Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study.

BACKGROUND: The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. PURPOSE: To evaluate gender differences in clinical presentation and outcome of CaS. METHODS: Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. RESULTS: Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p = 0.002, and 3.7%, p = 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p = 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p = 0.044; 6.7% vs 31.5%, p = 0.001; 50.9% vs. 26.7%, p = 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p = 0.04), but no differences in terms of PFS (p = 0.51) and OS (p = 0.64) were found between gender. CONCLUSIONS: In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.

Diagnostic yield and safety of transbronchial lung cryobiopsy for diffuse parenchymal lung diseases diagnosis: Comparison between 1.7-mm and 1.9-mm probes.

PURPOSE OF THE RESEARCH: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. METHODS: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. PRINCIPAL RESULTS: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. CONCLUSIONS: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Pathophysiology of light phenotype SARS-CoV-2 interstitial pneumonia: from histopathological features to clinical presentations.

Little is known about the light phenotype of SARS-CoV-2 pneumonia, which behaves in an unusual way, unlike other known respiratory diseases. We believe that the histopathological features of early COVID-19 could be considered the pathophysiological hallmark of this disease. Lung cryobiopsies show almost pristine alveoli, enlarged/hyperplasic alveolar capillaries along with dilatation of the post capillary pulmonary venules. Hypoxemia could therefore be explained by a reduction of the normal V/Q ratio, due to blood overflow around well ventilated alveoli. This could clarify typical manifestations of type L COVID-19, such as happy hypoxemia, response to awake prone positioning, response to PEEP/CPAP and platypnea orthodeoxia.

Clinical analysis of multiple primary malignancies in the elderly.

BACKGROUND: Cancer incidence raises progressively during life span; it is estimated that by the year 2030 almost 70% of all neoplasms will occur in people over 65 years old. As carcinogenesis is a multistep, time-requiring process, it is expected that as people live longer they are more likely to develop cancer, and therefore, the prevalence of multiple primary malignancies (MPM) is destined to increase with age. PATIENTS AND METHODS: Records of all consecutive cancer patients referred to our center from January 2004 to January 2007 were reviewed. We chose the definition of MPM proposed by Warren and Gates. Multiple malignancies were assessed for elderly (>or=70 years old) and younger patients. t-Test and Mc Nemar test were used; subgroup analysis was also performed according to age stratification. RESULTS: A total of 1,503 consecutive patients were considered; 566 were 70 years old or more (mean age 76.5 years, range 70-96 years) and 878 were younger (mean age 57 years, range 18-69 years). The prevalence of multiple malignancies in the elderly people versus younger ones was 15% and 6%, respectively (P = 0.001). As far as the elderly population is concerned, 21% (56/271) of males compared with 14% (42/295) of females had developed MPM; no significant difference was found between the subgroups with MPM or not as far as age (P = 0.16), comorbidities (P = 0.79), medications (P = 0.76), CIRS-G score and index (P = 0.47, P = 0.54), and PS (P = 0.93) are concerned. Most frequent associations among cancer types were prostate with lung (10/87, 11%), prostate with colorectal cancer (10/87, 11%), and smoking-related cancer, namely lung and head and neck cancer (X/Y, 6%). CONCLUSIONS: Elderly patients are more likely to develop MPM compared to younger ones. Significant cancer association according to field cancerogenesis concept was the one of smoking-related cancer; other MPM patterns were apparently a random phenomenon.

[Pathophysiology and prevention of contrast-induced acute renal failure]. / Fisiopatologia e prevenzione della insufficienza renale acuta da mezzo di contrasto.

Although the infusion of iodinated contrast media in diagnostic and interventional procedures may cause acute renal failure (ARF) especially in older or diabetic patients with preexisting nephropathy, these procedures are often unavoidable. Contrast medium-induced ARF is defined as an increase in serum creatinine of 0.5 mg/dL or a 25% or greater relative increase from baseline within 72 hours of iodinated contrast medium infusion. Because it is often very difficult to employ alternative diagnostic procedures, it is mandatory to adopt prophylactic protocols to prevent radiocontrast nephropathy. Renal hemodynamic lesions leading to medullary hypoxia, oxygen free radicals inducing tubular cell alterations, and parenchymal vasoconstriction are the main factors in the pathogenesis of contrast-induced ARF. Among the many proposed protocols to prevent contrast-induced renal toxicity, the most effective procedure is hydration with 1 mL/kg/h of isotonic saline solution in the 12 hours before and after contrast medium infusion. Promising results in terms of cardiac and renal protection have been reported in a recent trial with the use of high-dose N-acetylcysteine acting as an oxygen free radical scavenger: an intravenous bolus of 1200 mg N-acetylcysteine was given before coronary angiography followed by 1200 mg orally twice a day for 48 hours after the procedure. The protective effect seemed to involve not only the kidney: the drug was found to induce a significant reduction of the necrotic area in myocardial infarction.

