High grade neuroendocrine carcinoma of the breast, first line and maintenance immunotherapy.

Small cell carcinomas (SCCs) are poorly differentiated neuroendocrine tumors that arise predominantly in the lung and gastrointestinal tract (GIT). Neuroendocrine carcinomas can occur in a variety of extrapulmonary sites throughout the body, including breast, larynx, GIT, prostate, urinary bladder, ovary and cervix. This is a case report of a 55-year-old Asian female patient with metastatic high-grade neuroendocrine carcinoma of unknown origin that responded notably to off-label nivolumab maintenance treatment after first-line carboplatin - etoposide chemotherapy and radiation. After 2 years of nivolumab after platinum-based chemotherapy results from PET-CT showed no residual disease and we proceeded to mastectomy.

Perforated appendicitis induced by pembrolizumab: a case report and review of the literature.

Monoclonal antibodies against programmed cell death protein 1 (PD-1) and PD-1 ligand 1 (PD-L1) are the main representatives in the field of immunotherapy and their indications are constantly increasing in medical oncology and hematology during the last decade. They are associated with long-lasting responses and an acceptable toxicity profile, although they may infrequently cause life-threatening complications requiring prolonged hospitalization or urgent interventions. With the current report, we present the case of a 75-year-old woman diagnosed with stage IV lung adenocarcinoma, who developed acute abdominal pain without preceding symptomatology while on pembrolizumab-pemetrexed maintenance treatment. A contained rupture of the appendix was found, for which she was managed conservatively. Subsequent endoscopic as well as histopathological findings from biopsies obtained via colonoscopy associated the clinical and imaging findings with grade 4 immune-mediated colitis. Interestingly, high-grade colitis is more frequent with anti-CTLA-4 agents in comparison to anti-PD-1 agents; moreover, most cases of anti-PD-1-mediated colitis present with preceding symptomatology (like diarrhea or vomiting), while cases or colonic perforation are extremely rare if ever described.

Can thromboprophylaxis build a link for cancer patients undergoing surgical and/or chemotherapy treatment? The MeTHOS cohort study.

BACKGROUND: Patients with active cancer have a 4-sevenfold increased risk for venous thromboembolism (VTE) especially during systematic anticancer treatment. Simultaneously, surgery is an additional risk factor. METHODS: The Metaxas's Hospital THromboprophylaxis program in Oncological & Surgical Patients (MeTHOS) is a prospective, phase IV, observational, non-interventional cohort study, aiming to record the thromboprophylaxis practice patterns in high-risk active cancer patients undergoing surgical and/or chemotherapy treatment. RESULTS: We are reporting results from 291 ambulatory patients (median age: 67 years, Q1-Q3: 59-73 years, 54.6% males) who received anti-neoplastic treatment and administered thromboprophylaxis. 59.8% had cardiovascular disease (mostly hypertension), 76.6% were reported as having at least one comorbidity, while 27.5% and 15.8% accumulated two and three comorbidities, respectively. 94.9% of the patients were receiving highly thrombogenic agents such as platinum-based agents, 5-FU, immunotherapy, antiangiogenics/anti-VEGF, or erythropoietin. 26.5% of the patients were initially surgically treated. In terms of anticoagulation, all patients were treated with tinzaparin (fixed dose, 10,000 Anti-Xa IU, OD). The median anticoagulation duration was 6.2 months. Six thrombotic events were observed (2.06%, 95% CI: 0.76-4.43%): 5 were DVT, and one PE. With respect to safety, 7 bleeding events occurred (2.6%, 95% CI: 1.0-5.3%); 6 of them were minor. CONCLUSIONS: Thromboprophylaxis with LMWH in patients with active cancer and high thrombotic burden was safe and effective. Intermediate dose of tinzaparin seems to be an appropriate agent for cancer-associated thromboprophylaxis management. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04248348.

Notable response of a young adult with recurrent glioblastoma multiforme to vincristine-irinotecan-temozolomide and bevacizumab.

