Lung Metastases - Diagnostic, Prognostic and Molecular Aspects with Focus on Colorectal Cancer

In Sweden 4200 patients are diagnosed with lung cancer and 6500 patients with colorectal cancer (CRC) annually. The lungs are a common site for metastases. Immunohistochemistry (IHC) is a helpful aid in diagnostics of a pulmonary tumour. Selected patients with metastatic CRC undergo pulmonary metastasectomy and knowledge about which patients benefit from it is important. In this thesis IHC markers to distinguish between primary lung cancer and lung metastases, survival and prognostic factors of CRC patients treated with pulmonary metastasectomy and genetic profiles of paired primary CRC, lung and liver metastases are studied. I: Lung adenocarcinoma (AC) was TTF-1 positive in 89, 93 and 93% of cases with clones 8G7G3/1, SPT24 and SP141 respectively. None of the lung squamous cell carcinoma (SqCC) was positive with clone 8G7G3/1 but 6 and 8% with clone SPT24 and SP141, respectively. Equivalent numbers for CRC lung metastases were 2, 7 and 8%. II: Lung adenocarcinoma (AC) was TTF-1 positive in 90%, napsin A in 84%, and CK7 in 99% of cases. 68% were positive for all three markers and negative for other evaluated markers. None of the lung squamous cell carcinoma (SqCC) was expressed CK5, p40 and p63 in 94-97% of cases, while 64% were positive for all three markers, CK7+/-, and negative for other evaluated markers. CRC lung metastases were CK20+ in 83% and CDX2+ in 99% of cases, while 78% were positive for both and negative for other evaluated markers. III: In total 216 patients with primary tumour in the rectum (57%), left colon (34%) or right colon (9%) underwent pulmonary metastasectomy. The 5-year overall survival was 56%. Age >60 years, >1 lung metastasis, size of metastasis >3 cm, disease-free interval <24 months, N2 status of the primary tumour, low RBM3 expression in the lung metastasis, and no adjuvant chemotherapy following pulmonary metastasectomy were prognostic factors for shorter overall survival. IV: Mutations were most frequent in the TP53, APC and KRAS genes with rates of 81-85%, 70% and 41-48%, respectively in the primary tumours and corresponding lung and liver metastasis. With TST26, identical mutational profile was found in 59% of paired triplet tumours. The concordance was higher between primary tumour and lung metastasis (74%) vs. primary tumour and liver metastasis (63%). For seven (54%) of the 13 KRAS-mutated cases the KRAS mutations were concordant. With TSO500, discordant KRAS mutational profiles could be confirmed, sometimes with discrepancy compared to TST26. There was no significant difference in TMB between primary tumour and metastases

Diagnostic gastrointestinal markers in primary lung cancer and pulmonary metastases

Funding Information: Open access funding provided by Lund University. The study was supported by Swedish governmental funding of clinical research (ALF), the Franke and Margareta Bergqvist Foundation, and the Swedish Cancer Society. The funding sources had no role in the design or conduct of the study. Publisher Copyright: © 2023, The Author(s).Histopathological diagnosis of pulmonary tumors is essential for treatment decisions. The distinction between primary lung adenocarcinoma and pulmonary metastasis from the gastrointestinal (GI) tract may be difficult. Therefore, we compared the diagnostic value of several immunohistochemical markers in pulmonary tumors. Tissue microarrays from 629 resected primary lung cancers and 422 resected pulmonary epithelial metastases from various sites (whereof 275 colorectal cancer) were investigated for the immunohistochemical expression of CDH17, GPA33, MUC2, MUC6, SATB2, and SMAD4, for comparison with CDX2, CK20, CK7, and TTF-1. The most sensitive markers for GI origin were GPA33 (positive in 98%, 60%, and 100% of pulmonary metastases from colorectal cancer, pancreatic cancer, and other GI adenocarcinomas, respectively), CDX2 (99/40/100%), and CDH17 (99/0/100%). In comparison, SATB2 and CK20 showed higher specificity, with expression in 5% and 10% of mucinous primary lung adenocarcinomas and both in 0% of TTF-1-negative non-mucinous primary lung adenocarcinomas (25-50% and 5-16%, respectively, for GPA33/CDX2/CDH17). MUC2 was negative in all primary lung cancers, but positive only in less than half of pulmonary metastases from mucinous adenocarcinomas from other organs. Combining six GI markers did not perfectly separate primary lung cancers from pulmonary metastases including subgroups such as mucinous adenocarcinomas or CK7-positive GI tract metastases. This comprehensive comparison suggests that CDH17, GPA33, and SATB2 may be used as equivalent alternatives to CDX2 and CK20. However, no single or combination of markers can categorically distinguish primary lung cancers from metastatic GI tract cancer.Peer reviewe

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta‑analysis

Background Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1–3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1–3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. Conclusions This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.publishedVersio

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-anal

Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome

Spontaneous splenic rupture and multiple lung embolisms due to cytomegalovirus infection: a case report and review of the literature.