Do elderly cancer patients achieve an adequate dose intensity in common clinical practice?

BACKGROUND: Elderly patients rarely receive adequate dose intensity (DI) using conventional regimens. Possible causes are improper patient assessment, the chemotherapy (CT) regimen chosen, the number and severity of comorbidities, patient compliance and physician experience. To explore this issue, DI was retrospectively analyzed in elderly patients treated with conventional CT regimens for advanced solid cancer. PATIENTS AND METHODS: Patients > or =69 years were evaluated. All patients had metastatic solid tumors. Comorbidities, performance status (PS), toxicities, number of CT cycles, dose reduction and discontinuation of treatment were recorded. Relative DI (RDI) was calculated and regressed against these parameters. RESULTS: 108 patients were eligible. The most frequent diagnoses were: lung, head-and-neck and colorectal cancer. In 48 patients (44%), their initially scheduled treatment was modified. Mean RDI was 79% (range 19-100%, SD 20.6). Grade 3/4 non-hematological and hematological toxicity occurred in 27 (35/130) and 8% of patients (11/130), respectively. In regression analysis, RDI was significantly associated with hematological toxicity. RDI affected response rate but not overall survival. CONCLUSIONS: RDI is significantly affected by toxicity. These data suggest the importance of the treatment schedule and patient selection as predictorsof adequate treatment. Some non-ratable variables, however, might also play a role regarding the dose intensity delivered.

[Sepsis, acute renal failure and multiple organ dysfunction syndrome]. / Sepsi, insufficienza renale acuta e "multiple organ dysfunction syndrome".

The so-called systemic inflammatory response syndrome (SIRS ) represents the cellular inflammatory and neuroendocrine systemic reaction in response to many adverse events. epsis is defined as IR induced by bacterial, mycotic or viral toxins. The circulating toxins deriving from the bacterial wall can activate the septic cascade that induces many systemic reactions involving the activation of the cellular immunity, complement and coagulation system. The endothelial cell is the target of the systemic phlogistic reaction; its stimulation is followed by the production of many vasoactive paracrine and systemic agents. In this context, local and systemic cytokine production plays a major role in inducing the septic cascade, which although meant to be a phlogistic defense reaction, can often become an uncontrolled and dangerous inflammatory reaction. The sepsis-derived lesions can involve many organs and apparatus leading to the picture of sepsis syndrome. Sepsis syndrome often induces severe pulmonary lesions with a picture of acute respiratory distress syndrome (ARDS ). The combination of acute renal failure and sepsis is associated with a high mortality rate, namely in patients with a nitric oxide-induced systemic reduction in peripheral vascular resistances and septic shock. The toxinemia can also induce myocardial damage with a reduction in cardiac performance. Therefore, septic patients who have a combination of pulmonary, cardio-vascular, renal and cerebral lesions present with the picture of multiple organ dysfunction syndrome, that can increase mor-tality to > 0%.

Randomized comparison of vaporizing electrode and cutting loop for endometrial ablation.

OBJECTIVE: To compare endometrial ablation using a vaporizing electrode with resection using a standard cutting loop, evaluating distension fluid absorption, operating time, and ease of procedure. METHODS: Premenopausal menorrhagic women with normal hysteroscopic and endometrial biopsy findings were allocated randomly to endometrial vaporization (n = 47) or resection (n = 44). Distension medium deficit, operating time, and degree of difficulty of the procedure were determined at surgery. Menstrual pattern of women in both groups was also assessed after 1-year follow-up. RESULTS: Mean +/- standard deviation (SD) distension fluid deficit was 109+/-126 mL in the vaporization and 367+/-257 mL in the resection group (mean difference 258 mL; 95% confidence interval 175, 341 mL; P < .001, unpaired t test). Mean +/- SD operating time was, respectively, 9.2+/-3.1 minutes versus 10.7+/-2.5 minutes. The surgeon classified intraoperative difficulties as none in 32, minimal in 11, moderate in four, and severe in none in the vaporization group, and 17, 14, seven, and six in the resection group. Menstrual pattern at 1 year in the former group was amenorrhea in 17 (36%) cases, hypomenorrhea or spotting in 20 (43%), normal flows in 10 (21%), and menorrhagia in none compared with, respectively, 21 (48%), 14 (32%), seven (16%), and two (5%) in the latter group. CONCLUSION: Endometrial ablation with the vaporizing electrode limited fluid absorption compared with resection by the standard cutting loop. Long-term effects on uterine bleeding were similar.

Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding.

OBJECTIVE: To compare the effect of a levonorgestrel-releasing intrauterine device with that of endometrial resection on menstrual bleeding, patient satisfaction, and quality of life in menorrhagic women during 12 months of follow-up. METHODS: Seventy premenopausal women with dysfunctional uterine bleeding were enrolled in a prospective, open, parallel-group, controlled trial. They were randomized to either insertion of an intrauterine system releasing 20 micrograms/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The women were evaluated at baseline, and thereafter, uterine bleeding was assessed monthly with a pictorial blood loss assessment chart. Clinical gynecologic examination was performed bimonthly, and the hematologic variables were measured at 6 and 12 months. On the latter occasion, the women were requested to rate the degree of satisfaction with the effect of their treatment and to complete the Short Form 36 General Health Survey questionnaire. RESULTS: Recurrent menorrhagia was observed at 12 months in four women in the intrauterine device group (including two with partial expulsion of the device) and in three women in the resection group. Compared with baseline values, at 1 year, the pictorial blood loss assessment chart score was reduced by 79% in the former group and by 89% in the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the women with an intrauterine device compared with 71% who underwent endometrial resection. The degree of satisfaction with treatment was high in both groups, with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine device group versus 33 of 35 (94%) in the resection group. Health-related quality of life perception was not significantly different in the two treatment groups. CONCLUSION: Somewhat less satisfactory results were obtained with a levonorgestrel-releasing intrauterine system compared with endometrial resection for dysfunctional uterine bleeding at 1 year of follow-up.

Paracervical anesthesia for outpatient hysteroscopy.

One hundred seventy-seven women aged 41 +/- 8 (mean +/- SD) years, referred for evaluation of excessive uterine bleeding, were enrolled in an open-label randomized trial to evaluate the efficacy of local anesthesia before hysteroscopy in an outpatient population. The patients underwent hysteroscopy and endometrial biopsy with paracervical block by 10 mL of 1% mepivacaine hydrochloride solution (n = 87) or no local anesthesia (n = 90) and assessed lower abdominal and pelvic pain according to a 10-point linear analog scale. The mean +/- SD pain score was 4.5 +/- 2.0 at hysteroscopy and 5.2 +/- 2.1 at endometrial biopsy in the 87 subjects given a paracervical block versus 4.9 +/- 2.2 and 5.7 +/- 2.4 in the 90 women not given local anesthesia, without statistically significant differences. Paracervical anesthesia for routine outpatient hysteroscopy in premenopausal women may be superfluous.

Preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels as prognostic indicators in resected non-small cell lung cancer.

In 62 patients affected by resectable non-small cell lung cancer (NSCLC) submitted to radical surgery we evaluated the prognostic significance of CEA, NSE, SCC, TPA, and CYFRA 21.1 serum levels at diagnosis, as well as the predictive ability of these tumor markers with respect to histological type and pathological stage. The group was composed of 56 male and 6 female patients; the median age was 62 years (range 29-73 years). Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinoma; with regard to pathological stage, 32 patients had stage 1, 4 patients stage II and 23 patients stage IIIA disease. A good predictive ability with respect to histological type was obtained with SCC serum levels; as for pathological stage, TPA and CYFRA 21.1 were found to have moderate predictive ability. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at diagnosis were reliable predictors of overall survival, high values of these markers being associated with a worse prognosis.

Adenomyosis: a déjà vu?

Adenomyosis is a relatively frequent finding in series of hysterectomies performed for menorrhagia and dysmenorrhea. Evident selection biases of the available studies on adenomyosis have always limited the possibilities of defining the real clinical importance of the condition. Until now the only certain diagnoses have been made by histopathologists on uteri removed at surgery, but recently various sufficiently accurate techniques have been suggested which allow diagnosis on the uterus in situ. With the these methods it might be possible to obtain correct information on the epidemiologic characteristics of adenomyosis and to clarify whether it has a pathogenic role in unexplained ovulatory menorrhagia and juvenile dysmenorrhea. Furthermore, resectoscopic treatment has been proposed in some mild forms of adenomyosis to avoid hysterectomy, whereas it seems improbable that medical treatment can offer a definitive solution. The adoption of standard histologic criteria for adenomyosis seems important. Until this is done, it will be difficult to establish whether adenomyosis is really a disease or merely a paraphysiologic condition.

