Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis: A case report.

BACKGROUND: Pulmonary carcinoids are rare, low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi. Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5% of patients with neuroendocrine tumors. Due to such nonspecific presentation, most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed. CASE SUMMARY: We report the case of a 48-year-old male who presented with cough, dyspnea, a history of recurrent pneumonitis, and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid. CONCLUSION: We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Circulating Hsp70 Levels and the Immunophenotype of Peripheral Blood Lymphocytes as Potential Biomarkers for Advanced Lung Cancer and Therapy Failure after Surgery.

Lung cancer remains a devastating disease with a poor clinical outcome. A biomarker signature which could distinguish lung cancer from metastatic disease and detect therapeutic failure would significantly improve patient management and allow for individualized, risk-adjusted therapeutic decisions. In this study, circulating Hsp70 levels were measured using ELISA, and the immunophenotype of the peripheral blood lymphocytes were measured using multiparameter flow cytometry, to identify a predictive biomarker signature for lung cancer patients pre- and post-operatively, in patients with lung metastases and in patients with COPD as an inflammatory lung disease. The lowest Hsp70 concentrations were found in the healthy controls followed by the patients with advanced COPD. Hsp70 levels sequentially increased with an advancing tumor stage and metastatic disease. In the early-recurrence patients, Hsp70 levels started to increase within the first three months after surgery, but remained unaltered in the recurrence-free patients. An early recurrence was associated with a significant drop in B cells and an increase in Tregs, whereas the recurrence-free patients had elevated T and NK cell levels. We conclude that circulating Hsp70 concentrations might have the potential to distinguish lung cancer from metastatic disease, and might be able to predict an advanced tumor stage and early recurrence in lung cancer patients. Further studies with larger patient cohorts and longer follow-up periods are needed to validate Hsp70 and immunophenotypic profiles as predictive biomarker signatures.

[Surgical treatment of chest wall tumors]. / Chirurgische Therapie von Brustwandtumoren.

The term chest wall tumor summarizes a heterogeneous group of malignant and benign tumors, whereby primary and secondary chest wall tumors are differentiated. The incidence of secondary chest wall tumors is higher than that of primary tumors. Primary chest wall tumors can arise from any anatomic structure of the chest wall. Surgical resection is usually the treatment of choice. Resection status and tumor differentiation are relevant prognostic factors. Treatment of secondary chest wall tumors is performed depending on the patient's symptoms and prognosis of the underlying disease. Lung carcinomas infiltrating the chest wall can be resected primarily or secondarily as part of multimodal therapeutic strategies. Anatomic lung resections combined with chest wall resection have a higher mortality than standard resections. Chest wall reconstruction after resection has the goal of reducing paradoxical respiratory motion, although not every chest wall defect requires reconstruction.

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.

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.

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.

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.

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.

Extended thymectomy including lung-sparing pleurectomy for the treatment of thymic malignancies with pleural spread.

OBJECTIVE: To investigate the outcome of extended thymectomy including lung-sparing pleurectomy (extended surgery) in primary clinically advanced Masaoka-Koga stage IVa thymic malignancies. PATIENTS AND METHODS: Thirteen patients diagnosed with thymic malignancies at primary clinically Masaoka-Koga stage IVa were retrospectively analyzed between January 2000 and December 2012 at the Department of Thoracic Surgery, Dr. Horst Schmidt Klinik, Wiesbaden. Chi-square tests, Kaplan-Meier analyses, log-rank tests, and Cox regression analyses were used to estimate survival and determine prognosticators of survival. RESULTS: World Health Organization (WHO) classification were type C (n = 6), type B3 (n = 5), and type AB (n = 2), respectively. Nine patients underwent extended surgery. Morbidity was observed in three patients (33%). Mortality occurred in one patient. Four patients (31%) were unresectable at the time of surgery and underwent chemoradiation. Despite the clinically staging, five patients had lymph node metastases and thus pathologic Masaoka-Koga stage IVb. Median survival (MS) for all patients was 49 months. Extended surgery (MS 89 months) was associated with prolonged survival compared with patients who underwent only chemoradiation (MS 5 months). Stage migration due to lymph node metastases, WHO-classification type C, and T3/4-status were associated with inferior survival in the univariate analysis. Extended surgery remained the only independent significant prognosticator in the multivariate analysis. CONCLUSION: Extended surgery within multimodality treatments might offer survival advantage for advanced thymic malignancies with pleural spread. Patients with lymph node metastases and WHO classification type C might be at high risk of unresectability.

