Aggressive treatment for urothelial cancer-complete urinary tract extirpation: Operative feasibility in two cases.

Bladder cancer (BC), the most common malignancy of the urinary tract, accounts for 90-95% of all urothelial carcinomas (UCs), while upper urinary tract UC (UUTUC) accounts for only 5-10%. Radical nephroureterectomy with excision of bladder cuff, and radical cystectomy with pelvic lymph node dissection and a urinary diversion (UD) are the gold standard treatments for UUTUC and muscle-invasive bladder cancer (MIBC), respectively. These two treatments can be performed simultaneously when a bilateral or unilateral UUTUC is present with a MIBC, and are called complete urinary tract extirpation (CUTE) and hemi-CUTE, respectively. This complex surgery can help the patient by avoiding multi-staged surgeries, repeated anesthesia, and delay in completion of treatment. Herein, we report the first cases of a hemi-CUTE and CUTE in our department and share our experience with this aggressive and complex surgical treatment.

Adjuvant carboplatin and paclitaxel after concurrent cisplatin and radiotherapy in patients with locally advanced cervical cancer.

INTRODUCTION: Standard treatment for locally advanced cervical cancer (LACC) includes concomitant chemoradiotherapy (CRT) that typically controls localized disease. However, most patients develop distant metastasis, ultimately leading to death. OBJECTIVE: To determine the role of adjuvant carboplatin and paclitaxel for clinical outcomes in patients with LACC. METHODS: Between 2010 and 2017, 109 patients with LACC were retrospectively evaluated. All patients received cisplatin (40 mg/m2) with concurrent external-beam radiotherapy (up to 50.4 Gy), followed by intra-cavitary brachytherapy. Forty-six of 109 patients received a median of six cycles (range 3-6 cycles) of adjuvant chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (CRT + chemotherapy group; area under the curve 5). The remaining 63 patients did not receive adjuvant chemotherapy (CRT group). RESULTS: Disease-free survival and overall survival after a median follow-up of 24.5 months (range 2.6-94.75 months) were 93.5% and 95.7% and 69.8% and 82.5 % for the CRT + chemotherapy and CRT groups, respectively (p = 0.001, p = 0.012, respectively). No acute grade 3/4 gastrointestinal or genitourinary toxicities were seen during CRT. During adjuvant chemotherapy, the most troublesome side effects were hematologic and neurologic toxicities; however, most were manageable. No chronic grade 3/4 genitourinary toxicities were seen. DISCUSSION: Adjuvant chemotherapy in patients with LACC significantly improved both disease-free survival and overall survival without increasing unmanageable toxicity. Future larger prospective trials are warranted to verify these findings.

Beta-Hydroxy-Beta-Methyl-Butyrate, L-glutamine, and L-arginine Supplementation Improves Radiation-Induce Acute Intestinal Toxicity.

We aimed to evaluate effects of ß-hydroxy-ß-methylbutyrate, L-glutamine, and L-arginine (HMB/GLN/ARG) on radiation-induced acute intestinal toxicity. Forty rats were divided into four groups: group (G) 1 was defined as control group, and G2 was radiation therapy (RT) control group. G3 and G4 were HMB/GLN/ARG control and RT plus HMB/GLN/ARG groups, respectively. HMB/GLN/ARG started from day of RT and continued until the animals were sacrificed 10 days after RT. The extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis were quantified on histological sections of intestinal mucosa. Statistical analyses were performed using the analysis of variance (ANOVA) test. There were significant differences between study groups regarding extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis and crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis (p values were 0.019 for fibrosis, <.001 for the others). Pair-wise comparisons revealed significant differences regarding surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, vascular dilatation, and congestion between G2 and G4 (p values were <.001, .033, <.001, .007, and <.001, respectively). Fibrosis score was significantly different only between G1 and G2 (p = .015). Immunohistochemical TGF-ß score of G2 was significantly higher than G1 and G3 (p values were .006 and .017, respectively). There was no difference between TGF-ß staining scores of G2 and G4. Concomitant use of HMB/GLN/ARG appears to ameliorate radiation-induced acute intestinal toxicity; however, this finding should be clarified with further studies.

Pelvic radiotherapy does not deteriorate the quality of life of women with gynecologic cancers in long-term follow-up: A 2 years prospective single-center study.

