Low-dose nivolumab and cabozantinib in recurrent intestinal-type papillary adenocarcinoma of the sinonasal region.

Intestinal-type sinonasal adenocarcinoma is a rare epithelial malignancy primarily treated with surgery and chemoradiation. The combination of low-dose immunotherapy and a tyrosine kinase inhibitor in recurrent disease has not been previously studied.A man in his 20s with papillary adenocarcinoma of the sinonasal region, following surgical resection, was treated with six cycles of concurrent chemoradiotherapy, followed by four cycles of docetaxel, cisplatin and capecitabine. While on treatment, he was found to have extensive residual disease and he was started on low-dose nivolumab and cabozantinib. Repeat imaging after ten months of treatment revealed a significant reduction in lesions.Non-squamous head and neck cancers are often excluded from major trials, and the effect of immunotherapy in these histologies is poorly understood. The response seen with low-dose immunotherapy underscores the need for further research in this setting.

A Case of Paraneoplastic Myoclonus Attributed to Non-Small Cell Lung Cancer.

Background: It is well known that myoclonus can be a paraneoplastic manifestation of underlying malignancy. Case Report: A 78-year-old male diagnosed with papillary variant non-small cell lung cancer (NSCLC) presented with tremulousness that rapidly evolved into severe, diffuse myoclonus with prominent palatal involvement requiring intubation. The generalized myoclonus resolved with on levetiracetam, chemotherapy and immune modulation. While low titer positive P/Q type calcium channel autoantibodies were detected, it's etiologic relevance is unclear. Discussion: This case highlights a rare neurologic paraneoplastic presentation of papillary NSCLC. It also illustrates the importance of monitoring airway safety when myoclonus is generalized. Highlights: A new, rare paraneoplastic presentation of papillary variant non-small cell lung adenocarcinoma is described. The patient presented with severe diffuse myoclonus with prominent palatal involvement without encephalitis that responded to a combination of chemotherapy, immune modulation, and levetiracetam. No clear causal antibody was found.

Micropapillary Predominant Lung Adenocarcinoma in Stage IA Benefits from Adjuvant Chemotherapy.

PURPOSE: The benefit of adjuvant chemotherapy remains unknown for patients with stage IA micropapillary predominant (MPP) lung adenocarcinoma (ADC). This study investigated the effect of adjuvant chemotherapy in ADC and MPP patients in stage IA. METHODS: A total of 5220 stage IA lung ADC patients from SEER database and 152 MPP subtype patients from Qilu Hospital of Shandong University were retrospectively analyzed. Propensity score matching analysis was used to adjust the confounding factors. The benefits of improved overall survival (OS) or progression-free survival (PFS) from adjuvant chemotherapy in patients with resected stage IA ADC or MPP patients were investigated. RESULTS: Based on SEER database, for ADC patients in stage IA, chemotherapy (no vs. yes: hazard ratio [HR]: 0.674, 95% confidence interval [CI] 0.474-0.958, P = 0.030), together with radiotherapy (no vs. yes: HR: 0.519, 95% CI 0.358-0.751, P = 0.001), race, gender, age, and T stage were all statistically significant independent factors for OS. However, in propensity model, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not. Only age was a significant prognostic predictor for OS. For patients with MPP subtype in stage IA, multivariate analysis revealed that chemotherapy (no vs. yes: HR: 2.054, 95% CI 1.085-3.886, P = 0.027) as well as T stage were prognostic predictors for OS. Chemotherapy (no vs. yes: HR: 2.205, 95% CI 1.118-4.349, P = 0.022) and T stage also were significant predictors for PFS. CONCLUSIONS: Adjuvant chemotherapy is a favorable prognostic factor for MPP patients in stage IA but not for lung ADC patients. MPP subtype could benefit from adjuvant chemotherapy.

Use of synthetic stomata in abdominal carcinomatosis. Case report and literature review.

