Blood lactate in mild and moderate ARDS secondary to SARS COV 2.

BACKGROUND AND OBJECTIVES: Elevated blood lactate levels are associated with poor outcome in several critical conditions. Patients with SARS-CoV-2 rarely develop hyperlactatemia. The purpose of this study is to evaluate the trend of lactatemia in patients affected by mild/moderate SARS-Co V-2-ARDS and if it affected prognosis. METHODS: We analyzed blood lactate levels in thirty-eight patients with severe SARS-CoV-2 infection admitted to COVID Care Unit of Santa Maria delle Grazie Hospital, Pozzuoli. RESULTS: Twenty patients survived and were discharged at home and 18 patients died. Despite severe hypoxia that affected all patients enrolled, T0 lactate was within normal values. All survivors showed a significant increase in lactate concentration the day prior to clinical improvement. In not-survivors levels of lactate did not increase significantly. CONCLUSION: In our study, patients who survive SARS CoV-2 ARDS have a fleeting increase in lactate, which precedes clinical improvement by one day.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

PURPOSE: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. RESULTS: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. CONCLUSIONS: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

Sinusal localization of nodal micrometastases is a prognostic factor in breast cancer.

BACKGROUND: Breast cancer micrometastases are frequently found during pathological examination of sentinel lymph nodes and complete axillary lymph node dissection. Despite this, their clinical relevance is still debated. The aim of this study is to investigate features that affect disease-free survival (DFS) and overall survival (OS) in patients with nodal micrometastases from breast cancer. MATERIAL AND METHODS: We retrospectively investigated the outcome of 122 patients with nodal micrometastases from breast cancer followed up for 60 months. RESULTS: At univariate analysis, worse DFS was related to features of primary tumor (multifocality P = 0.002; size >2 cm, P = 0.022; grade P = 0.022; absence of estrogen P < 0.001 and progesterone P < 0.001 receptors; HER-2 overexpression P = 0.006; vascular invasion P = 0.039; proliferative fraction > or =20% P = 0.034) and micrometastases (sinusal localization P = 0.010). Among the above-mentioned features, two were strongly associated with worse DFS in the multivariate model, i.e. negative receptorial status [hazard ratio (HR) = 11.24, 95% confidence interval (CI) 4.06-31.09; P < 0.001] and sinusal localization of micrometastasis (HR = 3.66, 1.18-11.36; P = 0.025). The OS was influenced by multifocality (P < 0.001) and receptor status (P = 0.005). CONCLUSION: Our results indicate that in patients affected by breast cancer, in addition to the well-known pathological features of primary tumor, sinusal localization of micrometastasis strongly impacts on the prognosis.

Outcome of T1N0M0 breast cancer in relation to St. Gallen risk assignment criteria for adjuvant therapy.

T1N0M0 (stage I) breast cancer (BC) has been increasing in recent decades but the optimal adjuvant approach remains controversial. To assess the outcome of BC patients stratified and treated with multimodal therapies according to St. Gallen consensus meeting recommendations, we retrospectively evaluated an unselected cohort of T1N0M0 BC patients, with respect to the St. Gallen criteria. At a median follow-up of 5 years, the recurrence rate, recurrence-free survival and overall survival were 7%, 94% and 96% respectively, and 60% of relapses were locoregional. No statistically significant difference was observed between T1a,b/T1c groups, or among risk categories (high/intermediate/low). The very low rate of distant recurrences even in patients with unfavorable prognostic factors seems to support the use of adjuvant systemic therapies but better prognostic and predictive factors are strongly needed for this subset of patients.

Oral biopsy. A prospective study on 286 consecutive procedures.

AIM: The aim of the present study was to survey oral biopsy procedures, with particular regard to the incidence of adverse events, patients experience and adequacy of the sample. METHODS: This prospective survey was conducted by collecting detailed information from consecutive patients undergoing oral biopsy; data were obtained on the same day of oral biopsy and after 7 days. RESULTS: Data on 286 procedures were collected. About half of the patients had a relevant medical history and were taking one or more medications. During biopsy, the majority of patients (83%) felt no pain, the others reported mild discomfort. Intraoperative adverse events occurred occasionally (4.5%) and were always easily resolved; 18% patients admitted taking painkillers in the days following surgery. The pathologist was always able to make histological diagnosis, although some samples did not include healthy mucosa (32%) or connective tissue (11%). CONCLUSION: Oral biopsy is a safe and well accepted surgical procedure.

