Facing Trauma and Surgical Emergency in Space: Hemorrhagic Shock.

Although the risk of trauma in space is low, unpredictable events can occur that may require surgical treatment. Hemorrhage can be a life-threatening condition while traveling to another planet and after landing on it. These exploration missions call for a different approach than rapid return to Earth, which is the policy currently adopted on the International Space Station (ISS) in low Earth orbit (LEO). Consequences are difficult to predict, given the still scarce knowledge of human physiology in such environments. Blood loss in space can deplete the affected astronaut's physiological reserves and all stored crew supplies. In this review, we will describe different aspects of hemorrhage in space, and by comparison with terrestrial conditions, the possible solutions to be adopted, and the current state of the art.

Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

Motivations for the recreational use of erectile enhancing medications in urban gay and bisexual men.

OBJECTIVES: Recreational erectile enhancing medication (EEM) use has been associated with a number of health risk behaviours among gay and bisexual men. This study aims to extend previous findings about the associations between recent EEM use and illegal drug use, incident sexually transmitted infections (STIs) and unprotected sex, as well as to report on motivations for EEM use. METHODS: A cross-sectional, street-intercept survey method was used to collect data from 912 gay/bisexual men at two large lesbian, gay and bisexual community events in New York City in 2006. RESULTS: Lifetime EEM use was reported by 28.0% of the men; 17.4% used EEM in the past 3 months. EEM users were more likely to be white and HIV positive. EEM users were more likely to engage in unprotected anal insertive sex with seroconcordant and serodiscordant partners. EEM users who were HIV negative were more likely to report using alcohol and other drugs before and during sex, especially crystal methamphetamine (AOR 18.66; 95% CI 6.82 to 51.02) as well as to endorse incident STIs. The most frequent responses for EEM use were to "add to the fun", "maintain an erection while using a condom" and "to have sex for hours". Men with HIV were 2.93 times (95% CI 1.24 to 6.88) more likely to endorse using EEMs to bareback. CONCLUSIONS: Gay and bisexual men use EEMs to enhance their sexual experiences among other motives. Different motives and correlates emerged by HIV status. Overall, EEM use was correlated with multiple health risk behaviours. EEM users who were HIV negative appear to be at particularly high risk of acquiring HIV.

Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study.

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m(-2)), 5-FU (400 mg m(-2)), leucovorin (40 mg m(-2)) and epirubicin (60 mg m(-2)) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.

Long-term survival in metastatic melanoma patients treated with sequential biochemotherapy: report of a Phase II study.

The overall survival for patients with metastatic melanoma is very poor, with a median survival of 8.5 months. In this Phase II trial, we assessed the efficacy, safety, and tolerability of a sequential biochemotherapy schedule, using dacarbazine as antiblastic agent and immunomodulant doses of interleukin-2 and interferon-alfa. Thirty-one eligible patients with metastatic melanoma received dacarbazine IV as antiblastic therapy and interluekin-2, plus interferon-alfa SC as sequential immunotherapy, for 6 months. Responding and nonprogressing patients were subsequently maintained on immunotherapy treatment for further 6 months. Twenty-nine patients had an adequate trial, and were assessable for both response and toxicities, with a median follow-up of 49 months. The overall response rate was 52 percent (3 CR and 12 PR), SD was 8 (27 percent) and PD were achieved in 6 patients (21 percent). The median survival duration of responders was 28 months, significantly longer (p < 0.001) than the 16 months of nonresponders. Therapy was well tolerated and produced a significant improvement in progressive-free survival. Further studies, thus, are recommended for larger groups of patients not only to confirm these results, but also to apply this biochemotherapy regimen as adjuvant postsurgical treatment in early stages of malignant melanoma.

Management of true splenic artery aneurysms. Two case reports and review of the literature.

Few series of splenic artery aneurysms (SAA) have been reported, but today asymptomatic SAA are detected with increasing frequency. Their importance lies from their potentially fatal consequences as life-threatening hemorrhage. SAA management still remains controversial as reported in this review. Our 2 patients treated with resection of the aneurysms, both located in the middle third of the splenic artery. Some authors demonstrated that when splenic artery has been ligated (or embolized) and the patients remain anatomically splenic, they may not retain any splenic function. Laparoscopic SAA ligation repair appears to be optimal and useful for aneurysms protruding from the pancreas and it is gaining interest because clinical recovery is rapid with a poor morbidity and economic and cosmetic advantages. Transcatheter embolization too offers a temporary control in urgency to stop hemorrhage and go back at later date to make much better elective operation. Endovascular interventions as percutaneous embolization has recently gained popularity: it offers a safe alternative or adjunctive therapy to traditional surgery. We hope in the future instrumentation will likely improve so that this procedure can be done percutaneously by development of prosthetic devices in the 21th century.