PURPOSE: To evaluate the emotional, sexual and health-related quality of life (HRQoL) concerns of the women with gynecologic malignancy treated with curative radiotherapy (RT). PATIENTS AND METHODS: A 100 women with diagnosis of gynecologic malignancy were prospectively enrolled. HRQoL at baseline, at the end of RT and during follow-up was assessed using European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 (EORTC QLQ-C30), EORTC QLQ-cervical cancer module 24, and Hospital Anxiety and Depression Scale. RESULTS: The appetite loss, diarrhea, fatigue, dyspnea, insomnia, nausea and vomiting, pain scores, and sexual activity and sexual enjoyment scores were deteriorated after RT (P = 0.02 for pain scores and P < 0.001 for all other). Body image scores were higher in patients with endometrial cancer (P < 0.01). The emotional function, nausea and vomiting, body image and symptom experience scores were higher in patients who underwent chemotherapy (P = 0.04 and P = 0.01). All the complaints of patients improved during follow-up period. The global health status scores and the level of depression deteriorated in patients with locoregional recurrent disease and distant metastasis. The anxiety (P = 0.001) and depression (P = 0.007) levels were higher in basal and after-RT visits but then decreased through the subsequent follow-up visits. CONCLUSION: Although pelvic RT deteriorated HRQoL in patients with gynecologic malignancy, HRQoL improved during the follow-up period. The progressive disease had a negative impact on HRQoL.

Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient.

Kaposi sarcoma (KS), a vascular tumor caused by infection with human herpesvirus 8 (HHV8), is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

Hyoid osteoradionecrosis accompanied by candida infection.

Osteoradionecrosis of the hyoid bone is a rare complication of therapeutic irradiation performed for head and neck cancer. In this article, we present a 52-year-old male patient who admitted with severe odynophagia following chemo-radiotherapy administration for tonsil carcinoma. Fluorine-18-fluorodeoxy-glucose positron emission tomography-computed tomography revealed a metabolic activity in hyoid bone. The pathological findings were consistent with fungal infection and hyoid bone necrosis. Hyoid osteoradionecrosis should be kept in mind in patients with intractable dysphagia following irradiation for head and neck tumors.

HER-2 positive primary solid neuroendocrine carcinoma of the breast: a case report and review of the literature.

Primary pure neuroendocrine carcinoma of the breast is an extremely rare tumor. We report a case of primary solid neuroendocrine carcinoma in a 77-year-old postmenopausal woman who was admitted to the hospital with masses on her right breast and axillary region. Radical mastectomy with axillary lymph node resection was performed. Immunohistochemical stainings of the tumor cells with synaptophysin, GCDFP-15, estrogen, progesterone, and c-erbB-2 were positive. Five of 16 lymph nodes were metastatic. She did not receive adjuvant chemotherapy. After 15 months of follow-up she is free of the disease. Literature review revealed that this is the second case of HER-2 positive primary neuroendocrine tumor of the breast.

Differential diagnosis between secondary and tertiary hyperparathyroidism in a case of a giant-cell and brown tumor containing mass. Findings by (99m)Tc-MDP, (18)F-FDG PET/CT and (99m)Tc-MIBI scans.

Brown tumor is one of the skeletal manifestations of hyperparathyroidism. It is a benign but locally aggressive bone lesion and its differential diagnosis with giant cell containing skeletal tumors or metastases may be complicated. We present a male patient with chronic renal failure who was initially misdiagnosed as having a giant-cell rich neoplasm of bone in his right thumb. Diffusely increased fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the axial and appendicular skeleton and multiple (18)F-FDG avid lytic lesions suggesting multiple metastases were observed on the (18)F-FDG positron emission tomography/computed tomography (PET/CT) scan. On the usual technetium-99m methylene diphosphonate ((99m)Tc-MDP) bone scan we noticed diffusely increased uptake in the skeleton and two focuses with very much increased uptake, which suggested a metabolic bone disease rather than a multiple metastatic giant cell tumor or bone metastases. Additional investigation documentated increased levels of parathyroid hormone. Parathyroid hyperplasia was finally diagnosed with (99m)Tc-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy. Fluorine-18-FDG avid lytic lesions were attributed to hyerparathyroidism associated brown tumors instead of multiple metastases. In conclusion, we present a patient with chronic renal insufficiency, who suffered from secondary and later from tertiary HPT with polyostotic brown tumors, which were best shown by the (18)F-FDG PET/CT than by the (99m)Tc-MDP or the (99m)Tc-MIBI scans.

Basal renal function reserve and mean kidney dose predict future radiation-induced kidney injury in stomach cancer patients.

