Prevalence of occult leiomyosarcomas and atypical leiomyomas after laparoscopic morcellation of leiomyomas in reproductive-age women.

STUDY QUESTION: What is the prevalence of leiomyosarcomas and atypical leiomyomas after laparoscopic morcellation of fibroids in reproductive age women? SUMMARY ANSWER: No case of leiomyosarcomas but seven atypical leiomyomas were found in 1216 subjects. WHAT IS KNOWN ALREADY: Although uterine sarcoma is a rare entity affecting usually older peri- or post-menopausal women, the Food and Drug Administration discourages use of laparoscopic power morcellation of uterine fibroids. STUDY DESIGN, SIZE, DURATION: Retrospective review of data extracted from a single center database of 1216 consecutive women who underwent laparoscopic morcellation of 2582 unsuspicious leiomyomas between June 2003 and December 2015 and were followed-up until December 2016. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 1216 women, aged 18-45 years, underwent laparoscopic morcellation of 2582 apparently benign leiomyomas by the same surgeon and all specimen slides were examined by the same experienced pathologist. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of leiomyosarcomas and atypical leiomyomas was 0% (95% CI: 0-0.3%) and 0.6% (95% CI: 0.23-1.18%) (six atypical-bizarre and one mitotically active leiomyoma) respectively. In addition, there were identified 34 cases of adenomyomas, 45 leiomyomas with infarcts, 81 cellular leiomyomas and 133 degenerated leiomyomas. No morcellator-associated complication was recorded and none of the patients included in this study required conversion to laparotomy. LIMITATIONS, REASONS FOR CAUTION: Retrospective and single referral center study design. WIDER IMPLICATIONS OF THE FINDINGS: Laparoscopic morcellation of unsuspicious leiomyomas after careful preoperative work up seems to be safe in women of reproductive age. STUDY FUNDING/COMPETING INTEREST(S): None.

Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype.

BACKGROUND: We sought to determine biomarker expression differences in head and neck squamous cell cancers (HNSCCs) based on p16/human papillomavirus (HPV) classification. In addition, our aim was to explore how expression of biomarkers is modulated after E6/E7 repression in HPV16⁺ oropharyngeal cancer cells. METHODS: HPV16⁺ and HPV⁻ HNSCC cells were infected with retroviruses expressing short hairpin RNA targeting HPV16 E6/E7. Components of the epidermal growth factor receptor (EGFR) pathway before and after E6/E7 gene silencing were analyzed by immunoblotting and qRT-PCR. Protein expression of 13 biomarkers was analyzed using AQUA on a tissue microarray (TMA). The HPV16 status was determined using HPV16 in situ hybridization (ISH). RESULTS: In HPV16⁺ cells, E6/E7 silencing was associated with PTEN upregulation and reduction of phosphorylated EGFR. Tumors were classified into four categories based on the HPV and p16 status. HPV⁺/p16⁺ tumors expressed significantly higher levels of E-cadherin (P = 0.003), PTEN (P = 0.004), lower levels of PI3Kp110 and ß-catenin (P = 0.07). There was a significant difference in overall survival (OS, P = 0.016) among the four subsets. The median OS was 24.83 months for p16⁻/HPV⁻ patients, 11.63 for p16⁻/HPV⁺ patients and was not reached for p16⁺/HPV⁻ and p16⁺/HPV⁺ groups. CONCLUSIONS: Aberrant EGFR signaling contributes to malignant conversion of HPV16⁺ HNSCC cells. These results validate ß-catenin as a distinct biomarker in HPV⁺/p16⁺ HNSCC. Wnt signaling inhibitors merit exploration in HPV⁺/p16⁺ HNSCC.

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.

BACKGROUND: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. PATIENTS AND METHODS: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). RESULTS: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. CONCLUSION: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

Laparoscopic management of unexpected borderline ovarian tumors in women of reproductive age.

