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Quality of life of patients with end-stage peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

BACKGROUND Quality of Life (QoL) plays an important role in patients with peritoneal metastasis and is deteriorating continuously until death. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative palliative treatment of peritoneal metastasis. We present the first QoL results under PIPAC therapy. METHODS Retrospective analysis of QLQ30 questionnaire results during repeated courses of PIPAC applications in palliative patients with pretreated peritoneal metastasis. RESULTS 91 patients (M:F = 40:51, median age 64 (34-77) years) with 158 PIPAC applications were analyzed. 86% patients had previously received systemic chemotherapy. Peritoneal metastasis was advanced (Peritoneal Carcinomatosis Index I = 16 ± 10). At admission, only moderate impairment of functioning (62-83%) and symptom scores (17-47%) was observed. 48 patients received at least 2 PIPAC every 6 weeks. After PIPAC # 1, the global physical score deteriorated slightly (from 82% to 75%), but improved after PIPAC # 2 (up to 89%). Gastrointestinal symptoms (nausea/vomiting, constipation, diarrhoea, anorexia) remained stable under PIPAC therapy. CONCLUSIONS Quality of life was relatively high in this group of patients with advanced, pretreated peritoneal metastasis, explaining their wish for further therapy. Functioning scores and disease-related symptoms were not altered for at least 3 months in the patients able to receive repeated PIPAC. Except for a transient moderate increase of pain scores, PIPAC did not cause therapy-related QoL deterioration, especially no gastrointestinal symptoms.

Development of a duodenal gallstone ileus with gastric outlet obstruction (Bouveret syndrome) four months after successful treatment of symptomatic gallstone disease with cholecystitis and cholangitis: a case report

IntroductionCases of gallstone ileus account for 1% to 4% of all instances of mechanical bowel obstruction. The majority of obstructing gallstones are located in the terminal ileum. Less than 10% of impacted gallstones are located in the duodenum. A gastric outlet obstruction secondary to a gallstone ileus is known as Bouveret syndrome. Gallstones usually enter the bowel through a biliary enteral fistula. Little is known about the formation of such fistulae in the course of gallstone disease.Case presentationWe report the case of a 72-year-old Caucasian woman born in Germany with a gastric outlet obstruction due to a gallstone ileus (Bouveret syndrome), with a large gallstone impacted in the third part of the duodenum. Diagnostic investigations of our patient included plain abdominal films, gastroscopy and abdominal computed tomography, which showed a biliary enteric fistula between the gallbladder and the duodenal bulb. Our patient was successfully treated by laparotomy, duodenotomy, extraction of the stone, cholecystectomy, and resection of the fistula in a one-stage surgical approach. Histopathological examination showed chronic and acute cholecystitis, with perforated ulceration of the duodenal wall and acute purulent inflammation of the surrounding fatty tissue. Four months prior to developing a gallstone ileus our patient had been hospitalized for cholecystitis, a large gallstone in the gallbladder, cholangitis and a small obstructing gallstone in the common biliary duct. She had been treated with endoscopic retrograde cholangiopancreatography, endoscopic biliary sphincterotomy, balloon extraction of the common biliary duct gallstone, and intravenous antibiotics. At the time of her first presentation, abdominal ultrasound and endoscopic examination (including esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography) had not shown any evidence of a biliary enteral fistula. In the four months preceding the gallstone ileus our patient had been asymptomatic.ConclusionIn patients known to have gallstone disease presenting with symptoms of ileus, the differential diagnosis of a gallstone ileus should be considered even in the absence of preceding symptoms related to the gallbladder disease. Gallstones large enough to cause intestinal obstruction usually enter the bowel by a biliary enteral fistula. During the formation of such a fistula, patients can be asymptomatic.