Glioblastoma multiforme is a malignant central nervous system (CNS) disease with dismal prognosis. Current treatment modalities only offer modest activity and usually of short duration, so there is an urgent need for the conduct of clinical trials exploring new treatment options and modalities. The vincristine-irinotecan-temozolomide and bevacizumab (VITb) regimen is an option of special interest, as it has produced encouraging results in young patients with various relapsed/refractory childhood and adolescence solid tumors, with an acceptable toxicity profile. With the current report, we present the case of a young male patient who was treated for GBM in second relapse at out institution, after previous surgical attempts and two radiotherapy sessions in conjunction with temozolomide and experienced a major and long-lasting response, weaned off steroids, to the VITb regimen followed by bevacizumab maintenance. The above case is discussed in the context of the existing literature regarding available evidence of synergy between the drugs used and the activity of certain components of the combination (i.e. combination of temozolomide-irinotecan ± vincristine, or bevacizumab-irinotecan in GBM) or the complete VITb regimen in other pediatric/adolescence solid tumors and the few cases reported with GBM.

Central neurotoxicity induced by trastuzumab emtansine (T-DM1): a case report.

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (Her2) - targeted antibody-drug conjugate that is approved for patients previously treated with trastuzumab and a taxane for Her2-positive advanced breast cancer and those who have progressed within 6 months of completion of adjuvant chemotherapy, as well as for patients with residual invasive Her2-positive disease after the completion of adjuvant chemotherapy. Peripheral neuropathy is a common adverse event; however, ocular events have also been described. With the current report we present the case of a 67-year old woman who developed transient grade 2-3 blurred vision after the first T-DM1 infusion, which was complicated with grade 2 diplopia causing vertigo after the second infusion. After extended investigation, this symptomatology was attributed to central neurotoxicity, and gradually resolved after T-DM1 discontinuation.

Multidisciplinary approach for repeat musculoskeletal lesion biopsy after nondiagnostic initial sampling: A 10-year single-center experience.

BACKGROUND AND OBJECTIVES: Success rates for initial image-guided biopsy of musculoskeletal (MSK) lesions have been well documented; evidence regarding success rates for repeat biopsy following initially nondiagnostic (ND) image-guided biopsy of MSK lesions is more limited. This study evaluates the outcomes of repeat computerized tomography-guided MSK biopsies following ND biopsies using a multidisciplinary approach. MATERIALS AND METHODS: Electronic medical record search covering a 10-year period identified patients that received two or more biopsies for an MSK tumor or tumor-like process. The decision for initial and repeat image-guided biopsy of each lesion was made following multidisciplinary MSK tumor board review. Lesion location, histopathology results, size of biopsy needle when available, and change in technique between biopsy attempts was documented. RESULTS: Repeat biopsy rate was 1.6%. 23 patients with repeat MSK biopsy were identified. A total of 17 of 23 (74%) repeat biopsy attempts were diagnostic. A total of 22 of 23 (96%) repeat biopsy attempts were clinically useful. Diagnostic repeat biopsies were described as employing one or more of five technical differences compared to the first biopsy attempt, the most common being improved targeting of the lesion itself. CONCLUSIONS: A multidisciplinary approach may yield improved repeat-biopsy rates and clinical utility of repeat MSK biopsies compared to prior reports.

Myeloablative chemotherapy and autologous stem cell transplantation can lead to successful postengraftment mobilization of hematopoietic progenitors to support planned subsequent cycle(s) of high-dose chemotherapy and autografting in a patient with relapsed germ-cell tumor.

Salvage high-dose chemotherapy (HDC) together with autologous hematopoietic stem cell (HSC) transplantation (ASCT) represents a curative treatment option for patients with relapsed/refractory germ-cell tumor. Usually, 2-3 cycles of HDC are administered with encouraging results, and a sizeable percentage of patients experience long-term survival. However, an appreciable number of patients fail to mobilize adequate numbers of HSCs, adequate to support more than one HDC cycle. There have been no data so far on remobilization of HSCs after prior autografting. We report a unique case with relapsed germ-cell tumor that had undergone the first cycle of HDC with myeloablative doses of carboplatin-etoposide, and HSCs were mobilized successfully in the early posthematopoietic engraftment period to support further cycles of HDC. Four weeks after the first ASCT, an identical second cycle of myeloablative HDC was administered and rescued successfully with the HSCs collected after engraftment following the previous HDC cycle. The present case report illustrates that HSCs can be mobilized successfully in the early postengraftment period after myeloablative doses of carboplatin-etoposide, and these cells can be applied as the sole source of hematopoietic rescue in planned sequential cycles of myeloablative HDC, leading to successful multilineage engraftment. Provided that more extensive experience is gathered in future studies in large numbers of patients, this strategy could prove helpful in patients who cannot initially collect sufficient HSC numbers, before the first autografting cycle, and are in need of sequential HDC+ASCT cycles. A detailed literature review is provided to highlight the uniqueness of the presented case.

