Feasibility and Safety of Laparoscopic D2 Gastrectomy in Combination with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Gastric Cancer at High Risk of Recurrence-The PIPAC-OPC4 Study.

BACKGROUND: Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m2) and doxorubicin (2.1 mg/m2) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy. RESULTS: Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy. CONCLUSIONS: Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe.

Treatment of Peritoneal Metastasis with Pressurized Intraperitoneal Aerosol Chemotherapy: Results from the Prospective PIPAC-OPC2 Study.

BACKGROUND: Pressurized Intraperitoneal Aerosol chemotherapy (PIPAC) is a local treatment for peritoneal metastasis (PM). Prospective data are scarce and evaluation of treatment response remains difficult. This study evaluated the use of the Peritoneal Regression Grading score (PRGS) and its prognostic value. PATIENTS AND METHODS: This was a prospective, controlled phase II trial in patients with PM from gastrointestinal, gynaecological, hepatopancreatobiliary, primary peritoneal, or unknown primary cancer. Patients in performance status 0-1, with a non-obstructed gastrointestinal tract, and a maximum of one extraperitoneal metastasis were eligible. Colorectal or appendiceal PM had PIPAC with oxaliplatin, other primaries had PIPAC with cisplatin and doxorubicin. Biopsies were taken at each PIPAC and evaluated using the PRGS. Quality-of-life questionnaires were reported at baseline and after three PIPACs. RESULTS: One hundred ten patients were treated with 336 PIPACs (median 3, range 1-12). One hundred patients had prior palliative chemotherapy and 45 patients received bidirectional treatment. Complete or major histological response to treatment (PRGS 1-2) was observed in 38 patients (61%) who had three PIPACs, which was the only independent prognostic factor in a multivariate analysis. The median overall survival (mOS) from PIPAC 1 was 10 months, while patients with PM from gastric, colorectal, and pancreatic cancer had a mOS of 7.4, 16.7, and 8.2 months, respectively. Global health scores were significantly reduced, but patients were less fatigued, nauseated, constipated, and had better appetite after three PIPACs. CONCLUSIONS: PIPAC with oxaliplatin or cisplatin and doxorubicin was able to induce a major or complete histological response during three PIPACs, which may provide significant prognostic information, both at baseline and after treatment.

Clinically decisive (dis)agreement in multidisciplinary team assessment of esophageal squamous cell carcinoma; a prospective, national, multicenter study.

BACKGROUND: Decisions regarding tumor staging, operability, resectability, and treatment strategy in patients with esophageal cancer are made at multidisciplinary team (MDT) conferences. We aimed to assess interobserver agreement from four national MDT conferences and whether this would have a clinical impact. METHODS: A total of 20 patients with esophageal cancer were included across all four upper gastrointestinal (GI) cancer centers. Fully anonymized patient data were distributed among the MDT conferences which decided on TNM category, resectability, operability, curability, and treatment strategy blinded to each other's decisions. The interobserver agreement was expressed as both the raw observer agreement and with Krippendorff's α values. Finally, a case-by-case evaluation was performed to determine if disagreement would have had a clinical impact. RESULTS: A total of 80 MDT evaluations were available for analysis. A moderate to near-perfect observer agreement of 79.2%, 55.8%, and 82.5% for TNM category was observed, respectively. Substantial agreement for resectability and moderate agreement for curability were found. However, an only fair agreement was observed for the operability category. The treatment strategies had a slight agreement which corresponded to disagreement having a clinical impact in 12 patients. CONCLUSIONS: Esophageal cancer MDT conferences had an acceptable interobserver agreement on resectability and TM categories; however, the operability assessment had a high level of disagreement. Consequently, the agreement on treatment strategy was reduced with a potential clinical impact. In future MDT conferences, emphasis should be on prioritizing the relevant information being readily available (operability, T & M categories) to minimize the risk of disagreement in the assessments and treatment strategies, and thus, delayed or suboptimal treatment.

Endoscopic ultrasound-guided fine-needle marking of lymph nodes.