BACKGROUND: The successful performance of ostomies for the treatment of different diseases has been described since 1706. We report herein the first case of successful ostomy utilizing a synthetic stoma created in a patient with peritoneal carcinomatosis. CLINICAL CASE: A 40-year-old woman presented with abdominal carcinomatosis due to psammomatous papillotubular adenocarcinoma consistent with primary ovarian carcinoma. The patient had negative estrogen and progesterone receptors and Ki-67 proliferative activity was 83%. She was initially treated with cytoreduction therapy, chemotherapy, and hyperthermic intraperitoneal chemotherapy. Because the patient presented with enteric perforations and the extensive tumor invasion and adhesions in all the intestinal segments made it impossible to create autologous decompression stomas, a synthetic stoma was constructed. CONCLUSIONS: Synthetic stomas can be a good treatment option when autologous stomas can not be created.

INTRODUCCIÓN: Desde el año 1706 se han descrito ostomías realizadas con éxito para el tratamiento de diferentes enfermedades; los autores describen el primer caso de éxito en una ostomía sintética en la carcinomatosis peritoneal. CASO CLÍNICO: Mujer de 40 años de edad con carcinomatosis abdominal por adenocarcinoma papilar tubulopapilar psamomatoso más consistente con cáncer primario de ovario, negativo a receptores de estrógenos y progesterona, con marcador Ki-67 al 83% de actividad. De modo inicial se trató con cirugía de citorreducción, quimioterapia, quimioterapia intraperitoneal hipertérmica y por último realización de estomas sintéticos debido a perforaciones entéricas e imposibilidad de realizar estomas descompresivos autólogos por la invasión tumoral extensa y adherencias de todas las asas intestinales. CONCLUSIONES: Los estomas sintéticos pueden ser una buena opción terapéutica cuando es imposible realizar estomas autólogos.

Type VI choledochal cyst with gall bladder carcinoma.

An isolated dilatation of the cystic duct (type VI choledochal cyst (CDC)) is extremely rare with only 21 cases reported in the world literature until now. There is only one case of in situ gall bladder cancer (GBC) reported in association with type VI CDC in the literature. Here we are reporting a case of type VI CDC with papillary GBC.

Use of apatinib combined with pemetrexed for advanced ovarian cancer: A case report.

INTRODUCTION: Ovarian cancer is the most deadly gynecologic cancer, and the therapy is very difficult. Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. At present, there are few studies or case reports on apatinib treatment for patients with ovarian cancer. CASE PRESENTATION: A 75-year-old Chinese woman had a medical history of ovarian high-grade serous papillary adenocarcinoma, who got many lines of chemotherapy and apatinib-an antiangiogenesis drug therapy. Either alone or in combination, apatinib may extend the survival time of patients with advanced ovarian cancer. CONCLUSION: Apatinib may be an option for advanced ovarian cancer after failure of chemotherapy or other targeted therapy. The role of apatinib in the treatment of advanced ovarian cancer needs further study.

Sperm associated antigen 9 (SPAG9) a promising therapeutic target of ovarian carcinoma.

SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated in ovarian cancer cells by real time PCR and Western blot. SPAG9 involvement in cell cycle, DNA damage, apoptosis, paclitaxel sensitivity and epithelial- mesenchymal transition (EMT) was investigated employing RNA interference approach. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro. Quantitative PCR and Western blot analysis revealed SPAG9 expression in A10, SKOV-3 and Caov3 compared to normal ovarian epithelial cells. SPAG9 ablation resulted in reduced cellular proliferation, colony forming ability and enhanced cytotoxicity of chemotherapeutic agent paclitaxel. Effect of ablation of SPAG9 on cell cycle revealed S phase arrest and showed decreased expression of CDK1, CDK2, CDK4, CDK6, cyclin B1, cyclin D1, cyclin E and increased expression of tumor suppressor p21. Ablation of SPAG9 also resulted in increased apoptosis with increased expression of various pro- apoptotic molecules including BAD, BID, PUMA, caspase 3, caspase 7, caspase 8 and cytochrome C. Decreased expression of mesenchymal markers and increased expression of epithelial markers was found in SPAG9 ablated cells. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro assays which showed that ablation of SPAG9 resulted in increased paclitaxel sensitivity and caused enhanced cell death. In vivo ovarian cancer xenograft studies showed that ablation of SPAG9 resulted in significant reduction in tumor growth. Present study revealed therapeutic potential of SPAG9 in ovarian cancer.

