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.

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.

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.

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.

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.

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.

A study of plasma CEA by a direct radioimmunoassay method in 1704 cases.

The authors have used an original method of direct radioimmunoassay of plasma CEA for testing plasma of 1704 patients affetected by various neoplastic and non-neoplastic diseases. The percentage of positive results in blood from patients with adenocarcinoma of the gastroenteric tract was 66.8%. The positivity in other non-neoplastic diseases was 2.7%, except for liver cirrhosis and other chronic hepatopathies, which showed 29.6% of positive reactions. The test should be clinically useful in the differential diagnosis of gastro-enteric carcinoma.

[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.

The value of the CEA test in the diagnosis of metastases of adenocarcinoma of the gastroenteric tract.

Of 174 patients previously resected for gastric, colon or rectal adenocarcinoma, 75 had distant metastases at the time of the first examination and provided information on the specific characters of different types of tumors as regards CEA sensitivity. The remaining 99 cases, all without clinical evidence of disease, showed positive CEA levels in 26 and negative CEA levels in 73. Of the 26 CEA-positive cases, 24 showed clinical signs of metastases in a period of times varying from 1 to 11 months. The remaining 2 cases, although CEA positive at subsequent tests, did not develop clinical metastases and have been disease-free for 5 years after the first test. Of 73 CEA-negative patients, 30 developed metastases: in 17 the clinical appearance of recurrences was preceded by a positive CEA test, while in 13 the CEA test remained negative even with the presence of disease. The remaining 43 cases are still CEA negative and without metastases from 44 to 51 months from the first examination. Altogether, in 22 cases CEA was negative, but the clinical evidence of recurrences was positive, and in these cases 63.6% were undifferentiated carcinomas; 2 patients were CEA positive but without signs of evident metastases.

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.

Intravenous administration of BCG in advanced melanoma patients.

From June 1975 to August 1977, 19 patients with distant metastases of malignant melanoma of the skin that were no longer responsive to chemotherapy were treated with BCG given intravenously. A single dose of lyophilized Pasteur BCG ranging from 2 X 10(7) to 3 X 10(8) viable units was given in 500 ml of saline infused in 5 to 6 h. Seven of the 16 evaluable patients benefited from treatment; 3 showed an objective regression of more than 50% of the original tumor volume, and 4 an arrest of tumor growth. The objective regressions lasted from 2 to 5 months, and 1 case had an arrest of tumor growth for 29 months. The regression rate was related to the BCG dosage: 2 X 10(8) viable units appears to be the dosage that gives severe but reversible toxicity and is able to induce objective regression. The most responsive lesions were skin and subcutaneous deposits (5 of 7) and lung metastases (1 of 4). Toxic effects seem to be related to the number of bacilli injected. In the group of 10 cases treated with less than 10(8) units, toxicity was modest: 4 patients had fever (up to 38.5 degrees C) that lasted a few days, and in 3 cases it was associated with shivering during the infusion period and weakness. One case only had vomiting and jaundice. Toxicity was severe in the 9 patients that were treated with a dosage higher than 10(8): patients had fever and weakness for at least 4 days and shivering during the infusion. Two had adrenal insufficiency and 7 had liver enlargement and jaundice with return to normality by day 21. In the whole series 8 patients had leucopenia and 5 thrombocytopenia for 2 to 3 days: only 1 patient required blood and platelet transfusion. No significant variations in immunoglobulin levels were observed. No variations of PPD or BCG skin tests were observed after treatment. Three patients expired; the first treated with 6 X 10(7) unit, had an intercurrent disease (autopsy showed a heart infarction); the second, treated with 1.8 X 10(8), showed a rapid growth of lung metastases and died 15 days after treatment; the death of the third patient was probably due to anaphylactic shock. All 3 patients had been previously treated with BCG, given by scarification or intranodular injection.

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.

[Immediate and long-term results of anterior resection in tumors of the rectum and sigmoid (author's transl)]. / Risultati immediati e a distanza della resezione anteriore nei tumori del retto e del sigma

127 anterior resections for adenocarcinoma of the rectum and sigmoid were performed at the Istituto Nazionale Tumori from 1950 to 1972. In 48% of cases the site of tumor was upper rectum and recto-sigmoid. The surgical mortality rate was 4,7%. Complications were observed in about 40%, fecal fistula being the most frequent. It seems correlable with the anastomotic technique and is significantly reduced by colostomy. Local failure occurred in 8,3% of patients with maximum rate (28,5%) for tumors located under 12 cm from the anus. The 5-year over-all survival rate was 73,3% with substantial differences according to the extent in initial disease.

[Topical ampicilin and local infectious complications in oncological surgery]. / Ampicillina topica e complicanze infettive locali in chirurgia oncologica

420 consecutive patients having clean surgical operations were studied: 210 of them, selected at random, received 0.5-1 g of ampicillin into the wound before closure, the remainder being controls. Patients were examined for wound infection during the first postoperative week, in line with the opinion that topical antibiotic treatment can afford significant protection against wound infection caused by peroperative contamination. Wound infection has been defined as a local inflammation (redness and hyperthermia), usually with fever and/or discharge of pus. In some doubtful cases, a longer observation period was necessary to obtain a correct interpretation. Four out of 210 clean wounds (1.9%) became infected in the patients receiving ampicillin compared with 12 out of 210 (5.7%) in the control group. The difference could have arisen by chance less that one in a hundred times (p less than 0.01). It is our opinion therefore that after clean operations, the higher the risk of local infection, the more effective the topical use of antibiotics.

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.

[Direct radioimmunological determination of plasma CEA in 1704 patients]. / Dosaggio radioimmunologico diretto del CEA plasmatico in 1704 pazienti.

An original technique for the direct radioimmunological measurement of plasma CEA has been prepared. Compared to the other in use, this has the advantage of a very low incidence of false positivity. 1704 patients make up the series: the percentage of positivity in 247 suffering from gastroenteric adenocarcinoma was 66.8%, in 60 with lung cancer 30%, in 243 with malignant tumours in various sites 7.4%, in 199 with chronic liver diseases 29.6% while in 598 cases of other non-neoplastic diseases it was only 2.5%. 212 patients who underwent radical surgery for gastroenteric adenocarcinoma were also followed up and the test provided early diagnosis of the clinical re-onset of the neoplastic lesion. It is considered that plasma CEA measurement represents a useful aid to the clinician althouth it cannot be employed at present to screen gastroenteric adenocarcinomas.

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.