A 53-year-old woman presented with a spontaneous splenic rupture. The splenic rupture was considered a complication of a primary cytomegalovirus (CMV) infection as well as multiple pulmonary embolisms. CMV infections are common but are most often asymptomatic, and to our knowledge only 15 cases complicated with splenic rupture have been published

Michel Panaieff as the Scotsman (centre left), Tatiana Stepanova as La Sylphide (centre right), and artists of the company, in Graduation ball, The Original Ballet Russe, Australian tour, His Majesty's Theatre, Melbourne, 1940 (2) [picture] /

From: Graduation ball : ballet in one act / by David Lichine ; music by Johann Strauss ; compiled, arranged and orchestrated by Antal Dorati.; Inscription: "4B/26".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Performed April - June 1940.; Choreography by David Lichine ; scenery and costumes by Alexandre Benois ; scenery executed by Nadejda Benois ; ladies' costumes executed by O. Larose and Antoinette ; male costumes executed by A. H. Leiser.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4174748. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Kirtilkrabbamein í botnlanga á islandi 1990-2009 -- lýdgrundud rannsókn

OBJECTIVE: Adenocarcinoma of the appendix is less than 0.5% of all gastrointestinal cancers. The aim of this study was to analyse the incidence, symptoms, pathology and treatment of appendiceal adenocarcinoma in a well defined cohort as well as the prognosis of the patients.MATERIALS AND METHODS: This is a retrospective study on all patients diagnosed with adenocarcinoma of the appendix in Iceland from 1990-2009. Information on epidemiological factors, survival and treatment was collected. All histological material was reviewed. Overall survival was estimated with median follow up of 15 months (range, 0-158).RESULTS: A total of 22 patients were diagnosed with appendiceal adenocarinoma in the study period (median age 63 yrs, range: 30-88, 50% males). Age-standardized incidence was 0.4/100,000/year. The most common symptom was abdominal pain (n=10). Eight patients had clinical signs of appendicitis. Most patients were diagnosed at operation or at pathological examination but one patient was diagnosed at autopsy. Five patients had an appendectomy and 11 a right hemicolectomy. One patient was not operated on and in three patients only a biopsy was taken. Twelve patients had chemotherapy and seven of them for metastatic disease. Eight patients had adenocarcinoma, seven mucinous adenocarcinoma, three signet ring adenocarcinoma, one mixed goblet cell carcinoid and mucinous adenocarcinoma,one mixed adenocarcinoma and signet ring adenocarcinoma and two a mucinous tumour of unknown malignant potential. In eight cases the tumor originated in adenoma. Most of the patients had a stage IV disease (n=13), three stage III, three stage II and three stage I. Operative mortality was 4.8% (n=1). Disease specific five year survival was 54% but overall five year survival was 44% respectively.CONCLUSION: Adenocarcinoma of the appendix is a rare disease. No patients were diagnosed pre-operatively. Over half of the patients presented with stage IV disease

Indications and surgical outcome following pulmonary metastasectomy: a nationwide study.

The aim of this retrospective nationwide study was to investigate indications and surgical outcome after pulmonary metastasectomy (PM) in a well-defined cohort of patients and to calculate the proportion of cancer patients who were operated on. Between 1984 and 2008, 81 patients (age 54.8 years, 50.6% men) underwent 100 PMs with curative intent in Iceland. For all patients, information on demographics, number of metastases, type of surgery, and complications were collected. Overall survival was estimated with median follow-up of 45 months. For the three most common malignancies, the proportion of patients who underwent PM was calculated using information from the Icelandic Cancer Registry on all cases diagnosed. Of 100 PMs, there were 62 wedge resections, 34 lobectomies, and 4 pneumonectomies. The most common complication was persistent air leakage (>96 hour; 11.1%), and operative mortality was 1.2%. Of the 12 kinds of primary malignancies operated, three were most common: colorectal carcinoma (CRC, n = 27), sarcoma (n = 21), and renal cell carcinoma (RCC, n = 14). The proportion of patients who underwent PM was 1.0% for CRC, 6.5% for sarcoma, and 1.4% for RCC, and their 5-year overall survival was 45.2, 18.6, and 38.5%, respectively (p = 0.11). Survival for all patients was 30.8%. The surgical outcome and survival of patients who underwent PM in Iceland are comparable to those in the other studies. Although there was no control group and selection bias cannot be eliminated, the survival of PM patients was better than for the nonoperated patients. However, a relatively small proportion of patients with CRC, RCC, and sarcoma underwent metastasectomy.Landspitali Research Fun

Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumours

Background The lungs are the second most common site of metastases in colorectal cancer (CRC). The aim of this study was to investigate prognostic factors, including RNA‐binding motif protein 3 (RBM3) expression, in patients with CRC treated with pulmonary metastasectomy (PM). Methods The cohort included all patients treated with PM at Skåne University Hospital, Lund, Sweden, from 2000 to 2014. Clinicopathological, treatment, and survival data were collected. Immunohistochemical staining of RBM3 was evaluated on tissue microarrays with samples from all lung metastases and a subset of paired primary tumors. Kaplan–Meier analysis and Cox proportional hazards modeling were applied to examine the associations of investigative factors with overall survival (OS) and recurrence‐free survival. Results In total, 216 patients with a primary tumor in the rectum (57%), left colon (34%), or right colon (9%) underwent PM. The 5‐year OS rate was 56%. Age > 60 years, more than one metastasis, size of metastasis > 3 cm, disease‐free interval < 24 months, low RBM3 score in the lung metastasis, and no adjuvant chemotherapy following PM were prognostic factors for shorter OS. Conclusions Several prognostic factors, including RBM3 expression, may be of aid in selecting CRC patients with lung metastases for PM as well as adjuvant therapy