Severity and 1-month outcome of SARS-CoV-2 infection in patients with solid cancers: a Danish nationwide cohort study.

BACKGROUND: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. METHODS: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study's primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. RESULTS: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). CONCLUSIONS: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.HighlightsAge, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection.Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19.Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients with solid cancer.

ProHNPs are specific markers of normal myelopoiesis.

Pro human neutrophil peptides (proHNP)s are proforms of α-defensins produced by precursors of human neutrophils. They are secreted to bone marrow plasma in large amounts by myelocytes. We hypothesized that the plasma concentration of proHNPs might serve as a specific marker of myelopoietic activity, heralding the onset of normal myelopoiesis before reappearance of neutrophils, in the setting of bone marrow regeneration. To investigate this, plasma levels of proHNPs were measured by enzyme-linked immunosorbent assay in blood samples collected from patients undergoing allogeneic (n=11) or autologous (n=16) stem cell transplantations (SCTs) and patients receiving chemotherapy for acute leukemia (n=14). To compare proHNPs with previously suggested myeloid markers, myeloperoxidase (MPO), lysozyme and neutrophil gelatinase-associated lipocalin (NGAL) were also assayed. In all but one patient, chemotherapy led to the complete disappearance of ProHNPs from plasma. It reappeared in plasma on average 6.3 days before reappearance of neutrophils in the allogeneic setting, whereas this was reduced to an average of 2.8 days in the autologous SCT patients who received granulocyte colony-stimulating factor. Patients with acute myeloid leukemia (n=19) had significantly lower levels of plasma proHNPs than healthy controls, indicating that proHNPs are not produced by leukemic blasts. We conclude that plasma concentration of proHNPs is a clinically useful marker of normal myelopoiesis.

Result of the implementation of multidisciplinary teams in rectal cancer.

AIM: In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. METHOD: A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow-up recorded by the National Patient Registry in September 2010 was used. The end-points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over-all and disease-free survival. RESULTS: Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival. CONCLUSION: There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.

Endobiliary brush biopsy: Intra- and interobserver variation in cytological evaluation of brushings from bile duct strictures.

OBJECTIVE: Obtaining cytological specimens by wire-guided endobiliary brushing at the time of endoscopic retrograde cholangiopancreatography (ERCP) is a convenient way to reach a diagnosis. Sensitivity for malignant disease is generally around 50% and specificity around 100%. The present study was designed to assess the reproducibility of the cytological examination. MATERIAL AND METHODS: Samples were obtained from 55 consecutive patients with biliary duct strictures that eventually turned out to be caused by malignant disease in 41 patients (73%). The cytology specimens were evaluated twice in different random order with an interval of at least 4 months by two pathologists blinded to the final diagnoses. Suitability for diagnosis (suitable, suboptimal or unsuitable) and cytologic diagnosis (benign, atypical, suspicious for malignancy and malignant cells) were registered. Kappa analysis was applied. RESULTS: Regarding suitability for diagnosis, the two observers reproduced their findings in 84% (kappa 0.76) and 87% (0.59) (p>0.05), while the interobserver variations on the two occasions were 76% and 78% (kappa 0.49 and 0.58, respectively) (p>0.05). Five percent of samples were rated as inadequate for diagnosis in at least one reading; 18% were suboptimal and 62-82% were suitable. The observers reproduced their cytological diagnosis in 77% and 71% (weighted kappa 0.83 and 0.75) (p>0.05), and agreed on the cytological diagnosis in 65% and 73% (weighted kappa 0.65 and 0.75) (p>0.05). CONCLUSIONS: The intra- and interobserver agreement in cytological evaluation of endobiliary brushings from bile duct strictures is generally good. The rates of inadequate and suboptimal samples can probably be reduced by modifications of the brush design.

Eosinophilic cystitis--diagnosis and treatment in Denmark.

OBJECTIVE: The purpose of this study was to evaluate the incidence, diagnostic criteria and treatment of eosinophilic cystitis (EC) in Denmark during the period 1989-94. MATERIAL AND METHODS: A questionnaire was sent to all Danish departments of surgery, urology and pathology. RESULTS: Fifty-six cases of EC were diagnosed in the departments of surgery and urology, and 135 patients were diagnosed in the departments of pathology. The therapy was most often steroid instillation in the bladder or peroral antihistamines. Success rates of treatment were reported to be acceptable. CONCLUSION: The questionnaire confirmed that EC is a rare disease, which is often confused with other bladder diseases. We recommend strict histological criteria combined with clinical information when making the diagnosis of EC. Therapy is generally symptomatic. A diagnostic code number from the Danish Health Board is needed.

[Eosinophilic cystitis. A survey]. / Eosinofil cystit. En enquete.