PURPOSE OF INVESTIGATION: The aim of this study was to review the clinical features of women with unexpected borderline ovarian tumours. METHODS: Between October 1992 and December 2010, 1332 out of 4016 laparoscopies were performed for adnexal masses in women of reproductive age and 1838 cysts were removed. When ultrasonographic findings did not meet the criteria for low risk malignancy, tumour markers, colour Doppler and MRI/CT were applied. At laparoscopy any solid component or papilla was sent for rapid frozen section. RESULTS: Borderline ovarian tumours were found in eight (0.6%) out of 1332 patients, two of which were bilateral. The mean age was 28.75 +/- 9.27 years and the mean diameter of the cysts was 5.1 +/- 1.7 cm. In two cases unexpected malignancy was discovered during the diagnostic and in six cases during the operative phase of the intervention. CONCLUSION(S): Risk of failure to diagnose cancer could be minimised with careful patient selection preoperatively. Adequate training on laparoscopic oncology is the necessary prerequisite for a safe laparoscopic approach.

Primary angiosarcoma of the brain: case report.

A 41-year-old patient with a primary angiosarcoma of the brain is reported. The tumor was located in the left parietal lobe and was radically removed. The diagnosis of angiosarcoma was established by immunohistochemistry. The patient was postoperatively treated with adjuvant chemotherapy and then radiation therapy. After 41 months, she was in excellent clinical and neurological condition without any sign of recurrence.

p53 and bcl-2 expression in locally advanced squamous cell head-neck cancer treated with platinum based chemotherapy and radiotherapy.

BACKGROUND: The role of apoptosis regulating oncoproteins in defining response to cytotoxic therapy remains poorly understood. Loss of wild type p53 function and bcl-2 protein overexpression are well known to inhibit the apoptotic pathway in in vitro studies. METHODS: We immunohistochemically examined the nuclear accumulation of mutant p53 and the cytoplasmic overexpression of bcl-2 proteins in 76 patients with locally advanced inoperable squamous cell cancer of the head and neck area. Patients were treated with platinum based chemotherapy and radiotherapy (37 with induction and 39 with concurrent chemotherapy). The median follow up period was 72 months. RESULTS: Thirty five (46%) cases were positive for p53 and 41 (54%) negative, whilst 19 (25%) and 57 (75%) cases were positive and negative for bcl-2 respectively. A high percentage of bcl-2 positive cells was associated with a low incidence of nodal involvement. A statistically significant higher percentage of p53 positive cells was observed in the group of patients with complete disappearance of the disease as compared to the group with residual disease after treatment (p = 0.01). High percentage of p53 positive cells and concurrent chemoradiotherapy was associated with better local progression free survival (p = 0.05 and 0.02). In multivariate analysis, the type of chemotherapy (concurrent vs. induction) was the only significant prognostic variable for local relapse (p = 0.02) and overall survival (p = 0.03). CONCLUSIONS: The present study provides evidence that p53 nuclear accumulation may be associated with better response to DNA damaging cytotoxic agents. The association of wild type p53 loss with decreased DNA repair enzyme activity is a possible explanation. Induction platinum based chemotherapy may contribute to the selection of clonogenic cells with a radioresistant phenotype.

Extragonadal choriocarcinoma in a patient with Down syndrome.

There are several reports suggesting that there is a higher incidence of leukemia and testicular cancer in patients with Down syndrome. Fifteen patients with Down syndrome and testicular cancer were previously reported. The median age at diagnosis of testicular cancer was 18 years, (range: 3-45). The histologic subtypes were seminoma in 9 patients, not specified in 2 patients, and 1 patient each of adenocarcinoma, yolk sac, embryonal, and teratocarcinoma. In this article we describe a case of extragonadal choriocarcinoma in a patient with Down syndrome. To our knowledge, this is the first case ever reported. The patient had a complete remission following chemotherapy with cisplatin, etoposide, and bleomycin and is disease-free with a follow-up of 32 months. Patients with Down syndrome and advanced testicular cancer should be treated with potentially curative chemotherapy.

