Efficacy and Safety of FOLFIRINOX in Locally Advanced Pancreatic Cancer. A Single Center Experience.

The management of locally advanced pancreatic cancer (LAPC) is a major challenge. Although new drugs are available for the treatment of metastatic disease, the optimal treatment of non-metastatic cases remains controversial. The role of neoadjuvant therapy is still a question of debate in this setting. The aim of the study was to prospectively collect and analyse data on efficacy and safety of a modified FOLFIRINOX regimen in LAPC patients treated in a single institution. Another major objective was to assess the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. No bolus fluorouracil was given and a 20% dose reduction of oxaliplatin and irinotecan was applied. Primary G-CSF prophylaxis was applied to prevent febrile neutropenia. Thirty-two patients (mean age 60.2 years, range: 40-77 years) have been enrolled into the study. All patients had ECOG performance status of 0 or 1. Best response to therapy was stable disease (SD) or partial regression (PR) in 18 (56.2%) and 6 (18.8%) cases. Two patients (6.3%) underwent surgical resection (100% R0). The most frequent grade 3/4 adverse events were nausea (18.8%), fatigue (12.5%) and diarrhea (12.5%). The incidence of severe neutropenia was 28.1%, with only one documented case of febrile neutropenia. The probability of disease progression was 25% and 50% after 75 and 160 days with 88.4% of possibility of disease progression after 500 days. OS probability was 92.1, 71.5% and 49.5% at 180-, 365 and 540 days. Our data does not support the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. However, due to the high disease control rate observed, FOLFRINOX might be recommended as first line option for the palliative treatment of LAPC. Despite reduced chemotherapy doses significant toxicity has been seen.

Comparison of immunophenotypes of primary breast carcinomas and multiple corresponding distant metastases: an autopsy study of 25 patients.

Phenotypical change in metastatic breast carcinoma has widely been accepted as an inherent biological feature rather than technical fault. We analyzed the immunohistochemical phenotype and histopathological features of 25 primary breast carcinomas and 90 corresponding distant metastases in 23 organs retrospectively. Histological slides were reviewed for prognostic and predictive factors. Overall, metastases were more similar to each other and often differed from the primary tumor. We created a 3-step grouping system based on the localization of metastases. Regions: tumors metastasizing to the abdominal region were likely to lose ER (p = 0.002); we detected loss of PR in metastases to the thorax (p = 0.039) and abdomen (p < 0.001). Organ systems: loss of ER and PR was observed in metastases to the gastrointestinal system (p = 0.026 and p = 0.001, respectively), in the respiratory system only the loss of PR was significant (p = 0.05). Individual organs: the primaries were likely to lose the hormone receptors in liver metastases (ER p = 0.026; PR p = 0.004). In lung metastases only loss of PR was apparent (p = 0.049). We did not observe significant change in HER2 status, regarding Ki67 change occurred only in bone metastases compared to the primary (p = 0.048). 7/25 patients' distant metastases had heterogeneous immunoprofiles. The later the metastasis was discovered the more likely it had a differing IHC profile compared to the primary tumor, patients who had longer OS had a higher chance to develop a discordant metastasis. Immunoprofile of metastases may differ from primary breast cancer and from each other, probably resulting in different response to therapy.

Changes in the operating time of laparoscopic cholecystectomy of the surgeons and novices between 1994-2012.

BACKGROUND: The technique of laparoscopic cholecystectomy(LC) has not changed over the past recent years; therefore the possibility is open to study its learning curve. METHODS: Retrospectively, every third year's LCs were analysed between 1994 and 2012. The learning curves of surgeons and novices were defined in the department. The surgeons have scored the laparoscopic technique of their colleagues on a scale of 1 to 10 and operation time (OT) was examined in light of the assistant's technique. RESULTS: 2,216 LCs were performed in the examined period.The average OT of the department was 78.3 minutes in 1994,which had decreased to 45.4 minutes (42.0%) by 2003. The improvement rates of surgeons and novices were 36.7% and respectively 9.9%, and the variance between the minimum and maximum OT changed in parallel. The OT in the initial 3 years of learning had become 13% shorter by 2006 and the first section of the learning curve has also become steeper. In case of surgeons whose technical points were low and OT was short, the assistants average technical score was significantly higher than in case of surgeons whose technical score was high and the OT was short. CONCLUSION: The OT alone is not an objective factor in the definition of the surgical technique.

