Predictive value of computed tomography on surgical resectability in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: Results from a prospective, multicentre phase 2 trial (NEOLAP-AIO-PAK-0113).

PURPOSE: To assess the role of current imaging-based resectability criteria and the degree of radiological downsizing in locally advanced pancreatic adenocarcinoma (LAPC) after multiagent induction chemotherapy (ICT) in multicentre, open-label, randomized phase 2 trial. METHOD: LAPC patients were prospectively treated with multiagent ICT followed by surgical exploration within the NEOLAP trial. All patients underwent CT scan at baseline and after ICT to assess resectability status according to national comprehensive cancer network guidelines (NCCN) criteria and response evaluation criteria in solid tumors (RECIST) at the local study center and retrospectively in a central review. Imaging results were compared in terms of local and central staging, downsizing and pathological resection status. RESULTS: 83 patients were evaluable for central review of baseline and restaging imaging results. Downstaging by central review was rarely seen after multiagent ICT (7.7%), whereas tumor downsizing was documented frequently (any downsizing 90.4%, downsizing to partial response (PR) according to RECIST: 26.5%). Patients with any downsizing showed no significant different R0 resection rate (37.3%) as patients that fulfilled the criteria of PR (40.9%). The sensitivity of any downsizing for predicting R0 resection was 97% with a negative predictive value (NPV) of 0.88. ROC-analysis revealed that tumor downsizing was a predictor of R0 resection (AUC 0.647, p = 0.028) with a best cut-off value of 22.5% downsizing yielding a sensitivity of 65% and a specificity of 61%. CONCLUSIONS: Imaging-based tumor downsizing and not downstaging can guide the selection of patients with a realistic chance of R0-resection in LAPC after multi-agent ICT.

Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113).

BACKGROUND: The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs). PATIENTS AND METHODS: A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy [ICT; either nab-paclitaxel/gemcitabine alone or nab-paclitaxel/gemcitabine followed by FOLFIRINOX (combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin)] followed by surgical exploration of all patients without evidence of disease progression. CA 19-9 was determined at baseline and after ICT and correlated with overall survival (OS) and secondary R0 resection rate. RESULTS: From the NEOLAP study population (N = 165) 133 patients (81%) were evaluable for CA 19-9 at baseline and 81/88 patients (92%) for post-ICT CA 19-9 response. Median OS (mOS) in the CA 19-9 cohort (n = 133) was 16.2 months [95% confidence interval (CI) 13.0-19.4] and R0 resection (n = 31; 23%) was associated with a significant survival benefit [40.8 months (95% CI 21.7-59.8)], while R1 resected patients (n = 14; 11%) had no survival benefit [14.0 (95% CI 11.7-16.3) months, hazard ratio (HR) 0.27; P = 0.001]. After ICT most patients showed a CA 19-9 response (median change from baseline: -82%; relative decrease ≥55%: 83%; absolute decrease to ≤50 U/ml: 43%). Robust CA 19-9 response (decrease to ≤50U/ml) was significantly associated with mOS [27.8 (95% CI 18.4-37.2) versus 16.5 (95% CI 11.7-21.2) months, HR 0.49; P = 0.013], whereas CA 19-9 baseline levels were not prognostic for OS. Multivariate analysis demonstrated that a robust CA 19-9 response was an independent predictive factor for R0 resection. Using a CA 19-9 decrease to ≤61 U/ml as optimal cut-off (by receiver operating characteristic analysis) yielded 72% sensitivity and 62% specificity for successful R0 resection, whereas CA 19-9 nonresponders (<20% decrease or increase) had no chance for successful R0 resection. CONCLUSIONS: CA 19-9 response after multiagent ICT provides relevant prognostic and predictive information and is useful in selecting LAPC patients for explorative surgery. CLINICAL TRIAL NUMBER: ClinicalTrials.govNCT02125136; https://clinicaltrials.gov/ct2/show/NCT02125136; EudraCT 2013-004796-12; https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results.

[Advanced training of general and visceral surgeons in life-saving emergency surgery : Results of a survey among participants of a surgery course]. / Fortbildung von Allgemein- und Viszeralchirurgen in der lebensrettenden Notfallchirurgie : Ergebnisse einer Umfrage unter Operationskursteilnehmern.

BACKGROUND: Due to a decreasing number of emergency procedures for body cavity injuries, surgical training is inadequate and current educational concepts must be reconsidered. The German Society for General and Visceral Surgery has set up a surgical training course in 2014 to overcome this shortage. In order to assess the eligibility, needs, benefits and success of such a training format, participants were asked to evaluate the program. MATERIAL AND METHODS: All participants evaluated the course during participation and were later asked to answer an online survey regarding their age, gender, level of surgical education, surgical discipline, level of care of the hospital, emergency surgical experience and frequency of performing emergency surgery, participation in other programs, experiences after participating in the course, rating of the current training curriculum and funding of such courses. RESULTS: Out of 142 participants 83 replied to the online survey. Over 90% reported a lasting positive influence of the course on emergency surgical skills. More than half of the responders remembered a clinical situation which they successfully managed due to the skills they gained during the course. Surgeons experienced in emergency treatment felt significantly more benefit than less experienced colleagues. A consultancy position, the level of care of the hospital, age and sex of the participants did not influence the overall benefits reported. The majority of responding surgeons were in favor of including such a training course in surgical education and stipulated public financial support. CONCLUSION: Course formats that mediate emergency surgery strategies and skills are established and well accepted. Training of surgeons in life-saving emergency surgery is in the public interest and is also partly the responsibility of society.

