Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

AIMS: We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab. The authors extracted relevant information on participants, characteristics, treatment-related death and information on the methodology of the studies. RESULTS: After exclusion of ineligible records, 18 clinical trials were included in the analysis. The odds ratio for treatment-related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95% confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval 0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of treatment-related death. CONCLUSIONS: Analysis of our data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be associated with a higher risk of treatment-related death compared with control regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) do not cause the same risk. Clinicians have to be fully aware of these differential risks and council their patients appropriately.

Treatment-associated Fatigue in Cancer Patients Treated with Immune Checkpoint Inhibitors; a Systematic Review and Meta-analysis.

AIMS: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, nivolumab, pembrolizumab and tremelimumab. The authors extracted relevant information on participants(') characteristics, all-grade and high-grade fatigue and information on the methodology of the studies. RESULTS: In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade fatigue for CTLA-4 inhibitors was 1.23 (95% confidence interval 1.07, 1.41; P = 0.003) and for high-grade fatigue was 1.72 (95% confidence interval 1.26, 2.33; P = 0.0005). Moreover, the odds ratio for all-grade fatigue for PD-1 inhibitors was 0.72 (95% confidence interval 0.62, 0.84; P < 0.0001) and for high-grade fatigue was 0.36 (95% confidence interval 0.23, 0.56; P < 0.00001). CONCLUSIONS: The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade fatigue compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade fatigue compared with control regimens.

Influence of type of mesh fixation in endoscopic totally extraperitoneal hernia repair (TEP) on long-term quality of life.

INTRODUCTION: Laparoscopic total extraperitoneal mesh repair (TEP) of inguinal hernia has become well accepted with low recurrence and high patient satisfaction rates. However, inguinal pain has also been reported. Source of this pain has been suggested to be the fixation method, especially the use of tacks. Introduction of fibrin glue and absorbable tacks were suggested to lower chronic pain and inguinal discomfort rates. This study analyses the different methods of fixation. PATIENTS AND METHODS: 201 patients were analysed. Primary end-points were patients' satisfaction, health-related quality of life, and specific inguinal conditions (e.g. pulling, swelling, troubles at coughing). Secondary endpoints were duration of operation, length of hospital stay, and material costs. RESULTS: Fibrin glue was used in 101 patients and tacks in 100 patients, in 21 of those absorbable tacks. Patients were fully satisfied with the results in more than 90%, irrespective of the fixation method. Health-related quality of life along the SF-12(®) questionnaire attested no differences. Inguinal pulling occurred significantly more often after fibrin glue (25.7 %) than after tack fixation (11 %; p = 0.026), whereas no differences in the other specific inguinal sensations occurred. CONCLUSION: Mesh fixation in TEP can be performed either by tacks or by fibrin glue with similar long-term results concerning satisfaction, health-related quality of life, and pain. No advantage of fibrin glue could be found, in fact, a higher percentage of patients had inguinal pulling and burning sensations after the use of fibrin glue. The use of absorbable tacks showed no advantage.

[Ascites and hematuria after falling in an alcoholic patient]. / Der PRAXIS-Fall. Aszites und Makrohämaturie nach Bagatelltrauma unter Alkoholeinfluss.

Isolated ruptures of the urinary bladder following minor traumas are a rare abdominal lesion. Diagnosis and treatment are a challenge to emergency physicians and surgeons. This case shows a 46-year-old patient admitted for a minor brain injury after falling during an episode of alcoholic intoxication. Ultrasound and CT scan of the abdomen showed intraabdominal fluid without a parenchymatous lesion. Also a hematuria was significant. The retrograde cystography showed intraabdominal contrast agent. The rupture of the urinary bladder was confirmed by laparoscopy and was intracorporal sutured in double layer technique. Without any postoperative complications the patient was discharged after 4 days. The retrograde cystography after 10 days showed no leckage and the urinary catheter could be removed.

