Efficacy of XELOX adjuvant chemotherapy for gastric mixed adenoneuroendocrine carcinoma: A case report.

RATIONALE: Mixed adenoneuroendocrine carcinoma (MANEC) is a rare neoplasm, and consensus on the treatment is unavailable. PATIENT CONCERN: A 60-year-old Chinese man presented with obstructive symptoms while eating and paroxysmal stomach pain for more than a month. DIAGNOSIS: MANEC was diagnosed based on clinical manifestations, imaging findings, and pathological examinations. INTERVENTIONS: The patient underwent radical gastrectomy and received XELOX adjuvant chemotherapy (oxaliplatin 200 mg day 1 + capecitabine 1.5 g twice a day) after surgery. OUTCOMES: After 4 cycles of XELOX adjuvant chemotherapy were administered, abdominal computerized tomography and liver magnetic resonance showed liver metastasis. LESSONS: The therapy of gastric MANEC is based on surgical operation, and adjuvant chemotherapy program has an important influence on its prognosis. Therefore, further studying the effectiveness of XELOX adjuvant chemotherapy for gastric MANEC is necessary.

[Multimodal treatment of malignant mixed Müllerian tumor]. / Malignus kevert Müller-cso-eredetu tumor komplex kezelése.

INTRODUCTION AND AIM: The aim of our study was to evaluate the prognostic factors and treatment options of a very rare and highly aggressive type of uterine neoplasms, the malignant mixed Müllerian tumor, known as carcinosarcoma. METHOD: Between 2009 and 2017, 29 patients were treated with malignant mixed Müllerian tumor. At stage I, surgery and postoperative radiotherapy were performed. At stages II-IV, trimodal treatment (surgery, chemotherapy and radiotherapy) was administered. RESULTS: The average age of patients was 68.51 (49-90) years, mean body mass index was 30.22 (20.90-37.22). We have experienced recurrence of disease after complete resection in 6 cases (4 of 6 patients did not accept radiation therapy). Local recurrence has occurred after an average 15.52 (6-36) months, distant metastasis with an average 19.2 (8-32) months. Overall survival was 11.92 (1-75) months. Six patients are free of tumours at the moment. CONCLUSIONS: As overall survival has not increased in recent decades by using combined chemotherapy, there is no congruent consensus associated with the optimal treatment. The standard surgical treatment is total abdominal hysterectomy with bilateral oophorectomy, although due to high rates of recurrence and metastases, the necessity of lymphadenectomy and postoperative treatment is in the focus of recent studies. Though postoperative irradiation improves local control, the beneficial effect on overall survival is still not proven. Adjuvant chemotherapy decreases the rate of both pelvic and extrapelvic recurrence at the same time, although there is no recommendation for the optimal chemoterapeutic agent. Multimodal therapy should lead to better outcomes. Recently there are many ongoing studies with biologic and target therapies to improve efficiency, however, the relevant results will be disclosed in many years only, due to the small number of patients. Orv Hetil. 2018; 159(19): 741-7747.

Metaplastic carcinoma of the breast with mesenchymal differentiation (carcinosarcoma). A unique presentation of an aggressive malignancy and literature review.

Metaplastic carcinoma of the breast with mesenchymal differentiation (MCMD), previously known as carcinosarcoma, is a very rare and aggressive tumor that has been recently classified as a subtype of metaplastic breast carcinoma. It accounts for 0.08%-0.2% of all breast cancers, with only a few cases reported in the literature. Histologically, MCMD is characterized by a biphasic pattern of malignant epithelial and sarcomatous components without evidence of a transition zone between the two elements. We herein describe a unique case of metaplastic carcinoma of the breast with chondrosarcomatous differentiation in a postmenopausal woman who presented with a large, rapidly growing, ulcerated, bleeding mass and signs of impending sepsis. Metaplastic breast carcinomas (MBC) are rare and aggressive tumors. They are characterized by larger size, lower rates of axillary node involvement, higher rates of triple negativity and distal metastases, earlier local recurrence and poorer survival compared with classic invasive breast cancer. Because of the rarity of MBC, the optimal treatment has not been well defined. Surgery is the main curative treatment modality since MBC has shown a suboptimal response to standard chemotherapy. Patients with MBC may be appropriate candidates for novel targeted therapies.