Scintigraphic peritoneography reveals a non-uniform 99m Tc-Pertechnetat aerosol distribution pattern for Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a swine model

BackgroundAlthough recent data are contradictory, it is still claimed that Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) would deliver an aerosol which distributes homogeneously throughout the entire abdominal cavity.Methods99mTc-Pertechnetat was administered in four postmortem swine using either PIPAC or liquid intra-peritoneal chemotherapy (IPC). The animals were examined by planar scintigraphy and SPECT/CT. Planar distribution images were divided into four regions of interest (ROIs: right/left upper and lower abdominal quadrant). SPECT/CT slices were scanned for areas of intense nuclide accumulation (“hot spots”). The percentage of relative distribution for planar scintigraphy was calculated by dividing the summed individual counts of each ROI by total counts measured in the entire abdominal cavity. The relative distribution of the “hot spots” was analyzed by dividing the counts of the local volume of interest (VOI) by the summed volume counts measured in the entire abdominal cavity.ResultsIn all four animals, planar scintigraphy showed inhomogeneous nuclide distribution. After PIPAC only 8–10% of the delivered nuclide was detected in one ROI with a mean deviation of 40% and 74% from a uniform nuclide distribution pattern. In all animals, SPECT/CT revealed “hot spots” beneath the PIPAC Micropump, catheter tip, and in the cul-de-sac region which comprise about 25% of the total amount of delivered nuclide in 2.5% of the volume of the entire abdominal cavity.ConclusionsOur present data indicate that the intra-abdominal aerosol distribution pattern of PIPAC therapy is non-homogeneous and that the currently applied technology has still not overcome the problem of inhomogeneous drug distribution of IPC.

Effect of Irradiation on Tissue Penetration Depth of Doxorubicin after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a Novel Ex-Vivo Model.

Background: This study was performed to assess the impact of irradiation on the tissue penetration depth of doxorubicin delivered during Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC). Methods: Fresh post mortem swine peritoneum was cut into 10 proportional sections. Except for 2 control samples, all received irradiation with 1, 2, 7 and 14 Gy, respectively. Four samples received PIPAC 15 minutes after irradiation and 4 other after 24 hours. Doxorubicin was aerosolized in an ex-vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. Results: Doxorubicin penetration after PIPAC (15 minutes after irradiation) was 476 ± 74 µm for the control sample, 450 ± 45µm after 1 Gy (p > 0.05), 438 ± 29 µm after 2 Gy (p > 0.05), 396 ± 32 µm after 7 Gy (p = 0.005) and 284 ± 57 after 14 Gy irradiation (p < 0.001). The doxorubicin penetration after PIPAC (24 hours after irradiation) was 428 ± 77 µm for the control sample, 393 ± 41 µm after 1 Gy (p > 0.05), 379 ± 56 µm after 2 Gy (p > 0.05), 352 ± 53 µm after 7 Gy (p = 0.008) and 345 ± 53 after 14 Gy irradiation (p = 0.001). Conclusions: Higher (fractional) radiation dose might reduce the tissue penetration depth of doxorubicin in our ex-vivo model. However, irradiation with lower (fractional) radiation dose does not affect the tissue penetration negatively. Further studies are warranted to investigate if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC.

Hyperthermic intracavitary nanoaerosol therapy (HINAT) as an improved approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC): Technical description, experimental validation and first proof of concept

Background: The delivery of aerosolised chemotherapeutic substances into pressurised capnoperitonea has been reported to be more effective than conventional liquid chemotherapy for the treatment of peritoneal carcinomatosis. However, recent reports reveal limitations of the currently available technology. Material and Methods: A novel approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC), called hyperthermic intracavitary nanoaerosol therapy (HINAT), based on extracavitary generation of hyperthermic and unipolar charged aerosols, was developed. The aerosol size distribution, the spatial drug distribution and in-tissue depth penetration of HINAT were studied by laser diffraction spectrometry, differential electrical mobility analysis, time of flight spectrometry, scintigraphic peritoneography and fluorescence microscopy. All experiments were performed contemporaneous with conventional PIPAC for the purpose of comparison. Furthermore, a first proof of concept was simulated in anesthetised German Landrace pigs. Results: HINAT provides a nanometre-sized (63 nm) unipolar-charged hyperthermic (41 °C) drug aerosol for quasi uniform drug deposition over the whole peritoneum with significantly deeper drug penetration than that offered by conventional PIPAC.

Sind prä-endoskopische Scores als prognostische Instrumente bei oberengastrointestinalen Blutungen geeignet?