[Alveolar adenoma--a rare pulmonary mass: case report and review of the literature]. / Das alveoläre Adenom als Differenzialdiagnose zum Bronchialkarzinom: Fallvorstellung und Literaturreview.

This report describes the case of a 58-year-old man presenting with haemoptysis. Chest X-ray and CT scans showed a solitary pulmonary mass in the right lower lobe without radiographic signs of malignancy. Definitive histology following thoracoscopic wedge resection showed the distinctive findings of an alveolar adenoma, a very rare benign tumour of the lung of unknown histogenesis. Its existence was first described in 1986 with less than 30 cases published to this day. Alveolar adenoma usually presents as a peripheral solitary lesion in asymptomatic, older patients. Its histological features, the benign proliferation of alveolar epithelium and septal mesenchyme, allow for its distinction from other benign lesions of the lung. Complete excision is considered curative on the basis of current knowledge.

Early introduction of laparoscopic sigmoid colectomy during residency.

BACKGROUND: Laparoscopic sigmoid colectomy for benign diseases is becoming the standard of care. However, few residency programmes incorporate the procedure. This study evaluated the safety and feasibility of the early introduction of laparoscopic sigmoid colectomy during residency. METHODS: From a database of consecutive laparoscopic sigmoid colectomies collected prospectively over 6 years, those for cancer and primary open sigmoid colectomies were excluded. Surgeons were categorized into five levels of experience in colonic surgery. Patient demographics, operative data, complications and conversion rates were assessed. RESULTS: A total of 262 sigmoid colectomies were performed by 13 surgeons. American Society of Anesthesiologists grade and diverticular disease classification were similar across the five experience levels. There were no significant differences in morbidity, mortality or readmission rates between experience levels. However, operative time (230 versus 145 min, P < 0.001) intraoperative blood loss (200 versus 100 ml, P < 0.001) and conversion rate (13.6 versus 2.1 per cent, P = 0.002) all decreased with increasing surgical experience (trainee versus trainer). CONCLUSION: It is safe and feasible to introduce laparoscopic sigmoid colectomy to a structured residency.

Pseudo-achalasia following laparoscopically placed adjustable gastric banding.

BACKGROUND: The complication of pseudo-achalasia may occur after laparoscopic adjustable gastric banding (LAGB) in patients with normal band position and normal stomal width. We hypothesized that this complication occurs especially in patients with preexisting insufficiency of the lower esophageal sphincter (LES), who show poor compliance secondary to lacking the sensation of satiety and who therefore also have insufficient weight loss at follow-up. METHODS: Early and late postoperative barium meal studies of 120 LAGB patients were retrospectively analyzed to identify patients who developed esophageal widening and dysmotility despite normal band position and normal stomal width. Results were compared with preoperative endoscopies, clinical findings, each patient's compliance with dietary instructions and postoperative weight loss. RESULTS: 9/120 patients developed pouch dilatation, esophageal widening and esophageal dysmotility as a late complication, despite normal band position and normal stomal width. All these patients had shown preexisting insufficiency of their LES endoscopically. They all showed bad compliance with dietary instruction, and they all abused their distal esophagus as an additional pouch. 7 of these patients presented with insufficient weight loss at follow-up, whereas of 3 other patients with pre-existing LES insufficiency who had shown good compliance, only 1 showed insufficient weight loss. Insufficient weight loss after 1 year was significantly more common in patients with pre-existing LES insufficiency (8/12 patients, 67%) than in patients with a competent LES (26/108 patients, 24%). CONCLUSION: Patients with pre-existing LES insufficiency appear to be at risk for pouch dilatation and esophageal decompensation despite normal band position and normal stomal width. These patients are prone to show lack of satiety and poor compliance with dietary instruction, use of their lower esophagus as additional space for food, and tend to have insufficient weight loss. Preoperative manometry should be used to identify such patients, where the indication for gastric banding should be discussed very critically.