[Sentinel lymphnode: surgical standard in breast cancer]. / Linfonodo sentinella: standard chirurgico?

Evaluation of the sentinel lymph node (SLN) is capable of avoiding dissection in a high percentage of node negative patients (> 90). It is essential that "useless" treatment not be performed as the negative collateral effects are not justifiable and furthermore present financial laws do not reimburse dissections carried out in the absence of node disease. The intraoperative evaluation of the SL is an extremely expensive procedure, due both to the personnel required and to the time necessary for the patient to remain in the operating room awaiting histology results. In fact, it is far easier to retrieve the SLN in day hospital and to examine the specimen on fixed material and not frozen. Twenty three cases of deferred SLN were evaluated, the results of which were highly reliable because of these, only 3 dissections were performed after an average of 4 days from biopsy. As SL evaluation does not increase the "curability" of the disease but only reduces any eventual complications, we believe it should be restricted to extremely selected and specialistic institutions due to the great economical and organizational cost involved.

Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

PURPOSE: To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS: Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION: HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

Malignant pheochromocytoma in multiple endocrine neoplasia type 2B syndrome. Case report and review of the literature.

A malignant behavior (i.e., distant metastatic spread) has been recorded in 3-4% pheochromocytomas occurring in the context of multiple endocrine neoplasia type 2A syndrome, but has never been documented in patients with the type 2B form. In this report we describe a case of malignant pheochromocytoma arising in the latter syndrome setting. The patient, a white young male, had the full-blown syndrome, including multicentric, bilateral medullary thyroid carcinoma metastatic to regional lymph nodes, mucosal neuromas, digestive ganglioneuromatosis, marfanoid habitus, and bumpy lips. Three and a half years after surgical resection of an apparently benign adrenal pheochromocytoma he developed widespread osseous metastases. The presence of hypertensive crises and high urinary catecholamine excretion rates, coupled to moderate hypercalcitoninemia, normal circulating carcinoembryonic antigen levels, negative whole-body 99mTc-(V) dimercaptosuccinic acid scan, and absence of neck or mediastinal disease by magnetic resonance imaging, proved that the metastases were from his previous adrenal and not thyroid tumor. Furthermore, since the bone metastases strongly accumulated 131I-metaiodobenzylguanidine, several courses of the radiocompound were given, which resulted in an objective, though partial, tumor regression.

Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor.

The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.

Effect of two-4-hydroxyandrostenedione doses on serum insulin-like growth factor I levels in advanced breast cancer.

A number of endocrine treatments for advanced breast cancer seem to affect serum insulin-like growth factor I (IGF-I). The aim of our study was to investigate IGF-I levels in 33 postmenopausal patients with metastatic disease receiving the selective aromatase inhibitor 4-hydroxyandrostenedione: 250 mg (16 patients) or 500 mg (17 patients) i.m. fortnightly. Blood samples were collected before, and at one month and 3 months after the beginning of treatment for radioimmunoassay determinations. The median patient age was 56 and 60 years in the 250 and 500 mg groups respectively. Most patients had a disease free interval > or = 2 years and were oestrogen receptor positive. Objective responses were obtained in 3 patients (complete response, 1) in the 250 mg group, and in 7 patients (complete response, 3) in the 500 mg group. No significant IGF-I variations were seen in the 250 mg group, whereas a significant increase after 3 months (181.57 +/- 84.78 ng/ml versus 272.47 +/- 213.22 ng/ml, p = 0.0032) was observed in the 500 mg group. No IGF-I variations were seen between responsive and unresponsive patients in either treatment group. Our results in the 500 mg group are close to those obtained with aminoglutethimide and seem to agree with the hypothesis of an oestrogen-induced suppression of IGF-I circulating levels.

