Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal surface malignancies (PSM): a prospective single-center registry study.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new, palliative approach for patients with peritoneal surface malignancies (PSMs). Its main goals are to control symptoms and ascites. For this experimental procedure, treatment efficacy and patient safety need to be closely monitored. METHODS: We performed a prospective registry study for patients with PSMs. Cisplatin (C) (7.5 mg/m2 body surface) and doxorubicin (D) (1.5 mg/m2) were administered laparoscopically via PIPAC. RESULTS: Between November 2015 and June 2020, we recorded data from 108 patients and 230 scheduled procedures. Tumor burden, patient fitness, quality of life, operating time and in-hospital stay remained stable over consecutive procedures. We recorded 21 non-access situations and 14 intraoperative complications (11 intestinal injuries, and three aspirations while inducing anesthesia). Three or more previous abdominal surgeries or cytoreductive surgery (CRS) with intraperitoneal hyperthermic chemoperfusion (HIPEC) were risk factors for non-access and intestinal injuries (χ2, p ≤ 0.01). Five Grade IV and three Grade V postoperative complications according to the Clavien-Dindo Classification (CDC) occurred. Median overall survival was 264 days (interquartile range 108-586). Therapies were primarily discontinued because of death (34%), progressive (26%), or regressive (16%) disease. CONCLUSION: PIPAC is effective in stabilizing PSMs and retaining quality of life in selected patients. Earlier abdominal surgeries and CRS with HIPEC should be considered when determining the indication for PIPAC. Randomized controlled studies are needed to evaluate PIPAC's therapeutic benefits compared to systemic chemotherapy (sCHT) alone. TRIAL REGISTRATION: NCT03100708 (April 2017).

[Treatment recommendations for early esophageal cancer : Endoscopic and surgical options]. / Therapieempfehlungen beim Frühkarzinom des Ösophagus : Endoskopische und chirurgische Optionen.

BACKGROUND: Esophageal cancer represents a complex tumor entity with an increasing proportion of adenocarcinomas. Early esophageal cancer is staged as m1-m3 depending on the depth of infiltration into the mucosa and as sm1-sm3 depending on invasion into the submucosa. The risk of lymph node metastasis is strongly correlated with the depth of invasion and increases by leaps and bounds with submucosal infiltration. MATERIAL AND METHODS: This review is based on publications retrieved by a selective database search (MEDLINE, PubMed, Cochrane Library, International Standard Randomised Controlled Trial Number, ISRCTN, registry) on the current management of early esophageal cancer. RESULTS: The endoscopic diagnostics and evaluation of the dignity of superficial esophageal cancer by traditional staining techniques have been expanded by virtual chromoendoscopy. Endoscopic resection is the diagnostic and therapeutic procedure of choice for mucosal low risk adenocarcinomas (grade 1 or 2, no blood or lymph vessel invasion). Under certain prerequisites adenocarcinomas of the upper submucosa (sm1) can also be endoscopically removed. All other stages necessitate surgical treatment. In squamous cell carcinoma without risk factors a surgical oncological esophageal resection is indicated after infiltration of the third mucosal layer (m3). Endoscopic submucosal dissection (ESD) shows high rates of en bloc and R0 (curative) resections even with large lesions. CONCLUSION: Borderline cases between endoscopic and surgical treatment of early esophageal cancer necessitate an interdisciplinary approach and individually adapted management, which in the locally advanced stage are always embedded in a multimodal concept.

[Neoadjuvant and perioperative treatment of gastric cancer, current studies and new biomarkers]. / Neoadjuvante und perioperative Therapie des Magenkarzinoms, aktuelle Studien und neue Biomarker.

According to current German and European clinical practice guidelines perioperative chemotherapy is the recommended standard of care for localized gastric cancer beyond early cancers, i.e. in stage IB (T2 N0 M0 and T1 N1 M0) or greater. For patients who are able to tolerate intensive chemotherapy, the FLOT regimen (5-fluorouracil, folinic acid, oxaliplatin, docetaxel) should be administered preoperatively and postoperatively for four cycles each. Locally advanced nonmetastatic adenocarcinoma of the esophagogastric junction (AEG) should be treated with perioperative chemotherapy as for gastric cancer or alternatively with neoadjuvant chemoradiotherapy. The best approach for AEG is currently being investigated in ongoing clinical trials. The recommendation of perioperative treatment applies to all histopathological subtypes of gastric cancer. The article summarizes the contemporary data and provides an outlook on current progress in the field of medicinal perioperative treatment.