Laparoscopic wedge resection for benign gastric tumors.

BACKGROUND: Both laparoscopic wedge resection and formal laparoscopic resection are used in the treatment of benign and malignant gastric diseases. METHODS: We performed totally laparoscopic wedge resection using stapling devices and three or four trocars. PATIENTS: Four patients were treated with this technique. All four suffered from gastrointestinal stromal tumors (GIST), and one presented with an additional gastric adenoma. Two were morbidly obese, and two had additional operations performed at the same time. Two patients were admitted for acute upper GI bleeding. RESULTS: All of the tumors were removed successfully. Operating time ranged from 135 to 215 min. Oral feeding commenced on days 2-4. Postoperative hospital stay ranged from 5 to 11 days. CONCLUSION: Laparoscopic wedge resection of benign gastric tumors is a safe, reliable method that should be further investigated and used on a broader scale.

The effects of laparoscopic adjustable gastric banding on the proximal pouch and the esophagus.

BACKGROUND: Pouch development is a potentially serious problem following gastric banding, and reoperation is often demanded to maintain long-term function of the lap band. Laparoscopic gastric banding was performed with two different calibrations of the pouch. Within a period of 12 months, postoperative pouch behavior with regard to volume and shape was evaluated retrospectively, as were changes in the distal esophagus. METHODS: The pouches of 14 patients with intraperitoneal band positioning were calibrated at 25 ml. The volumes of 54 patients operated by a suprabursal technique were set at 15 ml. We performed three radiological examinations and calculated the volumes using the ellipsoid formula d1 x d2 x d3 x pi/6. Four morphologically different pouch types have been observed: regular, concentric, eccentric-medial and eccentric-lateral. The phi-angle corresponds to the angle between the spinal column and the gastric band. RESULTS: In the first group, the pouch volume increased from 21.2 ml +/- 21.2 to 87.9 ml +/- 64.6 (p=0.006) and the BMI fell from 47.1 kg/m2 +/- 8.4 to 38.1 kg/m2 +/- 7.0 (p=0.001). The pouch volume of the second group increased from 10.4 ml +/- 5.8 to 38.8 ml +/- 29.1 (p<0.001), and the BMI reduced from 48.4 kg/m2 +/- 6.9 to 39.3 kg/m2 +/- 6.7 (p<0.001). If the phi-angle is smaller than 4 degrees, the pouch is of the eccentric-medial type. CONCLUSIONS: The transbursal operative technique is responsible for the development of the eccentric-medial pouch. If the anterior sero-muscular fixative sutures tear, an eccentric-lateral pouch results. All pouch types are affected by changes at the pouch-esophageal junction and by pathological developments in the distal and middle oesophagus.

Spontaneous volume changes in gastric banding devices: complications of a semipermeable membrane.

The goal of this study was to prove that adjustable laparoscopic gastric banding (LAP-BAND) is semipermeable and that luminal adjustment with saline leads to spontaneous fluid loss, luminal widening, and effect loss which makes repeated readjustments necessary. In 64 patients stoma adjustment was performed with saline according to the guidelines of the manufacturer (group 1). In 32 patients hyperosmolar contrast material was used for stoma readjustments with the intention to detect a system leakage after spontaneous fluid loss and spontaneous luminal widening was observed (group 2). After spontaneous luminal narrowing had occurred in group 2, all patients from group 2 and all additional patients (n = 148) underwent stoma (re-) adjustment with iso-osmolar contrast material (group 3). Spontaneous fluid changes which led to spontaneous changes of the luminal width were then analyzed for the different filling substances in each group. Fifty-two patients from group 1 presented with effect loss because a spontaneous luminal widening had occurred secondary to a fluid loss of 0.1-0.2 ml/month. All 32 patients from group 2 presented with increasing obstruction and food intolerance because a spontaneous luminal narrowing had occurred secondary to a spontaneous fluid gain of 0.1-0.3 ml/month. In our patients from group 3, where stoma adjustment was performed with iso-osmolar contrast material, no spontaneous fluid changes were observed and luminal width/degree of obstruction did not change. The LAP-BAND is semipermeable. Stoma adjustment should not be performed with saline in order to avoid spontaneous luminal widening and the need for repeated readjustments. Stoma adjustments with hyperosmolar contrast material are clearly contraindicated since osmotic fluid gain leads to increasing obstruction. Stoma adjustments should be performed using iso-osmolar filling media which provide a stable luminal obstruction.