Experimental models of hemorrhagic shock: a review.

Massive blood loss leading to hypovolemic shock is still a life-threatening situation. Recently, a great number of investigations have been conducted in order to understand the pathophysiological and immunological changes taking place during shock and to develop treatment strategies. These preclinical trials are based on animal studies. Although a wide spectrum of species and experimental models are available to researchers, it is rather difficult to create an ideal animal model to study hemorrhagic shock. A major challenge for investigators is the generation of a system which is simple, easily reproducible and standardized, while being an accurate replica of the clinical situation. The goal of this review is to summarize the current experimental models of hemorrhagic shock, highlighting their advantages and disadvantages to help researchers find the most appropriate model for their own experiments on hypovolemic shock.

ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation.

Enhanced recovery of patients after surgery ("ERAS") has become an important focus of perioperative management. From a metabolic and nutritional point of view, the key aspects of perioperative care include: Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and if necessary tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in surgical patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1980. The guideline was discussed and accepted in a consensus conference. EN is indicated even in patients without obvious undernutrition, if it is anticipated that the patient will be unable to eat for more than 7 days perioperatively. It is also indicated in patients who cannot maintain oral intake above 60% of recommended intake for more than 10 days. In these situations nutritional support should be initiated without delay. Delay of surgery for preoperative EN is recommended for patients at severe nutritional risk, defined by the presence of at least one of the following criteria: weight loss >10-15% within 6 months, BMI<18.5 kg/m(2), Subjective Global Assessment Grade C, serum albumin <30 g/l (with no evidence of hepatic or renal dysfunction). Altogether, it is strongly recommended not to wait until severe undernutrition has developed, but to start EN therapy early, as soon as a nutritional risk becomes apparent.

Technical modifications for improving the success rate of PEG tube placement in patients with head and neck cancer.

BACKGROUND: Patients with head and neck cancer (HNC) benefit from nutritional support by means of PEG tubes, but endoscopy may be impossible when there is partial or complete trismus and/or stenosis or occlusion of the upper aerodigestive tract. METHODS: PEG tubes were placed in 277 patients with HNC. Oral insertion of an endoscope into the esophagus was impossible in 27 patients. Transnasal endoscopy was performed (n = 4). In the cases of high-grade tumor obstruction, the endoscope was introduced into the esophagus through a straight laryngoscope (n = 9). When upper aerodigestive tract occlusion was present, endoscopy with PEG placement was successfully performed during surgery by means of the opened pharynx after tumor resection (n = 12). RESULTS: In 25 of the 27 cases PEG tubes could be placed by using the above alternative techniques. There were no immediate complications, and no complications occurred within 30 days of PEG placement. CONCLUSIONS: Transnasal, straight laryngoscopic, or intraoperative open endoscopy can improve the success rate for PEG tube placement in patients with HNC.

[Successfully operated infraperitoneal hemangiopericytoma infiltrating the left ureter]. / Infraperitoneális elhelyezkedésú, urétert infiltráló haemangiopericytoma sikerrel operált esete.

Hemangiopericytoma is a very rare tumour originating from the lining cells of small vessels. Despite benign histology it is clinical presentation similar to malignancy. There are only less than hundred cases reported sporadically in the literature. Authors report a case and successful radical removal of an infraperitoneal hemangiopericytoma infiltrating the left ureter. The literature of this strange, rare pathology is also analysed in the article.

[Rare indication for surgery: liver metastasis of planocellular laryngeal cancer]. / Ritka mútéti javallat: planocellularis gégerák májáttéte.