The purpose of this study was to evaluate the incidence, diagnostic criteria and treatment of eosinophilic cystitis in the period 1989-94 in Denmark. A questionnaire was sent to all Danish surgical, urological and pathological-anatomical departments. Fifty-six patients were diagnosed as having eosinophilic cystitis at the surgical departments and 135 patients were diagnosed at the pathological-anatomical departments. The treatment was most often instillation of steroids in the bladder or oral antihistamine. Success of treatment was generally acceptable. The questionnaire confirmed that eosinophilic cystitis is a rare disease. We recommend the pathological-anatomical departments to use certain diagnostic criteria for eosinophilic cystitis. The treatment is symptomatic. A diagnostic number from the Danish Health Board is needed.

Pyelitis cystica.

We present four cases of pyelitis cystica. Aetiology, pathogenesis, diagnoses, treatment and differential diagnosis are discussed. We recommend follow-up until malignant disease has been excluded.

Papillary transitional cell tumour in the vagina.

A case of non-invasive transitional cell tumours in the vagina in a 62-year-old woman is presented. Earlier, the patient had a left nephroureterectomy and a cystectomy performed due to invasive transitional cell tumours. The tumours in the vagina were located in an otherwise normal stratified squamous epithelium.

[Cervical cancer in Frederiksborg County 1990-1991]. / Livmoderhalskraeft i Frederiksborg Amt 1990-1993.

One hundred and eight patients from Frederiksborg County, Denmark with cervical cancer diagnosed from 1990 to 1993 were analysed concerning type of carcinoma, tumour stage and screening history. The following types of carcinoma were found: 87 (81%) squamous, 5 (5%) adenosquamous, 15 (14%) adenocarcinoma and one (1%) small cell carcinoma. All women aged 23-60 receive a written invitation to participate in the screening programme. Of the 57 patients who had never or only sporadically been screened 23 were outside the target population. Tumour stage was generally higher for the non-screened, i.e. only 57.9% stage I compared to 82.4% for the screened population. In 51 cases the following errors had occurred: seven sampling errors, 21 screening errors, 15 lack of follow-up of abnormal or inadequate smears, six inadequate cryotherapy and two interval cancers.

US-guided fine needle biopsy of solid renal masses--comparison of histology and cytology.

We report on 134 fine needle biopsies in 127 patients with an ultrasound finding suggesting renal malignancy. Biopsy was performed guided by dynamic ultrasound using an 0.6 mm aspiration needle for cytology and an 0.8 mm Surecut needle for histology. The retrieval rate for cytology was 97.8% compared to 79.1% for histology. Sensitivity for cytology and histology was 89.4% and 70.6%, respectively. The specificity of cytology was 85.4% giving a predictive value of a positive result of 91.6%. Specificity and positive predictive value for histology were both 100%. We conclude that fine needle aspiration biopsy from renal masses in our hands carries too high a false positive rate to be clinically safe. We recommend that fine needle histological biopsy replaces the aspiration biopsy in case of renal masses.

Ultrasonically guided histological and cytological fine needle biopsies of the pancreas. Reliability and reproducibility of diagnoses.

In 100 consecutive patients ultrasonically guided histological and cytological fine needle biopsy specimens were obtained from pancreatic lesions using two different needles with an outer diameter of 0.6 mm. Specimens taken by both cytological and histological fine needle biopsy were examined blindly by two pathologists. When related to the final and reliable diagnosis obtained in 57 patients, the predictive value of a malignant diagnosis was 1.00 for both types of biopsy. The predictive value for a benign diagnosis was 0.25 for histological specimens for both examiners and 0.33 and 0.45 for the two evaluations of the cytological specimens. False benign diagnoses seemed to be related to both sampling error and difficulties in interpreting the biopsy specimens. The intraobserver and interobserver kappa values concerning reproducibility of diagnoses were higher for histological specimens (0.80 and 0.74) than for cytological specimens (0.70 and 0.61). Consistent malignant diagnoses, however, occurred more often with cytological specimens (51 cases) than with histological specimens (39 cases) (p less than 0.05) and consistent diagnoses of insufficient material were more common with histological specimens (18 cases v six cases). Cytological fine needle biopsy seems to be the method of choice if only one method is used and a 0.6 mm needle is used.

Nonsurgical treatment of primary hyperparathyroidism with sonographically guided percutaneous injection of ethanol: results in a selected series of patients.

Twelve patients with primary hyperparathyroidism were treated with sonographically guided percutaneous injection of ethanol (96%) into solitary parathyroid tumors verified by biopsy. The patients were all selected for nonoperative chemical parathyroid ablation either because of acute severe hypercalcemic symptoms (four patients), a high surgical risk or an advanced age (four patients), or refusal of a surgical intervention (four patients). Before treatment, the serum concentration of ionized calcium ranged from 1.38 to 2.39 mmol/l (median, 1.59 mmol/l), and after the last treatment the serum concentration ranged from 0.80 to 1.47 mmol/l (median, 1.32 mmol/l) (p less than .001). Normocalcemia was achieved in eight patients, and evident clinical improvement was seen in seven patients. The only complication was a permanent unilateral vocal cord paralysis due to involvement of the recurrent laryngeal nerve. The present study confirms the possibility of percutaneous treatment of hyperactive parathyroid glands. However, the treatment was not found to be beneficial to all patients and hypercalcemia recurred. On the basis of our experience with these patients, we conclude that sonographically guided chemical parathyroidectomy should be considered an alternative treatment to surgery in patients who are not suited for surgical intervention.