Adjustable laparoscopic gastric banding in patients with morbid obesity: radiographic management, results, and postoperative complications.

PURPOSE: To determine the role of radiographic assessment in patients who underwent an adjustable laparoscopic gastric banding (ALGB) for the treatment of morbid obesity, and to evaluate the frequency and type of postoperative complications. MATERIALS AND METHODS: From September 1995 to March 1998, 98 consecutive patients (18 men, 80 women; mean age, 39 years; age range, 22-62 years) with morbid obesity (mean body weight, 132 kg; mean body mass index, 47.1 kg/m(2)) underwent ALGB. In all patients, fluoroscopy was performed postoperatively to confirm band position and to exclude perforation and at 6-8 weeks later to measure and adjust the stoma between the pouch and stomach for optimal weight loss. All patients underwent another examination 12 months postoperatively, whereas patients with unsatisfactory weight loss or patients suspected of having complications were examined earlier and on several occasions. RESULTS: Port puncture was feasible in all cases, and stomal adjustments could easily be repeated. Absolute (ie, total) weight loss after 1 year ranged from 8.8% to 39.2% (mean, 18.3%). Twenty patients showed unsatisfactory weight loss. No early complications occurred. Late complications occurred in 34 patients and included pouch dilatation (concentric or eccentric with posterior slippage), eccentric band herniation, band penetration, disconnection, axial pouch herniation, and port-site infection. CONCLUSION: ALGB is an effective method in the treatment of morbid obesity. Radiographic assessments are crucial in the management of weight loss and detection of postoperative complications.

[The "buried bumper syndrome"--a rare complication of percutaneous endoscopic gastrostomy]. / Das Buried Bumper-Syndrom--Eine seltene Komplikation nach perkutaner endoskopischer Gastrostomie (PEG).

The buried bumper syndrome is a rare complication of percutaneous endoscopic gastrostomy (PEG). Hereby the PEG bumper is overgrown by hypertrophic gastric mucosa and embedded into the gastric wall. This is probably a consequence of enforced tightening of the PEG tube causing an ulcer in the gastric mucosa. Endoscopically the bumper is not visible anymore. The symptoms of the buried bumper-syndrome are a poorly transporting PEG tube, a PEG tube that cannot be mobilised, secretion along the tube and upper abdominal pain. Most often an endoscopic approach to remove the bumper is successful. If not, the operative removal of the plate is necessary. After endoscopic removal of the tube an endoscopic replacement of a PEG tube is technically possible.

Laparoscopic gastro- and hepaticojejunostomy for palliation of pancreatic cancer: a case controlled study.