Clinical utility of endoscopic ultrasound-guided fine-needle aspiration in mixed adenoneuroendocrine carcinoma with signet-ring cells of the pancreas: a case report and review of the literature.

A man in his 60s visited our hospital because of a pancreatic head tumor. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed that the tumor consisted of a neuroendocrine carcinoma (NEC) and adenocarcinoma, including signet-ring cell carcinoma, and that the ratio of these components was approximately 50:50. Therefore, he was diagnosed with mixed adenoneuroendocrine carcinoma (MANEC). Because of liver and lymph node metastases, systemic chemotherapy was initiated using a regimen for the NEC component based on an increase in neuron-specific enolase (NSE). Although the patient achieved stable disease after two chemotherapy cycles, the tumor increased in size after three cycles, which was associated with a gradual increase in carcinoembryonic antigen and a decrease in NSE level. An EUS-FNA reexamination revealed that the adenocarcinoma component accounted for 90 % of the tumor. Thus, an adenocarcinoma chemotherapy regimen was started, and a slight reduction in tumor size was observed. Here, we report an extremely rare and remarkable case of MANEC of the pancreas that demonstrates the effectiveness of EUS-FNA for helping to decide the chemotherapy regimen.

Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid.

BACKGROUND: Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. PURPOSE: Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. METHODS: PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. RESULTS: Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. CONCLUSIONS: Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.

Mixed squamous and large-cell carcinoma of the lung: a case study and literature review.

Lung tumors with combined histological pattern are seldom seen exhibiting a more aggressive clinicopathological picture than tumors with a single histology. Herein, we present a 58-year-old male with mixed squamous and large-cell lung carcinoma. The patient was initially diagnosed through fluoroscopy-guided transbronchial lung biopsy with large-cell lung carcinoma of the left upper lobe. He received neo-adjuvant chemotherapy and then underwent left upper lobectomy. Postoperative pathological diagnosis was combined squamous and large-cell neuroendocrine carcinoma. Two months after surgery, restaging revealed brain metastatic deposits. Local radiotherapy was promptly applied with relatively good response and the patient is under observation eight months after diagnosis. A brief review of the current literature is also included with special emphasis on the clinicopathologic aspects and prognosis of lung tumors with mixed histology.

Metaplastic breast carcinoma: a case report and systematic review of the literature.

A 78-year-old retired woman was diagnosed with metaplastic breast carcinoma (MBC), a rare tumor, in our hospital. We reviewed 15 articles with a total of 1328 patients to determine the epidemiology, clinical features, biomarkers, histology, management and outcome of patients with this tumor. The mean age at presentation is 58.5 years (range 32-83). Eighty-one percent of patients presented either with a breast mass or abnormal mammographic finding. Twenty-three percent of patients had a family history of breast cancer. Estrogen receptors were only found in 12%, progesterone receptors in 10% and HER2 in 6% of patients. The main method of treatment was mastectomy (66.9%) in combination with chemotherapy (57%) and radiotherapy (47%). Five-year disease-free survival ranged between 40% and 84% and 5-year overall survival ranged between 64 and 83%. We have further reviewed the nature of this disease in the light of advancement in genetics, such as microarray gene expression profiling. The relationship of MBC with triple-negative tumor and basal-like tumor is discussed. It is hoped that advances in genetics and biomarkers will bring forward the era of personalized medicine in the treatment of breast carcinoma.

Paclitaxel-ifosfamide-carboplatin combination chemotherapy regimen in advanced uterine and adnexal malignant mixed Mullerian tumours.

