Thoracic staging with 18F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to 18F-FDG PET/CT?

OBJECTIVE: To investigate whether differences in thoracic tumour staging between 18F-FDG PET/CT and PET/MR imaging lead to different therapeutic decisions in Non-Small Cell Lung Cancer (NSCLC). MATERIAL AND METHODS: Seventy-seven NSCLC patients that underwent whole-body 18F-FDG PET/CT from the base of skull to the upper thighs and thoracic PET/MR were enrolled in this retrospective study. Thoracic PET/CT and PET/MR images were staged according to the 7th edition of the AJCC staging manual. Staging results of both modalities were discussed separately in a simulated interdisciplinary tumour board and therapeutic decisions based on both imaging modalities were recorded. Descriptive statistics were used to compare the results and reasons for changes in the therapeutic decision were investigated. RESULTS: Staging results differed in 35 % of patients (27 patients) between thoracic PET/CT and PET/MR. Differences were detected when assessing the T-stage in 18 % (n = 14), the N-stage in 23 % (n = 18), and the M-stage in 1 % (n = 1). However, patient therapy management was changed in only six patients (8 %). CONCLUSION: Despite the variability of thoracic 18F-FDG PET/CT and PET/MR in TNM-staging, both modalities lead to comparable therapeutic decisions in patients suffering from NSCLC. Hence, 18F-FDG PET/MR can be considered an possible alternative to 18F-FDG PET/CT for clinical NSCLC staging. KEY POINTS: • PET/CT and PET/MR provide comparable results in early stages in NSCLC • Clinical impact of different staging results has not been investigated • PET/CT and PET/MR lead to comparable therapeutic decisions • PET/MR can be considered an alternative to PET/CT for NSCLC staging.

Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage.

PURPOSE: Up to 19% of all colorectal resections develop clinically apparent insufficiencies. Insufficient perfusion of the anastomosis is recognized as an important risk factor. As tissue perfusion can be objectified intraoperatively using laser fluorescence angiography (LFA), its effect on the rate of anastomotic complications was evaluated in a retrospective matched-pairs analysis. METHODS: Between 2003 and 2008, all anastomosis or resection margins in colorectal cancer resections were investigated intraoperatively using LFA (LFA group). Patients with colorectal cancer resections between 1998 and 2003 without LFA served as the control group. Four hundred two patients were matched for age, T-stage, type of resection and anastomosis, defunctioning stoma, administration of blood, emergency conditions, and body mass index. Statistical analysis was performed using the Fisher and the Wilcoxon tests. RESULTS: Twenty-two surgical revisions were necessary due to anastomotic leakage, seven (3.5%) in the LFA group and 15 (7.5%) in the control group. Subgroup analysis revealed that in elective resections the rate of revision was 3.1% (LFA group) and 7.7% (control group) (p = 0.04, risk of revision (ROR) reduced by 60%). In patients older than 70 years, the rate of revision was 4.3% (LFA group) compared to 11.9% (control group) (p = 0.04, ROR reduced by 64%). After hand-sewn anastomosis, the rate of revision was 1.2% (LFA group) and 8.5% (control group) (p = 0.03, ROR reduced by 84%). Hospital stay was significantly reduced in the LFA group (Wilcoxon test; p = 0.01). CONCLUSION: There was an overall reduction in the absolute revision rate of 4% in the LFA group and a significantly reduced rate of revision in the subgroup analysis of patients undergoing elective colorectal resections, in patients older than 70 years and in patients with hand-sewn anastomosis. This demonstrates that LFA is a method that may significantly reduce not only the rate of severe complications in colorectal surgery but also the hospital length of stay.

Prognostic markers in resected large cell neuroendocrine carcinoma: a multicentre retrospective analysis.

