Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma.

Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer.

Brain-derived neurotrophic factor in gastroenterology oncology - short review of current literature.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophins group which plays a crucial role in brain development and neurogenesis. In the hypothalamus it is described as playing a role in energy metabolism and feeding behaviour. The hippocampal concentration of BDNF is believed to play an important role in learning and memory, it has a protective role in neurodegeneration and stress responses. BDNF is also known to take part in many other processes, e.g. angiogenesis, proliferation, cell migration and apoptosis. With its receptor TrkB, neurotrophins are important agents that playa role in neural diseases, as well as in cardiovascular and metabolic disorders, such as diabetes mellitus or acute coronary syndrome. Over the last few years, BDNF interaction with TrkB has also been found to be involved in cancer development, including brain, breast, urinary and gastrointestinal cancer. TrkB expression itself has been described as an aggressive neural tumour. BDNF/TrkB signalling takes part in promoting tumour growth and metastasis. The presented review focuses on gastrointestinal cancer and presents the current literature concerning influence of BDNF and TrkB receptor in cancer progression. Special attention is also paid to data confirming the possible role of BDNF/TrkB interaction in chemotherapy resistance. This might present the opportunity to assess the BDNF and TrkB pathway as a possible novel target for anticancer therapies.

Brain derived neurotrophic factor declines after complete curative resection in gastrointestinal cancer.

BACKGROUND: Brain derived neurotrophic factor (BDNF) is a neurotrophin involved in neural and metabolic diseases, but it is also one of the crucial factors in cancer development and metastases. In the current study, we investigated serum BDNF concentrations in patients that underwent surgical treatment for colorectal cancer or pancreatic cancer. METHODS: Serum BDNF concentrations were measured with standard enzyme-linked immunosorbent assays, before and on the third day after the operation, in 50 consecutive patients with colorectal cancer and 25 patients with pancreatic cancer (tumours in the head of pancreas). We compared pre- and postoperative BDNF levels, according to the subsequent TNM stage, histologic stage, lymph node involvement, neuro- or angio-invasion, and resection range. RESULTS: In the pancreatic cancer group, BDNF concentrations fell significantly postoperatively (p = 0.011). In patients that underwent resections, BDNF concentrations fell (p = 0.0098), but not in patients that did not undergo resections (i.e., laparotomy alone). There were significant pre- and postoperative differences in BDNF levels among patients with (p = 0.021) and without (p = 0.034) distant metastases. Significant reductions in BDNF were observed postoperatively in patients with small tumours (i.e., below the median size; p = 0.023), in patients with negative angio- or lymphatic invasion (p = 0.028, p = 0.011, respectively), and in patients with lymph node ratios above 0.17 (p = 0.043). In the colon cancer group, the serum BDNF concentrations significantly fell postoperatively in the entire group (p = 0.0076) and in subgroups of patients with or without resections (p = 0.034, p = 0.0179, respectively). Significant before-after differences were found in subgroups with angioinvasions (p = 0.050) and in those without neuroinvasions (p = 0.049). Considering the TNM stages, the postoperative BDNF concentration fell in groups with (p = 0.0218) and without (p = 0.034) distant metastases and in patients with tumours below the median size (p = 0.018). CONCLUSION: Our results suggested that BDNF might play an important role in gastrointestinal cancer development. BDNF levels were correlated with tumour volume, and with neuro-, angio- and lymphatic invasions. In pancreatic cancer, BDNF concentrations varied according to the surgical procedure and they fell significantly after tumour resections. Thus, BDNF may serve as a potential marker of complete resections in underdiagnosed patients. However, this hypothesis requires further investigation. In contrast, no differences according to the procedure was made in patients with colon cancer.

Surgical Repair of Small Bowel Fistulas: Risk Factors of Complications or Fistula Recurrence.

