Pressurised Intraperitoneal Aerosolised Chemotherapy-Results from the First Hundred Consecutive Procedures.

PIPAC is a new and promising technique for the intraperitoneal administration of chemotherapy. It can be used in patients with various peritoneal cancer metastases. It is mainly a palliative treatment, but there is some neoadjuvant treatment potential. We have operated on 41 patients with various intra-abdominal cancers. PIPAC was performed every 6 weeks. The indication was extension of peritoneal carcinomatosis beyond the criteria for cytoreductive surgery and HIPEC. The effect was evaluated according to the peritoneal cancer index, the peritoneal regression grading score and the amount of ascites. Complications were classified according to the Clavien-Dindo system. We have performed 100 PIPAC procedures. There were two major complications, classified as Clavien Dindo III (2%). The number of procedures varied from 1 to 6. Five patients switched to cytoreductive surgery and HIPEC, and one was indicated for the watch and wait strategy due to total regression according to PRGS. Three patients are still continuing treatment. The others stopped treatment mainly because of progression of the disease and loss of metastases. We observed a reduction in ascites production soon after PIPAC application. PIPAC is a safe and well-tolerated treatment modality. It is mainly a palliative treatment that can improve the quality of life by reducing the production of ascites, but in about 10% of cases, it can reduce the extent of the disease and allow for further radical treatment.

Alarmins and Related Molecules in Elective Surgery.

Surgery is associated with alterations of alarmins' and related molecules' levels. The aim of this study was to investigate which biomarkers are most involved in surgery. The studied group consisted of 58 patients with inguinal or umbilical hernia or cholecystolithiasis and 21 healthy controls for compa-rison. We also added seven acute patients with appendicitis, cholecystitis and incarcerated hernia. Serum concentrations of soluble receptor of advanced glycation end-products (sRAGE), extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE), calprotectin, high mobility group box 1 (HMGB1) and interleukin 6 (IL-6) were analysed by ELISA before and after surgery. Preoperative concentrations of calprotectin were significantly decreased while concentrations of sRAGE were significantly increased in patients compared to controls; the concentrations of EN-RAGE and HMGB1 did not differ significantly. IL-6 levels were undetectable in elective patients preoperatively and in controls. Postoperatively, there was a significant increase of EN-RAGE, calprotectin, HMGB1, and IL-6 and a significant decrease of sRAGE compared to preoperative levels. In acute patients, all tested molecules except for sRAGE were significantly increased preoperatively, and sRAGE was significantly decreased. In contrast, after surgery, we could observe a further increase in IL-6; the other biomarkers did not differ significantly. We can conclude that the concentrations of all tested biomarkers are significantly influenced by elective surgery. The postoperative levels of all tested molecules increase except for sRAGE, whose level is significantly decreased after surgery. In acute states, these molecules are already increased, and the influence of surgery is, apart from IL-6, insignificant.

Diagnosis and Surgical Management of Insulinomas-A 23-Year Single-Center Experience.

Background and Objectives: Insulinoma is a rare tumor of the Langerhans islets of the pancreas. It produces insulin and causes severe hypoglycemia with neuroglycopenic symptoms. The incidence is low, at about 1-2 per 1 million inhabitants per year. The diagnosis is based on the presence of Whipple's triad and the result of a fasting test. Surgery is the treatment of choice. Objectives: A retrospective observational study of patients operated on for insulinoma in our hospital focused on the diagnosis, the type of surgery, and complications. Materials and Methods: We retrospectively reviewed patients operated on due to insulinoma. There were 116 surgeries between 2000 and 2022. There were 79 females and 37 males in this group. A fasting test and a CT examination were performed on all the patients. Results: The average duration of the fasting test was 18 h. Insulinoma was found in the body and tail of the pancreas in more than half of the patients. Enucleation was the most frequent type of surgery. Complications that were Clavien Dindo grade III or more occurred in 18% of the patients. The most frequent complications were abscesses and pancreatic fistula. Five patients had malignant insulinoma. Conclusions: Surgery is the treatment of choice in the case of insulinomas. The enucleation of the tumor is a sufficient treatment for benign insulinomas, which are not in contact with the main pancreatic duct. Due to the low incidence of the condition, the centralization of patients is recommended.

Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

Diaphragmatic Liver Herniation after Radiofrequency Ablation of a Secondary Liver Tumor.

Radiofrequency thermal ablation (RFA) is widely used and has been accepted for the treatment of unresectable tumors. The leading technique that is used is percutaneous RFA under CT or US guidance. Multicenter surveys report acceptable morbidity and mortality rates for RFA. The mortality rate ranges from 0.1% to 0.5%, the major complication rate ranges from 2% to 3%. Diaphragmatic injury is a rare complication and it is described after RFA of subdiaphragmatic tumors. Most of them are without clinical importance. There are some case reports about diaphragmatic herniation of the intestine into the pleural cavity. We present a case of diaphragmatic perforation resulting in the herniation of the liver into the pleural cavity. A thoracotomy was performed, the liver was lowered back into the peritoneal cavity and the perforation was closed with mesh.

A Randomized Comparison of Plasma Levobupivacaine Concentrations Following Thoracic Epidural Analgesia and Subpleural Paravertebral Analgesia in Open Thoracic Surgery.

BACKGROUND: The aim of this study was to compare plasma levobupivacaine concentrations in thoracic epidural and subpleural paravertebral analgesia. METHODS: Forty-four patients indicated for open lung resection had an epidural catheter inserted preoperatively or a subpleural catheter surgically. A bolus of 0.25% levobupivacaine at a dosage of 0.5 mg × kg-1 was given after the thoracotomy closure. Plasma levobupivacaine level at 30 min was the primary outcome. Pharmacokinetic modeling was performed subsequently. Secondary outcomes included the quality of analgesia, complications, and patients'mobility. RESULTS: Plasma concentrations were similar 30 min after application-0.389 mg × L-1 in the epidural and 0.318 mg × L-1 in the subpleural group (p = 0.33) and lower in the subpleural group at 120 min (p = 0.03). The areas under the curve but not maximum concentrations were lower in the subpleural group. The time to reach maximum plasma level was similar in both groups-27.6 vs. 24.2 min. No clinical symptoms of local anesthetic toxicity were recorded. CONCLUSIONS: Levobupivacaine systemic concentrations were low in both groups without the symptoms of toxicity. This dosage should be safe for postoperative analgesia after thoracotomy.

Peritoneal Carcinomatosis of Gastric Origin - Treatment Possibilities.

BACKGROUND: Peritoneal carcinomatosis of gastric origin is challenging to diagnose and treat. This disease is often misdiagnosed in the early stages using a non-invasive technique. Conventional surgery is unsuitable for treatment of patients with peritoneal seeding and positive peritoneal cytology. Peritoneal recurrence is the most frequent cause of therapeutic failure. The effectiveness of chemotherapy is low due to the plasma-peritoneal barrier. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for pseudomyxoma peritonei and mesothelioma and improves overall survival and disease-free survival. This approach is also widely used to prevent and treat peritoneal carcinomatosis of gastric origin. PURPOSE: This article aims to provide a short summary of the contemporary role of cytoreductive surgery and HIPEC for treatment of gastric cancer patients. Theoretically, there are four possible applications and indications. First, palliative application to improve quality of life without prolongation of overall survival. This application mainly affects malignant ascites. Second, therapeutic application using a combination of gastrectomy/cytoreductive surgery and HIPEC to treat advanced disease including peritoneal metastases. Localized peritoneal seeding is the only indication for this application (maximum peritoneal cancer index of 10-12 or Cy+). Third, adjuvant/prophylactic application in patients at high risk of peritoneal recurrence, typically those with T3, T4, N+ disease (without peritoneal seeding). Fourth, neoadjuvant application using a combination of repeated HIPEC and chemotherapy with the aim of decreasing peritoneal seeding and enabling radical surgery. In this indication, HIPEC is often replaced by pressurized intraperitoneal aerosol chemotherapy.

28 day post-operative persisted hypercoagulability after surgery for benign diseases: a prospective cohort study.