Metal Artifact Reduction in Routine Chest and Abdominal Examinations Using Virtual Monoenergetic Images From Spectral Detector Computed Tomography.

OBJECTIVE: The objective of this study was to investigate the quantitative and qualitative effects of virtual monoenergetic images (VMIs) by spectral detector computed tomography (SDCT) on metal artifacts in routine examinations. METHODS: Fifty-nine patients with metal artifacts (caused by pacemakers, ports, screws, or prosthetic joints) affecting muscular tissue in the chest and/or abdomen were scanned using SDCT. Attenuation values around the metallic device were compared with contralateral unaffected values, for conventional images and 80 to 200 keV VMIs. In addition, general image quality and artifact intensity were rated by 2 readers. RESULTS: The VMIs significantly decreased metal artifact intensity in all patients (P < 0.05). In 39 patients (66.1%), the attenuation values of the artifact and the unaffected area on the optimal keV level were very similar (≤5 Hounsfield unit difference). Qualitative analysis showed that high VMIs significantly improved artifact intensity, with best scores at 140 keV. CONCLUSIONS: High monoenergetic images of SDCT significantly reduce metal artifacts, with optimal assessment at 140 keV.

Dual-layer spectral computerized tomography for metal artifact reduction: small versus large orthopedic devices.

INTRODUCTION: Metal artifacts limit the diagnostic utility of computerized tomography (CT) for implant-related complications. Dual-layer spectral detector CT imaging has been suggested for artifact reduction. Our objective was to evaluate the utility of spectral CT in artifact reduction in patients with small and large metal implants. METHODS: In this prospective study, patients with metallic orthopedic implants underwent CT imaging using a prototype spectral detector CT scanner. Conventional images were generated with iterative reconstruction at 120 kVp, and virtual monochromatic images were generated at 20-keV intervals between 40 to 200 keV. Conventional and monochromatic images were compared quantitatively using signal-to-noise ratio (SNR) and artifact improvement. Qualitative analysis was performed independently by two musculoskeletal radiologists and included six image quality indicators. RESULTS: A total of 12 patients were scanned. In monochromatic images, as the energy level increased, the artifact size decreased progressively (p < 0.01). When conventional and monochromatic images were compared, maximum reduction was seen at 200 keV. Using qualitative assessments, 160 and 180 keV levels had the best overall diagnostic image quality. With increased energy level, there was improvement in qualitative ratings of bone-metal interface conspicuity (p = 0.002), degree of streak artifact (p = 0.010) and trabecular bone definition at 1 cm from implant (p = 0.023), and a trend towards significance for bone definition at 5 cm, soft tissue detail and overall diagnostic quality. Subgroup analysis revealed superior artifact reduction in small implants compared to large hardware. DISCUSSION: Our results support the utility of dual-layer spectral CT in metal artifact reduction. Virtual monochromatic images were diagnostically superior, especially for smaller implants. Virtual monoenergetic images at 160-180 keV are ideal for reducing artifacts.

Plerixafor mobilization of peripheral blood hematopoietic progenitors to support further high-dose chemotherapy cycles in a patient with germ-cell tumor relapsing after previous tandem high-dose chemotherapy and hematopoietic cell transplantation: report of a case.