BACKGROUND: Malignant mixed Mullerian tumours (MMMTs) of the uterus and adnexa represent aggressive gynaecologic malignancies with a high rate of loco-regional and distant failure. For that reason, we evaluated the paclitaxel-ifosfamide-carboplatin (TICb) combination in patients with advanced MMMTs. METHODS: Female patients with advanced MMMTs, WHO-PS 0-2, no prior chemotherapy for systemic disease, unimpaired haemopoietic and organ function were eligible. Chemotherapy was administered at the following doses; paclitaxel: 175 mg m(-2) on day 1, ifosfamide: 2.0 g m(-2) day(-1)--days 1 and 2, and carboplatin at a target area under the curve 5 on day 2, with prophylactic G-CSF from day 3. RESULTS: Forty patients of a median age 61 (45-72) years, performance status 0-2 with advanced MMMTs of the uterus (n=34), tubes (n=2) or ovary (n=4) have entered and all were evaluable for response and toxicity. Responses were as follows: 27 out of 40 (67.5%) evaluable patients responded, with 11 complete responses and 16 partial responses, while 10 had stable disease, and 3 developed progressive disease. The median response duration was 9 months (range, 4-40 months), median progression-free survival 13 months (range, 3-42 months), while median overall survival 18 months (range, 4-48 months). Grade 3/4 neutropenia was recorded in 22 out of 40 (55%)--with 13 developing grade 4 (≤7 days) and 7 out of 40 (17.5%) of patients at least one episode of febrile neutropenia. CONCLUSION: In this study, it appears that the TICb combination, yielded important activity with manageable toxicity in females with advanced MMMTs warranting further randomised comparison with current standard regimens.

[Mixed carcinoid-adenocarcinoma in transverse colon]. / Tumor mixto carcinoide-adenocarcinoma de colon transverso.

The following case is a 69-year-old woman with a presumptive diagnosis of adenocarcinoma in transverse colon, which was diagnosed by pathology as a mixed carcinoid-adenocarcinoma tumor after surgery. We have found very few cases published of this type of tumor in the colon (around 20) but not cases in the transverse colon. We discuss in the following report the diagnosis, the therapeutic conduct and its results. We point out with particular consideration that, due to the lack of information related to the functional behaviour and clinical characteristics of these mixed tumors, more studies, analysis, follow-up and descriptions are necessary to perform future diagnosis and therapeutic procedures.

Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer.

PURPOSE: We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer. MATERIALS AND METHODS: Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy. The chemotherapy has consisted almost exclusively of intravenously administered drugs. There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery. This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation. RESULTS: We report on our prospectively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy and reserving cystectomy for salvage as required. We report on the efficacy in terms of complete response rate, ultimate tumor-free bladder preservation, overall survival and patterns of failure. We detail the acute and chronic toxicity observed to date. CONCLUSIONS: This strategy has resulted in a durable high complete response rate and overall tumor-free bladder preservation rate of 75% while maintaining a survival comparable to that achieved with cystectomy. These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy.

Malignant mixed Müllerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome.