This is a report of a successfully operated case of a solid liver metastasis developed following radical total laryngeal extirpation. The biological characteristic of the laryngeal cancer is also discussed from the surgical point of view. We underline the importance of a detailed, regular control of patients with malignancies and encourage of active surgical treatment of solid metachronous liver metastases.

[Percutaneous endoscopic gastrostomy: experience of three years]. / Percutan endoscopos gastrostomia: 3 év tapasztalatai.

UNLABELLED: Patients who are not able to eat do need tube feeding. The most preferred way of artificial enteral nutritional support is feeding via percutaneous endoscopic gastrostomy (PEG) tubes. Head and neck cancer patients do represent a special group of patients needing a PEG. On the one hand at the time of admission to the hospital they are mainly undernourished. On the other hand the failure rate of placing a PEG is the highest among them. Furthermore in the perioperative period nasogastric tubes do cause a lot of complications in these settings. 188 PEG placements were carried out from July 1995 till November 1998. INDICATIONS: head and neck cancer (n = 171), neurologic disorders (n = 17). PEG tubes were placed 76 times during intratracheal narcosis and 112 times following local anaesthesia. 39 times there was a prior abdominal surgery in our patients medical history. The pull-through, the push-wire and the introducer techniques were used. Beside the usual oro-gastric way of endoscopying (n = 163), 25 times the following alternative ways of entering the upper gastrointestinal tract were used: transnasal route (n = 4), through a Kleinsasser type direct laryngoscope (n = 7) and via the opened pharynx (n = 14). No immediate or late onset procedure related complications occurred. During a follow-up of 22,480 tubedays 26 minor (dermatitis n = 24, ulcer n = 2) and 8 major (abscess n = 4, perforation/peritonitis n = 3, stomach and bowel wall necrosis n = 1) complications occurred. The success rate of placing a PEG was 98.9%. In head and neck cancer patients placing a PEG is suggested when there is a need for at least a 7 days time tube-feeding. Using the described alternative ways, a PEG tube can be placed almost always. Because of the uncertain outcome, nutritional support via PEG tubes is suggested also in cachectic patients and in vegetative state as well.

[Difficulties of artificial nutrition in short bowel syndrome]. / A mesterséges táplálkozás nehézségei rövidbél-szindrómában.

The authors expound the case of a 47 years old woman who was operated on 25 months ago for bowels necrosis caused from occlusion of arteria mesenterica superior. The operation was composed of a partial jejunale resection, total ileum resection and a right side hemicolectomy, the residual part of the intestine (jejunum) is 70-80 cm. Eleven months after the operation her status has got worse with 10-12 watery faeceses, abdominal pain and body weight losing (15 kg in 2 months). In the beginning a complete central parenteral and enteral nutrition was necessary. The authors expound the complications connected with the nutrition and the successful rehabilitation of the patient as well. They built her nutrition gradually completed with oral given nutriment. The nutritional status of the patient now is adequate and she is able to do the housekeeping.

Clinical nutrition in liver and pancreatic diseases.

According to international and national surveys, 5-15% of patients admitted to hospitals require partial or total artificial nutrition. The development or progression of malnutrition influences patients' lives significantly and also increases the costs of their treatment substantially and unnecessarily. Nutrition therapy, meaning a balanced intake of food or provision of nutrients, is an essential part of the critically ill patient's care. The proper concern of physicians today is not whether nutritional support is indicated in hepatic and pancreatic diseases, but when and how it should be given. Author, therefore, gives guidelines to the nutritional therapy of patients suffering from liver and pancreatic diseases since their metabolic support still remains the most challenging problems in clinical nutrition.

In vitro amylase release of preserved pancreas: a simple test to assess the viability of pancreatic allograft during preservation in the pigs.