BACKGROUND AND STUDY AIMS: No previous studies have evaluated the ability of endoscopic ultrasonography to describe the anatomic location of lymph nodes on the basis of a node-to-node comparison. The aim of this study was to assess the feasibility and safety of a new endoscopic ultrasound (EUS)-guided fine-needle technique for marking lymph nodes. PATIENTS AND METHODS: Twenty-five patients with suspected or confirmed malignancies of the upper gastrointestinal tract were prospectively included. EUS-guided fine-needle marking (EUS-FNM) was performed with a silver pin with a diameter that allowed it to fit into a 19-gauge needle. The position of the pin was verified by EUS. End points were the ability to identify and isolate the marked lymph node during surgery and a comparison between the location of the pin as suggested by EUS and the actual location found in the resected specimen. RESULTS: Twenty-three lymph nodes were marked. Nineteen intended surgical isolations were performed. The lymph nodes were isolated in the resection specimens in 18 patients (95 %). In 2 out of 20 cases the pin was not localized by laparoscopic ultrasonography. In 89 % of the cases the marked lymph node was in the same location as described by EUS. One pin (5 %) was not retrieved. In three cases, a small hematoma was observed. There was no sign of long-term complications. CONCLUSION: EUS-FNM with a silver pin in lymph nodes is feasible and safe. EUS-FNM seems to be a suitable tool for evaluating lymph nodes on the basis of a node-to-node comparison.

Combined preoperative endoscopic and laparoscopic ultrasonography for prediction of R0 resection in upper gastrointestinal tract cancer.

BACKGROUND: This study evaluated the ability of combined endoscopic and laparoscopic ultrasonography to predict R0 resection and avoid unnecessary surgery in patients with upper gastrointestinal tract cancer (UGIC). METHODS: A total of 411 consecutive patients with UGIC (182 pancreatic cancers, 134 gastric cancers and 95 oesophageal cancers) treated between January 2002 and May 2004 were analysed prospectively. The allocation of patients into resectability groups by endoscopic ultrasonography (EUS) and laparoscopic ultrasonography (LUS) was compared with the treatment actually undertaken. RESULTS: The combination of EUS and LUS correctly predicted R0 resection in 90.6 per cent, R1-R2 in 91 per cent and irresectability in 91.4 per cent of patients. Ten patients (2.4 per cent) had explorative laparotomy only. There were no complications associated with the EUS and LUS procedures. CONCLUSION: The routine use of EUS and LUS before surgery predicted R0 resection in nine of ten patients and reduced the number of unnecessary laparotomies to less than 3 per cent.

Prospective evaluation of patient tolerability, satisfaction with patient information, and complications in endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Prospective data are lacking on the safety of endoscopic ultrasonography (EUS) and on patient satisfaction with the procedure. We prospectively recorded complications related to EUS in order to establish morbidity and mortality. In addition the levels of patient satisfaction were evaluated, with regard to the tolerability of the procedure (pain, discomfort, and anxiety levels) and the provision of information. PATIENTS AND METHODS: 3324 consecutive patients who underwent EUS were studied with regard to complications. During the study period 300 patients were interviewed and followed up in detail as part of the evaluation of patient satisfaction. RESULTS: Ten patients (0.3 %) suffered from a complication related to the EUS procedure, and two patients died (0.06 %). There were no significant differences between the complication rates for EUS-guided fine-needle aspiration (EUS-FNA) and for EUS, but both fatal cases related to EUS-FNA/EUS-guided intervention. Nine of the ten patients with complications (90 %) had a diagnosis of malignancy, and esophageal perforation accounted for half of all complications. Although the majority of patients with nonlethal complications were managed well on conservative regimens, only one case, of self-limiting acute pancreatitis, could be classified as a mild complication. With regard to patient tolerability, only minor incidents occurred during the EUS procedure (tracheal suction 5 %, vomiting 0.3 %, aspiration 0.3 %) and no intervention was necessary. During the procedure, 80 % of the patients had no or only slight pain and more than 95 % experienced only slight or no anxiety, whereas more than half of the patients experienced moderate to severe discomfort. More than 90 % of the patients were satisfied or very satisfied with the information provided to them before and after the EUS, and the same number of patients were ready without hesitation to undergo an additional EUS examination if necessary. CONCLUSIONS: EUS, EUS-FNA and EUS-guided intervention are safe techniques, but severe and lethal complications do occur. The EUS procedures can be performed with a high level of patient satisfaction and with low levels of pain, discomfort and anxiety.

Cost-effectiveness of endoscopic ultrasonography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography in patients suspected of pancreaticobiliary disease.

