Mehmet Akif Ozturk

Voltage-gated sodium channel blockers can augment the efficacy of chemotherapeutics by their inhibitory effect on epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) is a process during which cancer cells become more invasive and chemo resistant. EMT may also be associated with tumor dormancy which prevents the cure of cancer with adjuvant treatment. Chemo resistance and dormancy may also decrease response to cytotoxic agents during treatment of metastatic disease. Voltage gated sodium channels (VGSCs) are overexpressed in many cancer types, particularly in those with more aggressive and metastatic potential. VGSCs are thought to be associated with increased invasive and migratory capacity of cancer cells. Inhibition of VGSCs may inhibit EMT and angiogenesis through interaction with intracellular calcium activity and endothelial cells respectively. Blockage of these channels combined with other anticancer therapies may be effective in both adjuvant and palliative setting. Colonization at secondary site may be decelerated by VGSCs inhibition through impeding angiogenesis. This may lead to a temporary palliation of symptoms related to tumor burden in patients with metastatic disease.

Pituitary Metastasis of Colon Adenocarcinoma: A Rare Occurrence

Metastasis to the pituitary gland from solid tumors is quite rare [1, 2]. It is usually detected in the presence of widespread metastatic disease [1–4]. The most common primaries of metastatic pituitary carcinomas are breast and lung cancers [2, 3]. Pituitary metastases are usually asymptomatic and constitute a small fraction of pituitary masses [3, 4]. Symptoms of pituitary metastasis may vary from visual disturbance to endocrine dysfunction such as diabetes insipidus [2, 5] and are caused by mass effect and compression of surrounding structures [5, 6]. Brain metastasis, particularly to the pituitary gland, from colorectal cancer is infrequent [7, 9]. Herein, we report a case of colon carcinoma with metastasis to the pituitary gland which developed diabetes insipidus and central hypothyroidism during follow-up.

Safety, Feasibility, and Efficacy of Capecitabine Maintenance in Patients With Advanced Gastric Cancer: A Retrospective Study

Gastric cancer is still one of the cancers with highest mortality. Most patients present with advanced-stage disease. Palliative chemotherapy is usually the only treatment option for patients with advanced gastric cancer (AGC). Maintenance chemotherapy is an evolving concept in medical oncology. Maintenance chemotherapy can be administered with the same drug(s) in the initial regimen or with an alternative agent. In this article, we report our experience with capecitabine as a maintenance agent for patients with AGC. No treatment-related death was observed due to use of capecitabine. Median progression-free survival was 10.4 months, and median overall survival was 19.7 months. Activity and toxicity profile of capecitabine seems favorable as a maintenance agent in AGC. We believe that capecitabine deserves further trials as a maintenance agent for patients with AGC.

Prevalence, associated factors and impact on mortality of chronic kidney disease in nursing home residents: A single-center experience.

We carried out the present study to determine the prevalence, associated comorbidities and impact on mortality of chronic kidney disease (CKD) in nursing home residents.

Cancer-related fatigue: can it be due to adrenal suppression secondary to high-dose steroids used as antiemetic?