Salvage high-dose chemotherapy (HDC) and autologous hematopoietic stem cell (HSC) transplantation represents a curative treatment option for patients with relapsed/refractory germ-cell tumors (GCTs). However, an appreciable proportion of these fail to mobilize adequate numbers of hematopoietic progenitors; thus, plerixafor is applied for that purpose. Limited data exist on remobilization of HSCs after previous autografting. Here, we report a unique case that had undergone successful previous tandem HDC for relapsed GCT, and 1 year later required remobilization of HSCs to support two further cycles of HDC after subsequent multiple relapses and refractoriness requiring various salvage regimens. Plerixafor in combination with granulocyte-colony stimulating factor showed its efficacy in mobilizing 6×10 CD34+/kg HSCs able to rescue two HDC cycles of carboplatin-etoposide, leading to stable hematopoietic engraftment. Plerixafor showed its potency to mobilize adequate numbers of HSCs in a patient with relapsed/refractory GCT after previous tandem HDC and autografting. The case is discussed in the context of HSC mobilization in patients who have undergone previous HDC and autografting and are deemed to have poor hematopoietic reserves, and a detailed literature review of this topic is provided.

Report of two cases of acute cardiac adverse events in patients with colorectal carcinoma receiving oral capecitabine.

Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after oral administration, is metabolized to its active cytotoxic compound: 5-fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a closely related fluorinated pyrimidine antagonist. In the present report, we report on two patients who were admitted to our department after being treated with oral capecitabine for colorectal carcinoma and developed symptoms and signs of acute myocardial infarction that resolved after appropriate treatment and monitoring. The above two cases are discussed in the context of fluoropyrimidine, 5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature review of relevant cases and patient series reports is presented.

Long-term clinical outcomes of dual-cycle radiofrequency ablation technique for treatment of osteoid osteoma.

PURPOSE: Radiofrequency ablation technique for treatment of OO including ablation time and temperature vary greatly between and within reported studies. This study evaluates the immediate and long-term efficacy and complication rate of a two sequential RFA technique for OO. MATERIALS AND METHODS: We retrospectively reviewed medical records and attempted interview follow-up for 25 patients treated with RFA for OO. Each treatment included 2 consecutive RFAs at 90 °C for 6 min with inter-ablation cooling to 40 °C and occasional inter-ablation probe adjustment. Additionally, we statistically compared the proportion of successful ablations using the DCRFA technique with published studies that utilized alternative OO ablation procedures. RESULTS: Long-term follow-up was obtained for 24 patients (96 %). Mean patient age at DCRFA was 17.2 years (range, 2.2-50.0 years). Mean time to follow-up was 60 ± 42 months (range 12-152 months). No acute DCRFA-related complications nor long-term recurrences were reported. All 24 interviewed patients reported partial relief of pre-procedural pain within 1 day of DCRFA and total relief within 1 week of DCRFA. One patient ultimately developed a major late complication (complex regional pain syndrome of the left ankle) after DCRFA of a cuboid lesion. Additionally, the DCRFA success rate was significantly higher when compared to two other published OO RFA treatment results. CONCLUSION: DCRFA employing two sequential 6-min cycles is an effective treatment of OO. The 100 % primary success rate, 0 % long-term recurrence rate, and low complication rate compare favorably and may be superior to results of prior reports.

Computed tomography-guided percutaneous biopsy for vertebral neoplasms: a department's experience and hybrid biopsy technique to improve yield.

OBJECTIVE Recent articles have identified the poor diagnostic yield of percutaneous needle biopsy for vertebral osteomyelitis. The current study aimed to confirm the higher accuracy of CT-guided spinal biopsy for vertebral neoplasms and to identify which biopsy technique provides the highest yield. METHODS Over a 9-year period, the radiology department at University Hospitals Case Medical Center performed 222 CT-guided biopsies of vertebral lesions, of which clinicians indicated a concern for vertebral neoplasms in 122 patients. A retrospective chart review was performed to confirm the higher sensitivity of the percutaneous intervention for vertebral neoplasms. RESULTS A core sample was obtained for all 122 biopsies of concern (100.0%). Only 6 cases (4.9%) were reported as nondiagnostic per histological sampling, and 12 cases (9.8%) were negative for disease. The question of vertebral neoplastic involvement warrants follow-up, and the current study was able to determine the subsequent diagnosis of each lesion. Of the 122 total, 94 (77.0%) core samples provided true-positive results, and the sensitivity of core biopsy measured 87.9%. The technical approach did not demonstrate any significant difference in diagnostic yield. However, when the vertebral cortex was initially pierced with a coaxial bone biopsy system and subsequently a 14-gauge spring-loaded cutting biopsy needle was coaxially advanced into lytic lesions, 14 true positives were obtained with a corresponding sensitivity of 100.0%. CONCLUSIONS This study confirms the higher sensitivity of image-guided percutaneous needle biopsy for vertebral neoplasms. In addition, it demonstrates how the use of a novel cutting needle biopsy approach, performed coaxially through a core biopsy track, provides the highest yield.

