Metastases of Urothelium Carcinoma: Differential Diagnosis, Resection, and Survival.

BACKGROUND: Due to its very aggressive nature and low survival chances, the metastasized urothelium carcinoma poses a challenge in regard to therapy. The gold-standard chemotherapy is platinum based. The therapy options are considered controversial, including new systemic therapies. In this respect, surgical therapies, as already established for pulmonary metastases of other tumor entities play an increasingly important role. The consumption of nicotine is a risk factor not only for urothelium carcinoma but also for a pulmonary carcinoma. Thus, we examined the frequency of a second carcinoma in this cohort. METHODS: We retrospectively examined patients who had a differential diagnosis of pulmonary metastases, as well as those patients who underwent a surgery due to pulmonary metastases of a urothelium carcinoma between 1999 and 2015. RESULTS: A total of 139 patients came to our clinic with the differential diagnosis of pulmonary metastases of a urothelium carcinoma. The most common diagnosis was pulmonary carcinoma (53%). Thirty-one patients underwent surgeries due to pulmonary metastases of a urothelium carcinoma. The median survival was 53 months and the 5-year survival was 51%. With the univariate analysis, only the relapse-free interval of more than 10 months was statistically significant (p < 0.001). CONCLUSION: There is a high coincidence of urothelial carcinoma and lung carcinoma. A histological confirmation should be endeavored. Selected patients undergoing a pulmonary metastasis resection have a survival advantage during the multimodal treatment of pulmonary metastasized urothelial carcinomas. For a definitive recommendation, randomized trials including a uniform multimodal therapy regimen and higher numbers of patients are necessary.

The impact of primary tumor location on prognosis after colorectal lung metastasectomy.

PURPOSE: Currently, right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (REC) are typically seen as different tumor entities. It is unknown if this subdivision by primary tumor location has an influence on the survival of patients with colorectal pulmonary metastasectomy (PM). METHODS: We retrospectively analyzed our prospective database of 233 patients operated on for colorectal lung metastases between 1999 and 2014. Differences in the patient characteristics and the primary tumor and metastatic tumor burden were analyzed using χ2-tests. The long-term survival after PM of the three groups was analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: In total, PM was performed for 37 patients with RCC, 57 patients with LCC, and 139 patients with REC. Patients with LCC were significantly more likely to have UICC stage IV primary tumor (44.2% LCC vs. 37.5% RCC vs. 22.8% REC, p = 0.012) and significantly more likely to have a history of additional liver metastases (45.6% LCC vs. 32.4% RCC vs. 27.3% REC, p = 0.046). The 5-year survival rates after PM for patients with RCC, LCC, and REC were 47, 66, and 39%, respectively (p = 0.001). The median survival times of patients with RCC, LCC, and REC were 55 months (95% CI: 42.2-66.8), 108 months (95% CI: 52.7-163.3), and 44 months (95% CI: 50.4-63.6), respectively. CONCLUSIONS: This study demonstrated a prognostic impact of the primary tumor localization in patients undergoing PM for colorectal lung metastases. Nevertheless, long-term survival was achievable in all groups.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. MATERIALS AND METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Short-term and long-term outcomes after resection of thoracic growing teratoma syndrome.

PURPOSE: Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available. METHODS: We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan-Meier method. RESULTS: Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19-50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13-237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively. CONCLUSIONS: TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections.

Long-term Outcome After Resection of Isolated Thoracic Lymph Node Metastases of Renal Cell Cancer.

BACKGROUND: Isolated thoracic lymph node metastases (ITLNMs) without any lung metastases of renal cell cancer are rare. Other than a few case reports and one study, there is no further literature on ITLNMs. For this reason, the goal of this study was to analyze our experiences, the long-term survival outcomes, and recurrence-free survival outcomes after the resection of ITLNMs. METHODS: We analyzed our database of 15 patients with ITLNMs who underwent metastasectomy by systematic lymph node dissection from 2003 to 2017. The long-term outcomes and survival curves were analyzed with the Kaplan-Meier method. RESULTS: The median disease-free interval between primary cancer and ITLNM was 40 months (range, 0-171 months). The R0 resection rate was 93.3% (n = 14). There was one R2 resection, which was due to a tracheal and left main bronchial infiltration. The postoperative morbidity and 30-day mortality rates were 13.3% and 0%, respectively. Altogether, 14 patients were included in the long-term follow-up with a median follow-up time of 35.5 months (range, 2-108 months). The 1-, 3-, and 5-year survival rates were 93%, 73%, and 73%, respectively. The median overall progression-free survival after metastasectomy was 18 months (95% confidence interval, 8.6-27.4 months), and the 5-year local recurrence-free rate was 65%. CONCLUSIONS: Because of the long disease-free interval between primary cancer and ITLNM, a long oncologic follow-up that includes chest images should be mandatory. Altogether, metastasectomy of ITLNMs is feasible with low morbidity and mortality rates and might be associated with promising survival rates. Early detection and resection of ITLNMs may avoid severe complications.