Non-prostatic malignant disease mimicking prostatic cancer.

Three patients with pelvic tumours (2 cases of pelvic sarcoma and 1 case of metastatic bronchial carcinoma) presented with symptoms and signs suggestive of prostatic carcinoma. Transrectal ultrasonic scanning with perineal biopsy facilitated the diagnosis. The prognosis of pelvic sarcoma was poor following radiotherapy.

Ultrasound-guided chemical parathyroidectomy in patients with primary hyperparathyroidism: a prospective study.

Twenty of 31 consecutive ultrasound examined patients with primary hyperparathyroidism were selected for treatment with ultrasound-guided percutaneous injection of ethanol (96%) into biopsy-verified solitary parathyroid tumours following a strict protocol with regard to dose, number of treatments and a minimum of 6 months follow-up. Of 18 patients completing the above protocol, a biochemical improvement was observed in 12, of whom eight became normocalcaemic during the follow-up period of 6 months after the last treatment. An obvious clinical improvement was seen in eight of the patients. In four patients, a unilateral vocal cord paralysis was observed, but was permanent in only one patient. Progressive fibrosis of the parathyroid tumours following injections impeded the intraglandular dissemination of ethanol. Another problem noted was the inability of ultrasound to detect multiglandular involvement. We find ultrasound-guided chemical parathyroidectomy an attractive alternative to surgery in patients who are not well suited for surgical intervention. However, the technique has not been fully developed, and in the present study, possible improvements are indicated.

Ultrasound-guided, histological, fine-needle biopsy from suspect parathyroid tumours: success-rate and reliability of histological diagnosis.

Ultrasound-guided, fine-needle tissue biopsies were performed in 60 suspected parathyroid tumours in 55 consecutive patients with biochemically proven hyperparathyroidism. The specimens were randomly arranged and re-read "blind" by two pathologists. The interobserver agreement, corrected for chance agreement, was 0.92 (= kappa coefficient). Twenty-three of the 60 suspect parathyroid tumours were verified histologically following surgery. No diagnostic errors were seen but the percentage of insufficient biopsies from suspect parathyroid tumours or surgically verified parathyroid tumours was high (45 and 47%, respectively). We conclude that a reliable tissue diagnosis can be made by ultrasound-guided, fine-needle tissue biopsy. However, when the material is insufficient for histological diagnosis, we recommend the additional use of ultrasound-guided, fine-needle aspiration for cytology or parathyroid hormone determination.

Diagnostic reliability of histological and cytological fine needle biopsies from focal liver lesions.

In 175 consecutive cases of ultrasonically detected focal liver lesions both cytological and histological fine needle biopsies were performed using two different 0.6 mm needles. The cytological and histological material was evaluated blindly and separately by two examiners, who had no access to clinical data. In 65 cases a reliable final diagnosis as defined by autopsy or surgical biopsy within 6 months could be reached. Eleven cases of benign liver lesions were correctly classified by the two examiners by both cytological and histological fine needle biopsies, resulting in a predictive value of 100% for a malignant diagnosis. The predictive value for a benign diagnosis was 85% for both examiners' evaluation of cytological fine needle biopsies, while it was 73% and 85%, respectively, for histological fine needle biopsies. At reevaluation both sampling error and difficulties in interpretation of biopsies of poor quality were responsible for the false benign diagnosis. The origin of the primary tumour was correctly diagnosed in about 50% of the cases by both techniques. Correct tumour typing could most often be made by both methods in cases of hepatocellular carcinoma, breast carcinoma, colonic carcinoma and small cell carcinoma of the lung.

Histological and cytological fine needle biopsies from focal liver lesions. Intra- and interobserver reproducibility of diagnoses.

In 175 consecutive cases of ultrasonically detected focal liver lesions both cytological (CFNB) and histological (HFNB) fine needle biopsies were performed with two different 0.6 mm needles and evaluated twice and blindly by two examiners. The intra- and interobserver kappa values for reproducibility concerning a malignant diagnosis were higher for CFNB (0.94-0.96) than for HFNB (0.89-0.93). At re-evaluation most inconsistent diagnoses could be related to biopsies of poor quality (CFNB 4 cases, HFNB 13 cases). In three cases (CFNB 2, HFNB 1) false interpretation of the biopsies could have been the cause of inconsistent diagnoses. CFNB resulted in significantly more consistent, malignant diagnoses than HFNB, and CFNB is therefore recommended as the method of choice in cases of a known primary tumour. A morphological diagnosis of a breast carcinoma and of a colonic carcinoma as the primary tumour was better reproduced by HFNB than by CFNB. A diagnosis of a primary liver tumour and of a small cell carcinoma of the lung had a reasonable reproducibility with both methods (kappas greater than 0.60). Other diagnoses were poorly reproduced or occurred infrequently. Both methods are recommended for use in cases of an unknown primary tumour.