[Possibilities and perspectives of hyperspectral imaging in visceral surgery]. / Möglichkeiten und Perspektiven der Hyperspektralbildgebung in der Viszeralchirurgie.

HyperSpectral Imaging (HSI) technology enables quantitative tissue analyses beyond the limitations of the human eye. Thus, it serves as a new diagnostic tool for optical properties of diverse tissues. In contrast to other intraoperative imaging methods, HSI is contactless, noninvasive, and the administration of a contrast medium is not necessary. The duration of measurements takes only a few seconds and the surgical procedure is only marginally disturbed. Preliminary HSI applications in visceral surgery are promising with the potential of optimized outcomes. Current concepts, possibilities and new perspectives regarding HSI technology together with its limitations are discussed in this article.

[Perioperative safety of intraperitoneal aerosol chemotherapy : Analysis of our first 111 pressurized intraperitoneal aerosol chemotherapy (PIPAC) procedures]. / Perioperative Sicherheit der intraperitonealen Aerosolchemotherapie : Analyse unserer ersten 111 PIPAC("pressurized intraperitoneal aerosol chemotherapy")-Prozeduren.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new tool in the treatment of patients with peritoneal carcinomatosis. The aerosol containing chemotherapeutic drugs is administered laparoscopically into the abdominal cavity to achieve a local treatment effect. This can be carried out in combination with systemic chemotherapy. MATERIAL AND METHODS: Within the framework of a register study, we prospectively documented and evaluated the data of our first 111 PIPAC procedures. The analysis focused on perioperative patient safety and safety at the workplace. Perioperative clinical patient data were analyzed and the platinum concentration in the operating room was checked by wipe samples. RESULTS: A total of 62 patients were scheduled for PIPAC and 121 operations were carried out. In 9 procedures a secure access to the abdomen could not be found and 54 patients received 111 PIPAC treatments. One patient died as a result of intestinal perforation, six bowel lesions were treated immediately and healed without further complications. A further patient developed a postoperative renal failure. Otherwise, there was no major complications and no cases of toxicity. CONCLUSION: The PIPAC procedure can be used as a supplement to systemic drug treatment for peritoneal carcinomatosis. An exact selection of suitable patients is important. The PIPAC is a low-risk procedure when performed under strict inclusion criteria and under standardized conditions, for the patients and also the surgical staff.

[Deterministic record linkage with indirect identifiers: data of the Berlin Myocardial Infarction Registry and the AOK Nordost for patients with myocardial infarction]. / Deterministisches Record Linkage mit indirekten Identifikatoren: Daten des Berliner Herzinfarktregisters und der AOK Nordost zum Herzinfarkt.

AIM OF THE STUDY: How can 2 pseudonymised data sets be linked? Using the example of data from the Berlin Myocardial Infarction Registry and from a German sickness fund (AOK Nordost) we will demonstrate how record linkage can be achieved without personal identifiers. METHODS: In different steps the method of deterministic record linkage with indirect identifiers: age, sex, hospital admission date and time, will be explained. RESULTS: We were able to show that 80.6% of the expected maximum number of patients were matched with our approach. As a result we had no duplicate matches in the linkage process, where one AOK patient was linked to 2 or more BMIR patients or vice versa. The matching variables produced enough uniqueness to be used as indirect patient identifiers. CONCLUSION: Deterministic record linkage with the following indirect indicators: age, sex, hospital admission date and time was possible in our study of patients with myocardial infarction in a circumscribed geographical region, which limited the number of cases and avoided mismatches.

Development of somatic hybrids Solanum × michoacanum Bitter. (Rydb.) (+) S. tuberosum L. and autofused 4x S. × michoacanum plants as potential sources of late blight resistance for potato breeding.