Pregnancy at forty and over: a case-control study.

We compared obstetric prognosis in 327 women > or = 40 years old (148 nulliparas, 279 multiparas) with 20-30-year-old matched controls who delivered at our department between 1988 and 1990. Gestational diabetes and chronic hypertension were the only more frequent antepartum complications in cases than controls (2.4% vs. 0.3% and 3.4% vs. 0.3%, respectively). There were more premature deliveries in cases than controls (19% vs. 8%) but no difference in postdate deliveries. Cesarean section was more frequent in cases than controls in both nulliparas (64% vs. 30%) and multiparas (43% vs. 12%). Incidence of abdominal delivery for acute obstetrical indications was not increased in older gravidas. Significant differences were observed in low birthweight (17% vs. 5%) and 5-min Apgar score < 7 (8% vs. 2%). Most of the abnormal Apgar scores were recorded after cesarean section; values for vaginally-delivered infants were comparable in older and younger women. Perinatal mortality was similar in the two groups.

GnRH agonists before surgery for uterine leiomyomas. A review.

OBJECTIVE: To clarify whether preoperative treatment with gonadotropin-releasing hormone (GnRH) agonists offers substantial advantages to patients undergoing conservative or definitive surgery for uterine leiomyomas. STUDY DESIGN: A review of data from the most recent English-language literature. RESULTS: Inducing amenorrhea in patients with heavy menorrhagia and severe sideropenic anemia before both conservative and definitive surgery for uterine fibroids raises hemoglobin and hematocrit values to within the normal range, limits homologous blood transfusions and enables operations to be scheduled with the patients in better condition. A temporary 30-50% reduction in mean uterine volume theoretically may convert an abdominal into a vaginal hysterectomy in "borderline" cases or sometimes allow a transverse instead of longitudinal abdominal incision. No trial has yet demonstrated "clinically" significant reductions in operating time, operative blood loss or postoperative morbidity in patients undergoing myomectomy or hysterectomy after a course of GnRH agonists as compared with those operated on immediately. There seems insufficient scientific evidence to justify the routine use of GnRH agonists before myomectomy at laparotomy, except possibly in the case of extremely bulky uteri. GnRH agonist treatment before hysteroscopic myomectomy induces endometrial thinning, reduces bleeding and mucous debris, and decreases the diameter of submucous leiomyomas, improving visibility and limiting operating time and fluid intravasation. CONCLUSION: The available data seem to support the use of GnRH agonist treatment before surgery for uterine leiomyomas in selected circumstances. Administration of GnRH agonist for only two or three months preoperatively seems to achieve all the advantages of this treatment, limiting side effects and cost.

Abnormal uterine bleeding associated with iron-deficiency anemia. Etiology and role of hysteroscopy.

We reviewed the clinical and histologic records of 61 consecutive premenopausal women with abnormal uterine bleeding and moderate to severe iron-deficiency anemia investigated in a tertiary care and referral center. Excessive bleeding was caused by benign lesions in 67% of the cases and by anovulation in 25% and was unexplained in 8%. Hysteroscopy revealed an organic intrauterine lesion (submucous myomas in 38%, endometrial polyps in 13%, submucous adenomyomas in 3%) that could be treated endoscopically in more than half the patients. In populations without nutritional deficiencies, a woman of reproductive age with sideropenic anemia and no other evident cause of blood loss or systemic disease should be considered menorrhagic until proven otherwise. Hysteroscopy should be included in evaluations of abnormal uterine bleeding.

Intensive care of patients requiring open abdomen treatment: a case-series analysis.