Perioperative systemic magnesium sulphate to minimize acute and chronic post-thoracotomy pain: a prospective observational study.

BACKGROUND: Thoracotomy leads to acute and chronic post-thoracotomy pain (CPTP). The purpose of this study was to investigate the effect of magnesium sulphate (MgSO4) administered perioperatively on acute postoperative and CPTP syndrome. METHODS: One hundred patients were enrolled in this prospective, observational study. Analgesic medication was provided according to the World Health Organization pain relief ladder (control group). The study group received additionally MgSO4 (40 mg/kg over 10 minutes) during induction of anesthesia followed by an infusion over 24 hours (10 mg/kg/h). The presence and severity of pain were assessed before surgery, on postsurgical days 1-8, 30 and 90, respectively. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was used pre- and postoperatively for documentation of neuropathic pain. The incidence and severity of CPTP were assessed by a telephone survey 30 and 90 days after surgery. RESULTS: Numerical rating scale (NRS) pain scores at rest were significantly lower in the study group receiving MgSO4 at days 1 to 8 (P<0.05). Thirty days after surgery, 2.1% of the MgSO4-patients had a LANSS score ≥12 compared to 14.3% in the control group (P=0.031). No patient had a LANSS score ≥12 in the study group compared to the control group (0% vs. 12.2%, P<0.05) 90 days following surgery. CONCLUSIONS: MgSO4 administration reduces postoperative pain at rest according to the NRS pain scores and is effective in preventing chronic neuropathic post-thoracotomy pain measured by LANSS score. Prospective-randomized trials are needed to confirm the results of the present study.

Resection of retrocrural germ cell tumor metastases: Two surgical approaches.

OBJECTIVES: The goals of retrocrural metastasectomy are complete resection with preservation of the diaphragmatic function while avoiding phrenic nerve injury and spinal cord ischemia. We describe 2 approaches for metastasectomy depending on the pattern of metastases. METHODS: Between 1999 and 2017, 44 patients underwent 50 retrocrural metastasectomies. In case of lower retrocrural, bilateral retrocrural, and or additional retroperitoneal and abdominal metastases, an abdominal approach with mobilization of the liver and the kidney followed by longitudinal incision of the diaphragmatic crus was performed. In case of upper retrocrural metastases and additional thoracic disease, a thoracic approach was performed. The Kaplan-Meier method and log-rank test were used to analyze survival and prognosticators. RESULTS: The minor morbidity, major morbidity, and mortality were 16.6%, 0%, and 0% for the abdominal approach, respectively, and 15.4%, 3.8%, and 0% for the thoracic approach. There was no phrenic nerve palsy, diaphragmatic hernia, or spinal cord ischemia. Additional retroperitoneal, mediastinal, pulmonary, or further resection was necessary in 10, 25, 9, and 6 cases, respectively. In all cases, a R0 resection was achieved. The 15-year survival rate was 95%. CONCLUSIONS: Depending on the pattern of metastases, a complete retrocrural metastasectomy with low morbidity and without mortality by thoracic or abdominal approach is possible. Both approaches preserve diaphragmatic function. Furthermore, the lateral abdominal approach provides a good view and might lead to less tension at the spinal arteries and therefore might reduce the risk of paresis. Good long-term survival is achievable. These patients should be operated on in specialized centers.

Survival following Multimodality Treatment Including Surgery for Stage IA-IIIB Small-Cell Lung Cancer.