KEY MESSAGE: Phytophthora infestans resistant somatic hybrids of S. × michoacanum (+) S. tuberosum and autofused 4 x S. × michoacanum were obtained. Our material is promising to introgress resistance from S. × michoacanum into cultivated potato background. Solanum × michoacanum (Bitter.) Rydb. (mch) is a wild diploid (2n = 2x = 24) potato species derived from spontaneous cross of S. bulbocastanum and S. pinnatisectum. This hybrid is a 1 EBN (endosperm balance number) species and can cross effectively only with other 1 EBN species. Plants of mch are resistant to Phytophthora infestans (Mont) de Bary. To introgress late blight resistance genes from mch into S. tuberosum (tbr), genepool somatic hybridization between mch and susceptible diploid potato clones (2n = 2x = 24) or potato cultivar Rywal (2n = 4x = 48) was performed. In total 18,775 calli were obtained from postfusion products from which 1,482 formed shoots. The Simple Sequence Repeat (SSR), Cleaved Amplified Polymorphic Sequences (CAPS) and Random Amplified Polymorphic DNA (RAPD) analyses confirmed hybrid nature of 228 plants and 116 autofused 4x mch. After evaluation of morphological features, flowering, pollen stainability, tuberization and ploidy level, 118 somatic hybrids and 116 autofused 4x mch were tested for late blight resistance using the detached leaf assay. After two seasons of testing three somatic hybrids and 109 4x mch were resistant. Resistant forms have adequate pollen stainability for use in crossing programme and are a promising material useful for introgression resistance from mch into the cultivated potato background.

mRNA expression in rabbit blastocyst and endometrial tissue of candidate gene involved in gestational losses.

Gestation is a complex process that involves different growth factors, cytokines and adhesion proteins related with embryo development, cellular differentiation and proliferation, embryo-endometrium interaction, angiogenesis, maternal-embryonic recognition and growth development of placenta and embryos. In this study, we examine pre-implantational (at 6 days of gestation) and gestational (at 12 days and total from ovulation to birth) losses in two rabbit lines selected by different criteria (post-weaning daily gain and litter size) and the pattern of a set of candidate transcripts, at 6 days of gestation, related with embryo development and implantation process, such as Oct-4, epidermal growth factor receptor 3 (erbB3), Transforming Growth Factor ß2, Vascular Endothelial Growth Factor and Interferon γ and related with insulin-like growth factors signalling as insulin growth factors I and II and their receptors in rabbit blastocysts and endometrial tissue. Similar pre-implantational losses were obtained in both lines. However, the gestational losses of the line selected by post-weaning daily gain clearly mirrored an increase in losses by 50% at 12 days and at birth (22.4 vs 9.5 and 50.2 vs 25.4, respectively, between line selected by post-weaning daily gain and line selected by litter size). In blastocysts and endometrial tissue at 6 days of gestation qRT-PCR assays indicated that the mean insulin-like growth factor (IGF)-IIR mRNA expression was down-regulated in line selected by post-weaning daily gain. Dysregulation of the IGF-IIR could be potential reasons for induced gestational losses. We conclude that IGF-IIR gene expression in blastocyst and endometrial tissue at 6th day of gestation tends to decline in line selected by post-weaning daily gain. The functional significance related with gestational losses is uncertain.

Acute interstitial nephritis associated with loracarbef therapy.

We describe a biopsy-confirmed case of acute interstitial nephritis associated with the use of loracarbef in an 18-month-old boy, which resulted in end-stage renal failure. This complication has been documented with the use of beta-lactam antibiotics, and it seems likely the loracarbef was responsible for acute interstitial nephritis in this patient.

HWA-448 reduces gentamicin toxicity in LLC-PK1 cells.