BACKGROUND: Adjuvant chemoradiotherapy (CRT) improves the survival in patients with locally advanced stomach cancer. The kidneys are the major dose-limiting organs for radiotherapy (RT) in upper abdominal cancers. We aimed to evaluate the impact of adjuvant CRT on renal function of patients with stomach cancer. MATERIAL AND METHODS: Fifty-nine stomach cancer patients who underwent postoperative CRT were included. Demographic parameters (age, gender), and basal and 12th-month biochemical parameters were recorded. Mean kidney dose (MKD) administered was determined. Estimated glomerular filtration rate (eGFR) was calculated by modification of diet in renal disease formula. RESULTS: Fifty-nine patients were recruited (age 60.8 ± 11.9 years; female/male 25/34; follow-up duration 15.6 ± 9.8 months). Twenty-one patients (35.6 %) had basal eGFR <90 ml/min/1.73 m(2). When the basal and 12th-month eGFR was compared, eGFR decreased in 27 patients (45.8 %), whereas eGFR remained stable in 32 (54.2 %) patients. Cox regression analyses revealed that a MKD ≥1,500 cGy and basal eGFR <90 ml/min/1.73 m(2) significantly increased the risk of a decreased eGFR at 12th month (HR = 2.288, 95 % CI 1.009-5.188, p = 0.048 and HR = 2.854, 95 % CI 1.121-7.262, p = 0.028, respectively). CONCLUSION: MKD ≥1,500 cGy and a basal eGFR <90 ml/min/1.73 m(2) significantly increased the risk of a decreased eGFR at 12th month. We suggest that patients with stomach cancer be evaluated for their basal renal reserve prior to RT, and it may be more convenient to further minimize the dose to the kidneys with more sophisticated RT techniques in patients with stomach cancer, more specifically in patients with decreased renal reserve.

Does spironolactone ameliorate trastuzumab-induced cardiac toxicity?

The ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Trastuzumab, a humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma. Additionally, ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes which accounts for the trastuzumab-induced cardiotoxicity. Moreover, in metastatic breast cancer patients treated with trastuzumab, endomyocardial biopsy documented focal vacuolar changes, pleomorphic mitochondria, myocardial cell hypertrophy, and mild interstitial fibrosis on electron microscopy without accompanying light microscopic abnormalities, a finding consistent with a reversible pattern of cardiac injury. On the other hand, aldosterone and mineralocorticoid receptor (MR) researches have experienced a revival after the discovery that aldosterone and MR are not only involved in the electrolyte and volume balance but also in the pathophysiological processes of the reno-cardiovascular system. Aldosterone has both genomic and nongenotropic effects on epidermal growth factor receptor (EGFR) expression. Genomic effect induces genomic up-regulation of the EGFR protein expression via EGFR promoter, whereas nongenotropic effect leads to the EGFR transactivation resulting in persistent pathophysiological effects including formation of extracellular matrix and myocardial hypertrophy. Spironolactone, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. The underlying mechanism for the genomic interactions seem to be the stimulation of the EGFR promoter by aldosterone-bound MR, which then dose-dependently enhances the EGFR protein levels, which may be successively inhibited by spironolactone. By the light of these findings, we hypothesize that spironolactone may ameliorate trastuzumab-induced cardiotoxicity via inhibition of transactivation of the EGFR by aldosterone and reversing myocardial hypertrophy. This issue warrants further studies.

Comparison of "sandwich chemo-radiotherapy" and six cycles of chemotherapy followed by adjuvant radiotherapy in patients with stage IIIC endometrial cancer: a single center experience.

OBJECTIVE: To compare "sandwich chemo-radiotherapy" with six cycles of chemotherapy followed by adjuvant radiotherapy with respect to tolerability and acute toxicity. MATERIALS AND METHODS: Twenty-five women with surgically staged IIIC endometrial cancer were included. Treatment consisted of either three cycles of paclitaxel (175 mg/m²) and carboplatin (AUC 6) on a q21-day schedule followed by irradiation (45-50.4 Gy) or six cycles of the same chemotherapy followed by radiotherapy. Acute toxicity related to either chemotherapy or radiotherapy was evaluated. RESULTS: Median age was 61.5 years (range 36-83 years). Eleven patients had sandwich chemo-radiotherapy, and the other 14 patients had 6 cycles of chemotherapy followed by radiotherapy. Three out of the five patients who could not complete all the cycles in the sandwich chemo-radiotherapy group had pelvic and para-aortic radiotherapy. Acute radiotherapy related grade 1-2 gastrointestinal system (GIS) and genitourinary system (GUS) toxicities were observed in 72.8 and 63.6 % of patients, respectively, for sandwich group. Undesired treatment breaks in the course of radiotherapy were observed in six patients for sandwich chemo-radiotherapy and in one patient receiving six cycles of chemotherapy followed by radiotherapy. All the patients who had undesired treatment breaks in the sandwich chemo-radiotherapy group had pelvic and para-aortic radiotherapy. CONCLUSION: Sandwich chemo-radiotherapy seems to be more toxic particularly for patients who had pelvic and para-aortic irradiation. Therefore, it might be more convenient to delay radiotherapy after six cycles of chemotherapy for patients with the indication of pelvic para-aortic radiotherapy.