Dynamic Phenotypic Transition of Breast Cancer Cells In Vitro Revealed by Self-floating Cell Culture.

BACKGROUND: Breast tumor heterogeneity leads to phenotypic diversity, such as tumor-initiating and metastatic properties and drug sensitivity. MATERIALS AND METHODS: We found that a self-floating cell (SFC) culture enriches a drug-resistant subpopulation in a HER2-positive breast cancer cell line. SFCs were analyzed for cancer stem cell markers, gene expression profiles, and sensitivity for anticancer drugs. RESULTS: SFCs expressed cancer stem cell markers, such as aldehyde dehydrogenase (ALDH) activity and elevated HER2 autophosphorylation. Gene expression profiles of SFCs showed a dramatic difference compared to those of parental or forced floating cells. SFCs also expressed CD133, a marker of drug resistance, and resisted cytotoxic drugs by drug efflux transporters. In contrast, HER2 kinase inhibitors efficiently reduced SFC viability. CONCLUSION: SFCs enrich drug-resistant subpopulations even in vitro and might reflect the highly plastic nature of breast cancer cells even in vitro.

Comparative Study of Antitumor Efficiency of Intraperitoneal and Intravenous Cytostatics in Experimental Rats with Disseminated Ovarian Cancer.

Antitumor efficiencies of cytostatics dioxadet, cisplatin, mitomycin C, melphalan, and paclitaxel after a single intraperitoneal or intravenous injection in doses of 1.5, 4, 1.5, 2, and 5 mg/kg, respectively, were studied on the model of transplanted ovarian tumor in 124 rats. The antitumor effects were evaluated by the increase in median survival. Dioxadet, cisplatin, and melphalan injected intraperitoneally significantly prolonged the lifespan median - by 79, 88, and 114%, respectively, and were in fact ineffective, when injected intravenously. Intraperitoneal mitomycin C prolonged lifespan median by just 35%, intravenous - by 152%. Paclitaxel injected intraperitoneally and intravenously prolonged the lifespan median by 45 and 81%, respectively.

Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A Case Report and Review of the Literature.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm with a high recurrence rate and metastatic potential. In this study, the authors describe a case that originally appeared to benign spiradenoma, but took an ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman developed a gradually growing nodule on the second toe of her left foot, which she had first noticed 4 years previously. An excisional biopsy was performed followed by histological examination. The authors initially considered the tumor to be a benign spiradenoma and did not perform reexcision. However, she experienced local recurrence 24 months later, and multiple pulmonary metastasis 31 months later. On histological examination, both the primary and locally recurrent tumors were found to be composed of discrete and well-circumscribed solid nodules, lacking cystic space. All tumors (the primary tumor, locally recurrent tumor, and lung metastases) presented with a pattern of fused back-to-back tubular structures and myoepithelial differentiation confirmed by immunohistochemical examination. On the basis of these findings, the authors finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent chemotherapy, but died of disease 49 months later. This case highlights the importance of high clinical suspicion of ADPA when digital lesions present.

Prevalence and Clinicopathological Characteristics of BRAF Mutations in Chinese Patients with Lung Adenocarcinoma.