BACKGROUND: Large cell neuroendocrine carcinomas (LCNEC) are rare pulmonary malignancies. Reported survival rates are heterogeneous and the optimal therapeutic strategy is still debated. The prognosis of LCNEC is generally inferior compared to other non-small lung cancers. In early stages, surgery is recommended but might not be sufficient alone. METHODS: We retrospectively analyzed all consecutive LCNEC patients operated at three institutions with curative intent between May 2005 and January 2017. Data retrieved from individual clinical databases were analyzed with the aim to identify prognostic parameters. RESULTS: A total of 251 patients with LCNEC underwent curative intent surgery during the observation period. The median age was 64 years, 156 patients (62.2%) were male and 88.4% were smokers. The pathologic AJCC stage was I in 136 patients, II in 77, III in 33, and IV in 5 patients. Median follow-up was 26 months. Lymphatic vessel invasion (P=0.031) was identified as significant prognostic factor by multivariable analysis. There was a trend towards decreased survival in patients with blood vessel invasion (P=0.067). Even in earlier tumor stages, adjuvant chemotherapy had a positive effect on survival. The overall 1-, 3- and 5-year survival rates were 79.2%, 48.6% and 38.8% respectively. CONCLUSIONS: Lymphatic invasion (L1) is an independent prognostic factor. Surgery in LCNEC is beneficial in early tumor stages and platinum-based adjuvant chemotherapy may help in achieving better long-term outcomes resulting in most obvious survival differences in stage Ib.

Hernia recurrence after laparotomy: how to close an incised light-weight mesh?

A rising number of patients require relaparotomy after implantation of mesh materials for incisional hernia (IH) repair. No published recommendation concerning how to close the incision in a surgical mesh exists. We describe a central IH recurrence through a partly absorbable mesh positioned in the retromuscular plane 16 months after laparotomy due to a small bowel ileus. This recurrence was repaired using a heavy-weight, monofilament polypropylene mesh, again in the retromuscular position. Reducing the amount of nonabsorbable material in large pore hernia meshes leads to markedly reduced scar formation rather than the formation of a thick scar plate. Once cut and resutured, this scar may be too weak to withstand the mechanical strain, giving rise to a 'blow-out' IH recurrence, as demonstrated in our case. In these cases, re-enforcement with a nonabsorbable, small, porous polypropylene mesh in the retromuscular space is feasible and leads to the development of a mechanically stable scar.

The role of surgery in high grade neuroendocrine tumours of the lung.

High grade lung neuroendocrine tumours are a heterogeneous subtype of pulmonary cancers including small cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). LCNEC represents approximately 2-3% of lung cancers, whereas SCLC represents 15-20% of lung cancers. Patients with SCLC and LCNEC have a poor prognosis compared with patients with non-small cell lung cancer (NSCLC). LCNEC is treated with primary surgical resection in stages I-II, which is similar to other NSCLCs. Neo-adjuvant treatment in stage III is similar to NSCLC but has not been well studied. LCNEC tumours have an unfavourable prognosis in higher stages but a more favourable prognosis in earlier stages. Surgery plays a minor role in treatment of SCLC because tumours are often locally advanced or have metastasized at the time of presentation and treatment relies on chemo- or chemoradiotherapy. However, patients with limited cancer may demonstrate better disease control upon surgical treatment. The resection rate of limited disease (LD) SCLC is low (1-6%), but 5-year survival rates of 31-42% after surgical resection are encouraging and are significantly higher than the survival rates of comparable patients that did not have surgery. Curing SCLC in stage I is reported in up to 66% of cases. Local treatment with either resection or radiotherapy alone is followed by high rates of locoregional and distant recurrences, so preoperative or adjuvant treatment is recommended. Here, we summarise the similarities and differences of SCLC and LCNEC and highlight the role of surgery in the treatment of SCLC and LCNEC and its effect on local recurrence prevention.

Growth patterns of pulmonary metastases: should we adjust resection techniques to primary histology and size?