Weekly gemcitabine plus Epirubicin as effective chemotherapy for advanced pancreatic cancer: a multicenter phase II study.

The current role of chemotherapy in pancreatic carcinoma is limited, and progress in the treatment of this disease represents a significant challenge to medical oncology. The most promising drug under study is gemcitabine, a relatively new antimetabolite that represents an attractive candidate for combination chemotherapy because of its excellent side-effect profile and the absence of overlapping toxicities with other chemotherapeutic agents. Combined administration of gemcitabine and anthracyclines could result in the induction of DNA breaks that are not easily repaired by the cell's machinery, thus enhancing the apoptotic signals triggered by these lesions. Forty-four patients with locally advanced and/or metastatic pancreatic adenocarcinoma were enrolled in this multicenter study. Patients received Epirubicin 20 mg m(-2) for 3 weeks followed by 1 week of rest (1 cycle) and gemcitabine 1000 mg m(-2) after Epirubicin on the same day. All were assessable for toxicity and response, 11 patients responded to treatment with one complete response and 10 partial responses, for an overall response rate of 25%. Median survival was 10.9 months (range, 2-26 months). Therapy was well tolerated, with a low incidence of haematologic grade >2 toxicity. A total of 12 of 27 (44.4%) eligible patients attained a clinical benefit response. Our findings suggest that the gemcitabine-epirubicin schedule is active and well tolerated in patients with advanced pancreatic cancer.

Raltitrexed plus oxaliplatin as first-line chemotherapy in metastatic colorectal carcinoma: a multicentric phase II trial.

For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and oxaliplatin (L-OHP), have recently shown interesting results. Preclinical and clinical studies suggest that this combination, because of its favorable toxicity profile, high response rate and convenient schedule of administration, can be administered successfully in this disease. In our phase II study, 37 non pre-treated patients with metastatic colorectal carcinoma were treated with TOM (3 mg/m(2)) and L-OHP (130 mg/m(2)) every 3 weeks. In total, 222 cycles were administered; all patients received at least 2 cycles (median 6, range 2-8). There were two complete and 14 partial responses for an overall response rate of 43% (95% CI 27-69%). The median time to response was 2.5 months (range 2-4) and the median duration was 10.3 months (range 5-18). Twelve of the 23 (52%) patients with symptomatic colorectal cancer were classified as clinical benefit responders for at least 4 weeks during the study period. Treatment was well tolerated, and both acute, essentially hematologic, and cumulative hepatic and neurologic toxicities were manageable and reversible. Response rate and toxic effects observed during this study warrant additional studies comparing this TOM-L-OHP regimen with CPT-11 and/or capacitebine-containing regimens in metastatic colorectal carcinoma.

[Genetic anomalies of pancreatic carcinoma and clinical applications]. / Le anomalie genetiche del carcinoma pancreatico e le applicazioni cliniche.

Pancreatic cancer is a dismal disease. The 5-years overall survival ranges from 1% to 5%. Surgery is the only curative treatment available. Survival of selected patients with small lesion (< 2 cm) confined to the pancreas is improved to 19-41%. Presently the major effort is on studies of the cancer development phenomena to improve detection of patients with early lesions. The analysis of oncogene and tumor-suppressor gene activation may enable us to better define and cure this disease. Molecular genetic new tecnquiques performed on pancreatic juice, duodenal juice and stool, probably are the most promising new approach for early diagnosis of pancreatic cancer. This could be the right path to diagnose pancreatic malignant lesions at a curable stage, and to discriminate patients with a more favourable prognosis candidates to be submitted to adjuvant therapy with a curative intent, and also to discriminate real pancreatic cancer from patients with chronic pancreatitis.

Improved survival in small pancreatic cancer.

BACKGROUND: Although the incidence of pancreatic cancer is relatively low compared with other tumors (2.4%), the death rate is high. Tumor detection and treatment at an early stage is necessary to improve the poor prognosis of patients, as is demonstrated by some reports showing a 5-year survival rate varying between 19 and 41% for patients undergoing radical pancreatectomy with the highest survival in patients with small tumors. METHODS: In our study we retrospectively reviewed the histologic and demographic data of 596 patients who were admitted to the surgical units of the Careggi Hospital (University of Florence-AOC of Florence) between 1988 and 1994 with the incoming diagnosis of pancreatic cancer. RESULTS: Results are reported as the mean +/- standard deviation. The postoperative survival rate was calculated by the Kaplan-Meier method and statistical analysis was performed by the log rank test (significance p < 0.05). 247 patients had surgery, 110 with a curative intent. Postoperative mortality was 5.45%. The crude 5-year survival rate for patients who underwent curative surgery was 16.36% (18 patients), but for patients with small lesions confined to the pancreas (T1N0M0, 29 patients) this was even 31.03% (9 patients; p < 0.01, chi2 test). CONCLUSIONS: Our results indicate that it seems reasonable to consider these cancers as 'small', with survival reported in literature from 35 to 41%, so they probably represent the only curable condition at the present time.