BACKGROUND: This study was designed to identify the prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma, and to reveal the association between BRAF mutations and clinicopathological characteristics in these patients. METHODS: From October 2007 to February 2013, patients with newly diagnosed primary lung adenocarcinoma were detected for mutations in BRAF, EGFR, KRAS, HER2 and ALK. Clinicopathological characteristics, including sex, age, TNM stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed. RESULTS: Of 1358 patients with lung adenocarcinoma, 20 patients were harboring BRAF mutations, including five BRAF V600E mutations and 15 BRAF non-V600E mutations. Among these, BRAF N581I and BRAF G593S were newly reported. BRAF mutations were associated with smoking status (odds ratio 3.28; 95 % CI 1.33-8.08; p = 0.008). In patients less than 60 years of age, BRAF mutations tended to have poor differentiation in tumor samples (70.0 vs. 35.1 %; p = 0.014), and were more likely to relapse (70 vs. 28 %; p = 0.008). A significant difference was found in relapse-free survival (RFS) between BRAF mutations and other mutations, but not in overall survival. CONCLUSIONS: The prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma was approximately 1.5 %. BRAF mutations were more frequent in current smokers. Patients harboring BRAF mutations had a higher rate of recurrence and worse RFS compared with other patients.

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PURPOSE: For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. MATERIALS AND METHODS: Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. RESULTS: All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. CONCLUSIONS: Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.

Intravitreal bevacizumab in the successful management of choroidal metastases secondary to lung and breast cancer unresponsive to systemic therapy: a case series.

PURPOSE: Management of choroidal metastases is commonly with systemic chemotherapy; however, if tumours are refractory to treatment and vision is endangered, local therapy modalities are feasible. A novel option is the use of intravitreal bevacizumab. This report presents three cases of choroidal metastatic tumours secondary to lung and breast cancer treated with intravitreal bevazizumab. PATIENTS AND METHODS: Three patients with choroidal metastases secondary to lung and breast tumours were treated at the Ophthalmology Unit, University of Rome 'Sapienza', S.Andrea Hospital from January 2009 to August 2012. All patients developed vision loss with diagnosis of chorioidal metastasis during systemic chemotherapy. Off label intravitreal bevacizumab treatment was performed with two 1.25 mg injections in two patients and four injections in one patient at 30-day intervals. RESULTS: Vision improved, subretinal fluid resolved, and choroidal tumour regression was obtained in all cases. Follow-up was 6, 9, and 12 months and there were no complications related to treatment. CONCLUSIONS: Intravitreal bevacizumab administration represented an efficacious therapeutic option with rapid effect in the treatment of choroidal metastatic tumours unresponsive to systemic therapy. It can have a role in the management of these tumours by preventing vision loss and improving the quality of life of patients.

Bevacizumab combined with chemotherapy in the treatment of recurrence or platinum-refractory ovarian cancer: a retrospective study of 37 cases.

BACKGROUND: Ovarian cancer was one of the most diagnostic cancers for women and leading cause of death from gynecologic cancer. Most of the cases were at advanced stage when diagnosed. Platinum-based regimen was considered as the firs-line chemotherapy treatment modality. But most of the cases developed recurrence or resistance to platinum. The aim of this retrospective study was to evaluate the activity and toxicity of bevacizumab combined with chemotherapy in the treatment of recurrence or platinum-refractory ovarian cancer. MATERIALS AND METHODS: Totally, 37 ovarian cancer patients with complete data who treated with bevacizumab combined with chemotherapy were reviewed from the databases of Beijing Cancer hospital and included in this retrospective study. All included patients received >1 cycle of bevacizumab based combination therapy with eligible for the efficacy and toxicity assessments. The objective response rate (ORR) and toxicity were recorded and evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) National Cancer Institute's Common Toxicity Criteria. RESULTS: The ORR and disease control rate were 32.4% and 54.1% respectively by the RECIST criteria and 43.2%, 67.6% by CA125 criteria. The median progression-free survival for the 37 cases was 5.4 months with its range of 2.3-11.2 months. The two complete response patens had longest disease-free survival interval with one for 10.0 months and another for 11.2 months. The total grade III-IV hematologic toxicity and nonhematologic toxicity were 8.1% and 21.6% respectively. CONCLUSIONS: With acceptable toxicity and relative well clinical activity, the bevacizumab combined chemotherapy can be a potential treatment modality for the recurrent or platinum-refractory ovarian cancer.

[A case of small bowel cancer with positive peritoneal cytology and five-year recurrence-free survival].