Comparing core needle to surgical biopsies in breast cancer for cell kinetic and ploidy studies.

The evaluability and reliability of proliferative activity (expressed as 3H-thymidine labeling index, 3H-TdR LI) and ploidy determinations on core needle biopsies were compared with those obtained on surgical material from the same breast cancers. The evaluability of 3H-TdR LI on core needle biopsies was markedly lower than that on surgical material (53% vs 100%), and the association between 3H-TdR LI values in the 16 cases with both evaluable determinations was poor (rs = 0.45). Conversely, determinations of ploidy on core needle biopsy and surgical material provided superimposable results, in terms of evaluability (91% vs 100%) and reliability (rs = 0.99). Further efforts are needed to improve sampling procedures for a reliable assessment of biological markers.

Proliferative activity of primary breast cancer and of synchronous lymph node metastases evaluated by [3H]-thymidine labelling index.

The [3H]-thymidine labelling index ([3H]TdR LI) has been used to evaluate and comparatively analyse the proliferative activity of different tumour lesions from the same patient. The analysis was performed on the primary tumour and its synchronous lymph node metastasis from 210 patients operated on for breast cancer. A direct relation was observed between the proliferative activity of the two different lesions (Spearman correlation coefficient = 0.46, P less than 0.0001), but there was considerable scatter amongst the data. The [3H]TdR LI of primary and of metastatic lesions belonged to the same proliferation classes in only 47% of the cases. Higher or lower [3H]TdR LI values, categorized on the basis of the tertiles of the frequency distribution, occurred in the node metastasis than in the primary tumour in an almost similar percentage of the remaining cases. Menopause, receptor status and pathological features did not affect interlesion kinetic patterns. The prognostic role of the proliferative activity of the two different lesions was investigated on 107 patients with stage II tumours homogeneously treated with surgery and systemic adjuvant therapy. Relapse-free survival at 3 years was significantly affected by the proliferative activity of the primary tumour but not by that of the lymph node metastasis.

Use of monoclonal antibody MBr1 to detect micrometastases in bone marrow specimens of breast cancer patients.

Bone marrow specimens obtained from 121 breast cancer patients immediately after surgery were examined by an immunofluorescence method with monoclonal antibody MBr1 to detect tumour cells undetectable by other diagnostic procedures. 80 women were node-negative and 41 node-positive. In no case could conventional histology demonstrate tumour cells, whereas MBr1 was positive in 20 (16.5%) of the 121 cases. No difference was observed in MBr1 positivity between node-negative and node-positive cases (17% vs. 15%). With regard to clinical outcome (median follow-up 48 months) 27 women relapsed, including 6 of 20 MBr1-positive and 24 of 101 MBr1-negative patients. First distant metastases or death from progression of disease were taken as end-points. Multivariate analysis showed that the additional contribution of MBr1 positivity, after making allowance for other prognostic factors, was negligible.

Monoclonal antibody detection of carcinoma cells in bone marrow biopsy specimens from breast cancer patients.

The possibility of using immunologic methods for detecting metastatic cells in bone marrow samples from breast cancer patients was investigated. The MBr1 monoclonal antibody, which recognizes a membrane antigen on breast carcinoma cells and is unreactive on normal bone marrow cells, seemed to be an adequate reagent for this kind of approach. When human leukocyte suspensions artificially contaminated with mammary tumor cells were tested by MBr1 immunofluorescence, it was demonstrated that the added tumor cells could be specifically discriminated from normal cells and that as little as one tumor cell in 200,000 could be detected. With the same methodology we screened bone marrow biopsies from breast cancer patients with apparently uninvolved lymph nodes at the moment of surgery. Immunoreactive tumor cells were detected by the MBr1 antibody in 17% of N- patients. None of the bone marrow samples showed any evidence of tumor involvement by conventional histologic analysis.

The use of lympho-venous anastomoses to prevent complications from ilio-inguinal dissection.