Vertebral body enhancement mimicking sclerotic osseous lesions in the setting of bilateral brachiocephalic vein thrombosis.

Contrast enhancement of the vertebral body marrow may be seen secondary to collateral venous blood flow via the vertebral venous plexus in the setting of superior vena cava obstruction. We report a 48-year-old woman presenting with bilateral brachiocephalic vein obstruction and multilevel thoracic spine hyperdensities as seen on venous-phase CT angiography (CTA), initially concerning for sclerotic neoplastic lesions. A contrast-enhanced CT of the neck obtained 1 day prior to the chest CTA did not demonstrate any osseous abnormality, and inspection of the chest CTA demonstrated filling of perivertebral venous collateral vessels. The abnormal vertebral body enhancement was therefore feltsecondary to retrograde collateral venous flow via the basivertebral venous plexus in the setting of functional SVC obstruction. Vertebral body enhancement should be considered in patients with thoracic central venous obstruction when enhancement or apparent sclerosis of the vertebral bodies is seen on CTA.

Plerixafor added to G-CSF-supported paclitaxel-ifosfamide-cisplatin salvage chemotherapy enhances mobilization of adequate numbers of hematopoietic stem cells for subsequent autografting in hard-to-mobilize patients with relapsed/refractory germ-cell tumors: a single-center experience.

An appreciable percentage of patients with relapsed/refractory germ-cell tumors (GCTs), candidates for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (HCT), fail to mobilize adequate hematopoietic stem cells (HSCs) numbers with granulocyte colony-stimulating factor (G-CSF)±salvage chemotherapy. Plerixafor has shown a potential to mobilize adequate CD34+HSCs numbers in this context. Here, we applied plerixafor in combination with G-CSF after salvage chemotherapy in 'poor' mobilizers with relapsed/refractory GCTs for HDC+HCT. Patients with relapsed/refractory GCTs (n=10) received salvage paclitaxel-ifosfamide-cisplatin (TIP) chemotherapy+G-CSF to mobilize adequate HSCs to support HDC, mainly with two courses of high-dose thiotepa-etoposide-carboplatin (TEC). Patients failing to achieve the minimum collection threshold of 2.0×10/kg CD34+ cells, to support at least one cycle of HDC, were administered plerixafor before the anticipated HSC collection during subsequent cycle(s). Overall, seven patients mobilized adequate CD34+ cells (>5.0×10/kg) aiming to support two cycles of HDC. Three patients did not mobilize adequate numbers of CD34+ cells after previous G-CSF plus salvage TIP, and plerixafor was added in subsequent cycle(s). This led to a collection of adequate CD34+ cells, able to support HDC with TEC (1-2 cycles). Hematopoietic engraftment for neutrophils (absolute neutrophil count>500/µl) and platelets (platelet count>20 000/µl) with plerixafor-mobilized HSCs occurred after a median of 9 and 14 days, respectively. Salvage TIP+G-CSF leads to successful HSC mobilization in patients with less heavily pretreated GCTs, whereas the addition of plerixafor to G-CSF+TIP led to mobilization of adequate HSCs that supported autografting after one to two TEC cycles.

Computed tomography-guided percutaneous biopsy for vertebral osteomyelitis: a department's experience.

