9 serum levels, which were elevated 5-fold at time of diagnosis, returned to normal after 16 weeks of treatment. The performance status stabilized and intravenous alimentation could be discontinued.ConclusionOur experience from one patient with CC suggests, that a combination of cytotoxic chemotherapy together with cetuximab may show promising efficacy in respect to survival and quality of life. Therefore cetuximab, as a component of palliative chemotherapy in biliary tract cancer, needs further evaluation in prospective randomized trials.

Diagnosis and Treatment of Pancreatic Metastases of a Papillary Thyroid Carcinoma

BACKGROUND Apart from regional lymph node metastases, systemic metastases occur sporadically in papillary thyroid carcinomas (PTC). The lung and bones are the most frequent localizations. Additionally known but extremely rare locations are metastases of the skeletal muscles, ovaries, submandibular gland, sphenoidal sinus, brain, adrenals, and, as shown in only two previously published cases to date, the pancreas. SUMMARY In this article we report about two additional patients with pancreatic metastases from PTC. There is almost no prior experience about therapeutic approaches to this type of metastases. In both patients distant metastases within the pancreas were successfully removed. Postoperative histology confirmed the diagnoses. Supplemental genetic analysis did not demonstrate a BRAF V600E mutation or expression of a RET/PTC1 rearrangement in one case, but revealed a BRAF V600E mutation in the second case. Surgery avoided impending complications maintaining quality of life. One patient had a tumor-specific survival of 42 months. The other patient has occult disease. CONCLUSIONS Our two patients benefited of a calculated aggressive surgical action. Thus, if low perioperative mortality and morbidity can be warranted, surgical measures are justifiable in selected cases.

Successful Treatment of Adult Multisystemic Langerhans Cell Histiocytosis With Psoralen–UV-A, Prednisolone, Mercaptopurine, and Vinblastine

BACKGROUND Langerhans cell histiocytosis (LCH) is a rare disease with a peak incidence in childhood. There is limited experience with treatment options for adult patients having multisystemic LCH involvement. We report successful treatment of a 70-year-old woman with adult onset of LCH and multisystem disease (diabetes insipidus centralis, bone marrow infiltration, and lung and skin involvement). OBSERVATIONS A 70-year-old woman with erythematous plaques and papules of the submammary and inguinal skin attended our outpatient clinic and was diagnosed as having LCH. Organ involvement was found in the infundibulum of the pituitary gland, associated with diabetes insipidus centralis, bone marrow infiltration, and several micronodules of the thoracic and lumbar spine and lungs. Based on the Histiocyte Societys LCH-A1 study in adults, the patient was treated for 12 months with a combination of corticosteroids, vinblastine, and mercaptopurine. No major adverse effects were observed. The skin was also treated with a combination of psoralen-UV-A and local corticosteroids. Restaging revealed regression of all clinical symptoms (skin involvement and diabetes insipidus centralis) and regression of organ infiltration (pituitary gland, bone marrow, and lungs). CONCLUSION Effective treatment of adult multisystemic LCH disease was achieved using prednisolone, vinblastine, and mercaptopurine, which was well tolerated.

Serum S100B Levels Correlate with Clinical Benefit in a Metastatic Melanoma Patient Treated by CTLA-4 Blockade: A Case Report

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells. In patients with metastatic melanoma, anti-CTLA-4 antibody therapy with ipilimumab achieves durable cancer regression in approximately 10-15% of patients. In the face of complex and sometimes delayed tumor response patterns, prognostic and predictive biomarkers are needed to monitor therapy outcomes and to identify early potential long-term survivors who might also benefit from therapy re-induction. Case Report: The clinical case of a 49-year-old male patient with metastatic melanoma and unfavorable prognostic factors is presented. The time course of the serum biomarker S100B during initial anti-CTLA-4 therapy correlated very well with the clinical situation and, in the present case, proved its potential value as an early biomarker of a subsequently observed radiological response in this stage IV melanoma patient. The observed clinical response lasted for more than 24 months. Conclusions: Further efforts are required to better understand the patterns of response and the immunological tumor response in patients undergoing CTLA-4 blockade. A validation of S100B as a marker to identify early long-term responders among patients treated with ipilimumab is warranted.

Impact of combined FDG-PET/CT and MRI on the detection of local recurrence and nodal metastases in thyroid cancer