BACKGROUND AND OBJECTIVES To evaluate the predictive value of pre-endoscopic risk scores in patients with upper gastrointestinal bleeding (UGI-B). PATIENTS AND METHODS The medical records of patients evaluated by emergency esophago-gastro-duodenoscopy (E-EGD) for suspected UGI-B outside regular working hours were retrospectively analysed. RESULTS During the 75 months of the study period 112 E-EGDs met the inclusion criteria. Mean age was 65.5 ± 14.7 years. 38.4 % of patients were female. Endoscopy revealed 41 gastro-duodenal ulcers, 16 Mallory-Weiss, 13 varices, 4 neoplasia. 72 patients received transfusions, 39 had endoscopic interventions. 2 patients were surgically treated, 16 had recurrent bleeding. 16 of the 110 patients died during hospitalisation. The following sensitivities were found for the Blatchford score (cut-off > 1), the clinical Rockall score (cut-off > 0) and the Adamopoulos score (cut-off > 2) in predicting need for clinical intervention (endoscopic or surgical intervention or transfusion): 100/97.7/93%, recurrent bleeding: 100/100/93.8%, in-hospital mortality: 100/93.8/93.8%, respectively. CONCLUSIONS The Blatchford score is a suitable tool in determining the need for clinical intervention and the risk of recurrent bleeding and death in patients with UGI-B. The clinical Rockall score and the Adamopoulos score (the latter had originally been developed to predict active UGI-B at endoscopy and was used with a lower cut-off in our study) are inferior alternatives.

Möglichkeiten der Endoskopie in der Onkologie

ZusammenfassungDer vorliegende Beitrag beleuchtet endoskopische diagnostische und therapeutische Optionen in der Onkologie. Die Endosonographie ist ein Verfahren, das die Möglichkeiten der Endoskopie wesentlich bereichert, da es einen Blick über die Oberfläche der Mukosa hinaus in die umgebenden Strukturen und gezielte Interventionen ermöglicht. Es hielt Einzug in viele Leitlinien. Die Möglichkeiten und Grenzen der endoskopischen Behandlung von Frühkarzinomen werden für den Ösophagus, den Magen und das Kolorektum aufgezeigt. Neue Materialien und Methoden bereichern die gastrointestinale Stenttherapie. Durch Stents oder mit den bereits gut etablierten perkutan-enteralen Sonden lassen sich in vielen kurativen und palliativen onkologischen Situationen maßgeschneiderte Lösungen finden.AbstractEndoscopic diagnostic and therapeutic options in gastrointestinal oncology are summarized in this article. Endoscopic ultrasound greatly adds to the possibilities of endoscopy by expanding the view beyond the surface of the mucosa into the adjacent organs and making targeted interventions possible. Many guidelines have recently incorporated this elegant method. Furthermore, endoscopic treatment options for early cancer of the esophagus, the stomach and the colorectum are depicted. Advances in gastrointestinal stent technology as well as the established percutaneous enteral tubes make it easier to provide a tailored therapy in many curative and palliative oncologic situations.

[Demands for endoscopy service outside of regular hours: a retrospective study and literature analysis].

BACKGROUND AND OBJECTIVE Many acute care hospitals provide round-the-clock emergency endoscopy to guarantee immediate diagnosis and treatment of acute conditions of the gastrointestinal tract. This study is the first one to assess the demand for emergency endoscopy outside usual working hours. PATIENTS AND METHODS This study evaluated retrospectively 315 consecutive emergency endoscopies done at an acute care hospital (575 beds; catchment population 100,000, in the Ruhr area of Germany) between 26.7.2003 and 01.11.2009 (6 years and 3 months) outside usual working hours (i.e. during the weekend and from 6 pm to 8 am during weekdays). This represents 50 emergency endoscopies outside working hours per 100,000 people per year. RESULTS 56.8 % of the examinations took place during the weekend (Saturday or Sunday), 26.7 % during the night (10 pm - 8 am). The distribution of the different endoscopic modalities was: 228 EGD (72.4 %), 42 incomplete colonoscopies or recto-sigmoidoscopies (13.3 %), 28 retrograde cholangio- or cholangiopancreatographies (8.9 %), 16 complete colonoscopies (5.2 %) and one oral enteroscopy. 208 (66%) of endoscopic procedures were purely diagnostic without any therapeutic intervention. The indication for endoscopy was documented in 243 of the 315 procedures. In 76.5 % of those cases the suspicion of a gastrointestinal bleeding was the indication for endoscopy. CONCLUSION In an acute care hospital in Germany 50 emergency endoscopies outside working hours were performed per 100,000 population per year. This rate exceeds that reported in other European countries (Great Britain: 26.7, Norway: 24). Further studies are needed to evaluate the impact of different emergency endoscopic strategies on patient outcome and treatment costs.