BACKGROUND: Prognosis in limited disease small-cell lung cancer (SCLC) after concurrent chemoradiotherapy is poor. While some studies show better survival after multimodality treatment including surgery, other trials failed to prove a surgery-related survival benefit. Therefore, this study investigated survival in stage IA-IIIB SCLC following surgery combined with chemotherapy and/or thoracic radiotherapy. METHODS: We retrospectively reviewed all stage IA-IIIB SCLC patients without supraclavicular lymph node involvement at a single institution between January 1999 and August 2016 after multimodality treatment with curative intent. This comprised surgery consisting of primary tumor resection and systematic lymph node dissection combined with chemotherapy, chemoradiotherapy, or thoracic radiotherapy. Survival was determined using the Kaplan-Meier method, and differences were compared using log-rank tests. The risk of locoregional relapse was calculated. RESULTS: A total of 47 patients (29 men, 18 women; mean age: 62 years) were included. Thirty-day mortality was 0%. Overall median survival was 56 months, and 2-, 3-, 5-, and 10-year survival rates were 69, 54, 46, and 30%, respectively. The only significant prognostic factor (p = 0.006) was R0 resection (n = 40) increasing median survival to 64 versus 17 months in case of technical inoperability (n = 5). The risk of locoregional relapse was 2.5% (n = 1) after R0 resection. CONCLUSIONS: Multimodality treatment including surgery was safe and led to considerable survival. R0 resection was the only factor extending survival. It could be achieved in most patients and was associated with a low risk of locoregional relapse. Prospective randomized controlled studies are needed to define best practice in stage IA-IIIB SCLC.

Morbidity, mortality, and survival in elderly patients undergoing pulmonary metastasectomy for colorectal cancer.

PURPOSE: The number of elderly patients with colorectal cancer is increasing. Nevertheless, they are undertreated compared to younger patients. This study compares postoperative morbidity, mortality, survival, and morbidity risk factors of elderly and younger patients undergoing pulmonary metastasectomy (PM). METHODS: We retrospectively analyzed our prospective database of 224 patients operated for colorectal lung metastases between 1999 and 2014. Two groups were defined to evaluate the influence of the patients' age (A: < 70 years; B: ≥ 70 years). Morbidity, mortality, and risk factors for morbidity were analyzed using χ2-test and Fisher's exact test. The Kaplan-Meier method, log-rank test, and multivariate Cox regression were used to assess survival and prognosticators. RESULTS: Altogether, minor morbidity, major morbidity, and mortality were 17%, 5.8%, and 0%, respectively. Between groups A (n = 170) and B (n = 54), there was no difference in minor and major morbidity (p = 0.100) or mortality (0%). Heart arrhythmia was a risk factor for increased morbidity in group B (p = 0.007). The 5-, 10-, and 15-year survival rates were 43%, 30%, and 27%, respectively, in group A and 55%, 36 and 19%, respectively, in group B (p = 0.316). Disease-free interval ≥ 36 months (p = 0.023; OR 2.88) and anatomic resections (p = 0.022; OR 3.05) were associated with prolonged survival in elderly patients. CONCLUSIONS: Morbidity, mortality, and overall survival after PM with lymphadenectomy for elderly patients were comparable to younger patients. A disease-free interval > 36 months and anatomic lung resections might be associated with prolonged survival. However, elderly patients should also be evaluated for a curative treatment.

Sternal Resection for Breast Cancer Metastases.

BACKGROUND: Sternal infiltration of breast cancer (BC) is a rare but known phenomenon. Sternal resection for this cancer is not completely investigated. For this reason, the aim of this study was to examine long-term survival and prognosticators for prolonged survival of our patients after sternal resection. Also, morbidity and mortality were investigated. MATERIALS AND METHODS: We retrospectively analyzed our prospective database of 20 patients who underwent a sternum resection (partial/complete) for BC in our institution between 2003 and 2014. Furthermore, patients with additional lung metastases were included. All patients received a mesh-methyl methacrylate technique ("sandwich technique") and soft tissue coverage with myocutaneous muscle flap. Long-term outcomes and survival curves were performed by the Kaplan-Meier method. Survival differences and prognosticators were investigated using the log-rank test. RESULTS: Median survival was 32 months (95% confidence interval, 8-56 months). One-, 3-, and 5-year overall survivals were 79, 39, and 39%. There was a low morbidity and mortality with 35% (minor complications 30% and major complications 5%) and 0%. As prognosticators for longer survival, a positive hormone status (estrogen or progesterone) (p = 0.070) showed a trend. Neither age, primary mastectomy, disease-free interval < 24 months, primary N-status, nor preoperative chemotherapy showed a significant influence on survival. Furthermore, additional lung metastases did not influence survival significantly (p = 0.826). CONCLUSION: Sternal resections for BC patients can be associated with promising long-term survival. R0 resection, good functional and cosmetic results are achievable with low morbidity and mortality. Patients with additional lung metastases should not be routinely excluded from resection and should be discussed in interdisciplinary tumor boards.