BackgroundSuspected recurrence of thyroid carcinoma is a diagnostic challenge when findings of both a radio iodine whole body scan and ultrasound are negative. PET/CT and MRI have shown to be feasible for detection of recurrent disease. However, the added value of a consensus reading by the radiologist and the nuclear medicine physician, which has been deemed to be helpful in clinical routines, has not been investigated. This study aimed to investigate the impact of combined FDG-PET/ldCT and MRI on detection of locally recurrent TC and nodal metastases in high-risk patients with special focus on the value of the multidisciplinary consensus reading.Materials and methodsForty-six patients with suspected locally recurrent thyroid cancer or nodal metastases after thyroidectomy and radio-iodine therapy were retrospectively selected for analysis. Inclusion criteria comprised elevated thyroglobulin blood levels, a negative ultrasound, negative iodine whole body scan, as well as combined FDG-PET/ldCT and MRI examinations.Neck compartments in FDG-PET/ldCT and MRI examinations were independently analyzed by two blinded observers for local recurrence and nodal metastases of thyroid cancer. Consecutively, the scans were read in consensus. To explore a possible synergistic effect, FDG-PET/ldCT and MRI results were combined. Histopathology or long-term follow-up served as a gold standard.For method comparison, sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated.ResultsFDG-PET/ldCT was substantially more sensitive and more specific than MRI in detection of both local recurrence and nodal metastases. Inter-observer agreement was substantial both for local recurrence (κ = 0.71) and nodal metastasis (κ = 0.63) detection in FDG-PET/ldCT. For MRI, inter-observer agreement was substantial for local recurrence (κ = 0.69) and moderate for nodal metastasis (κ = 0.55) detection. In contrast, FDG-PET/ldCT and MRI showed only slight agreement (κ = 0.21). However, both imaging modalities identified different true positive results. Thus, the combination created a synergistic effect. The multidisciplinary consensus reading further increased sensitivity, specificity, and diagnostic accuracy.ConclusionsFDG-PET/ldCT and MRI are complementary imaging modalities and should be combined to improve detection of local recurrence and nodal metastases of thyroid cancer in high-risk patients. The multidisciplinary consensus reading is a key element in the diagnostic approach.

AFP Measurement in Monitoring Treatment Response of Advanced Hepatocellular Carcinoma to Sorafenib: Case Report and Review of the Literature

Background: The multi-targeted tyrosine kinase inhibitor sorafenib was the first agent to demonstrate a significant improvement in overall survival in patients with advanced hepatocellular carcinoma (HCC). However, survival under sorafenib treatment is still lower than 1 year in most patients in clinical practice. Sorafenib rarely produces radiological tumor regression, pointing out limitations in using conventional radiological assessment of response to targeted therapy. Serial alpha-fetoprotein (AFP) measurement may be useful in monitoring treatment response in patients with advanced HCC undergoing systemic therapy; however, this approach is poorly defined for the case of sorafenib. Case Report: We herein report the case of a 48-year-old patient with advanced HCC presenting with normalization of highly elevated AFP levels after 5 months of reduced-dose sorafenib treatment, resulting in a sustained radiological and clinical response. Conclusions: Complete response to sorafenib may be possible in a small subgroup of patients with advanced HCC, strongly depending on one or more of the targets inhibited by sorafenib. Serial AFP measurement may provide additional information in monitoring treatment response to sorafenib and should be evaluated in future clinical trials in advanced HCC.

Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic melanoma

Immune checkpoint inhibitors targeting PD-1 (programmed cell death receptor 1) are indicated in the treatment of advanced melanoma. Cutaneous complications represent the most common immune-related adverse events (irAEs) [ 1 ] . We present the case of an advanced melanoma patient with complete response to treatment with the anti-PD-1 antibody pembrolizumab who developed lichen planus pemphigoides (LPP). A 64-year-old Caucasian man with metastatic melanoma was enrolled in the MK-3475-002 phase II trial comparing pembrolizumab 2 mg/kg or 10 mg/kg (randomized and blinded for the dose received) with standard chemotherapy. Tumor staging showed a partial response after nine cycles of pembrolizumab (given at three-week intervals). However, a CTCAE (Common Terminology Criteria for Adverse Events) grade 2 bullous pemphigoid (BP)-like drug reaction with vesicular lesions of the oral mucosa (Figure 1 a) and scattered papules with central vesicles on the skin prompted the patients exclusion from the trial. Subsequent treatment with topical clobetasol, prednisolone (1 mg/kg PO, followed by a slow taper over the course of four months), and rituximab (375 mg/m2 IV every four weeks; discontinuation after three doses due to CTCAE grade 3 thrombocytopenia) only led to minor improvement of the skin lesions. Six months later, the patient presented with a complete tumor response but also with CTCAE grade 3 white reticular lesions of the oral mucosa ( Wickham striae , Figure 1 b) and pruritic erythematous papules and plaques with central vesicles on the trunk and extremities (Figure 1 c). Histology (biopsy taken from the back) was consistent with lichen planus (LP), showing orthohyperkeratosis, hypergranulosis, cytoid bodies, and lichenoid interface dermatitis with a band-like lymphocytic infi ltrate obscuring the dermoepidermal junction (Figure 1 d, e). Repeated treatment with topical clobetasol and prolonged therapeutic attempts with systemic prednisolone (1 mg/kg PO, followed by a gradual taper over the course of eight months), PUVA therapy (methoxsalen 60 mg PO and UVA 1,2 J/cm2 four times weekly for three weeks), acitretin (50 mg PO once a day for one week), and sirolimus (2 mg PO once a day, discontinuation after eight weeks due to CTCAE grade 3 heart failure) were unsatisfactory.