To the editor: The use of dexamethasone for cancer-related fatigue (CRF) in patients with advanced cancer is a controversial issue. Beneficial effects of dexamethasone may be counterbalanced by its serious side effects. The exact mechanism of the action of steroids on cancer-related fatigue is unknown. Recently, Yennurajalingam et al. hypothesized that dexamethasone exerts its effects on CRF mainly by interfering with the peripheral effects of proinflammatory cytokines [1]. We believe that this may not be the case for some of patients with CRF. The exact pathogenesis of CRF is unknown. A role of systemic inflammation or imbalance between hypothalamicpituitary-adrenal (HPA) axis and systemic cytokines has been proposed [2, 3]. Advanced stage cancer represents a state of chronic stress. Low levels of endogenous cortisol, which may be associated with symptoms in advanced cancer, had been demonstrated by Lundstrom et al. [4]. Major symptoms of adrenal insufficiency (i.e., fatigue, nausea, loss of appetite) may be misinterpreted as CRF. Indeed, some patients treated for CRF may have unrecognized adrenal insufficiency. High dose of dexamethasone (8–16 mg/day) is commonly used as antiemetic therapy in highly and moderately emetic regimens. Updated ASCO guidelines on antiemetics recommend a 4-day course of dexamethasone (12 mg on day 1 and 8 mg on days 2–4) for highly emetogenic chemotherapy and 1–3-day 8 mg course for moderately emetogenic chemotherapy [5]. Highdose steroids may suppress the hypothalamic pituitary and adrenal axis, even with short-term use [6]. Han et al. published their article on adrenal suppression related to the use of dexamethasone as an antiemetic therapy in patients with cancer in July 2012 [7]. Patients receiving dexamethasone as an antiemetic for at least 3 days per cycle and for more than 3 months were included in this study. Adrenal suppression was demonstrated biochemically in 45 of the 103 patients (43.7 %). Adrenal suppression was more common in patients receiving megestrol acetate concomitantly. Daily replacement therapy with 7.5–10 mg of prednisolone for 1–2 weeks in patients with suppressed HPA axis resulted in the improvement of symptoms associated with adrenal insufficiency. This dose of prednisolone is approximately equivalent to 1 mg of dexamethasone [8]. This is about one eighth of the dose recommended in the study of Yennurajalingam et al. We believe that this lower dose may allow the use of steroid for longer periods and spare some of the patients with CRF from serious side effects of higher doses of steroids. Metabolic (i.e., hyperglycemia, hypokalemia) and muscular side effects (i.e., proximal muscle weakness) of long-term use of steroids may be confused with CRF or even increase the severity of CRF. Lower dexamethasone dose will probably cause less metabolic and muscular side effects. For those patients with continuing symptoms of CRF, steroid dose may be gradually increased. In the current study, no follow up for the quality of life was made after cessation of dexamethasone [1]. As CRF is a chronic problem, symptoms may become worse after cessation of high-dose dexamethasone. Lesser dose of dexamethasone may be used more safely for longer periods of time for some patients with this chronic problem. There are still unanswered questions about CRF: What should be done for patients without biochemical evidence of HPA axis suppression? Should we search for biochemical evidence of inflammation (i.e., C-reactive protein) in this group of patients? Should we start with higher doses of dexamethasone when we have laboratory evidence of both systemic inflammation and HPA axis suppression? Should adrenal insufficiency be in the routine checklist of evaluation O. O. Eren (*) :B. Oyan Medical Oncology Section, Department of Internal Medicine, Yeditepe University Hospital, Devlet yolu, Ankara Caddesi, 102-104 Istanbul, Turkey e-mail: droneren@hotmail.com

A case of rectal adenocarcinoma presented with palatine tonsil metastasis

The most common metastatic sites of colorectal cancer are liver, lung, peritoneum and lymph nodes. Metastasis of colorectal carcinoma to palatine tonsil is rarely seen. To our knowledge, only 11 patients were documented in English literature. Atypical metastases can sometimes lead to misdiagnosis. Precise diagnosis of atypical metastases requires a careful physical examination, good imaging method and comprehensive pathological evaluation. Here, we report a case of rectal adenocarcinoma presented with palatine tonsil metastasis.

Bilateral synchronous adrenal metastasis of invasive ductal carcinoma treated with multimodality therapy including adrenalectomy and oophorectomy.

A 38-year-old woman presented with a mass in the left breast. Biopsy of the lesion revealed invasive ductal carcinoma. Bilateral adrenal metastasis was detected in whole body positron emission tomography scanning. Needle biopsy of the left adrenal lesion proved infiltration of malignant cells from breast carcinoma. After eight cycles of neoadjuvant (preoperative) chemotherapy, mastectomy, bilateral adrenalectomy, and bilateral oopherectomy were performed. No further hormonal treatment was recommended due to the resection of both adrenal glands and ovaries. The patient is still followed without any sign of progression. To our knowledge, this is the first case representing multimodality approach to breast cancer with bilateral synchronous adrenal metastasis. Patients with oligometastatic disease may benefit from aggressive treatment including local therapies.