Repeat resection for recurrent pulmonary metastasis of colorectal cancer.

PURPOSE: Resection of recurrent lung metastases from colorectal cancer is not completely investigated. We analyzed overall survival and prognosticators after metastasectomy. METHODS: We retrospectively reviewed our database of 238 patients with lung metastases of colorectal cancer, undergoing metastasectomy with systematic lymph node dissection from 1999 to 2014. Lymph node metastases were found in 55 patients, and liver metastases were found in 79 patients. RESULTS: The 5- and 10-year survival rates for all patients were 48 and 32%. Of the 238 patients included in the study, 101 developed recurrent lung metastases (42.4%). Recurrence had no impact on survival (p = 0.474). The 5- and 10-year survival rates from the beginning of recurrence for all patients with recurrence were 40 and 25%. Overall, 52 patients had been reoperated for recurrent lung metastases. 5-year survival for reoperated patients was 75% and significantly prolonged compared with nonreoperated patients (p < 0.001). Also, survival from beginning of recurrence was significantly longer (p < 0.001). Recurrence was more often detected in the case of multiple metastases (p = 0.002) and atypical resections (p = 0.029) at first metastasectomy. Lymph node metastases (p = 0.084) and liver metastases (p = 0.195) had no influence on recurrence. For reoperated patients, lower grading of the primary tumor was the only independent prognosticator for survival in multivariate analyses (p = 0.044). CONCLUSION: Good long-term survival is achievable for patients with resectable recurrent lung metastases. Multiple metastases and atypical resection at first metastasectomy were associated with recurrent disease. Neither lymph node metastases nor liver metastases were significantly associated with recurrence. Lower grading of the primary tumor was the only independent prognosticator for survival. All in all, the factors that can be influenced by the surgeon are patient selection and R0 resection.

Primary and Secondary Tumors of the Diaphragm.

Primary tumors of the diaphragm are rare. Secondary tumors of the diaphragm with origin in thoracic or abdominal cavity occur more frequent than primary tumors. In most cases, the therapy of choice includes a complete surgical resection of these tumors. This article reports on different types of tumors of the diaphragm, as well as surgical and reconstructive techniques.

Differential miRNA-Expression as an Adjunctive Diagnostic Tool in Neuroendocrine Tumors of the Lung.

Pulmonary malignancies with neuroendocrine differentiation represent a rare subclass of lung carcinomas, which vary in the extent of differentiation and grade of biological aggressiveness. In particular, neuroendocrine tumors are classified into well differentiated typical and atypical carcinoids as well as poorly differentiated large cell neuroendocrine and small cell lung carcinomas. Tiny MicroRNAs have been identified as reliable classifiers in distinct cancer types and seem to play important roles in cellular processes like regulation of cell growth, differentiation and apoptosis. In the present study, two different microRNAs (miR-21 and miR-34a) were explored for their involvements in pathogenesis of subtypes and finally in differential diagnosis of pulmonary neuroendocrine tumors. miR-21 was upregulated in poorly differentiated neuroendocrine tumors (mean rank: 26.8; 28.75) as compared to carcinoids (mean rank: 12.33; 12.07) with a significance of 0.00033. High-expression levels of miR-34a were associated with atypical carcinoids (p = 0.010). A close association is implicated between the elevated miR-21 values in high-grade and miR-34a patterns in low-grade atypical neuroendocrine lung carcinomas, which could potentially be exploited as practical supportive markers for differential lung cancer diagnosis in routine. However, some additional extended research and validation studies are needed to utilize them as routine markers or potential molecular targets for personalized medicine.

Results of Pulmonary Resection: Other Epithelial Malignancies.

This article summarizes the interdisciplinary work, survival, prognostic factors, and prognostic groups for lung metastases from breast cancer and renal cell cancer. Furthermore, the prevalence of lymph node metastases and the importance of a systematic lymph node dissection in metastasectomy of breast cancer and renal cell cancer for a true R0 resection are discussed.