Lympho-venous anastomoses (LVA) were performed in 30 patients, immediately after the completion of ilio-inguinal dissection for metastatic nodal involvement. This surgical procedure, originally devised to treat post-mastectomy lymphedema from radical mastectomy, was intended in this series of cases to prevent complications from ilio-inguinal nodal dissection. Actually, when compared to another group of 84 patients previously operated on by ilio-inguinal nodal dissection without lympho-venous anastomoses, the series showed a lower rate of local-regional complications (38% vs 65.9%). The mean duration of hospital stay was also reduced (18.5 vs 34.7 days). Distant lymphedema of the lower limb was observed in 7 of 23 patients who had received LVA, whereas in the control group, lymphedema was recorded in 39 of 52 patients who were regularly followed-up (30% vs 75%). LVA should be routinely used, as a useful surgical procedure, to prevent or reduce the occurrence of local-regional complications following ilio-inguinal nodal dissections.

Complications in surgery of the right colon.

One hundred and fifteen cases of right hemicolectomy for cancer or others pathological conditions, operated on over a 5-year period, were evaluated. The overall incidence of complications was high (47%). A more thorough analysis of data showed that infective complications, such as bronchopneumonia (27.8%) and urinary infections (10.4%) markedly affected this incidence. In contrast, there was a much lower incidence of surgical complications mainly wound infection (14.8%) and anastomotic fistulas (4%), the incidence of which was lower than that reported in the literature. Furthermore, the difference between stapled and hand-made sutures, in terms of fistulas, was only 2%, in favour of the former.

Intrahepatic doxorubicin in unresectable hepatocellular carcinoma. The unfavorable role of cirrhosis.

To investigate the relationship between the presence of cirrhosis and the antitumor effects of locoregional chemotherapy with doxorubicin, 16 patients with nonresectable hepatocellular carcinoma (HCC) and satisfactory baseline clinical conditions (Child class A or B, Karnofsky index greater than 70%) were studied. Eight patients had post-necrotic cirrhosis, five had serum HBsAg. The dose of doxorubicin was 0.3 mg/kg body weight/day, given by continuous intracoeliac infusion for 8 consecutive days. Eight patients (six with cirrhosis) died prematurely after the first course of chemotherapy. Six (2 with cirrhosis) responded to therapy; they survived 3-33 months (median: 10). In these patients, the type and severity of drug-related side effects were comparable to those reported for patients treated by intravenous chemotherapy. The implication that in many patients with cirrhosis intrahepatic chemotherapy with doxorubicin may hasten death, lessens our interest in its use for nonresectable HCC. In fact, in Italy these cancers frequently occur in association with cirrhosis.

Delayed cutaneous hypersensitivity reaction to carcinoembryonic antigen in cancer patients.

The delayed cutaneous hypersensitivity reaction to carcinoembryonic antigen (CEA) was tested in 84 patients with different diseases including large bowel adenocarcinoma and breast carcinoma, with or without metastasis, liver cirrhosis and inflammatory or degenerative diseases. Positive skin test to CEA was observed in a small proportion (11%) of the patients tested. No difference in positive skin test reactions was observed in the 6 different groups of patients. Similar delayed cutaneous hypersensitivity reactions were found to various amount of CEA ranging from 0.5 to 25 micrograms. No correlation was seen between the results of skin test and blood CEA levels.

[Percutaneous transhepatic biliary drainage in obstructive jaundice. Report of 19 cases (author's transl)]. / Il drenaggio biliare transepatico percutaneo nell'ittero ostruttivo. Considerazioni su 19 casi.

The development of percutaneous transhepatic techniques of access to biliary tree with the fine needle made possible the wide diffusion of percutaneous biliary drainage. Results of 19 attempts of biliary drainage are presented; success rate in positioning external or external-internal drainage was 79% (92.3% in the last year). The technique employed is described and discussed comparing it with the methods proposed by other authors. Early therapeutic effects and long-term benefits on bilirubin levels and survival were good. Only 2 major complications were observed (hepatic abscess and biliary subcapsular cyst) but they did not require surgery. Cholangiocarcinomas and ilar hepatic metastases appeared to be elective indications to definitive palliative drainage, but pre-surgical or palliative drainage is also recommended in all cases of obstructive jaundice. Careful follow-up and check of patients with the biliary drainage improves the drainage function and reduces the complications.