To determine an in vitro marker of viability during pancreatic preservation, 12 pigs underwent total pancreas harvesting, and graft were stored in Euro-Collins or Belzer perfusion solution for up to 24 hours. Amylase concentration of the storage solution was analyzed in regular periods and tissue samples were taken for acridine-orange histochemical evaluation of viability in the same time. In vitro pancreatic amylase release (IU/g pancreas tissue) was calculated from the volume of solution and the weight of graft. A significant increase of amylase release was found in the course of preservation in both media. Comparing amylase release in different solutions we found significant difference between Euro-Collins and Belzer media (4 hours: 6.45 IU/g vs. 2.2 IU/g, 8 hours: 11.5 vs. 3.58, 24 hours: 8.7 vs. 42.8, respectively). Comparison of amylase release with histochemical evaluation of viability showed strict correlation. We concluded that amylase release is a good marker for exocrine tissue destruction as well as viability of preserved pancreas. Our data confirms that Belzer solution is superior in pancreatic preservation. It is suggested that after adaptation into human model in vitro pancreatic amylase release could be a time- and cost-saving, useful method in predicting pancreatic transplant function prior graft implantation.

Pancreatic pseudocysts associated with chronic pancreatitis--early and late results of 1367 operations.

The authors hereby review the data of 1367 operations for pancreatic pseudocysts. The surgical procedures of choice in particular pancreatic pathologies are analysed in the light of early morbidity and mortality, as well as long term follow-up results. The best operations for pancreatic pseudocysts have been the internal drainage procedures, which resolve the pathological alterations without the necessity of pancreatic resection. The treatment of chronic pancreatitis may require combined surgical procedure, such as cysto-Wirsungo-gastrostomy. The pancreatic resections performed for the treatment of small pseudocysts in the pancreatic head have been superseded by the less invasive blunt, forced cysto-duodenostomies, representing better results secondary to the smaller perioperative risk for the patient. The cyst-to-stomach and cyst-to-duodenum internal drainage techniques are just as effective, but with shorter operation time, than the Roux-en-Y cysto-jejunostomies.

Multimodality treatment of pancreatic pseudoaneurisms.

Vascular lesions of pancreatitis manifest in the form of haemorrhage into the pseudocyst (PC), the development of pseudoaneurisms (PA) or splenic lesions. Between 1987 and 1996 31 patients were found to develop vascular lesions either in the form of haemorrhage into a PC (12) or PA (19). Diagnosis of pancreatic PA was established preoperatively in 8 cases only. Gastrointestinal (GI) bleeding manifested in 12 patients, but only in 6 of them was the pancreatic origin of the bleeding considered. All patients were operated. For the management of the lesions resection of the pancreas (11 cases) or ligation of the bleeding vessel with external or internal drainage of the PC was performed (12 cases). Simple external drainage of a haemorrhaged PC in 3, and cystoduodenostomy or cystogastrostomy was performed in 5 cases respectively. Intraoperatively moderate bleeding gave some concern (7 cases), while post operatively pancreatic fistula developed in 9 patients drained externally. All stopped spontaneously. In two cases severe GI bleeding occurred post operatively. In both cases embolization of the bleeding vessels was performed successfully. No operative mortality occurred. The mean follow-up time was 40.6 months (5-106). Five patients died of unrelated causes, 3 patients underwent subsequent pancreatic operation, and 74.2% of the patients are doing well. Development of pancreatic PA was associated with a longer observation or conservative treatment period. Angiography should be considered whenever severe upper GI bleeding occurs in patients with known pancreatic disease and the source of bleeding is obscure. In selected cases selective embolization of the bleeding site may provide definitive treatment.

Limited indication of gastrocystoplasty.

A 28-year-old woman presented a huge vesico-vagino-rectal fistula after radiotherapy applied because of a gynaecological tumour. Reconstruction consisted of a colostomy, closure of the rectal hole with a pedicled perineal skin graft, a bivalve opening of the bladder and, with the two halves coverage of the vaginal suture line, and augmentation gastrocystoplasty. The fistulas healed but the patient suffered from an intolerable burning sensation. That is, why the stomach wall was removed and ureteroileocutaneostomy was created. The colostomy was closed, and now the patient has a well-functioning urine stoma.