Primary leiomyosarcoma of the pancreas: a case report and review of literature.

Primary leiomyosarcoma of the pancreas is a rare tumor for which only 21 reports appear in the world literature. We describe an additional case of pancreatic leiomyosarcoma in a 76-year-old man, who complained of persistent high fever. Histologic examination revealed a pleomorphic spindle cell tumor. Reactivity for muscle-specific actin, alpha-smooth muscle actin, and basement membrane components, along with negative staining for epithelial and neural markers, were consistent with a smooth muscle sarcoma. The patient died of disease 1 year after complete surgical excision. This report highlights the need to use a complete antibody panel in order to accurately immunophenotype pleomorphic malignant tumors of the pancreas. A review of the cases compiled in the literature indicates that pancreatic leiomyosarcoma, like its counterpart arising in deep soft tissues, is an aggressive neoplasm characterized by short survival and a high rate of metastases.

[An angiogenesis study of Dukes' B colonic tumors]. / Studio sull'angiogenesi nei tumori colici Dukes' B.

PURPOSE: To evaluate the angiogenesis in Dukes' B colon cancer. PATIENTS AND METHODS: In 60 patients (age, 39-75 years), the microvessel density and the relationship between the angiogenesis and other histologic features were retrospectively evaluated. In an ongoing prospective study, 25 patients have been enrolled to determine the possible therapeutic implications of VEGF quantitative analysis. RESULTS: The retrospective portion of this study confirms the prognostic value of the angiogenesis in terms of recurrences and survival. At present, no conclusions can be drawn from the prospective portion of the study.

[On the subject of pancreatic ductal carcinoma]. / In tema di carcinoma duttale pancreatico.

Pancreatic cancer is a dismal disease. The 5-year overall survival ranges from 1% to 5%. Surgery is the only curative treatment available for this cancer, but it is indicated only in selected patients with a less than 4 cm tumor. In these patients, survival rate is about 30%. We have considered several aspects: the very difficult early diagnosis, the correct diagnostic flow chart, actual surgical procedures and new trends in biologic and genetic research. It is likely that better results can be achieved by defining an "early pancreatic cancer" and establishing how to detect it. This could be the wrigth one way is to significantly improve the survival of these patients.

Results of leucovorin and doxifluridine oral regimen in the treatment of metastatic colorectal cancer.

We conducted a multicentric phase II study on advanced colorectal cancer to determine the efficacy and toxicity of oral treatment with leucovorin (LV) plus doxifluridine (5'DFUR), a novel fluoropyrimidine derivative with proven antitumor activity in different experimental models. Thirty-six outpatients with measurable disease entered the trial and received orally LV 20 mg in the morning and in the afternoon, and 2 h later 5'-DFUR 500 mg/m2 every 2 days for 3 months. Thirty-four evaluable patients underwent a total of 408 weeks of treatment. The response rate was 35%, with two complete remissions and 10 partial responses. The median survival of patients who responded to treatment (responders) was 17.1 months (range 4-32), which was significantly longer (p<0.001) than the 6.5 months (range 2-11) of the patients who did not respond (non-responders). Therefore, after 4-8 weeks of treatment, 14 patients (41%) had an improvement in their performance status and/or stabilization of pain. General toxicity was usually mild, myelo and gastrointestinal toxicity were moderate, and there was no evidence of relevant neurological toxicity. These results show that a home therapy with oral LV-5'DFUR is a safe and effective treatment regimen for metastatic colorectal carcinoma.

Analysis of clinicopathologic prognostic features in patients with gastric adenocarcinoma.