BACKGROUND: Most patients presenting with pancreatic cancer are irresectable at the time the diagnosis is made. Therefore, they are in need of palliative treatment that can guarantee minimal morbidity, mortality, and hospital stay. To address this need, we designed a study to test the feasibility of laparoscopic gastroenterostomy and hepaticojejunostomy and to compare their results with those achieved with open techniques. METHODS: We performed a case control study of a new concept in laparoscopic palliation based on the findings of preoperative imaging and diagnostic laparoscopy. Laparoscopic side-to-side gastroenterostomy and end-to-side hepaticojejunostomy (Roux-en-Y) were done in irresectable cases. Of 14 patients who underwent laparoscopic palliation, three had a laparoscopic double bypass, seven had a gastroenterostomy, and four underwent staging laparoscopy only. The results were compared with a population of 14 matched patients who had conventional palliative procedures. RESULTS: Postoperative morbidity was 7% vs 43% for laparoscopic and open palliation, respectively (p < 0.05). There were no mortalities in the laparoscopic group, as compared to 29% in the group who had open bypass surgery (p < 0.05). Postoperative hospital stay averaged 9 days in the laparoscopic group and 21 days in the open group (p < 0.06). Operating time tended to be shorter in the laparoscopic group (p < 0.25). Morphine derivatives were necessary for a significantly shorter period after laparoscopic surgery (p < 0.03). CONCLUSIONS: Our preliminary experience strongly suggests that laparoscopic palliation can reduce the three major drawbacks of open bypass surgery-i.e., high morbidity, high mortality, and long hospital stay.

[Laparoscopic palliation of pancreatic carcinoma: initial experiences]. / Laparoskopische Palliation des Pankreaskarzinoms: erste Erfahrungen.

The greater part of patients presenting with pancreatic cancer is irresectable at the time of diagnosis. They are in need of palliative treatment. We report our first experience with a new concept of laparoscopic palliation based on the findings of preoperative imaging and diagnostic laparoscopy. Between 1995 and 1998, 10 patients underwent laparoscopic palliation. In 3 cases laparoscopic double bypass and 7 patients gastroenterostomy was performed, in some instances combined with endoscopic stenting. Postoperative morbidity was 10% for laparoscopic palliation. There was no mortality in laparoscopic bypass surgery. Postoperative hospital stay averaged 11 days. Our preliminary experience strongly suggests that laparoscopic palliation may greatly reduce the three major drawbacks of open bypass surgery, i.e. high morbidity and mortality, and long postoperative hospital stay. Prospective trials in larger study populations will be needed to define the place of this technique in the palliation of pancreatic cancer.

Donor and recipient treatment with the Lazaroid U-74006F do not improve post-transplant lung function in swine.

OBJECTIVE: U-74006F is the only Lazaroid which is currently in clinical use. A number of experimental studies demonstrate that Lazaroids reduce ischemia/reperfusion injury in various organ systems. We evaluated the effect of U-74006F on reperfusion injury in a large animal model of lung allo-transplantation. METHODS: Two different treatment modalities were evaluated and compared with corresponding control groups. Unilateral left lung transplantation was performed in 21 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.51 cold (1 degrees C) LPD solution and preserved for 20 h. In group I (n = 5), donor animals were pretreated with U-74006F (10 mg/ kg i.v.) 20 min before harvest. In addition U-74006F was added to the flush solution (10 mg/l). In group III (n = 6), the Lazaroid was given to the donor before flush and to the recipient before reperfusion (3 mg/kg i.v.). Group II and IV (n = 5) served as control. One hour after reperfusion, the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), mean pulmonary artery pressure, cardiac output, and gas exchange were assessed during a 5 h observation period. Lipid peroxidation (TBARS) and neutrophil migration (MPO activity) were measured at the end of the assessment in lung allograft tissue. RESULTS: A significant change of TBARS concentration was shown in group III (group III 78.7+/-4.6 pmol/g vs. group IV 120.8+/-7.2 pmol/g (P = 0.0065) normal lung tissue 41.3+/-4.2 pmol/g). MPO activity was reduced in group III 3.74+/-0.25 deltaOD/mg per min vs. group IV 4.97+/-0.26 deltaOD/mg per min (P = 0.027), normal lung tissue 1.04+/-0.27 deltaOD/mg per min). Pulmonary hemodynamics and gas exchange after reperfusion did not differ between groups. In group I and III, a tendency towards a reduced EVLWI was noted. CONCLUSION: We conclude that combined treatment of donor and recipient with U-74006F reduces free radical mediated injury in the allograft. However, this intervention did not result in a significant reduction of post-transplant lung edema or improvement of pulmonary hemodynamics. Donor pretreatment alone did not improve lung allograft reperfusion injury. These results indicate that the benefit of U-74006F is too small to consider clinical application in lung transplantation.