Should we be more cautious about replacement of vitamin B12 in patients with cancer receiving cytotoxic chemotherapy

Vitamin B12 (Cbl) deficiency may cause hematologic and neurologic dysfunction. Replacement therapy is effective in correcting hematologic abnormalities and improving neurologic symptoms. Cbl is known to have antioxidant activity. This antioxidant activity may antagonize the effects of chemotherapeutics (i.e. genotoxic effects of paclitaxel) on tumor DNA. We claim that Cbl replacement should be done more cautiously in patients receiving cytotoxic chemotherapy.

Gastric metastasis in a patient with lobular breast carcinoma 6 years after diagnosis.

To the editor: The stomach is a rare site of metastasis for solid tumors. Breast cancer is among the most common tumors that metastasize to the stomach [1]. Herein we present a case of breast cancer with gastric metastasis 6 years after diagnosis. A 37-year-old woman presented with chief complaint of abdominal pain in 2008. Ascites and left adnexal mass were detected on radiologic imaging. Diagnostic laparotomy was performed. Pathologic examination of adnexial mass revealed metastasis of invasive lobular carcinoma of the breast. The tumor stained immunohistochemically positive for estrogen and progesteron receptors. Magnetic resonance imaging showed diffuse bilateral infiltration in the breasts. Biopsy of the breast revealed invasive lobular carcinoma staining positively for estrogen and progesteron receptors. The patient was treated with palliative intent with various cytotoxic and hormonal agents. In December 2013, she presented with dyspepsia refractory to proton pump inhibitors and antiacid medications. Many millimetric eroded areas were detected at gastric corpus at upper gastrointestinal endoscopy. Mucosa was pale and edematous at peripyloric region where raised and eroded lesions from mucosa were seen. Multiple biopsies from these lesions were performed (Fig. 1). Pathologic examination revealed submucosal infiltration with atypical epithelial cells. These cells were immunostaining positively for estrogen receptor and gross cystic disease fluid protein (GCDFP-15) (Fig. 1). These findings were compatible with metastasis of invasive lobular carcinoma. Treatment with eribulin started due to disease progression. Ascites accumulation was detected at the same time, and paracentesis was performed for palliation. Ascitic fluid was containing malignant cells. The patient died 3 months after stomach metastasis due to septic shock. Invasive lobular carcinoma of the breast have higher risk of metastasis to atypical sites (e.g., peritoneum, adnexa, stomach) than invasive ductal carcinoma [2]. Most of the breast tumors that metastasize to the stomach are histologically lobular carcinomas [3, 4]. Pain and epigastric symptoms are commonly seen in gastric metastasis. We performed upper gastrointestinal system endoscopy for persistent and refractory epigastric pain. Endoscopic view was compatible with erosive gastritis albeit final pathologic examination of the endoscopic biopsy revealed metastasis of lobular carcinoma. Breast cancer may metastasize to the stomach many years after diagnosis, usually in the presence of widespread metastatic disease. In our case, positive immunostaining for O. O. Eren :O. Sonmez : B. Oyan Department of Medical Oncology, Yeditepe University Hospital, Istanbul, Turkey

Are male gender and non-adenocarcinoma histology valid prognostic factors for breast cancer?

Clinic Rochester: effect of surgical year and preoperative magnetic resonance imaging. J Clin Oncol 2009; 27(25): 4082–4088. 5. Pengel KE, Loo CE, Teertstra HJ et al. The impact of preoperative MRI on breastconserving surgery of invasive cancer: a comparative cohort study. Breast Cancer Res Treat 2009; 116: 161–169. 6. Bleicher RJ, Ciocca RM, Egleston BL et al. Association of routine pretreatment magnetic resonance imaging with time to surgery, mastectomy rate, and margin status. J Am Coll Surg 2009; 209: 180–187. 7. Turnbull L, Brown S, Harvey I et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010; 375(9714): 563–571. 8. Cebrecos I, Cordoba O, Deu J et al. Can we predict local recurrence in breast conserving surgery neoadjuvant chemotherapy? Eur J Surg Oncol 2010; 36 (6): 528–534.