A case of pyoderma gangrenosum in hand surgery.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that can take many clinical forms. Its diagnosis is difficult and often delayed. We report the case of a 36-year-old man with PG complicating a chemical burn of the wrist. This mode of atypical onset delayed the diagnosis and the initiation of appropriate treatment. This was not sufficient since the patient's hand was amputated at his request because of unbearable pain, and failed treatment. Surgeons should be aware of this pathology in cases of rapidly progressing ulcers, especially if aggravated by repeated debridement.

Results of wrist hemiarthroplasty for comminuted distal radius fractures in independent elderly people: A retrospective study on eleven patients.

The comminuted distal radius fractures among elderly people are usually linked to osteoporosis, and repairing them in this context is a therapeutical challenge. Several teams have reported good results of radius resurfacing. The goal of our study was to evaluate the usability of the wrist in a new series of patients after surgery. We performed a monocentric retrospective study on the data of the medical files. All the included patients were older than 65 years and received a wrist hemiarthroplasty according to the criteria that have been established by the in charge medical team. Eleven patients have been included, their average age was 80.4 years old, and the average follow-up was 18.3 months. The average QuickDASH Score was 59 (27-95). The Visual Analogue Scale for pain was in average 3.8/10 and the average mobility was: flexion 36° (12-50), extension 27° (12-50), radial deviation 15° (12-15), ulnar deviation 26° (12-40), pronation-supination range of motion 164° (150-170). The average measured strength was 44% (16-72%) of the strength of the unaffected hand. Our results are rather modest, probably because of insufficient follow-up and very severe fractures. Furthermore, the implant that has been used does not take into account the distal radioulnar joint. Another bound of this treatment is the complexity of surgical revision in case of bad result. So far, hemiarthroplasty cannot be considered as the standard treatment for complex fractures of the distal radius.

[Management of traumatic intestinal injury of mass casualties]. / Vorgehen bei traumatischen Darmverletzungen bei MANV.

While intestinal injury is relatively rare in blunt abdominal trauma, it is common in penetrating abdominal trauma. Intestinal injury cannot be detected effectively by computed tomography (CT); therefore penetrating abdominal injury or abdominal signs in blunt trauma require liberal indications for explorative laparotomy. In mass casualty situations patients with hemodynamic instability and abdominal signs should be prioritized for surgery. Besides intra-abdominal hemorrhage the major issue is septic complications due to intestinal perforation. The current surgical strategy should reflect the number of injured patients and the individual pattern of injuries. Damage control surgery is not an effective strategy to improve survival rates in severely injured patients or in mass casualty situations. Damage control surgery focuses on lifesaving procedures especially bleeding control and control of contamination. This includes an open abdomen strategy with later definitive repair and abdominal wall closure.

Vibrational modes and changing molecular conformation of perfluororubrene in thin films and solution.

We investigate the vibrational properties of perfluororubrene (PF-RUB) in thin films on silicon wafers with a native oxide layer as well as on silicon wafers covered with a self-assembled monolayer and in dichloromethane solution. In comparison with computed Raman and IR spectra, we can assign the molecular modes and identify two molecular conformations with twisted and planar tetracene backbones of the molecule. Moreover, we employ Raman imaging techniques to study the morphology and distribution of the molecular conformation in PF-RUB thin films.

Photoluminescence spectroscopy of pure pentacene, perfluoropentacene, and mixed thin films.

We report detailed temperature dependent photoluminescence (PL) spectra of pentacene (PEN), perfluoropentacene (PFP), and PEN:PFP mixed thin films grown on SiO(2). PEN and PFP are particularly suitable for this study, since they are structurally compatible for good intermixing and form a model donor/acceptor system. The PL spectra of PEN are discussed in the context of existing literature and compared to the new findings for PFP. We analyze the optical transitions observed in the spectra of PEN and PFP using time-dependent density functional theory calculations. Importantly, for the mixed PEN:PFP film we observe an optical transition in PL at 1.4 eV providing evidence for coupling effects in the blend. We discuss a possible charge-transfer (CT) and provide a tentative scheme of the optical transitions in the blended films.

Fatal aluminum phosphide poisoning.