BACKGROUND: We evaluated the influence of several clinicopathologic variables on 5-year actuarial survival rate after curative resection of gastric adenocarcinoma. METHODS: Clinical characteristics were retrieved from the records of all patients who underwent gastric resection for curative intent between 1965 and 1986 at The University of Chicago Medical Center, and follow-up was obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. RESULTS: One hundred seventy-eight patients underwent a curative resection during the study period at our institution. Overall 5-year actuarial survival rate was 29%. The relationship between clinicopathologic variables and 5-year survival rate was evaluated by Kaplan-Meier survival curve construction and chi-squared analysis. Lymphatic and/or capillary microinvasion (absent vs present, p < 0.001), tumor location (antrum and body vs gastroesophageal junction, p = 0.05), local extent of disease (limited to the gastric wall versus involving adjacent organs, p = 0.003), stage (absence versus presence of lymph node metastases, p < 0.001), Lauren type (intestinal versus diffuse, p < 0.01), and Ming type (expanding versus infiltrative, p < 0.02) significantly influenced survival. When a multivariate analysis with logistic regression of 5-year survival was performed, lymphatic and/or capillary microinvasion emerged as the only statistically significant, independent prognostic factor associated with long-term survival (p = 0.039). If microinvasion was omitted from the analysis, lymph node metastases (p < 0.05) and the extension to adjacent organs (p < 0.04) became the only statistically significant variables. Multiple correlation analyses suggested that microinvasion is an early histopathologic finding that correlates with a more aggressive natural history. CONCLUSIONS: Lymphatic and/or capillary microinvasion is a more powerful predictor of 5-year survival than lymph node metastases or tumor extension to adjacent organs. Correlation among clinicopathologic variables suggests that microinvasion may represent an early finding, serving as a potential marker for a biologically more aggressive tumor.

Nitric oxide synthase immunoreactivity in the human ileocecal region.

The nitric oxide (NO) producing neurons in the human ileocecal region (pre-junctional ileum, ileocecal and cecocolonic junctions, cecum and post-junctional colon) have been evaluated by immunocytochemistry. The percentage of NO synthase-positive neurons was higher at the myenteric plexus than at the submucous plexus, independently of the levels examined. The inner portion of the circular muscle layer, except at the ileal level, was devoid of immunoreactive nerve fibers. Data obtained suggest that neuronal-released NO at the ileocecal region has a greater role in the relaxation of the muscle coat, except for the inner circular muscle layer, than in the regulation of blood flow, absorptive and secretory processes.

Distribution of VIP-immunoreactive nerve cells and fibers in the human ileocecal region.

VIP-containing nerve cells and fibers in the human ileocecal region (pre-junctional ileum, ileocecal and cecocolonic junctions, post-junctional cecum and colon) have been evaluated by immunocytochemistry. A high density of VIP-positive neurons and nerve fibers was found in all layers of the ileum. At all colonic levels examined and at both junctions, the percentage of VIP-containing cells was higher in the submucous plexus than in the myenteric plexus. At both junctions, the muscle wall was devoid of, and the myenteric plexus extremely poor in VIP-positive nerve fibers and cells. These data suggest that motility of these junctions is not--or only to a minor extent--regulated in man by VIP-containing nerves, at variance with other gut sphincteric areas.

Epidoxorubicin and high dose leucovorin plus 5-fluorouracil in advanced gastric cancer: a phase II study.

We conducted a multicentric phase II study on advanced gastric cancer to determine the efficacy and toxicity of treatment with epidoxorubicin (EPI) plus high doses of leucovorin (LV) and 5-fluorouracil (5-FU). Thirty-seven patients with measurable disease were enrolled into the trial and treated with EPI 75 mg/m2 on day 1 and LV 200 mg/m2 plus 5-FU 450 mg/m2 from day 1 to 3, the cycle being repeated every 3-4 weeks from a median of five cycles per patients. The response rate was 49% in 35 evaluable patients, with two complete remissions and 15 partial responses. Median response duration was 12.4 months; median survival for responding patients was 17.3 months, which was significantly longer than 8.7 months for non-responding patients. General toxicity was usually mild, myelotoxicity was moderate and there was no evidence of cardiac toxicity. These results show that EPI-LV-5-FU is an effective regimen for advanced gastric carcinoma. The efficacy of this combination should now be tested as an adjuvant therapy in resectable gastric cancer.

Morphological evidence for a cecocolonic junction in man and functional implications.

The region above, below and in front of the ileocecal valve opening has been studied in man using both light and electron microscopy. A cecocolonic junction, comprising the colonic basal portion of the ileocecal valve, could be demonstrated in man, due to the specific anatomy of the inner portion of the circular muscle. This muscle was arranged in anastomosing cords, richly innervated and enveloped by elastic fibers. Its smooth muscle cells were characterized by extremely wide sarcoplasmic cisternae and cell-to-cell junctions, numerous caveolae and large amounts of glycogen. Interstitial cells were rarely found. This junction might be considered responsible for (1) ileal flow accommodation, (2) colonic active movements and (3) ileocecal valve closing and opening.