OBJECT: Vertebral osteomyelitis has been reported to occur in approximately 0.2-2 cases per 100,000 annually. Elevated laboratory values such as erythrocyte sedimentation rate and C-reactive protein suggest inflammatory etiologies. Different imaging modalities, from radiography and CT scanning to nuclear medicine imaging and contrastenhanced MRI, can be employed to evaluate for osteomyelitis. Although MRI has a strong sensitivity and specificity for vertebral osteomyelitis, obtaining histological and microbiological samples remains the gold standard in diagnosis. Therapy can be geared toward the specific pathogen cultured, thereby preventing the need surgical intervention in the majority of cases. However, recent reports have questioned the percentage yield of image-guided percutaneous biopsy even when there is a high clinical suspicion for vertebral osteomyelitis. METHODS: After obtaining institutional review board approval, the authors performed a chart review of patients who had undergone image-guided percutaneous bone biopsies at University Hospitals Case Medical Center in Cleveland, Ohio. Data were filtered for patients in whom a biopsy sample of a vertebral body/disc was obtained. A total of 213 procedures were performed, of which clinicians indicated a concern for infection in 84, infection or neoplasm in 13, and a noninfectious etiology (the majority being neoplasms) in the remaining 116. RESULTS: Histological examination provided positive results in 25 (41.0%) of the 61 samples collected for suspected cases of osteomyelitis. Microbiology samples were less predictive, with only 16 of the 84 samples collected, or 19.0%, yielding a positive result. In 10 patients there were positive blood and/or urine cultures. Of these, 8 samples (80%) demonstrated the same pathogen identified by biopsy (for the remaining 2 positive systemic cultures, no pathogen was identified by the percutaneous intervention). In other words, half of the 16 cases that provided microbiological results from biopsy demonstrated the same results by systemic cultures. However, 89 (76.7%) of the 116 samples collected with the primary concern of neoplasm yielded results. CONCLUSIONS: Image-guided percutaneous biopsy for vertebral osteomyelitis demonstrates an extremely low probability of identifying specific microbes. Blood or urine cultures concurrently identified culprit pathogens in 50% of positive biopsy cultures. Therefore, in only 8 (9.5%) of 84 biopsies did the biopsy results provide additional information to clinicians as to the pathological microorganism present and how treatment might need to be adjusted.

Adhesive capsulitis: Utility of magnetic resonance imaging as a primary diagnostic tool and clinical management support.

OBJECTIVE: Adhesive capsulitis (AC) has traditionally been a clinical diagnosis characterized by progressive shoulder pain and decreased range of motion. Our aim is to examine the role of shoulder MRI in making the diagnosis of AC, and to identify the frequency of cases where MRI was the primary method in diagnosing AC amongst medical providers. METHODS: This was an anonymized retrospective analysis. Patients with positive MRI features suggestive for AC from 2015 to 2018 were included. Pre and post MRI clinical notes were assessed in order to ascertain the clinical suspicion of AC. A total of 117 cases were included for this study. RESULTS: Our results demonstrated the number of patients whose management were influenced by shoulder MRI. When all of the imaging parameters by MRI are taken into account by aggregate, there is a statistically significant difference (p-value < 0.01) with regards to orthopedists having their working diagnosis of AC confirmed by the MRI results as compared to the primary care physicians. CONCLUSION: This study supports the role of shoulder MRI in the evaluation of AC. Not only does shoulder MRI assist ordering clinicians with providing additional evidence to support a suspected diagnosis of AC, but also plays a primary role in making the diagnosis of AC in cases in which it was not initially suspected, ultimately impacting management.

Predictive tissue markers in testicular germ cell tumors: Immunohistochemical expression of MLH1 and REV-7 proteins.