Platinum-based induction chemotherapy followed by radiation as definitive treatment for patients with locally advanced cancer of the oral cavity, oropharynx and hypopharynx. A retrospective analysis of 32 cases.

Thirty-two patients with locally advanced cancer of oral cavity, oropharynx and hypopharynx were treated with three cycles of platinum-based induction chemotherapy followed by radiation therapy. After completion of the combined treatment 50% of the patients were in complete response (CR) and 28% in partial response (PR). So far, 24 patients have died. Local progression occurred in 20 patients. Survival is 29% at 24 months. Seven (22%) patients remain alive and have been disease-free for 22-59 months. In conclusion, induction chemotherapy followed by radiation therapy may omit radical surgery, without compromising survival, in some patients with locally advanced cancer of the oral cavity, oropharynx and hypopharynx.

Recurrent abdominal pain of gastro-intestinal origin.

A consecutive series of 71 children (mean age 8.6 years) with recurrent abdominal pain underwent endoscopic oesophageal, gastric and duodenal biopsy in order to determine whether the pain was of gastro-intestinal origin. Of these 71 children, 27 (38%) showed oesophagitis, 14 (20%) cardiac gastritis, 29 (41%) body gastritis, 38 (54%) antral gastritis, and 29 (41%) duodenitis. Thus, 66 of the 71 children studied had an inflammatory lesion explaining their complaints. One of the patients had a gastric ulcer. Helicobacter pylori colonisation was found in 5 of the children: One had H. pylori associated antral and body gastritis and 4 H. pylori associated antral gastritis only. Body gastritis without H. pylori was present in three of these four children. Our data do not support the widespread assumption that recurrent abdominal pain for which no medical cause can be found, is psychogenic; neither do they establish an association between H. pylori antral gastritis and recurrent abdominal pain. However, our data provide strong evidence that there is a gastro-intestinal origin of these patients' complaints.

Migraine of gastrointestinal origin.

UNLABELLED: A consecutive series of 31 children (median age 12 years) suffering from migraine with (n = 21) or without (n = 10) aura underwent endoscopic oesophageal, gastric and duodenal biopsy in order to determine whether the complaints were of gastro-intestinal origin. Of these 31 children, 13 (41.9%) showed oesophagitis, 16 (51.6%) gastritis of corpus, 12 (38.7%) antral gastritis and 27 (87.1%) duodenitis. Thus, 29 of the 31 children studied had an underlying inflammatory lesion explaining their complaints. Helicobacter pylori colonization was found in 7 of the children: one had H. pylori associated antral and corporal gastritis and 6 H. pylori associated antral gastritis only. Gastritis of corpus without H. pylori was present in all these 6 children. Our data do not support that H. pylori is a primary pathogen of inflammatory changes seen in children studied, neither do they establish an association between H. pylori, antral gastritis and migraine. However, our data strongly suggest that there is a gastro-intestinal origin of these patients' complaints. CONCLUSION: Our findings provide further evidence that recurrent abdominal pain is an early expression of migraine and strongly support a causal link between recurrent abdominal pain and migraine.

Clinical application of immunological markers as monitoring tests in celiac disease.

