Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade.

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus-myoclonus-ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%-25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.

Preoperative versus postoperative chemoradiotherapy in stage T3, N0 rectal cancer.

BACKGROUND: The study populations of previous preoperative chemoradiotherapy (pre-CRT) studies have consisted of mixed clinical stages, such as cT3-cT4 and/or cN positive. For this reason, it has not been possible to demonstrate whether pre-CRT is of benefit for individual subgroups. METHODS: The medical records of 137 rectal cancer patients with clinical stage T3, N0 disease who received either pre-CRT or postoperative chemoradiotherapy (post-CRT) between 2002 and 2011 were retrospectively analyzed. The regimen of pre-CRT consisted of slow fluorouracil (5FU) infusion and that of post-CRT consisted of bolus 5FU and leucovorin concurrent with radiation. RESULTS: Following pre-CRT, significant downstaging was achieved. However, administration of pre-CRT did not influence the type of surgical resection in tumours ≤5 cm distant from the anal verge (p = 0.14). Pathological complete response was achieved in 16 % of the patients in the pre-CRT group. The local recurrence rate (LRR) at 5 years was 5.7 % in the pre-CRT and 11.1 % in the post-CRT groups (p = 0.04). The distant recurrence rate (DRR) at 5 years was 76 % and 77 % in the pre-CRT and post-CRT groups, respectively (p = 0.1). Overall survival was similar in two groups (74.8 % vs. 75.3 %, p = 0.3). CONCLUSIONS: The treatment of stage T3, N0 rectal cancer patients with pre-CRT followed by surgery decreased LRR, but did not improve DRR or OS as compared with surgery followed by post-CRT in our patient cohort.

What is the optimal treatment in clinical stage T3N0M0 rectal cancer?

PURPOSE: Some previous studies suggested that certain rectal cancer patients with stage T3N0 and favorable features may be adequately treated with surgery and adjuvant chemotherapy. However, the optimal management of clinical (c) T3N0 rectal adenocarcinoma based on preoperative imaging is unclear. In this study, we aimed to determine the frequency of lymph node metastases in patients clinically staged as T3N0 rectal adenocarcinoma following preoperative chemoradiotherapy (CTR). METHODS: The medical records of 105 patients with clinico- imaging stage T3N0M0 rectal cancer who received preoperative CRT between 2004-2011 were retrospectively analyzed. Chemotherapy used concurrently with preoperative radiotherapy (RT) was protracted 5-fluorouracil (5FU) infusion. RESULTS: Twenty-seven percent of the patients clinically staged as T3N0 before preoperative CRT had pathological (p) lymph node involvement on surgical material. The rate of pathological lymph node involvement was 0% in pT1, 20% in pT2 , 35% in pT3 and 34% in pT4 patients. A significant association was demonstrated between pT stages and pN status (p=0.03). CONCLUSION: Our study demonstrated that the accuracy of preoperative imaging for staging rectal cancer is limited because at least 27% of the patients may have undetected lymph node involvement after preoperative CRT in surgical material.

Predictive significance of inflammatory markers and mGPS in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

BACKGROUND: Prostate cancer is a prevalent cancer in men worldwide, and castration-resistant prostate cancer (CRPC) is characterized by disease progression despite androgen deprivation therapy. While clinical and prognostic biomarkers have been identified in CRPC, the significance of serum inflammatory markers remains unclear. MATERIALS AND METHODS: This retrospective study included 79 CRPC patients treated with abiraterone or enzalutamide. Inflammatory markers, including the modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR), were assessed as predictive tools for treatment response. Patient data were obtained from medical charts, and statistical analyses were performed. RESULTS: The median age of the patients was 67 years, with most having a Gleason score of 8-10. The median values for NLR, PLR, and SII were 2.9, 168.5, and 713.5, respectively. The objective response rate (ORR) to abiraterone or enzalutamide therapy was 55.1%. mGPS showed a significant association with ORR, with the mGPS 0 group having the highest response rate (59.5%). Median progression-free survival (PFS) was 12.8 months, and median overall survival (OS) was 35.4 months. Palliative radiotherapy during therapy and PSA doubling time were independent prognostic factors for PFS. CONCLUSIONS: mGPS and PSA doubling time significantly impacted survival, and mGPS significantly predicted the treatment response in mCRPC, which may lead to further prospective studies.

Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

The relation between pathological complete response and clinical outcome in patients with rectal cancer.

BACKGROUND/AIMS: Preoperative chemoradiotherapy (CRT) is the standard treatment modality in locally advanced rectal cancer. The primary aim was to correlate pathological complete response (pCR) with patient outcome, and the secondary objective was to identify predictive factors of pCR. METHODOLOGY: Patients with clinical stage II/III rectal cancer who received preoperative CRT between 2002 and 2010 were retrospectively studied.The median radiotherapy dose was 54 Gy (range, 45 to 64 Gy), and all patients received concurrent infusional 5-fluorouracil-based chemotherapy. RESULTS: Median follow-up time was 48.3 months (range, 24 to 96 months) and 51 months (range, 44 to 110 months) for no-pCR and pCR groups, respectively. Eighteen patients (18.6%) had pCR. The 5-year overall survival was 95% for patients with pCR and 74.8% in patients without pCR (p=0.009). The 5-year local relapse free survival was 87.5% and 95% for the no-pCR and pCR groups, respectively (p=0.09). The 5-year distant relapse free survival was 93% in pCR group and 79.8% in no-pCR group (p=0.02). The 5-year distant free survival was 94% and 66% in patients with and without pCR, respectively (p=0.017). The clinical T4 (p=0.043) and pretreatment carcinoembryonic antigen level (CEA) >5ng/mL (p=0.012) were significantly associated with a lower pCR rate. In the multivariate logistic regression analysis, pretreatment CEA level >5ng/mL (p=0.008) was the only independent factor associated with a lower pCR rate. CONCLUSIONS: Patients with pCR after preoperative CRT had a significantly improved outcome. Furthermore, the pretreatment CEA level was independently associated with pCR.

Impact of Adjuvant Gemcitabine Containing Chemotherapy Following Radical Nephroureterectomy for Patients with Upper Tract Urothelial Carcinoma: Results from a Propensity-Score Matched Cohort Study.

BACKGROUND: The evidence regarding perioperative adjuvant chemotherapy and personalized surveillance strategies for upper tract urothelial carcinoma is limited. OBJECTIVE: To evaluate whether adjuvant gemcitabine containing chemotherapy affects the oncological outcomes of advanced upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry is an observational, international, multi-center study on patients diagnosed with UTUC. Patient and disease characteristics from 2380 patients with UTUC were collected, and finally 738 patients were included in this analysis. The primary outcome of this study was recurrence-free survival. Propensity score matching was performed. Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to the treatment of adjuvant chemotherapy. RESULTS: A total of 738 patients were included in this analysis, and 59 patients received adjuvant chemotherapy (AC), including 50 patients who received gemcitabine. A propensity score matching was performed, including 50 patients who received gemcitabine containing treatment and 50 patients without adjuvant chemotherapy. Disease recurrence occurred in 34.0% of patients. The recurrence rate in the AC group was 22.0%, which was significantly lower than the non-AC group (46.0%). Kaplan-Meier analyses also showed that AC was associated with a lower likelihood of tumor recurrence (p = 0.047). However, AC was not significantly associated with a higher overall survival (OS) (p = 0.908) and cancer-specific survival (CSS) (p = 0.979). Upon multivariate Cox regression analysis, AC was associated with a lower risk of tumor recurrence (HR = 0.297, p = 0.028). CONCLUSION: The present study confirms that adjuvant gemcitabine containing chemotherapy could decrease the risk of tumor recurrence in patients with locally advanced UTUC following nephroureterectomy. However, more studies are need to draw a clearer image of the value of this treatment method.

Prognostic significance of primary tumor localization in patients with metastatic colorectal cancer: Is it beneficial to select targeted treatment? Real-life experience from Turkey.

