Lymphangiosarcoma: Is Stewart-Treves Syndrome a Preventable Condition?

BACKGROUND: Stewart-Treves syndrome is a rare complication of breast cancer treatment, representing a lymphangiosarcoma commonly associated with lymphedema and severely impacting patient's outcome. The tumor typically develops in the atrophic, pachydermatous, hyperkeratotic skin of limbs affected by long-standing lymphedema. Clinical data associated with Stewart-Treves syndrome and lymphedema management have rarely been published. METHODS AND RESULTS: In the period between 1980 and 2009, ten patients with Stewart-Treves syndrome were diagnosed and treated at the Foeldiklinik, Hinterzarten, Germany. Nine of the ten patients were female. Five patients had previously suffered from breast cancer (and were treated with mastectomy); two from other malignancies; two patients had primary lymphedema, and one had undergone lower extremity lymphadenectomy. All cancer patients had undergone radiation treatment. In all cases, the sarcoma developed in non-irradiated areas 6-48 years (average 16.3 years) after the onset of lymphedema. None of the patients had received complex decongestive physical therapy (CDT). Two patients had above-elbow amputation, one had shoulder exarticulation, two patients had wide excision and skin grafting, two patients had above-knee amputation procedure, two patients had a below-knee amputation procedure, and one patient had no surgical treatment at all. The time to recurrence after surgery, time to metastasis, patient survival and CDT were recorded. CONCLUSIONS: Patients with lymphedema should be closely examined starting 5 years from the time of lymphedema onset, paying special attention to those with associated malignancies. Only early diagnosis and treatment by radical ablative surgery confers a reasonable prognosis with this rare but aggressive disease. A potential effect of CDT on lymphangiosarcoma has to be studied in a greater patient cohort.

Estimates of global research productivity in gynecologic oncology.

BACKGROUND: Societies worldwide invest considerably in research on oncological diseases of women. However, current literature lacks estimating this research production. We therefore evaluated quality and quantity of publications in gynecologic oncology. METHODS: Revisit of 6119 peer-reviewed articles published in Gynecologic Oncology and the International Journal of Gynecological Cancer from January 1996 to December 2006. Descriptive data on disease origin, main topic, and country of origin were collected and analyzed separately. Research productivity was adjusted to the national population and nominal gross domestic product per capita. RESULTS: Research production and international cooperative teamwork in the 2 main journals of gynecologic oncology increased within the 10 last years; 65.3% of all published articles dealt either with epithelial ovarian cancer, cervical cancer, or endometrial cancer. Endometrial cancer had the worst ratio number of publications to estimated national incidence (United States, 2007). The United States (41.15%) and Europe (29.72%) make up a striking 70.87% of the world's research production in the field of gynecologic oncology. However, the highest rate of increase shows in Turkey (22.5), the People's Republic of China (6.87), and South Korea (5.83). Adjusted to the national GDP per capita and population for the year 2006, research productivity seems best in Israel, Austria, and Turkey. CONCLUSION: Quantitatively, most publications come from the presumed countries. Within the limits of the methodology used in this study, adjustment to population and GDP per capita provides information on research output. The scientific output on endometrial cancer is comparably low.

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial.

The combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) > or =50% were treated with PLD 40 mg/m(2) every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF < or =44% or > or =10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 +/- 8.68% at baseline, 62.7 +/- 5.11% after 6 cycles of therapy, 64.4 +/- 7.61% at the first follow up and did not change significantly (61.0 +/- 5.56% even at the 5th follow-up). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies.

Transketolase protein TKTL1 overexpression: A potential biomarker and therapeutic target in breast cancer.

Malignant tumors degrade glucose to lactate even in the presence of oxygen via the pentose phosphate pathway (ppp). The non-oxidative part of the ppp is controlled by thiamine-dependant transketolase enzyme reactions. Overexpression of the transketolase-like-1-gene (TKTL1) in urothelial and colorectal cancer is associated with poor patient outcome. We analyzed the expression of the TKTL1 protein in a retrospective institution-based patient cohort with invasive breast cancer by immunohistochemical analysis of 124 paraffin-embedded breast cancer tissues. Our study revealed TKTL1 expression in 86% of breast cancer specimens with 45% showing high expression levels. In contrast, only 29% of corresponding non-neoplastic breast tissues were TKTL1 immunopositive, including 9% with high expression levels. High expression levels of TKTL1 correlated significantly to Her2/neu overexpression (p=0.015). However, TKTL1 expression failed to reach statistical significance for other common prognostic parameters. In contrast to recent data for e.g. colorectal cancer TKTL1 overexpression did not correlate to patient outcome and survival. However, in the context of novel insights into TKTL1-related tumor metabolism and the high proportion of TKTL1 overexpressing breast cancers, this enzyme represents a potential candidate for targeted inhibition of tumor growth in this tumor entity.