Small bowel cancer is frequently detected at an advanced stage and its prognosis is poor. We report on a patient with small bowel cancer with positive peritoneal cytology who survived for 5 years without recurrence after surgery.The case involved a 73-year-old woman who had undergone partial resection of the small intestine and lymphadenectomy for a small bowel tumor with obstruction. Pathological examination confirmed papillary adenocarcinoma with partial serosal invasion. Ascites cytology indicated a class V tumor. Adjuvant chemotherapy with TS-1 was administered for 20 months, and the patient has survived without evidence of disease for over 5 years.In this case, it is possible that TS-1 chemotherapy was effective for prevention against small bowel cancer recurrence.Furthermore , peritoneal cytology in patients with small bowel cancer should be evaluated as a predictor of prognosis.

Pulmonary adenocarcinomas with micropapillary component significantly correlate with recurrence, but can be well controlled with EGFR tyrosine kinase inhibitors in the early stages.

Pulmonary adenocarcinoma with a micropapillary component (PA-MPC) is known to exhibit biologically aggressive behavior. The aim of this study was to evaluate the clinicopathological characteristics of early-stage PA-MPC and to investigate the correlation between PA-MPC and epidermal growth factor receptor (EGFR) or KRAS mutation status. We reviewed 440 PA patients who underwent resection. We defined PA-MPC as adenocarcinoma with MPC occupying at least 5% of the entire tumor. EGFR and KRAS mutations were detected using established methods. Of the 440 cases, 256 cases were classified as stage IA, of which 53 cases (20.7%) had MPC. The 5-year disease-free survival rates in the MPC-negative and MPC-positive groups of patients with stage IA tumors were 92.1% and 77.6%, respectively. The difference in these rates was statistically significant (p = 0.003), whereas the difference in overall survival between the groups was not statistically significant (p = 0.973). The mean percentage of MPC was 20.4% in the recurrent group and 18.3% in the non-recurrent group, with no significant correlation (p = 0.996). Of the 10 recurrent cases, 6 cases exhibited EGFR mutations; the 5 cases treated with a tyrosine kinase inhibitor (TKI) achieved long survival (median, 64.6 months). No KRAS mutations were detected in any of the 10 cases. PA-MPCs were strongly associated with recurrence, but were not influenced by the MPC percentage even in early-stage lesions. Moreover, PA-MPCs with recurrence were associated with relatively better survival. These findings indicate that PA-MPCs were biologically aggressive but could be controlled with EGFR-TKIs.

Papillary-serous adenocarcinoma of the uterine cervix during tamoxifen therapy after bilateral breast cancer.

BACKGROUND: Papillary-serous adenocarcinoma (PSCC) is a very rare subtype of cervical cancer. To our knowledge, this is the first report on PSCC of the uterine cervix following bilateral breast cancer. CASE REPORT: A 61-year-old Caucasian woman underwent conserving surgery of both breasts at the age of 57 years, because of bilateral invasive ductal carcinoma. Radiation and tamoxifen treatment followed. Routine surveillance examinations, including pelvic examination, Papanicolaou (Pap) smear, and transvaginal ultrasound, were uneventful. Recently, a small contact-bleeding mass of the cervix was found. The Pap smear was II (reactive); HPV-DNA test was negative. The biopsy of the mass revealed PSCC with a high expression of p53, carcinoembryonic antigen (CEA), and Ki67 (50%). Staining for estrogen receptor (ER), progesterone receptor (PR), and vimentin was negative. The serum carbohydrate antigen 125 (CA-125) reached 159 U/ml. The patient was treated with radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. A poorly-differentiated papillary-serous, non-secretory adenocarcinoma, pT1b1, pN0 (0/44), pM0, G3, R0, V0, L0, was confirmed. According to the German recommendations for early-stage cervical cancer, the patient received no adjuvant treatment. Currently, the patient is free of relapse 38 months after the diagnosis of cervical cancer and 87 months after that of breast cancer. CONCLUSION: Immunohistochemistry is helpful in diagnosing rare entities. This case adds further evidence that the prognosis for early-stage PSCC is probably not poorer than that for other cervical adenocarcinomas.