PURPOSE: The purpose of this study was to investigate the prognostic value,and the effect of primary tumor location on targeted therapy selection in patients with metastatic colorectal cancer (mCRC). METHODS: A total of 201 patients with de novo mCRC who received first line treatment were retrospectively analyzed. Clinicopathological features, treatment outcomes, the primary tumor surgery, metastasectomies/local therapies and survivals were evaluated in terms of both RAS mutation status and primary tumor sidedness. RESULTS: Tumor localization showed 140 (69.7%) patients with left-sided and 61 (30.3%) with right-sided tumors. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with right-sided tumor than those with left-sided tumors (10.1 vs 12.9 months, p=0.005; 25 vs 44.4 months, p=0.008, respectively). In addition,the median OS interval of patients receiving anti-VEGF containing regimen was better than those treated with anti-EGFR containing regimen (50.7 vs. 26.9 months, p=0.001). Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors. CONCLUSIONS: Our results showed that primary tumor location is a prognostic factor in mCRC patients regardless of RAS status. Primary tumor location before treatment decision may be a simple indicator predicting survival and in choosing targeted agent.

Platelet to lymphocyte ratio is associated with tumor localization and outcomes in metastatic colorectal cancer.

ABSTRACT: The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization.A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (≤196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P < .001 and P = .023 respectively).Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization.

Prognostic Significance of Metastatic Lymph Node Ratio in Patients with pN3 Gastric Cancer Who Underwent Curative Gastrectomy.

BACKGROUND: Lymph node involvement is an important prognostic factor in patients with gastric cancer. The aim of this study was to determine the prognostic significance of metastatic lymph node ratio (MLNR) and compare it to the number of lymph node metastasis in pN3 gastric cancer. METHODS: We retrospectively analyzed 207 patients with pN3 gastric cancer who had undergone radical gastrectomy. Prognostic factors and MLNR were evaluated by univariate and multivariate analysis. RESULTS: An MLNR of 0.75 was found to be the best cut-off value to determine the prognosis of patients with pN3 gastric cancer (p = 0.001). The MLNR was significantly higher in patients with large-sized and undifferentiated tumors, vascular, lymphatic and perineural invasion, and total gastrectomy. In multivariate analysis, MLNR (p = 0.041), tumor differentiation (p = 0.046), and vascular invasion (p = 0.012) were found to be independent prognostic factors for disease-free survival, while both MLNR (p < 0.001) and pN stage (p = 0.002) were independent prognostic indicators, as was tumor size, for overall survival. There was significant difference with respect to the recurrence patterns between MLNR groups. Lymph node and peritoneal recurrences were significantly higher in patients with MLNR > 0.75 compared to the MLNR < 0.75 group (p < 0.05). However, recurrence patterns were similar between pN3a and pN3b. CONCLUSION: Our results showed that MLNR was a useful indicator to determine the prognosis and recurrence patterns of patients with radically resected gastric cancer. Moreover, MLNR is a beneficial and reliable technique for evaluating lymph node metastasis.

Thymoma with chronic diarrhea: report of two cases and review of the literature.

Thymoma associated with hypogammaglobulinemia and profound susceptibility to recurrent and serious infections was first reported by Good in 1954, after whom it was named as Good's syndrome. Chronic diarrhea associated with thymoma is almost always seen in patients with hypogammaglobulinemia. However, chronic diarrhea in a setting of normal gammaglobulins have been rarely reported. We hereby report two cases of thymoma with normal immune functions, presenting with chronic diarrhea as the only symptom of thymic malignancy. We discussed the etiopathogenic relation between thymic pathology and diarrhea and review the cases of thymoma associated with chronic diarrhea in the English literature.

Paraneoplastic pemphigus associated with fludarabine use.

Paraneoplastic pemphigus is a severe mucocutaneous disease associated with B-cell lymphoproliferative disorders. A 51-yr-old man presented to the oncology clinic with mucocutaneous skin lesions after six cycles of fludarabine for non-Hodgkin's lymphoma. A punch biopsy from the skin showed suprabasal acantholysis and blister formation in the epidermis and upper dermis. Direct immunofluorescence demonstrated intercellular IgG deposition in all epidermal layers and complement (C3) at the basement membrane. The indirect immunofluorescence on rat bladder showed intercellular binding of IgG. These findings were consistent with paraneoplastic pemphigus associated with fludarabine use. The temporal association between fludarabine use and paraneoplastic pemphigus suggests there is an etiopathological link between these two entities.

