Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience.

BACKGROUND: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Abdominal Ultrasound ­ The Leading Method in Duodenal Gist Diagnostics

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract and are generally asymptomatic. A 39-year-old female patient was hospitalized in 2012 at Clinical Department of Internal Medicine, Sestre milosrdnice University Hospital Center, for a focal hypodense irregular circular lesion located in segment III of the left hepatic lobe, accidentally found by ultrasonography and verified by computed tomography. The findings were also verified with nuclear magnetic resonance and esophagogastroduodenoscopy. A biopsy sample of the lesion was analyzed by histologic and immunohistochemical methods and identified as GIST. The patient underwent surgical operation (tumor excision with terminoterminal anastomosis created between the second segment of duodenum and jejunum and resection of liver segment III). The histopathologic findings matched GIST with a high probability of relapse according to the localization, size, mitotic activity and Ki-67 values. Therefore, therapy with imatinib at a dose of 400 mg/day was administered. Three years after the operation, the patient is still in remission.

GASTRIC CARCINOID TYPE 1 IN A PATIENT WITH AUTOIMMUNE POLYGLANDULAR SYNDROME: ADDITIONAL ENDOCRINOLOGICAL EVALUATION REQUIRED.

Autoimmune polyglandular syndrome by definition consists of two or more endocrinological insufficiencies or two organ specific autoimmune diseases. There are no stringent criteria for endocrinological evaluation of patients with one endocrine insufficiency. However, detailed endocrinological evaluation should be undertaken in patients with two autoimmune diseases. Additionally, follow up thereafter should be a must in these patients in order to avoid the possibility of not diagnosing subsequent autoimmune diseases that can occur. The aim of this case report is to point to the necessity of endocrinological screening to be made in patients presenting with gastric carcinoid type 1. We report on a 62-year-old woman who was diagnosed with primary hypothyroidism in 1993. In 2011, she was re-admitted to the hospital due to increasing fatigue. Macrocytic anemia, low vitamin B12 levels and positive parietal antibodies confirmed pernicious anemia. Furthermore, she underwent gastroscopy, which revealed two polyps in the corpus of the stomach and one in the fornix. Endoscopic mucosal resection was performed and histopathologic analysis confirmed three G1 gastric carcinoids (Ki67 2%). Additional endocrinological evaluation disclosed positive glutamic acid decarboxylase antibodies, but normal fasting and postprandial glucose and HbA1c. In 2013, she was diagnosed with glucose intolerance and subsequently with latent autoimmune diabetes of adulthood. Plasma glucose and HbA1c normalized after dietary intervention. Due to the increase of serum chromogranin A, prophylactic antrectomy was performed in 2014. The patient is still followed-up and has normal chromogranin A, gastrin and HbA1c levels.

Waldenström's macroglobulinemia as a diagnostic challenge: case report.

Waldenström's macroglobulinemia is a distinct clinicopathologic entity defined as a B-cell neoplasm characterized by lymphoplasmacytic infiltrate in the bone marrow, with an associated immunoglobulin (Ig) M paraprotein. Clinical manifestations are due to deposition of IgM in the liver, spleen, and/or lymph nodes, so it presents with anemia, hyperviscosity, lymphadenopathy, hepatomegaly, splenomegaly and neurologic symptoms. The main diagnostic criteria are a typical peak on serum protein electrophoresis and malignant cells in bone marrow biopsy samples. There is no standard therapy for the treatment of symptomatic Waldenstrom's macroglobulinemia and no agents have been specifically approved for this disease, but initial treatment usually starts with the monoclonal anti-CD20 antibody rituximab, either alone or in combination with other agents, rather than chemotherapy alone. This article confirms that, despite the existence of more modern imaging methods, ultrasonography still has a significant diagnostic role.

Diagnosis and treatment of chronic viral hepatitis B and C: doctrinary approach.

Association of Gastroenterologists and Hepatologists of Bosnia and Herzegovina based on the experiences of domestic and foreign centers operating in the field of hepatology and accepted guidelines of the European and the U.S. Association for Liver Diseases adopted the consensus for the diagnosis and treatment of chronic viral hepatitis B and C. The guidelines are intended for specialists in gastroenterology and hepatology, and infectious diseases physicians working in primary health care and family medicine, but also other physicians who are confronted with this disease in their practice, with the aim of facilitating and shortening the diagnostic and treatment protocols of patients with chronic viral hepatitis B and C. This ensures faster, more efficient, more rational and cost-effective care of patients with hepatitis, with an emphasis on stopping the deterioration of liver disease to liver cirrhosis and eventually hepatocellular carcinoma. Key words: Chronic hepatitis B and

The results of treatment of basoceltular carcinomas of the head skin.

INTRODUCTION: Basocellular skin carcinoma (BCC) is the most common cancer in the human population. BCC almost appeared at adult's people, but it can be found at children, too. THE AIM: The aim of this study was to determine which the position of BCC on the head skin is the most difficult for the treatment and what the reasons are for it. METHODS: With the prospective study, from June 2004 to June 2011, were compared the results of treatment of basocellular carcinomas (BCC) of the head skin. The examinees were divided into 3 groups. The first group, the group A (38 patients) was consisted of examinees treated of BCC on the nose. In the second group, the group B (42 patients) was classified of examinees treated of BCC on the face, temple, eyelids and forehead, while the third group, group C (35 patients) was classified of examinees treated of BCC on the scalp. The parameters for comparison the results of treatment were the method of treatment, number of the relapse, elapsed time from surgery to relapse and consequently defacement. RESULTS: There was found a statistical significant difference in terms of choice of methods of operative treatment for the significantly higher number of operations on the scalp operated with cutaneous transplants. It was confirmed that the localization of the tumors on the scalp, and then on the nose are with the highest incidence of the relapse, whereas the postoperative defacement is mostly on the scalp after skin graft placement. Key

The analysis of reasons for malignant skin tumors late diagnosis.