A 39-year-old man committed suicide by ingestion of aluminum phosphide, a potent mole pesticide, which was available at the victim's workplace. The judicial authority ordered an autopsy, which ruled out any other cause of death. The victim was discovered 10 days after the ingestion of the pesticide. When aluminum phosphide comes into contact with humidity, it releases large quantities of hydrogen phosphine (PH3), a very toxic gas. Macroscopic examination during the autopsy revealed a very important asphyxia syndrome with major visceral congestion. Blood, urine, liver, kidney, adrenal, and heart samples were analyzed. Phosphine gas was absent in the blood and urine but present in the brain (94 mL/g), the liver (24 mL/g), and the kidneys (41 mL/g). High levels of phosphorus were found in the blood (76.3 mg/L) and liver (8.22 mg/g). Aluminum concentrations were very high in the blood (1.54 mg/L), brain (36 microg/g), and liver (75 microg/g) compared to the usual published values. Microscopic examination revealed congestion of all the organs studied and obvious asphyxia lesions in the pulmonary parenchyma. All these results confirmed a diagnosis of poisoning by aluminum phosphide. This report points out that this type of poisoning is rare and that hydrogen phosphine is very toxic. The phosphorus and aluminum concentrations observed and their distribution in the different viscera are discussed in relation to data in the literature.

[Absolute and relative bioavailability of germanium in the rabbit]. / Biodisponibilités absolue et relative du germanium chez le lapin.

The debated consumption of germanium suggested the authors to compare biopharmaceutical parameters of germanium oxide and germanium sesquioxide. A first evaluation, in rabbit, has been based on Germanium blood levels determined by atomic absorption spectrometry, after cross administration of both products by the I.V. and oral routes. When given orally, the apparent oxide bioavailability is very low (about 10%) but better than that of the sesquioxide. That difference could result from differences of disposition parameters of both products, which have to be studied late.

[Subacute and subchronic oral toxicity of beta-bis carboxyethyl sesquioxide of germanium in the rat]. / Toxicités orales subaiguë et sub chronique du beta-bis carboxyéthyl sesquioxyde de germanium, chez le rat.

After a brief recall of toxicological data about germanium compounds, the authors relate subacute and subchronic oral toxicities of beta bis carboxyethyl-germanium sesquioxide in rats. During 28 days and six months, male and female animals have received 1 mg/kg/day. No particular toxic symptoms, no behaviour trouble except a small decrease of body weight, in male rats, at the end of the 6-month experimentation, were observed. A light decrease of erythropoiesis and a general stimulation of cellular metabolism has been noticed after 28 days. The only marked effect was a moderate renal deficiency characterized by a tubular disease with presence of cylinders, swelling of tubulus cells and floculus amounts after 6 months. Germanium urinary excretion was constant and linked to the received dose. Six months later, no preferential accumulation in organs was observed.

[Thermal degradation of tributyltin oxide and pulmonary toxicity of its combustion products in mice and guinea pigs]. / Dégradation thermique de l'oxyde de tributyletain (OTBE) et toxicité pulmonaire des produits de combustion chez la souris et le cobaye.

Relative to an industrial application, the authors relate results obtained from a peculiar study on the thermic degradation of bis (tri-n-butyltin) oxide (TBTO) at various temperatures and they account for the toxic effects observed after inhaling the combustion products in the mouse and guinea pig. Thermolysis of TBTO between 200 and 600 degrees C gives saturated hydrocarbon and olefin gas, a condensate of tetrabutyltin and dibutyltin oxide and a residue composed of stannous or stannic oxides according to the temperature. Pulmonary toxicity is very important at low temperatures but after heating, toxic effects decrease. The results are confirmed by localisation and histopathologic studies. At 600 degrees C no death appears but some behavioral troubles occur. It's possible that repeated exposures can induce delayed toxicity.

[Effects in the guinea pig of an aerosol with a tributylitin oxide base]. / Effets chez le cobaye, d'un aérosol à base d'oxyde de tributylétain (OTBE)

The authors report a toxicological study of bis (tributyltin oxide) (TBTO) given by inhalation (oily aerosol) to 105 Hartley albino guinea pigs. Doses vary from 1 mg to 0.1 mg of TBTO per liter of aerosol. Death occurs for doses of 0.2 mg per le more resistant than the male ones. The intoxication is marked by a period of ocular and nasal irritation followed by a short remission time, then death occurs after asphyxic convulsions. With doses less than 0.2 mg per liter of aerosol, we observe only an irritation without mortality after one hour intoxication. Seven days later the animals are alive. Because of its liposulibility, TBTO is present in the whole body, particularly in liver, kidney, lung, brain and heart. Histological study does not reveal any peculiar lesion of the examinated organs. Especially there is no specific alteration of the respiratory system. The merely observed trouble is a diffuse congestion.

[Fatal poisoning by water dropwort (Oenanthe crocata)]. / Intoxication mortelle par Oenanthe safranée (Oenanthe crocata)

The authors relate clinical and toxicological data concerning a recent deadly intoxication by OEnanthe crocata absorption and stress upon awkwardness of clinical diagnosis. Most frequent cases were observed by veterinarians in bovine and porcine intoxications. This plant grows in wet meadows of western France and south-west of England. In spite of its rarity, this intoxication is mostly dangerous and oftenest lethal.