Is lipid lowering treatment aiming for very low LDL levels safe in terms of the synthesis of steroid hormones?

Today atherosclerotic diseases are among the most important causes of death in the world. Epidemiological, clinical, genetic, experimental and pathological studies have clearly shown the role of lipoproteins in atherosclerosis. LDL is the major atherogenic lipoprotein and has been defined as the primary target of lipid lowering treatment by NCEP. Although the level of LDL, the primary target in the treatment of dyslipidemia, has been set as below 100 mg/dl in coronary heart diseases (CHD) and CHD risk equivalents, this level has been pulled down to below 70 mg/dl for the group defined as very high risk group by the ATP (Adult Treatment Panel) guide that has been updated following the new clinical studies. As we already know, cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids, besides being a structural component of the cell membrane. Both adrenal and non-adrenal (ovarian+testicular) all steroid hormones are primarily synthesized using the LDL-cholesterol in the circulation. In addition to this, there is 'de novo' cholesterol synthesis in both the adrenals and gonads controlled by the HMG-CoA reductase enzyme. A third pathway, which under normal circumstances has little contribution as compared to the first two, is the use of circulatory HDL-cholesterol by the adrenal and gonadal tissues for the synthesis of steroids. Our knowledge on extremely lowered LDL levels is quite limited. However, since statins both decrease circulatory LDL and inhibit de novo cholesterol synthesis, they are likely to affect the synthesis of steroid hormones.

Prevalance and risk factors for yeast colonization in adult diabetic patients.

The aim of this study is to describe the associations between various host characteristics and yeast colonization; biofilm and phospholipase production in diabetic patients. The study was conducted between January 2003 and June 2003 in Abant Izzet Baysal University, Duzce, Turkey. One hundred and fourty five diabetic patients were included to the study. All oral and faecal specimens were placed on Sabourand dextrose agar with chloramphenicol and gentamicin. All isolates were identified with classic methods and carbohydrate assimilation patterns using API 20 CAUX. C. dubliniensis isolates were identified by CHROM agar Candida and chlamydospore formation according to the referral to the literature. Biofilm and phospholipase production was assessed by using previously described methods. The most common colonized species were C. albicans in oral and faecal cultures. C. dubliniensis was isolated in four oral cultures of the patients. Dental prosthesis, tooth brushing, older age, antibiotic use in the previous two weeks were found to be the significant factors for the oral yeast colonization. Younger age, smoking, shorter duration of diabetes, hospitalization in the last year and antibiotic use in the previous two weeks were found to be the significant factors for the faecal yeast colonization. Biofilm production was found to be positive in nine cases of oral and seven of faecal isolates. Phospholipase production was determined to be positive in 18 cases oral and 14 of faecal isolates. In conclusion, glycaemia control and other diabetic factors are not effective for yeast colonlizing. There was not any significant correlation between biofilm and phospholipase production and host characteristics in yeast colonization. Oral hygiene may be an effetive for decreasing the oral colonization in diabetic patients.

Late relapse of testicular cancer: Recurrence after 24 years and treatment with chemotherapy alone.

Late relapse of testicular cancer, defined as >2 years interval between initial treatment and recurrence, is a rare disease with the incidence rate of 2.6%. Due to its chemoresistant features, treatment options of late relapses are controversial while surgical approach and cisplatin-based chemotherapies can be considered. We report here a patient with nonseminomatous germ cell tumor who experienced relapse 24 years after his first diagnosis. After detecting left supraclavicular lymphadenopathy and absence of any other malignant lesion in positron emission tomography-computerized tomography, patient was treated with three cycles of VeIP regimen (vinblastine/ifosfamide/cisplatin). Second complete response to this treatment was achieved with chemotherapy alone.

Platelet to lymphocyte ratio as a new prognostic for patients with metastatic renal cell cancer.