INTRODUCTION: Timely diagnosis is a prerequisite for the successful treatment of malignant skin tumors. Late diagnosis leads a patient into a situation of losing valuable time and chance for cure. MATERIAL AND METHODS: A prospective study was conducted from February 2006 until August 2011 which analyzed the reasons that led to establishing the diagnosis of malignant skin tumors in 220 patients. Patients were divided into two groups: Group A (102 patients), patients with diagnosed melanoma, and group B (118 patients) of patients suffering from basocellular (BCC) and planocellular cell (PCC) skin cancer. Parameters for comparison of analysis results were the reasons for coming to examination and reasons for not coming to the examination, because of which skin cancers were not diagnosed in time. GOAL: To determine the factors that influences the establishment of late diagnosis and treatment of skin tumors. RESULTS: It was confirmed that the prejudices of patients that tumors of the skin "should not be operated because it is dangerous" is the main reason for late diagnosis. At the same time it is confirmed that the belief that it is unnecessary to operate congenital changes of the skin is the second most important reason for delayed diagnosis of malignant skin tumors.

Isolated splenic metastasis from colorectal carcinoma in a high risk patient: a case report.

Isolated splenic metastasis arising from a colorectal carcinoma is a rare finding. We report a case of 74-year-old man with a medical history of diabetes type II and paroxysmal atrial fibrillation, who underwent a right hemicolectomy for an adenocarcinoma of caecum in August 2004. In June 2007 the patient was diagnosed with high grade aortic valve stenosis as well as long segment stenosis of the first obtuse marginal branch of left coronary artery. He was suggested aortic valve replacement with coronary artery bypass grafting but he refused the surgery. In October 2007 the patient underwent alpha 18FDG - PET scanning, due to increasing values of CEA serum level, which showed a 5 cm big isolated hypermetabolic lesion in the spleen. Due to operative risk, splenectomy was refused by surgeons. The patient underwent a chemotherapy with capecitabine in total of 8 cycles before his CEA level began to rise and MSCT showed a progression in size of splenic metastasis. The patients condition was reevaluated by a team of experts and splenectomy was performed in September 2008. In May 2009 during the postoperative follow up, MSCT scanning revealed enlarged lymph nodes in celiac region and hepatic lesion suspicious of metastasis and the patient was admitted for further chemotherapy treatment. There is still no standardized treatment for this condition due to small number of cases reported in literature. Splenectomy followed by chemotherapy seems to be an optimal treatment but still no final conclusions can be made.

Symptoms of annular pancreas exacerbated by pregnancy.

Annular pancreas is a rare embryonal abnormality. Its manifestation in adulthood is often pinpointed with a substantial delay, which is most often attributed to pancreatitis, biliary pathology or dyspepsia. We present a case of a 28-year-old woman who had exacerbating symptoms of high bowel obstruction from 20th week of pregnancy, progressing after premature delivery. Diagnostic work-up revealed partial annular pancreas compressing the duodenum. Despite attempts of conservative treatment, her state deteriorated to such an extent that surgery was indicated and gastrojejunal bypass created. Her postoperative recovery was uneventful. In cases in which symptoms of high bowel obstruction in pregnancy persist and prostration occurs, we suggest close monitoring and a more thorough diagnostic approach. The question remains whether annular pancreas presents a cause of pathologic findings, a cofactor, or a mere accidental diagnosis in the development of superposed pathologies.

Seminal vesicle cyst with ectopic ureteral insertion and ipsilateral renal dysplasia--an unexpected diagnosis.

An extremely rare case of seminal vesicle cyst associated with ipsilateral renal dysplasia and ectopic ureter is presented. A 36-year-old patient underwent nephroureterovesiculectomy. Considering the clinical and imaging profile of the patient, a diagnosis of ureterocele with megaureter was initially suspected, but intraoperative findings and definitive pathological analysis of the specimen revealed right renal dysplasia with ectopic ureter opening into seminal vesicle cyst. The clinical and therapeutic peculiarities of this rare condition are presented and the literature on this topic is reviewed.

Retained surgical textilomas occur more often during war.

Retained surgical textile foreign bodies are a problem despite precautions taken by surgeons. Computed tomography (CT) is a method of choice in diagnosing the cases of retained textilomas. Over 12 years, we diagnosed 11 acute textilomas in 10 patients in the early postoperative period within 3 months after abdominal surgery. The presence of considerable amount of air bubbles within textile fibers was the most representative sign. A 3-10 mm wide peripheral rim was present in all textilomas. In additional 3 cases, chronic, encapsulated foreign body granulomas were found, two were mimicking renal neoplasms. All granulomas contained discrete or coarse calcifications. The period between surgery and CT diagnosis was from 6 months to 14 years in chronic lesions. It is important to emphasize that 9 textilloma in 8 patients were associated with the years of war in Croatia (1991 and 1992), in hospitals on battle fronts, where surgeons worked under extremely strenuous conditions and with great inflow of wounded soldiers and civilians.