OBJECTIVES: Safety margins in pulmonary metastasectomy are not yet well defined. We hypothesize that histological subtype, size of the lesion and local growth characteristics must be taken into consideration during metastasectomy. This study was conducted to examine and classify growth patterns at resection margins and define the relationships between aggressive local growth, metastasis size and local recurrence to direct metastasectomy. METHODS: Histologic sections of pulmonary metastases were prospectively collected and haematoxylin-eosin stains were systematically evaluated and classified by their pattern of lung tissue infiltration. Logistic regression was used to model the association between the subgroups of colorectal, renal cell and epithelial cancers and melanomas and sarcomas. RESULTS: From 183 patients, 412 lung specimens were removed, which contained 459 pulmonary metastases. We found that 58% of all lesions had microscopic signs of aggressive local dissemination. The metastases showed histology-specific patterns of local growth: sarcoma was associated with pleural infiltration; colorectal metastases with interstitial spread and aerogenous spread of floating cancer cell clusters; and melanoma with perivascular growth and with lymph vessel involvement. Aggressive patterns of growth had an increasing probability of around 3% for each additional millimetre of metastasis diameter. Local intrapulmonary recurrence was significantly more common in association with interstitial growth and pleural penetration as well as safety margins <7 mm. CONCLUSIONS: Approximately 40% of all lung metastases have a smooth surface and might be resected with small margins. Growth characteristics within the lung differ with the histologic subtype and safety margins should generally increase with the size of the metastasis.

Sarcomatoid carcinoma of the lung: a rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages.

Objectives: Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype of non-small cell lung cancer and comprises a diagnostically and therapeutically challenging group of tumours. We explored the clinicopathological features and prognostic factors of this tumour. Methods: We conducted a retrospective study of all patients who were treated for PSC in the Department of Thoracic Surgery between May 2005 and December 2014. Primary outcomes of interest were patient survival and prognostic factors. Results: A total of 58 patients were treated for sarcomatoid carcinoma within the described period and 46 patients underwent surgical resection with curative intent. The mean follow-up period was 30 months. Of the operated patients, 21.7% had pathological stage I disease, and 78.3% had more advanced disease. There were 25 carcinosarcomas, 10 pleomorphic carcinomas, 7 spindle cell carcinomas, 3 giant cell carcinomas and 1 pulmonary blastoma. Overall 5-year survival of the operated patients was 28.7%. A total of 28 patients experienced recurrence and died cancer-related. Our analysis revealed that tumour size, gender, histological entity, lymphatic vessel invasion (L1) and vascular invasion (V1) did not influence survival. There was a trend for decreased survival in older patients (>65 years). Conclusions: Surgical treatment can achieve satisfactory results with low perioperative mortality, but the overall prognosis even with multimodality concepts and in earlier tumour stages is worse compared to other types of non-small cell lung cancer.

A Single-Institution Analysis of the Surgical Management of Pulmonary Large Cell Neuroendocrine Carcinomas.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is an uncommon tumor of the lung and represents approximately 3% of all lung cancers. LCNEC displays biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. LCNEC of the lung are considered aggressive. Reported prognoses are heterogeneous, and the optimum treatment remains undefined. METHODS: We conducted a retrospective study of all patients who were treated for LCNEC in our Department of Thoracic Surgery between May 2005 and December 2013. Primary outcomes of interest were patient survival and prognostic factors. Kaplan-Meier analysis was performed to determine the significant predictors of overall survival. RESULTS: Within the prescribed period, 127 patients were treated for LCNEC, and 125 underwent surgical resection with curative intent. Induction chemotherapy or radiochemotherapy was given to 9 patients, and 63 patients received postoperative chemotherapy. Complete resection was achieved in 99.2%. The overall 1-, 3- and 5-year survival rates were 83.7%, 63.2%, and 53.8% of all patients, and the 5-year survival in patients at stages I, II, and III was 64.5%, 40%, and 29.7%. There was a significant survival difference at 5 years between pT1/2 (58.5%) and pT3 tumors (22.4%; p = 0.043) and for patients with lymphatic involvement (L0 vs L1, p = 0.001; pN1 or pN2 vs pN0, p = 0.04). CONCLUSIONS: Surgical treatment can achieve satisfactory results in early tumor stages, which are comparable with other non-small cell lung cancers, with a low perioperative mortality rate.

Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group†.

OBJECTIVES: In 2012, the European Society of Thoracic Surgeons (ESTS) created the Lung Neuroendocrine Tumors Working Group (NETs-WG) with the aim to develop scientific knowledge on clinical management of such rare neoplasms. This paper outlines the outcome and prognostic factors of two aggressive NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs). METHODS: Using the ESTS NETs-WG database, we retrospectively collected data on 261 patients in seven institutions in Europe, between 1994 and 2011. We used a Cox regression model to evaluate variables affecting patient survival and disease-free survival. Univariate and multivariate analysis were also carried out. RESULTS: Five-year overall survival rates for ACs and LCNCs were 77 vs 28% (P < 0.001), respectively. We found that for ACs, age (P < 0.001), tumour size (P = 0.015) and sub-lobar surgical resection (P = 0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumours (P = 0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases developed in 93 patients and were statistically more frequent in LCNCs (P = 0.02). CONCLUSIONS: The biological aggressiveness of ACs and LCNCs has been demonstrated with this study. Our aim is to confirm these results with enhanced data collection through the ESTS NETs database.

Immunotherapy by gene transfer with plasmids encoding IL-12/IL-18 is superior to IL-23/IL-18 gene transfer in a rat osteosarcoma model.

BACKGROUND: Osteosarcomas are primary malignant tumors of bone or soft parts arising from bone-forming mesenchymal cells. Despite dramatic therapeutic advances, namely neo-adjuvant and adjuvant chemotherapy, progress is at a plateau. Cytokine-mediated gene therapy might represent a further advance in the therapy of the osteosarcoma. MATERIALS AND METHODS: We transfected UMR 108 osteosarcoma cells with different plasmids encoding IL-12, IL-23, proIL-18 and ICE (Interleukin-converting enzyme). IFN-gamma induction, which is known to induce antitumor effects mediated by the immune system, and cytotoxic effects of various cytokine combination were investigated. RESULTS: Our results show that local secretion of IL-12 by UMR 108 cells led to an induction of cytotoxic effects mediated by mononuclear cells, which were enhanced by additional administration of recombinant IL-18. In contrast to IL-18, IL-23 showed a moderate increase of IFN-gamma induction when transfected alone and could only slightly increase the IFN-gamma induction mediated by IL-12. IL-18 enhanced IFN-gamma induction when applied alone and was able to increase the IFN-gamma production that was induced by IL-12. CONCLUSION: IL-23 seems to be a less effective immuno-therapeutic for adjuvant treatment of osteosarcomas than IL-12 and IL-18, when taking only IFN-gamma induction into consideration.

Interleukin-12 and interleukin-18 induce indoleamine 2,3-dioxygenase (IDO) activity in human osteosarcoma cell lines independently from interferon-gamma.

PURPOSE: In this study we evaluated the ability of inducing activation of the enzyme indoleamine 2,3-dioxygenase (IDO) for the development of a new adjuvant therapy of osteosarcomas. The pathway that has described in the literature states that IDO activity is elevated by IFN-gamma. This mechanism is important because the increased IDO activation induces an intracellular degradation of the essential amino acid tryptophan and thereby activates apoptosis in human osteosarcoma cells. MATERIALS AND METHODS: Four different well-established human osteosarcoma cell lines (MNNG/HOS, KHOS-240, HOS and MG-63) were investigated in vitro. Several cytokines were tested for their ability to induce IDO activity. However special emphasis was placed to evaluate the synergistic effects of Interleukin-12 (IL-12) in combination with Interleukin-18 (IL-18). In the first series of experiments IDO induction was investigated by direct application of the cytokines IFN-gamma, TNF-alpha, IL-12 and IL-18 in different concentrations. Secondly, the increase of IDO expression from osteosarcoma cell lines was analysed in the presence of activated lymphocytes with or without cytokine application. RESULTS: Our results demonstrated that the combined application of IL-12 and IL-18 enhanced IDO activity in the human osteosarcoma cell lines HOS and MG-63, in the presence of activated lymphocytes. In the absence of activated lymphocytes, no significant enhancement could be detected. In all our experiments the increase in IDO expression was only partly inhibited by blocking INF-gamma. CONCLUSION: The presented study demonstrates that IL-12 and IL-18, or even more a combined application of both cytokines, induce IDO expression besides the known pathway via IFN-gamma. These mechanisms have been shown herein for the first time in human osteosacoma cell lines. Since IDO expression could still be shown after complete blocking of IFN-gamma, we conclude that at least a second pathway is responsible for inducing IDO activity. This is in contrast to the present knowledge about IDO activation.