AIM: The objective of this study was to evaluate the blood platelet-lymphocyte ratio (PLR) for its prognostic value in patients with metastatic renal cell cancer (RCC). METHODS: We retrospectively reviewed 100 patients diagnosed with metastatic RCC previously treated with tyrosine kinase inhibitors from three centers. We assessed the prognostic value of pretreatment PLR and other clinical and laboratory parameters based on univariate and multivariate analyses. RESULTS: Median progression-free survival (PFS) was 7.3 months and median overall survival (OS) was 15.3 months. Multivariate analysis revealed that PFS is significantly affected by ECOG PS (P = 0.047), PLR (P = 0.029) and calcium level (P = 0.023). Median PFS was 13.9 versus 5.3 months in patients with PLR ≤ 210 versus PLR > 210 (log rank; P = 0.001). Median OS was 25.9 versus 10.9 months with PLR ≤ 210 versus PLR > 210 (log rank; P = 0.013). CONCLUSIONS: This study shows that increased pretreatment PLR is an independent prognostic indicator in patients with metastatic RCC who use tyrosine kinase inhibitors.

Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function.

OBJECTIVE: We investigated the effects of thyroxine (T4) therapy on the cardiac function in subclinical hypothyroidism (SHT) by using the index of myocardial performance (IMP) and the conventional echocardiographic parameters. METHODS: Forty-five SHT patients (F/M:38/7, age 39.9+/-7.9) and 29 healthy subjects (F/M:25/4, age 38.3+/-8.6) were studied. Patients were randomly assigned, in a double-blind manner to receive T4 therapy (group I) or a placebo (group II) and for a period of up to 12 months, were followed up using thyroid function tests and both conventional and Doppler echocardiographic measurements. RESULTS: At the baseline, the SHT patients has a significantly higher isovolumic relaxation time (IRT) (98.3+/-23.7 vs. 81.7+/-14.7<0.01), IMP (0.52+/-0.06 vs. 0.42+/-0.05; P<0.001), A max (late mitral peak velocity) (83.4+/-12.6 vs. 74.3+/-13.5; P<0.01) and significantly lower (early mitral peak velocity) Emax/Amax ratio (1.19+/-0.18 vs. 1.34+/-0.17; P<0.01) than the individuals in the control group. In group I, the thyroid hormone profile became normalized after 1 year of L-T4 therapy, but there was no significant change in the left ventricular (LV) morphology or systolic function. After 1 year of follow-up, group I showed a significant reduction of MPI (0.53+/-0.05 vs. 0.42+/-0.07; P<0.001), Amax (84.2+/-13.7 vs. 74.5+/-11; P<0.001) and IRT (98.6+/-23.7 vs. 82.9+/- 23.3; P<0.001) along with a normalization of the E/A ratio (1.17+/-0.16 vs. 1.33+/-0.19; P<0.001). Conversely, no change was observed in group II. CONCLUSIONS: An impairment of left ventricular diastolic function, which may be reversible with T4 therapy, was observed in the SHT patients, and IMP may be useful in the evaluation of LV myocardial dysfunction in these patients.

Evaluation of dexamethasone suppression test in fibromyalgia patients with or without depression.

OBJECTIVE: While in most healthy persons dexamethasone administration suppresses cortisol synthesis from the adrenal cortex, such suppression is not usually observed in patients with depression. We set out to investigate whether the dexamethasone suppression test (DST) reveals any neurobiological relationship between fibromyalgia (FM) and depression related to the hypothalamic-pituitary-adrenal (HPA) axis. METHOD: To discover a relationship between depression and FM we performed the DST in 20 FM patients with depression, 26 FM patients without depression and 20 healthy subjects serving as a control group. RESULTS: Compared with the control group the cortisol level was found to be significantly higher in response to the DST in FM patients with depression (p = 0.03; z: -2.165), but not in those without depression (p = 0.153; z: -1.429). The cortisol level was not found to be statistically significant when patients with FM without depression were compared with the control group (p = 0.249; z: -1.152). In 7 FM patients with depression the DST failed to suppress cortisol; this was statistically significant compared with FM patients without depression (p = 0.014) and the control group(p = 0.008). Among FM patients without depression cortisol was not suppressed in one case. Cortisol was suppressed in all the controls. There was no statistically significant difference in cortisol suppression between FM patients without depression and the control group (p = 1.00). CONCLUSION: Our findings show that the DST reveals no neurobiological relationship between FM and depression related to the HPA axis.