BACKGROUND: Surgery for benign disease is associated with a low-risk of developing venous thromboembolism (VTE). Despite a relatively low incidence of postoperative VTE in patients after elective cholecystectomy and abdominal hernia repair there are data proving hypercoagulability in the early postoperative period. We focused on assessment of the systemic inflammatory response and coagulation status in these surgical patients after hospital discharge. METHODS: Prospectively, patients who underwent surgery for benign disease were included. Two hundred sixteen patients were enrolled - 90 patients in laparoscopic cholecystectomy (LC) group and 126 patients in hernia surgery (HS) group. Risk assessment of VTE according to the Caprini risk assessment model was performed in all patients. Prevalence of VTE in postoperative period was observed. Markers of systemic inflammatory response (IL-6, CRP, α-1-acid glycoprotein, transferrin) and coagulation markers (PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer) were measured before surgery, on 7-10th postoperative day and on 28-30th postoperative day. RESULTS: Clinically apparent deep vein thrombosis was diagnosed in only one patient - 0.46%. Statistically significant elevation of inflammatory markers IL-6, CRP and α-1-acid glycoprotein (p < 0.001; all) were proved in both groups of patients on 7-10th postoperative day. Statistically significant elevation of coagulation markers PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer (p < 0.001; all) were proved in LC and HS groups on 7-10th postoperative day. No statistical difference was observed in IL-6, CRP and α-1-acid glycoprotein levels a month after surgery as compared with preoperative levels within each group. Statistically significant elevation of fibrinogen and prothrombin fragment F1 + 2 levels (p < 0.001; both) persisted on 28-30th postoperative day in both groups. Persisted elevation of D-dimer levels was proved only in HS group (p < 0.001), not in LC group (p = 0.138), a month after surgery. CONCLUSIONS: Activated systemic inflammatory response and hypercoagulable condition were verified in patients after laparoscopic cholecystectomy and hernia surgery after their hospital discharge. Hypercoagulability persisted even a month after surgery. Nevertheless, we observed very low prevalence of clinically apparent VTE in patients with in-hospital postoperative VTE prophylaxis. TRIAL REGISTRATION: Trials of the Czech Ministry of Health No. RVO-VFN64165 and NT 13251-4 .

Pancreatic Cancer Diagnostics and Treatment--Current State.

Pancreatic ductal adenocarcinoma (PDAC) represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60-80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5). In contrast R0 resection shows the survival 18-27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2) have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10-20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the "vessel first" approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.

Premalignant and malignant lesions of the heterotopic pancreas in the esophagus: a case report and review of the literature.

Heterotopic pancreas is a congenital pathology of the gastrointestinal tract, particularly rare in the esophagus. Both symptomatology and findings during preoperative examinations are non-specific and therefore do not often lead to an accurate diagnosis, which is usually revealed only by histopathological assessment of a resected specimen. We report an unusual case of a patient suffering from severe dysphagia caused by heterotopic pancreas in the distal esophagus with chronic inflammation and foci of premalignant changes. This article also reviews 14 adult cases of heterotopic pancreas in the esophagus previously reported in the literature, with the aim of determining the clinical features of this disease and possible complications including rare premalignant lesions and malignant transformation. Especially with regard to those complications, we suggest that both symptomatic and incidentally found asymptomatic lesions should be resected.

Early and subacute inflammatory response and long-term survival after hip trauma and surgery.

BACKGROUND: Hip fractures represent major source of morbidity in elderly patients. There is little evidence about the impact of inflammatory changes induced by hip trauma and surgery on long term survival. METHODS: We evaluated the prognostic significance of the surgery-related dynamics of white blood cell count (WBC), neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6) and soluble adhesion molecules (including P-selectin, E-selectin and VCAM) on survival in 104 consecutive patients with traumatic hip fractures recruited within the 2 years period. RESULTS: In surviving patients, the minimum follow-up length was 48 and maximum 84 months (median 60 months). The mean age of the population was 80 ± 9 years, 72% were women. The survival rates were 69%, 45% and 38% at one, three and five years of the follow-up, respectively. Baseline serum creatinine, older age and subdural anesthesia type were associated with worse survival. The acute inflammatory response failed to predict the long term survival. In contrast, elevated WBC and IL-6 as assessed 21 days after the surgery were associated with a significantly worse outcome. CONCLUSION: The survival of elderly patients undergoing the surgery for acute hip fracture is unfavorable. In contrast to previous reports, we did not confirm that acute inflammatory response to the surgery predicts the long-term survival. On the contrary, persistent elevation of WBC and IL-6 three weeks after the surgery indicates a poor outcome.