rIL-18 triggered gene therapy based on a transduction with the IL-12 plasmid: a new option as immuno-therapy for osteosarcoma?

Gene therapy is a promising new method to treat tumors locally. Immuno-therapy for treatment of osteosarcomas is one option for hopefully improving the survival rate of patients with this tumor. Transduction of OS cells with the pCMV-IL-12neo plasmid induced a significant increase in IFN-gamma expression by mononuclear cells. This is known to induce antitumor effects mediated by the immune system. In combination with an administration of rIL-18, the IFN-gamma increase was multiplied in a dose-dependent manner. This study demonstrated that osteosarcoma cells can be targeted effectively in vitro by plasmids encoding the IL-12 gene. Considering the synergistic pathways it is reasonable to combine a local, gene transfer based on IL-12 with a rIL-18 administration to trigger the potentially promising immuno-effects for adjuvant treatment of osteosarcomas.

Management of a chest-wall soft-tissue tumor caused by an infection with the larval tapeworm pathogen Taenia crassiceps.

A chest-wall lesion of an immunocompetent patient was initially suspicious for a malignant tumor. Histopathological and polymerase chain reaction examinations revealed an infection with the larval stage of the tapeworm Taenia crassiceps. Curative resection of the tumorous lesion was performed. Treatment options for immunocompromised patients and patients without known immune defect are discussed, because most of the infections occur in immunocompromised individuals.

Modified Clagett Procedure Is Effective for Methicillin-Resistant Staphylococcus aureus Postpneumonectomy Empyema: A Case Report.

Postpneumonectomy empyema (PPE) with methicillin-resistant Staphylococcus aureus (MRSA) is a challenging problem because these germs have extensive virulence factors and mechanisms to escape from the host's immune system. The present case was successfully treated with accelerated repeated surgical debridement, vancomycin gauze packing and final obliteration of the postpneumonectomy space with latissimus myoplasty and vancomycin solution.

Interleukin-12 and interleukin-18 change ICAM-I expression, and enhance natural killer cell mediated cytolysis of human osteosarcoma cells.

Cytokines play important roles in the expression of adhesion molecules and the function of anti-tumor effector cells in the immune system. In this study, the influence of interleukin-12 (IL-12) and IL-18 on the expression of ICAM-1 and natural killer (NK)-cell mediated lysis in a human osteosarcoma cell line (HOS) was evaluated. ICAM-I expression of HOS cells were analyzed by flow cytometry following treatment with IL-12, IL-18 or both, and in co-cultures with peripheral lymphocytes. NK-cell activation in response to IL-12 and IL-18 was investigated by selective flow cytometry using propidium iodide. ICAM-1 expression on HOS cells was significantly enhanced by IL-12, but only when co-cultured in cell-to-cell contact with peripheral lymphocytes. Antibodies to interferon-gamma abrogated this effect. If HOS cells and peripheral lymphocytes were separated in co-cultures, IL-18 could substitute for cell-to-cell contact, facilitating IL-12-mediated enhancement of ICAM-1. Addition of IL-18 also enhanced NK-mediated cytolysis of HOS cells. These findings demonstrate that IL-12 can enhance the expression of ICAM-1 in the presence of IFN-gamma and, with IL-18, enhances NK anti-tumor activity. Immunomodulation via cytokine therapy may lead to improved eradication of chemotherapy-resistant osteosarcomas.