Clinicopathologic characteristics of patients with resected multifocal intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms of the pancreas are defined as mucin-producing neoplasms arising in the main pancreatic duct (main duct type), its major branches (branch duct type), or in both (mixed type). Intraductal papillary mucinous neoplasms of the pancreas can occur as a single collection of cysts or as multifocal lesions. While subtypes of intraductal papillary mucinous neoplasms of the pancreas are well described in literature, little is known about the importance of multifocal intraductal papillary mucinous neoplasms of the pancreas. This study evaluated the clinicopathologic characteristics of patients with surgically resected, multifocal intraductal papillary mucinous neoplasm of the pancreas. METHODS: Clinicopathologic features and preoperative imaging of patients resected for multifocal intraductal papillary mucinous neoplasm of the pancreas defined as intraductal papillary mucinous neoplasm of the pancreas occurring in more than just 1 area, from January 2004 to July 2010 at the Department of Surgery, University of Heidelberg were analyzed. Preoperative parameters, including number of cysts, cyst size, presence of nodules, and epidemiologic data, were assessed and compared to patients with unifocal intraductal papillary mucinous neoplasms of the pancreas. RESULTS: Among 287 patients with resected intraductal papillary mucinous neoplasms of the pancreas, 51 patients (17.8%) with multifocal cystic pancreatic lesions were identified by preoperative imaging. The median age of patients with multifocal intraductal papillary mucinous neoplasms of the pancreas was ≥ 68 years (P = .002) compared to patients with unifocal intraductal papillary mucinous neoplasm of the pancreas (median age, 64 years). Thirty-one multifocal intraductal papillary mucinous neoplasms of the pancreas were of mixed type (60.8%), 15 of branch duct type (29.4%), and 5 of main duct type (9.8%). Histologically, 10 multifocal intraductal papillary mucinous neoplasms of the pancreas had low-grade dysplasia (19.6%), 11 had moderate dysplasia (21.6%), 6 had high-grade dysplasia (11.8%), and 24 had invasive carcinoma (47.1%). CONCLUSION: Most multifocal intraductal papillary mucinous neoplasms of the pancreas involve the main pancreatic duct and synchronously its major side branches (mixed type). Patients with multifocal intraductal papillary mucinous neoplasm of the pancreas present at an older age compared to patients with single cystic pancreatic neoplasm. The risk of harboring malignancy-nearly 60% in the present study-seems to be increased in patients with multifocal intraductal papillary mucinous neoplasms of the pancreas compared to single lesions.

Prospective noninvasive analysis of hepatic fibrosis in patients with Crohn's disease: correlation of transient elastography and laboratory-based markers.

BACKGROUND AND AIMS: Hepatobiliary disorders, associated either with extraintestinal manifestations or with consequences of treatment, are prevalent among patients with inflammatory bowel disease (IBD). This study aimed to prospectively assess the potential of noninvasive markers for the evaluation of liver fibrosis in patients with Crohn's disease. METHODS: A total of 114 patients were recruited. Established markers of fibrosis, namely, aspartate transaminase-to-platelet ratio index (APRI), fibrotest, Forns, sonography, and transient elastography were performed and correlated with disease parameters. In addition to descriptive statistical analysis, Pearson's correlation coefficients were determined. The t-test and the Mann-Whitney U-test were applied and univariate and multivariate data analyses were performed. RESULTS: Ultrasound indicated hepatic steatosis in 33 patients, hepatomegaly in 10, and cirrhosis in two. Liver stiffness as quantified by transient elastography was determined to be 5.06±2.33 kPa (2.6-21.5). Results of noninvasive liver fibrosis markers were as follows: fibrotest,-1.65±0.94; APRI, 0.33±0.22; and Forns, 3.11±2.00. Correlation coefficients were found to be fibrotest/transient elastography: r=0.35291; APRI/transient elastography: r=0.38442; Forns/transient elastography: r=0.33949; fibrotest/APRI: r=0.52937; fibrotest/Forns: r=0.42413; and APRI/Forns: r=0.56491. Correlation of inflammatory markers and noninvasive liver fibrosis tests, respectively, was generally negative, whereas correlation of parameters indicating liver damage and liver fibrosis tests, respectively, was generally positive. CONCLUSION: In a center-based, unselected cohort of patients with Crohn's disease, the positive correlations between laboratory-based markers of fibrosis and transient elastography were highly significant. A study correlating noninvasive and invasive tools for the assessment of liver fibrosis in IBD is reasonable.