The aim of this study was to investigate anti-gliadin (IgA-AGA and IgG-AGA), endomysial (IgA-EmA), and anti-reticulin (Ig-ARA) antibodies for monitoring celiac disease (CD) patients while on gluten-free and gluten-containing diets. Sera from 30 confirmed CD patients (13 boys, 17 girls), 1-24 years old, were examined for antibodies using ELISA (AGA) and Immunofluorescence (EmA, ARA) at 1, 3, 6, 9, and 12 months following institution of gluten-free diet and also at 3 and 6 months after challenge with gluten. One month following the exclusion of gluten from the diet, most antibodies are still positive. Twenty-three to 43% of antibodies remained positive by the end of the third month. At 6 and 9 months, 17% and 10% were positive, respectively. At 12 months no positive antibodies were detected. After gluten challenge, positive IgA-AGA and IgA-EmA titers were already demonstrated at 3 months (90% and 86%, respectively), while Ig-ARA titers showed a slow increase. Finally IgG-AGA responded with a slow decrease of titers to gluten-free diet levels and a fast increase upon provocation. The morphology of the intestine at diagnosis and during the periods of gluten-free diet and gluten challenge corresponds with the antibody titers. On the basis of these results, immunological markers may be applied to follow-up CD patients. IgA-AGA and IgA-EMA appear to be the most sensitive to dietary changes in gluten and correlate best with intestinal mucosal morphology.

Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region.

Sixty-six patients with locally advanced (Stages III and IV) carcinoma of the head and neck were treated with three cycles of induction chemotherapy, consisting of cisplatin, fluorouracil (FU) infusion, bleomycin, mitomycin, and hydroxyurea, followed by radiotherapy and/or surgery. There were 48 men and 18 women with a median age of 55 years (range, 18 to 75 years) and Karnofsky performance status of 80 (range, 40 to 90). Primary site was nasopharynx (28 patients), followed by larynx (12) and others (26). Forty-one (62%) patients were presented with Stage IV disease. The response rate to induction chemotherapy was 27% complete response, 50% partial response, 20% stable disease, and 3% progressive disease. There was no significant difference in response rate between patients with cancer of nasopharynx or other sites (P greater than 0.1). Survival was 61% at 24 months. Patients with cancer of nasopharynx had a better survival than those with other primaries (P = 0.033). Toxicities from chemotherapy included alopecia (73%), nausea/vomiting (66%), leukopenia (54%), stomatitis (36%), anemia (32%), thrombocytopenia (16%), and diarrhea (9%). Grade IV toxicity was not observed. Induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and FU alone. It can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck. Chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers.

Cisplatin and continuous infusion of fluorouracil followed by radiation and weekly carboplatin in the treatment of locally advanced head and neck cancer: a Hellenic Cooperative Oncology Group study.

Induction chemotherapy followed by radiation has been extensively studied in an effort to improve local control and possibly overall survival of patients with locally advanced head and neck cancer. From June 1989 until May 1991, 39 patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy, consisting of cisplatin (100 mg/m2 d 1) and fluorouracil (1000 mg/m2 d 2-6) followed by radiation potentiated by weekly administration of carboplatin (60 mg/m2). Surgery was performed in selected patients with residual disease after the combined modality approach. Four cycles of adjuvant chemotherapy with carboplatin (325 mg/m2) and bleomycin (15 u) were administered in those patients who demonstrated a partial response after locoregional treatment. There were 36 men and 3 women with a median age of 56 (range 39-74) years and Karnofsky performance status of 70 (range 60-100). The primary site of the tumor was nasopharynx (8), oropharynx (8), hypopharynx (3), oral cavity (4), larynx (13), paranasal sinus (2), and salivary glands (1). Thirty-two (82%) patients presented with stage IV disease. After the completion of induction chemotherapy, 14 (36%, 95% CI 21-53%) patients achieved a complete response (CR). This CR rate was increased to 56% (95% CI, 42-74%) after locoregional treatment. Main toxicities included nausea/vomiting (56%), leukopenia (40%), anemia (30%), thrombocytopenia (10%), stomatitis (28%), diarrhea (17%), and alopecia (12%). Median relapse-free survival was 18 (1-50) months, median time to progression was 13 (0.3-58.5) months, and median survival 19 (0.3-59) months. Induction chemotherapy with cisplatin and fluorouracil followed by radiation potentiated with carboplatin is feasible. However, this combined modality approach, as applied in the present study, does not appear to yield superior results than those reported with chemotherapy followed by radiation alone.