PURPOSE: To determine the survival outcomes, prognostic factors, and patterns of failure in patients with malignant mixed Müllerian tumor (MMMT) of the uterus. METHODS AND MATERIALS: Between 1954 and 1998, 300 patients with clinical Stage I-III MMMT of the uterus were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. Their hospital records were reviewed to obtain patient and tumor characteristics; details of surgery, radiotherapy (RT), and chemotherapy; and long-term outcome. Surviving patients were followed for a median of 109 months (range 15-138). Survival rates were calculated using the Kaplan-Meier method, with differences assessed by log-rank tests. RESULTS: Of the 300 patients, 113 (38%) were treated with surgery alone, 160 (53%) with surgery plus adjuvant EBRT or ICRT, and 27 (9%) with RT alone. Forty-eight patients received adjuvant chemotherapy. At 5 years, the overall rates of survival and cause-specific survival were 31% and 33%, respectively. Women who were postmenopausal or had a history of prior pelvic RT, pain at presentation, clinical Stage II-III disease, uterine enlargement (>/=12 weeks), or an abnormal Papanicolaou smear finding had a significantly poorer prognosis than the other patients in the series. Of the 273 patients who underwent surgery, those who had positive abdominal washings, uterine length >10 cm, or extrauterine spread of disease to the cervix, adnexa, or peritoneum had a significantly worse prognosis than the other patients. Factors found on multivariate analysis to have an independent adverse influence on cause-specific survival included postmenopausal status (p = 0.0007, relative risk [RR] 3.3), uterine length >10 cm (p = 0.0001, RR 2.2), cervical involvement (p = 0.002, RR 1.8), and peritoneal involvement (p = 0.0001, RR 4.3). At 5 years, the rates of pelvic and distant disease recurrence for the entire group of 300 patients were 38% and 57%, respectively. The most common site of distant recurrence was the peritoneal cavity. Patients treated with pelvic RT had a lower rate of pelvic recurrence than patients treated with surgery alone (28% vs. 48%, p = 0.0002), but the overall survival rates (36% vs. 27%, p = 0.10) and distant metastasis rates (57% vs. 54%, p = 0.96) were not significantly different. However, patients treated with pelvic RT had a longer mean time to any distant relapse (17.3 vs. 7.0 months, p = 0.001) than patients treated with surgery alone. The use of adjuvant chemotherapy did not correlate with the survival rate or rate of distant metastasis. CONCLUSION: Adjuvant pelvic RT decreased the risk of pelvic recurrence and may delay the appearance of distant metastases after hysterectomy for MMMT. However, the survival rates remain poor because of a high rate of distant recurrence. As more effective systemic chemotherapy is developed to control microscopic distant disease, the role of RT in controlling locoregional disease in the pelvis and abdomen may become more important. Future research should consider programs that integrate surgery, RT, and chemotherapy to maximize the probability of cure.

In vitro efficacy of chemotherapeutics as determined by 50% inhibitory concentrations in cell cultures of mammary gland tumors obtained from dogs.

OBJECTIVE: To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations, SAMPLE POPULATION: 30 mammary gland tumors excised from dogs. PROCEDURE: Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation. RESULTS: Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor). CONCLUSION AND CLINICAL RELEVANCE: The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors.

Malignant mixed müllerian tumor of the fallopian tube.

Primary malignant mixed müllerian tumor of the fallopian tube is uncommon. Only 37 cases of malignant mixed müllerian tumor of the fallopian tube have been reported to date and of these only 16 contained heterologous components (mesodermal mixed tumor). This rarity made us report a case of malignant mixed müllerian tumor of the fallopian tube containing heterologous components which was operated on in our gynecologic oncology department. Postoperatively the patient was placed on six courses of adjuvant chemotherapy consisting of cis-platinum, adriamycin and cyclophosphamide (PAC). Second look laparotomy was performed after completion of chemotherapy. Presently, she is doing well, at two months follow-up, with no evidence of disease.

Mixed pituitary tumours--effects of bromocriptine treatment: Parlodel MR and Parlodel LAR.

Majority of pituitary tumours secrete one of the named hormones: PRL, GH, ACTH, proopiomelanocortine, alpha and beta subunit of TSH, LH, and FSH. Some of those tumours secrete two or more hormones. The aim of this study was to determine the effect of bromocriptine (Parlodel MR and LAR) upon secretion of hormones and tumour size in 10 patients with mixed pituitary tumours. In all patients pituitary and peripheral hormones, CT scan and visual fields were examined before and after treatment with bromocriptine: Parlodel MR and LAR. Bromocriptine treatment decreased PRL secretion in all 10 patients; GH--in all 6 in whom it was increased; TSH--in 2, FSH--in 2 and alpha-subunit in all 6 in whom they were increased. In 5 patients treatment resulted in shrinkage of the tumour mass by 20 to 35%. In all examined subjects clinical improvement was achieved. Our results demonstrate that bromocriptine (Parlodel MR and LAR) is very effective and well tolerated in the treatment of patients with mixed pituitary tumours particularly those with hyperprolactinemia.