PURPOSE: Testicular Germ Cell Tumors (TGCTs) are the most frequent solid malignancies in young adult men. Regardless of differences in their cell of origin, all TGCTs are considered highly curable malignancies. However, approximately 3-5% of all TGCTs do not respond to platinum-based chemotherapies. The purpose of our paper is to investigate whether immunohistochemical expression of MLH1 and REV-7 can be used as predictive tissue markers for TGCTs. MATERIAL AND METHODS: The main demographic and clinicopathological characteristics of 64 male patients with TGCTs who underwent orchiectomy from 2007 to 2022 were retrospectively obtained from two large Oncology Clinics in Greece. Both patients with chemosensitive and chemoresistant disease were included. Immunohistochemical staining for MLH1 and REV-7 proteins was applied in specimens of these patients. RESULTS: 31 seminomas and 33 non-seminomas were included. 48 patients had chemosensitive disease, while 16 had chemoresistant disease. 53 specimens showed preserved MLH1 expression, while 11 specimens had lost MLH1 expression. Expression of MLH1 was only significantly associated with patients' age. 16 specimens showed positive REV-7 expression, while 48 specimens were REV-7 negative. Interestingly, 50% of patients with chemoresistant disease and 16,7% of patients with chemosensitive disease were REV-7 positive. This difference was statistically significant. Moreover, REV-7 positivity was significantly associated with chemoresistance, various clinicopathological parameters and patients' prognosis and survival. CONCLUSION: Loss of MLH1 expression was only found to be significantly associated with lower patients' age. Positive immunohistochemical REV-7 expression was significantly associated with various clinicopathological parameters, while it was also associated with significantly lower survival and greater hazard. REV-7 positive percentages were significantly higher in patients with chemoresistant disease. Our findings imply that immunohistochemical staining for REV-7 could potentially be used as a predictive tissue marker for TGCT tumors. Moreover, targeting of REV-7 protein, could represent a potential therapeutic strategy for chemoresistant TGCT cases. The implementation of well-designed studies on a larger scale is of utmost importance, in order to draw safer conclusions. Additional studies are needed so as to draw safer conclusions.

Chemotherapy ± cetuximab modulates peripheral immune responses in metastatic colorectal cancer.

OBJECTIVE: To identify changes in peripheral immune responses in patients with metastatic colorectal cancer (mCRC) treated with irinotecan/5-fluorouracil/leucovorin (IFL) alone or in combination with cetuximab (C-IFL). METHODS: Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (n = 20) and patients with mCRC receiving treatment with either IFL (n = 30) or C-IFL (n = 30) were tested for cytokine production upon polyclonal stimulation with anti-CD3 monoclonal antibody, T cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR) and T regulatory cell (Treg) frequency. The respective results were evaluated over two treatment cycles and further assessed in relation to response to treatment. RESULTS: PBMCs prior to treatment exhibited significantly lower production of IL-2, IFN-γ, IL-12 and IL-18 cytokines and lower auto-MLR responses, whereas Treg frequency, IL-4, IL-10 cytokines were increased compared to healthy donors. During treatment, IL-2, IFN-γ, IL-12, IL-18 and auto-MLR responses increased, while Treg frequency and IL-10 secretion decreased significantly compared to the baseline. Responders to treatment exhibited a significantly higher increase in IL-2, IFN-γ, IL-12 and IL-18 production and auto-MLR responses, and higher decrease in IL-4, IL-10 secretion and Treg frequency. Among all patient subgroups analysed, responders to C-IFL demonstrated significantly higher increase in auto-MLR responses, IL-12 and IL-18 secretion and higher decrease in Treg frequency. CONCLUSION: The disturbed immune parameters observed in patients with mCRC at presentation can be significantly improved during treatment with IFL and this effect can be potentiated by the addition of cetuximab. Monitoring of the peripheral immune system function could be used as surrogate marker in predicting treatment-related outcome.

Control of relapsed germ cell tumor and SLE nephritis by high-dose chemotherapy and autologous hematopoietic cell transplantation.

High-dose chemotherapy and hematopoietic stem cell support remains a curative treatment option for relapsed or nonresponsive germ cell tumors, and has been applied experimentally to control severe autoimmune diseases. In the present study, we report on a patient with systemic lupus erythematosus nephritis who developed a nonseminomatous germ cell tumor that relapsed after standard chemotherapy and surgery. The patient received high-dose chemotherapy supported by autologous hematopoietic cell transplantation based on its indication for relapsed germ cell tumors. Prolonged control of his relapsed germ cell tumor and systemic lupus erythematosus was attained with high-dose chemotherapy and hematopoietic stem cell support. An extensive literature review is provided alongside a detailed discussion of the aforementioned case.