BACKGROUND: It is not known whether initial endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) is more cost effective than endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A cost-effectiveness analysis of EUS, MRCP and ERCP was performed on 163 patients. The effectiveness of an investigation was defined as the percentage of patients with no need for further evaluation after the investigation in question had been performed. Costs were assumed from the budget-holder's point of view. RESULTS: MRCP, EUS and ERCP had a total accuracy of 0.91, 0.93 and 0.92, respectively. Eighty-four (52%) patients needed endoscopic therapy in combination with ERCP, giving an effectiveness of MRCP, EUS, and ERCP of 0.44, 0.45 and 0.92, respectively. The cost-effectiveness of MRCP, EUS, and ERCP was 6622, 7353 and 4246 Danish Kroner (DKK) per fully investigated and treated patient (1 DKK=0.14 EUR). CONCLUSION: Within a patient population with a probability of therapeutic ERCP in 50% of the patients, ERCP was the most cost-effective strategy.

Is there a difference in diagnostic accuracy and clinical impact between endoscopic ultrasonography and magnetic resonance cholangiopancreatography?

BACKGROUND AND STUDY AIMS: It is still unknown whether there is a difference in diagnostic accuracy and clinical impact between endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP). PATIENTS AND METHODS: The test performance and potential clinical impact of EUS and MRCP, had each investigation been performed as the first examination method, were compared prospectively in 163 patients admitted for and examined by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The accuracies of EUS and MRCP were 0.93 and 0.91, respectively (no significant difference, P > 0.05). Had EUS or MRCP been performed as the first investigation in the 75 patients who had a presumed high probability for needing therapeutic ERCP, only 15 and nine patients, respectively, would have avoided ERCP. In this group of patients, one patient needed other diagnostic investigations following EUS compared with 11 patients following MRCP ( P = 0.004). For the 57 patients with an intermediate probability of needing endoscopic therapy, EUS and MRCP would have spared 37 and 38 patients, respectively, from the need to have an ERCP. In 31 patients with a presumed low risk of needing endoscopic therapy, 30 and 29 patients would have been spared from ERCP had EUS and MRCP, respectively, been performed initially. CONCLUSIONS: There was no difference in the diagnostic accuracy and clinical impact between EUS and MRCP in the majority of the patients. The impact of EUS or MRCP on the ERCP workload was highly dependent on the presumed probability of needing endoscopic therapy.

Is the 'Trondsen Discriminant Function' useful in patients referred for endoscopic retrograde cholangiopancreatography?

BACKGROUND: Ideally, patients should only be referred to endoscopic retrograde cholangiopancreatography (ERCP) if therapy is indicated. The aim of this study was to evaluate whether or not the 'Trondsen Discriminant Function' (DF) could be used for selecting patients directly for ERCP. METHODS: The DF was calculated in 163 patients referred for ERCP with the DF value being unknown to the endoscopist. Compared to the final diagnoses of the patients, the sensitivity and specificity of a positive DF value for predicting biliary obstruction and need of endoscopic therapy were calculated. RESULTS: Ninety-three (57%) patients had obstruction of the bile duct and 84 (52%) needed endoscopic therapy. A positive DF value had a sensitivity, specificity, positive predictive value and negative predictive value for predicting biliary obstruction of 81%, 72%, 79% and 73%, respectively. If only patients with a positive DF value had been examined by ERCP, 50 (31%) patients would have been saved from this investigation. Had a negative DF value stopped the patients from further diagnostic evaluation, 18 (11%) would have had undiagnosed pathological conditions. CONCLUSION: A positive DF value is useful for selecting which patients should be referred directly for ERCP because of a high probability that they will need endoscopic therapy. A negative DF value cannot be used to stop the patient from further diagnostic evaluation.

Clinical impact of endoscopic ultrasonography at a county hospital.

BACKGROUND AND STUDY AIMS: Although endoscopic ultrasonography (EUS) is a well-described examination method, there have been few reports concerning its clinical impact. The aim of this study was to describe EUS as it is performed at a county hospital, with an emphasis on the indications and clinical outcome. PATIENTS AND METHODS: Patients examined using EUS between December 1997 and November 2000 were recorded prospectively. Follow-up was conducted by examining each patient's medical records at least 3 months after the investigation. The EUS findings were compared with the patient's final diagnosis, and the decisions made by the referring department on the basis of each investigation were recorded. RESULTS: A total of 344 EUS procedures were performed. In the third year, the distribution of patients relative to the various referral diagnoses was: 78 with suspected benign pancreaticobiliary disease, 33 for staging of known upper gastrointestinal tract malignancy, 15 with suspected mediastinal disease or for staging of lung cancer, 13 with suspected submucosal lesions, and five with unclassified disease. Follow-up was possible in 340 patients (99 %). Compared to the final diagnosis in each patient, the sensitivity, specificity, and accuracy rates of EUS were 86 %, 90 %, and 88 %, respectively. The EUS findings made more invasive procedures unnecessary in 199 patients (58 %). EUS led to a switch to less invasive procedures in 61 patients (18 %), and it had no influence on the further management strategy in 80 patients (24 %). CONCLUSIONS: EUS has a high level of accuracy and a substantial clinical impact when performed in an unselected population. The estimated numbers of investigations needed appear to justify setting up an EUS center at institutions with a catchment population of 350 000 inhabitants.

Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study.

Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection to levels observed in nontransfused patients. Using a double-blinded, randomized design, we studied the postoperative infection rate in patients undergoing open colorectal surgery transfused with either leukocyte-depleted erythrocyte suspensions (LD-SAGM) or non-leukocyte-depleted erythrocyte suspensions (SAGM). Unselected patients (n 279) were allocated to receive LD-SAGM (n 139) or SAGM (n 140) if transfusion was indicated. Forty-five percent were transfused, yielding 48 patients in the LD-SAGM group and 64 in the SAGM group. Thirteen patients were excluded because they received one type of transfusion in spite of randomization to the other type. No significant differences in the rates of postoperative infections (P=0.5250) or postoperative complications (P=0.1779) were seen between the two transfused groups. Infection rates were 45% and 38% in the transfused groups and 21% and 23% in the nontransfused groups. No significant difference between the transfused groups was seen on any single infectious event, mortality rate, or duration of hospitalization. Leukocyte-depletion of erythrocyte suspensions transfused to patients undergoing open colorectal surgery does not reduce postoperative infection rates.

Initial experience with new dedicated needles for laparoscopic ultrasound-guided fine-needle aspiration and histological biopsies.

BACKGROUND AND STUDY AIMS: Laparoscopic ultrasonography (LUS) is an important imaging modality during laparoscopic staging of intra-abdominal malignancies, but LUS-assisted biopsy is often difficult or impossible. We report a newly developed inbuilt biopsy system for direct LUS-guided fine-needle aspiration (FNA) and Tru-cut biopsies. PATIENTS AND METHODS: LUS-guided biopsy was performed in 20 patients with upper gastrointestinal tract tumors. The biopsied lesions had either not been previously detected by other imaging modalities or had been inaccessible, or the biopsy sample had been inadequate. Primary diagnosis, duration of biopsy procedure, needle monitoring (visibility, penetration, and deviation), complications, technical failures, and pathological findings were prospectively recorded. RESULTS: 44 biopsies were performed with 25 needles (19, 20, and 22-G). Needle monitoring and penetration were good or acceptable in 18 patients (90%). Slight needle deviation (<10 mm) was seen in eight patients (40%). The LUS-guided biopsy specimen was sufficient for analysis in 13 patients (65%). In two additional patients, adequate material was obtained, but pathological examination was impossible owing to incorrect handling of the specimen. The biopsy procedures lasted 16.3 minutes (range 10-20 minutes) and no complications were seen. CONCLUSIONS: LUS-guided fine-needle aspiration or Trucut biopsy is possible using this newly developed biopsy system. These preliminary data suggest that LUS-guided biopsy may further improve the diagnostic possibilities of LUS.

Clinical impact of endoscopic ultrasound-guided fine needle aspiration biopsy in patients with upper gastrointestinal tract malignancies. A prospective study.

BACKGROUND AND STUDY AIMS: Several studies have evaluated the accuracy of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) in the upper gastrointestinal tract, but so far no studies have specifically evaluated the clinical impact of EUS-FNAB in upper gastrointestinal tract cancer patients. In this consecutive and prospective study, EUS-FNAB was only performed if a positive malignant finding would change the therapeutic strategy. PATIENTS AND METHODS: Between 1997 and 1999, 307 consecutive patients were referred for EUS with a diagnosis or strong suspicion of esophageal, gastric or pancreatic cancer; 274 patients were potential candidates for surgical treatment and had EUS. According to predefined impact criteria, 27% (75/274) of the patients had EUS-FNAB for staging or diagnostic reasons. RESULTS: The overall clinical impact of EUS-FNAB was 13%, 14%, and 30% in esophageal, gastric, and pancreatic cancer, respectively. The staging-related clinical impact was similar for all three types of cancer (11-12.5%), whereas the diagnosis-related impact was highest in pancreatic cancer patients (86%). EUS-FNAB was inadequate in 13% and gave false-negative results in 5%. The overall sensitivity, specificity and accuracy for EUS-FNAB were 80%, 78% and 80%, respectively. No complications related to the biopsy procedure were seen. CONCLUSIONS: If EUS-FNAB was performed only in cases where a positive malignant result would change patient management, then approximately one out of four patients with upper gastrointestinal tract cancer would require a biopsy. With this approach the actual clinical impact of EUS-FNAB ranged from 13% in esophageal cancer to 30% in pancreatic cancer. EUS-FNAB plays a limited, but very important clinical role in the assessment of upper gastrointestinal tract cancer.