BACKGROUND: This retrospective overview examines the management of patients with temporary open abdomen (OA). METHODS: The clinical characteristics and intensive care treatment of 34 consecutive patients with OA (1996-2012) were reviewed. RESULTS: Average age was 61 years, SAPS II score 43, SOFA 8. Two patients had non-contaminated abdomen; 12 had intact gut (only 8 later during stay); 7 repaired gut (only later 4); 13 cutaneous stoma (later 14), and 2 entero-atmospheric fistula (later 8+1 entero-enteral). The median ICU stay was 48 [36-94] days. One quarter of the 2376 ICU-days were classified as severe sepsis/septic shock (antibiotics were given for two thirds of the stay); three quarters were with ventilation; in 95% of days sedatives were given (mainly enterally). Continuous cavity lavage was done in three quarters of days; in 3% of days patients were fasted whereas >20 kcal/kg was given for 74% of days; we fed the gut in 95% of fed-days, in half of them combined with parenteral nutrition. Complications are discussed; mortality was 32.4%, limited to the ICU stay. CONCLUSION: The intensive care of patients with OA is challenging but can achieve better outcomes than expected. Continuous abdominal lavage improves the evacuation of contaminated fluid or debris and, coupled with antiseptics and low antibiotic pressure, reinforces the control of infection. The gut can be used for nutrition (even without gastrointestinal continuity), and long-term light sedation (mainly enteral) with minimal impact on perfusion, ventilation and gut motility.

Endometrial ablation with a vaporizing electrode. I. Evaluation of in vivo effects.

BACKGROUND: To evaluate histologically and histochemically the physical and thermal effects of a vaporizing electrode as compared with a standard cutting loop in the performance of endometrial ablation. METHODS: Operative hysteroscopy was performed on 20 menorrhagic patients immediately before hysterectomy. Part of the posterior uterine wall was treated with a cylindrical, grooved, vaporizing electrode and undamped current set at 200 watts, and part with a standard cutting loop and undamped current set at 100 watts. A mucosal strip of about 1 cm width was left intact between the two treatment areas. Specimens underwent histologic examination after hematoxylin and eosin staining and histochemical assessment of thermal injury was based on detection of the respiratory enzyme dihydronicotinamide adenine dinucleotide diaphorase. RESULTS: The mean (standard deviation) endometrial thickness as determined on the untreated area of the posterior uterine wall was 1.08 (0.36) mm. The mean depth of furrows was 3.10 (0.90) mm with the use of the vaporizing electrode and 3.41 (1.11) mm after passage of the cutting loop. Corresponding values when thermal necrosis beneath the ablated area was assessed by the dihydronicotinamide adenine dinucleotide diaphorase technique were, respectively, 1.80 (0.40) mm and 0.41 (0.20) mm (mean difference, 1.39 mm; 95% confidence interval, 1.19 to 1.59: p<0.001, Mann-Whitney U test). CONCLUSIONS: A vaporizing electrode and a standard cutting loop obtained a similar degree of endomyometrial ablation. However, the depth of the thermal effect of the former electrode was significantly greater. Clinical studies are warranted, also considering the potential limitation of fluid absorption and menorrhagia recurrence when a vaporizing electrode is used.

Endometrial ablation with a vaporizing electrode. II. Clinical outcome of a pilot study.

BACKGROUND: As a vaporizing electrode has been successfully used to treat submucous myomas, we evaluated its safety and efficacy in performing endometrial ablation. METHODS: Forty consecutive women with established menorrhagia with (n=26) and without (n=14) submucous myomas were enrolled in a prospective, noncomparative, pilot study. Hysteroscopic endometrial vaporization was performed with pure cutting current set at 200 watts. RESULTS: All procedures were completed without complications. Median (interquartile range, IQR) fluid deficit was 90 (0-200) ml and median (IQR) operating time 10 (7-12.5) min. A significant correlation was observed between operating time and fluid absorption (Spearman's test by ranks, r=0.47; p=0.002). The degree of difficulty of the operation was classified as none on 28 (70%) occasions, mild on 11 (27.5%) and moderate on one (2.5%). After a mean+/-s.d. follow-up of 20.3+/-2.4 months, amenorrhea or spotting were reported by 23 (57.5%) subjects, hypomenorrhea by 10 (25%), normal flows by six (15%), and menorrhagia by one (2.5%). The median (IQR) menstrual score calculated according to a pictorial blood loss assessment chart dropped from 282.5 (199-383) to 0 (0-15) (p<0.0001). Six (15%) subjects were very satisfied with the effect of surgery, 30 (75%) satisfied, two (5%) uncertain, one (2.5%) dissatisfied and one (2.5%) very dissatisfied. CONCLUSIONS: The vaporizing electrode seems to combine the benefits of the cutting loop (speed, efficacy and possibility of removing myomas) and the roller-ball electrode (safety and limited fluid absorption) while avoiding their respective disadvantages, and may be considered an interesting alternative in the hysteroscopic treatment of menorrhagia.