An LLC-PK1 cell culture model was used to evaluate for a direct protective effect of the pentoxifylline analogue HWA-448 in gentamicin nephrotoxicity at the cellular level. Cells exposed to 2 mM gentamicin for 6 days displayed a significant decrease in specific activities of leucine aminopeptidase, NaK ATPase, and N-acetyl glucosaminidase, and an increase in total cellular phospholipids (P < .05). Concomitant exposure to 0.125 mM HWA-448, a dose that did not alter cellular enzymes or total phospholipids under physiologic conditions, prevented the alterations in marker enzymes and total phospholipids induced by gentamicin (P < .05). Gentamicin binding and uptake studies revealed 0.125 mM HWA-448 had no effect on LLC-PK1 cell plasma membrane binding or cellular gentamicin uptake. We conclude that HWA-448 ameliorates gentamicin-induced alterations in LLC-PK1 cell enzymes and phospholipids by a mechanism independent of plasma membrane binding or cellular uptake.

Comparative bioavailability study of two haloperidol decanoate containing products.

In our hospital pharmacy an injectable solution of haloperidol decanoate 141 mg/ml (equivalent to haloperidol 100 mg/ml) in sesame oil was prepared. The aim of this study was to prove bioequivalence of this formulation with the reference product, Haldol Decanoas. 15 schizophrenic patients, already stabilized with Haldol Decanoas, were enrolled. Intramuscular injections were given every three weeks in the following doses: 100 mg (1 x), 200 mg (7 x) and 300 mg (7 x). In this open, randomized, cross-over study all patients received four injections of the reference product, and four injections of the test product. Only after the fourth injection of each product (when steady-state levels were reached) a concentration-time profile of haloperidol was established during the dose interval of 21 days. The pharmacokinetic parameters AUC0-21 and Cmax were statistically evaluated. Based on these parameters the conclusion was drawn that both products were bioequivalent. The preparation of this injectable haloperidol decanoate solution in our hospital pharmacy amounts to an annual saving of approximately $39,000.

Identification of cyclic metabolites of isopropylated phenyl phosphates in rabbit bile.

Some organophosphorous compounds, especially tri-o-cresylphosphate (TOCP), induce delay neuropathy. The cyclic saligenin phosphate (PSP) has been suggested to be the active metabolite of the protoxicant TOCP. The o-isopropylated triphenyl phosphates have been proven not to be neurotoxic. Studying the metabolism of these compounds we found the following cyclic metabolites: 2-phenyl-4H-4,4-dimethyl-1,1,3,2-benzodioxaphosphoran-2-oxide and 2-(o-isopropylphenyl)-4H-4,4-dimethyl-1,1,3,2-benzodioxaphospho ran-2-oxide. Additionally, monohydroxylated metabolites of the parent esters were detectable. The effect of glucuronidation on the formation of the cyclic metabolites is discussed in this paper.

Predicting neonatal morbidity after perinatal asphyxia: a scoring system.

Predicting immediate neonatal morbidity after perinatal asphyxia has been difficult. A review of asphyxiated neonates greater than or equal to 36 weeks' gestation admitted to The Children's Hospital Newborn Intensive Care Unit in 1983 was conducted to devise a scoring system that would rapidly predict organ dysfunction observed in the immediate neonatal period. Comparison of potential score components to morbidity by multiple regression analysis yielded significant association with abnormalities in fetal heart rate monitoring, the 5-minute Apgar score, and neonatal base deficit. A scoring system was devised whose sensitivity (93.8%) and specificity (81.3%) were more predictive than any of its individual components. Prospective analysis in a similar population in 1984 validated its ability to distinguish severe from moderate morbidity after asphyxia. Positive predictive value for the score in the combined study groups (n = 98) was 79% and the negative predictive value was 83%. The scoring system may offer a rapid and accurate prediction of organ dysfunction in the immediate neonatal period after asphyxia.

Changes in anterior fontanel pressure in preterm neonates during tracheal intubation.