The effect of Halofuginone in the amelioration of radiation induced-lung fibrosis.

The lung is one of the most sensitive organs to ionizing radiation, and damage to normal lung tissue remains a major dose limiting factor for patients receiving radiation to the thorax. Radiation induced lung injury (RILI) which is also named as "radiation pneumonpathy" is a continuous process and regarded as the result of an abnormal healing response. It has been shown that transforming growth factor ß-1 (TGF-ß1) plays an integral role in the radiation induced lung fibrosis formation by promoting the chemoattraction of fibroblasts and their conversion to myofibroblasts. Halofuginone is a, low molecular weight plant derived alkaloid, isolated from the Dichroa febrifuga plant that exhibits antifibrotic activity and inhibition of type I collagen synthesis. Halofuginone has been shown to protect against radiation induced soft tissue fibrosis by virtue of inhibiting various members of TFG-ß signaling pathway. By the light of these findings, we hypothesize that Halofuginone may be able to ameliorate the radiation induced lung fibrosis.

Comparison of the effects of aromatase inhibitors and tamoxifen on radiation-induced lung toxicity: results of an experimental study.

PURPOSE: The purpose of this study is to compare the effects of anastrozole, letrozole and tamoxifen on radiation-induced pulmonary fibrosis. METHODS: Eighty female Wistar albino rats were divided into eight groups. Group (G) 1 was defined as control group. G2 was radiation therapy (RT) only group. Groups 3, 4 and 5 were tamoxifen, anastrozole and letrozole control groups respectively. Groups 6, 7 and 8 were RT plus tamoxifen, anastrozole and letrozole groups, respectively. A single dose of 12 Gy RT was given to both lungs. Tamoxifen, anastrozole and letrozole were started 1 week before the RT and continued until the animals were sacrificed 16 weeks after the RT. As an end point, the extent of pulmonary fibrosis for each rat was quantified with image analysis of histological sections of the lung. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analyses. RESULTS: The congestion, inflammation and pulmonary fibrosis scores were significantly different between all the study groups (p values were <0.001 for each). When compared with RT only group, concomitant RT and tamoxifen group increased the radiation-induced pulmonary fibrosis (p = 0.005). However, using either anastrozole or letrozole with RT did not increase the radiation-induced pulmonary fibrosis (p values were 0.768 and 0.752, respectively). CONCLUSION: Concomitant use of tamoxifen with RT seems to increase radiation-induced pulmonary toxicity. However, the use of both anastrozole and letrozole appears to be safe with concomitant RT, without increasing the risk of pulmonary fibrosis. This finding should be clarified with further clinical studies.

Amelioration of radiation-induced acute inflammation and mucosal atrophy by beta-hydroxy-beta-methylbutyrate, L-glutamine, and L-arginine: results of an experimental study.

PURPOSE: We aimed to evaluate the effects of ß-hydroxy-ß-methylbutyrate, L-glutamine, and L-arginine (HMB/Glu/Arg) on radiation-induced acute inflammation and mucosal atrophy in the oral mucosa. METHODS: Twenty-eight rats were divided into four groups. group (G) 1 was defined as control group, and G2 was the radiation therapy (RT) group. G3 and G4 were HMB/Glu/Arg control and 17 Gy RT plus HMB/Glu/Arg groups, respectively. A single dose of 17 Gy RT was given to the head and neck area, and the active supplement consisting of 5.2 g of HMB, 29.6 g arginine, and 29.6 g of glutamine which was equivalent to 60 kg adult dose was calculated for each rat and administrated orally. HMB/Glu/Arg started from the day of RT and continued until the animals were sacrificed 7 days after the RT. The extent of acute inflammation and mucosal atrophy for each rat was quantified with image analysis of histological sections of the oral mucosa. RESULTS: There were significant differences in terms of epithelial thickness, subepithelial edema, inflammation, and congestion between all groups (p values were <0.001, 0.003, <0.001, and 0.001 for each parameter, respectively). Using HMB/Glu/Arg alone led to hypertrophic changes in the epithelial layer. Moreover, when used with RT, HMB/Glu/Arg reversed radiation-induced epithelial atrophy (p, 0.006) and decreased radiation-induced inflammation at a significant level (p, 0.007). CONCLUSION: Concomitant use of HMB/Glu/Arg appears to ameliorate the radiation-induced acute inflammation and mucosal atrophy which represent the early phase of acute oral mucositis; however, this finding should be clarified with further clinical studies.