[Role of laparoscopy in the management of acute appendicitis]. / Stellenwert der Laparoskopie für die Behandlung der Appendizitis acuta.

Minimal invasive surgery had a considerable impact on common surgical techniques and has almost replaced established operative procedures such as cholecystectomy. However, the laparoscopic approach for the treatment of acute appendicitis is still not very popular. We discuss the role of laparoscopy for appendectomy and include three studies from our institution (University Hospital Zürich, Switzerland) and prospective studies reported in the literature. We conclude that laparoscopic appendectomy, when compared with the open approach, has the following advantages for the diagnosis and treatment of acute appendicitis. (1) Diagnostic laparoscopy is an effective and relatively atraumatic tool to investigate the abdominal cavity, which results in a sensitivity of almost 100%. This allows for accurate decision making, which is especially advantageous in young women and obese patients. (2) Prospective studies demonstrate that laparoscopic appendectomy is at least as good as open appendectomy and that the laparoscopic approach results in a reduced postoperative infection rate. (3) The similar complication rate after laparoscopic appendectomy, when performed by residents rather than staff surgeons, underlines the feasibility and teaching potential of this minimal invasive procedure.

[Gastric pouch dilatation: complications after laparoscopic implantation of a silicone gastric band in pathologic obesity]. / Die Magen-Pouch-Dilatation: Komplikationen nach laparoskopisch implantiertem Silikon-Magenband bei pathologischer Adipositas.

In 20 patients with morbid obesity a laparoscopic silicon gastric banding was installed using a LAP-BAND. All patients were examined postoperatively with water-soluble oral contrast material according to the usual protocol. 8 weeks after the operation a second control with thickened barium sulfate was added to measure and adjust the width of the silicon band. There were no early postoperative complications. But in the follow-up three patients presented with a pathologic gastric pouch-dilatation. This severe complication, which can have different etiologies, requires early detection and specific therapy.

Laparoscopic sigmoid resection: a comparative experimental study between double-stapling and foreign material free-biostent technique (TESA). Transient endoluminally stented anastomosis.

In current clinical practice the "double-stapling technique" is the standard for reanastomosis following minimally invasive sigmoid resection. In the present study, we compared the TESA technique (transient endoluminally stented anastomosis) with conventional stapled anastomosis and evaluated the effect of remnant foreign material on follow-up examination with endosonography. Laparoscopic sigmoid resection was performed in 12 pigs (mean weight 63+/-5.9 kg). Animals were randomly divided into two groups: In Group A, reanastomosis was performed following a standard technique using a 29-mm circular stapler. In Group B, the TESA technique using a resorbable radiopaque stent of polyglycolic acid was applied. The anastomosis was examined by plain x-ray on days 1, 7, and 14, and by contrast enema on day 42, respectively. Endosonography, macroscopic inspection, and histological evaluation of the anastomosis were performed on day 42. All anastomoses in group A were patent. In one animal in Group B stent displacement with subsequent leak of the anastomosis was observed. Circumferential length of the anastomosis on day 42 did not differ between the groups (Group A: 8.00+/-0.45 cm vs. Group B: 7.8+/-2.0 cm, p = 0.82). The duration of the operation was 130+/-27 minutes in Group A and 100+/-18 minutes in Group B (p = 0.06). Weight gain was equal: Group A: 24+/-9.6 kg vs. Group B: 24+/-5.0 kg, p = 0.74. Endosonography on day 42 postoperatively in the area of the anastomosis in group A was impaired due to metallic staples. TESA is a competitive method for reanastomosis following laparoscopic sigmoid resection. In contrast to the conventional technique, the anastomosis is free of foreign material 1 month after the operation, which facilitates follow-up examinations with endosonography as well as other imaging diagnostics.