Anterior fontanel pressure (AFP), a noninvasive indicator of intracranial pressure (ICP), was monitored during tracheal intubation in two groups of preterm neonates without neurologic disease. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic and mean blood pressures were recorded at 1-min intervals. In group 1 (n = 6) patients, 0.02 mg/kg intravenous atropine was administered and awake intubation was performed. Group 2 (n = 6) patients received 0.02 mg/kg intravenous atropine and 0.1 mg/kg pancuronium and one of four anesthetics--0.75% isoflurane, 0.5% halothane, 20 micrograms/kg fentanyl, or 2 mg/kg ketamine--with intubation after 10 min of mask ventilation. In group 1, AFP increased from 7.7 cm H2O to 23.8 cm H2O (P less than 0.05); the mean increase in AFP was 197%. Anterior fontanel pressure did not change significantly in group 2. Significant increases in AFP may increase the risk of intraventricular hemorrhage in preterm neonates. The present data indicate that indirectly measured ICP increases significantly during awake tracheal intubation in preterm neonates and that this increase can be prevented by prior administration of pancuronium and a general anesthetic.

Changes in anterior fontanel pressure in preterm neonates receiving isoflurane, halothane, fentanyl, or ketamine.

The effects of anesthetics on intracranial pressure (ICP) may be different in preterm neonates than in adults because the neonate's cranial sutures are not yet fused. The authors monitored changes in anterior fontanel pressure (AFP), a noninvasive indicator of ICP, during anesthesia in 44 preterm neonates without neurologic disease. Atropine, 0.02 mg/kg, and pancuronium, 0.1 mg/kg, were given intravenously to all patients, who were ventilated with oxygen and air. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic blood pressure (SAP) and mean blood pressure (MAP) were recorded at 1-min intervals. After a 5-min control period of stable AFP, each of the four groups of 11 patients then received either 0.75% isoflurane, 0.5% halothane, 20 micrograms/kg fentanyl, or 2 mg/kg ketamine. Anterior fontanel pressure decreased 11% during isoflurane administration, 9% during halothane administration, 10% after fentanyl, and 10% after ketamine. These changes were statistically significant, but clinically mild, and AFP remained within the normal range. Statistically significant decreases in SAP and MAP occurred during isoflurane and halothane administration, but not after fentanyl or ketamine. The authors conclude that indirectly measured ICP decreases slightly in preterm neonates without neurologic disease after administration of the anesthetics studied. The difference between these results and those of studies of ICP in adults is presumably due to the compliance of the neonate's open-sutured cranium.

3-Azi-1-methoxybutyl D-maltooligosaccharides specifically bind to the maltose/maltooligosaccharide-binding protein of Escherichia coli and can be used as photoaffinity labels.

Maltooligosaccharides with two to six (alpha 1-4)-linked glucose residues, carrying at their reducing end a 3-azi-1-methoxybutyl group in either alpha or in beta glycosidic linkage, were synthesized. These maltooligosaccharide analogues inhibit maltose uptake via the maltose-binding-protein-dependent transport system in Escherichia coli. The concentration of half-maximal inhibition of maltose transport, at 15 nM concentration, decreases with increasing chain length of the analogue, levelling off at 40 microM after a chain length of four glucose residues in the alpha series and at 350 microM after a chain length of three glucose residues in the beta series. The inhibition of maltose transport occurs at the level of the periplasmic maltose-binding protein. 3-Azi-1-methoxybutyl alpha-D-[3H]maltotrioside was bound by the maltose-binding protein with a Kd of 0.18 mM. Irradiation at 350 nm of purified maltose-binding protein in the presence of 4 microM of this substrate labeled the protein covalently; labeling was prevented by 1 mM maltose. Using a crude preparation of periplasmic proteins two proteins were labeled, the maltose-binding protein and alpha-amylase. Thus, 3-azi-1-methoxybutyl alpha-D-maltooligosaccharides are potent photoaffinity labels for proteins with maltooligosaccharides-binding sites.

[10-year comparison of deposits of heavy metals in the human placenta]. / 10-Jahres-Vergleich an Ablagerungen von Schwermetallen in der menschlichen Plazenta.

The environmental influence on the heavy metal's (trace elements) content of the human placenta was determined in tissues from three different regions of the FRG by different analytical techniques. Besides the mean values and the standard deviation the frequency distribution curves of the elements cadmium, lead, zinc, copper, cobalt, manganese and nickel are given. Comparing the results with our findings from ten years ago it seems that cadmium concentrations in the placenta have reached an approximately equal level both in rural and in industrial districts. This is equally true for lead.