[Comparison of the overall stress during large bowel operations in senior patients (laparoscopy versus open surgery)]. / Porovnání stupne záteze pri operacích na tlustém streve u senioru (laparoskopie versus otevrené výkony).

BACKGROUND: Colorectal surgery particularly as a treatment option for colorectal cancer comprises considerable and ever expanding spectrum of surgical procedures. Seniors (over 65 years of age) form the majority of patients operated for benign or malignant colon disease. High age in general poses one of the significant risks of the operation. The study analyses overall stress caused to patients by laparoscopy and laparotomy surgical procedures. METHODS: Literature analysis of surgical stress in patients and prospective study of our patients' data collected over the period of four years. Comparable indicators: objectification of pre-operative stress and risks, per-operative cardiac and circulatory parameters, course of the lesion healing process, laboratory reactions of acute phase proteins, morbidity and lethality related to the surgery treatment. RESULTS: Comparable results of tissue response examinations demonstrated no fundamental difference between laparoscopic and laparotomic operations performed on otherwise healthy younger individuals. Laparoscopic surgery, however, appears to be fully appropriate treatment modality in majority of patients suffering from colorectal disease, even in senior age. In advanced or complicated stages of the disease the open-section surgery still remains more efficient. CONCLUSION: Age itself cannot be generally denoted as a fundamental risk factor. Co-morbid conditions, however, represent considerable risk, especially in high age patients. Laparoscopic surgery may well be applied even in senior age patients with no contra-indications. Yet, its application requires perfectly mastered laparoscopic technique and rational approach. Success of the operation in high-risk patients depends on close interdisciplinary cooperation, especially with anaesthetists.

[Our experience with pancreatic cancer and its relation to diabetes mellitus]. / Karcinom pankreatu--nase zkusenosti se vztahem k diabetes mellitus.

BACKGROUND: Despite the introduction of new imaging methods, the prognosis of pancreatic carcinoma (PC) remains hopeless. Therefore, there has been exerted much effort to elucidate the risk factor enabling the diagnosis of PC in the "preclinical state". At the time of PC diagnosis, more than 30% of patients suffer from diabetes mellitus, much more often than in the rest of the population. It is not clear whether DM is a risk factor for PC onset or DM appears secondary to the destruction of the gland by the tumor progression or by the effect of unknown factors produced by the cancer cells. METHODS AND RESULTS: We enrolled 204 individuals into the study, 69 of them were controls, 70 patients had type 2 diabetes mellitus and 65 cases had newly diagnosed PC. The patients with PC had in 68% of cases disturbed glucose homeostasis and significantly higher values of insulin resistance index (HOMA-IR) in comparison with the control group. The presence of glucose homeostasis disturbances does not influence tumor staging and localization. CONCLUSIONS: Results of our pilot study confirmed the so far unsatisfactory state of PC diagnostics (majority of cases fall to stages III and IV) and corroborated the close relation to DM. The early markers for the risk of pancreatic carcinoma development should be searched among the factors participating in the regulation of the glucose homeostasis and insulin sensitivity.

Older age and type of surgery predict the early inflammatory response to hip trauma mediated by interleukin-6 (IL-6).

Hip trauma and surgery are associated with systemic inflammatory reaction. However, little evidence exists about the role of IL-6. In order to assess the inflammatory response, we evaluated white blood cell (WBC) count, C-reactive protein (CRP) and IL-6 dynamics in sequential pre- and postsurgical samples collected from 125 elderly patients (mean age 78+/-9 years) undergoing osteosynthesis (OS) for extracapsular hip fractures (n=69), hemiarthroplasty (HA) or urgent total hip arthroplasty for intracapsular fractures (UA) (n=35), and elective total hip arthroplasty for osteoarthrosis (OA) (n=21). Both preoperative CRP and IL-6 levels were higher in patients with intracapsular fractures. IL-6 levels reached peak values immediately after the surgery, while CRP peak levels were reached 48 h after the surgery. The overall inflammatory reaction was more intense in HA patients compared to the other subgroups. Independent of each other, older age and the hip fracture type affected the IL-6 response, while the CRP response depended only on the type of surgery. The abrupt increase in IL-6 immediately after the procedure suggests its involvement in the early stages of the postoperative inflammatory reaction after hip surgery. This reaction is particularly pronounced in elderly patients receiving HA.