Cost-effectiveness of different diagnostic strategies in patients with nonresectable upper gastrointestinal tract malignancies.

BACKGROUND AND METHODS: Using a simple model, this retrospective study evaluated the cost-effectiveness of different diagnostic strategies used for pretherapeutic detection of patients with disseminated or locally nonresectable upper gastrointestinal tract malignancies (UGIM). Of 162 consecutive UGIM patients referred for treatment, 73 (45%) had disseminated or locally nonresectable disease, and these patients were eligible for evaluation. RESULTS: The noninvasive diagnostic strategies (computed tomography [CT] with ultrasonography [US] and endoscopic ultrasonography [EUS]) had a low procedure cost, but a diagnostic strategy based on CT with US or CT with US and laparoscopy was not cost-effective. The inclusion of endoscopic or laparoscopic ultrasonography seemed necessary to the provision of a cost-effective strategy because both techniques had a high diagnostic accuracy combined with a low cost. A change in diagnostic strategy from CT with US to CT with US and EUS resulted in a net saving regarding the cost of each additional nonresectable patient detected, but this strategy still required up to 20% futile explorative laparotomies. CONCLUSIONS: The combination of endoscopic and laparoscopic ultrasonography was cost-effective and had no complications in this study. We use this strategy as our standard in the pretherapeutic evaluation of UGIM patients.

[Neonatal pneumothorax]. / Neonatal pneumothorax.

INTRODUCTION: Neonatal pneumothorax (NP) is associated with an increased mortality. However, few studies have evaluated which parameters are associated with neonatal death and infant death. METHODS: Retrospective study of newborns treated for NP at a university hospital in the period 1.1.1989 to 31.12.1998. RESULTS: Forty-seven newborns (30 boys, 17 girls) had NP. Thirty-two infants (68%) had chest tube insertion, and 15 (32%) did not need chest tube. Nine infants (19%) died within one week after birth. Six of these were mature infants with additional major congenital malformations. The remaining three were premature infants with gestational ages of 25, 26 and 29 weeks, respectively. Another 29 week old infant died during the first year of life, bringing the total number of deaths within one year to ten (21%). No deaths occurred among infants with NP who did not have chest tube insertion. Apart from the presence of additional major congenital malformations (p = 0.001/0.003) and the need for mechanical ventilation after tube insertion (p = 0.058/0.035) none of the selected parameters (sex, birth weight, gestational age, way of delivery, CPAP treatment before tube insertion, mechanical ventilation before tube insertion, uni or bilateral pneumothorax, and total number of tubes) had significant relationship to neonatal death or infant death. DISCUSSION: The presence of additional congenital malformations and the need for mechanical ventilation after tube insertion were the only parameters in this series which were associated with an increased mortality in infants with NP demanding tube drainage.

[Abdominal skin affection caused by ectopic gut mucosa]. / Hudaffektion på abdomen forårsaget af ektopisk tarmslimhinde.

We report a case of skin affection on the abdomen in a 75 year-old woman with an ileostomy. The lesion developed during a period of two years on a site distant from the patient's present ostomy. However, it was located on the site of a former ileostomy removed 25 years ago. The lesion was due to proliferation of remaining gut mucosa.

[Thoracic surgery in children]. / Thoraxkirurgi hos børn.

In order to study non-cardiac thoracic surgery in children we reviewed the files of all children under 16 years, who had surgery at the Department of Thoracic and Cardiovascular Surgery, Odense University Hospital from 1987 to 1996. Thirty-three children had chest tube insertion because of neonatal pneumothorax. Twelve of these died within five days after birth. Fifty-five children had surgery for primary intrathoracic diseases. Congenital pulmonary malformations were most common in the youngest children. Traumatic diseases were most common in the oldest. No immediate postoperative deaths occurred, but seven children were dead at the follow-up. Thirty-eight had surgery for involvement of the thoracic organs secondary to other often malignant diseases. Eleven of these were dead at the follow-up. It is concluded, that thoracic surgery is required for a number of diseases in children and is well tolerated. However, severe primary diseases lead to an increased mortality.