BACKGROUND Definitive surgical repair of persistent fistulas of the small intestine remains a surgical challenge with a high rate of re-fistulation and mortality. The aim of this study was to evaluate the type and incidence of complications after definitive surgical repair, and to identify factors predictive of severe postoperative complications or fistula recurrence. MATERIAL AND METHODS This was a retrospective study of 42 patients who underwent elective surgical repair of a persistent fistula of the small intestine. The analysis included preoperative and intraoperative parameters. RESULTS The healing rate after definitive surgery was 71.4%. Postoperative complications developed in 88.1% of patients. The mortality rate was 7.2%. Fistula recurrence was recognized in 21.4% of cases. Overall, 93 complications occurred in 37 patients. The most common complications were septic (48.0%). Hemorrhagic and digestive tract-related complications accounted for 19.0% and 15.0% of all complications, respectively. Severe complications (Clavien-Dindo grade III-V) made up 28.0% of all complications. In univariate analysis, multiple fistulas (p=0.03), higher C-reactive protein level (p=0.01), and longer time interval from admission to definitive surgery (p=0.01) were associated with an increased risk of severe complications or fistula recurrence. In multivariate analysis, only multiple fistulas were an independent risk factor for severe complications or fistula recurrence (OR=8.2, p=0.04). CONCLUSIONS Fistula complexity determines the risk of severe postoperative complications or fistula recurrence after definitive surgical repair of the persistent small intestine fistulas. Inflammatory parameters should be normalized before definitive surgery.

Surgical management of the grade C pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Surgical management of severe pancreatic fistula after pancreatoduodenectomy remains challenging, and carries high mortality. The aim of this retrospective study was to compare different surgical techniques used at relaparotomy for pancreatic fistula after pancreatoduodenectomy, and to identify factors predictive of failure to rescue. METHODS: A total of 43 patients after pancreatoduodenectomy developed a pancreatic fistula requiring relaparotomy. The perioperative data and outcomes were reviewed retrospectively. RESULTS: Completion pancreatectomy, simple drainage of the pancreatic anastomosis and external wirsungostomy were performed in 17, 16, and 10 cases, respectively. The mortality rate for completion pancreatectomy was 47.1%, compared with 56.3% for simple drainage (p = 0.598) and 50.0% for external wirsungostomy (p = 0.883). Simple drainage was associated with a higher rate of further relaparotomies (56.3%) in comparison with completion pancreatectomy (23.5%, p = 0.055) and external wirsungostomy (0%, p = 0.003). A rescue resection of the pancreatic remnant after failed simple drainage resulted invariably in death. On multivariate analysis, the factors predictive of mortality after relaparotomy for pancreatic fistula were organ failure on the day of reoperation (p = 0.001) and need of further surgical reintervention (p = 0.007). CONCLUSION: Timely reintervention and appropriate surgical technique are essential for reducing mortality after reoperation for pancreatic fistula after pancreatoduodenectomy.

Carcinoembryonic antigen and matrix metalloproteinase 2 serum and peritoneal washes concentration in staging and prognosis in colorectal cancer patients.

PURPOSE: The aim of the study was to determine of carcinoembryonal antigen and matrix metalloproteinase 2 peritoneal washes and serum concentration in patients suffering from colorectal cancer concerning tumor staging and 5-year survival rate in these patients. METHODS: 80 patients who underwent curative surgery for colorectal cancer were included into the study. Preoperative serum and intraoperative peritoneal washes CEA and MMP-2 concentrations were measured. RESULTS: Concerning tumor penetration CEA-s and CEA-p concentration was higher in subsequent stages from T2 to T4. Both CEA-s and CEA-p concentration was lower in T2 comparing to T3 and T4. Significant difference of CEA-s and CEA-p was noted between T2 and T4 stages. MMP2-s concentration was higher in T3 comparing to T2, the highest MMP2-p concentration was in T4, with no statistical significance. Concerning nodular status significant difference of CEA-s was noted between N0 and N1. For CEA-p significance was found between N0 and N2 as between N1 and N2. MMP2-s concentration was the highest in N1, MMP2-p concentration was the highest in T4, with no statistical significance. 5-year survival rate for all patients was 63,53%. There were significant differences in CEA-s and CEA-p concentration between patients with negative and positive 5-year survival. CONCLUSION: Intraoperative peritoneal washes concentration of CEA may potentially serve as an important factor for more precise colorectal cancer staging. CEA-p and CEA-s concentration correlates with survival rate in patients suffering from colorectal cancer and can be useful as an additional prognostic factor. Usefulness of MMP2 measurement still requires further studies.

Surgical treatment of extra-appendiceal colorectal neuroendocrine tumors.

BACKGROUND: Extra-appendiceal colorectal neuroendocrine tumors are rare neoplasms with a variable biological behavior. MATERIALS AND METHODS: The study group consisted of 15 patients with an extra-appendiceal colorectal neuroendocrine tumor who underwent surgical resection (M/F=3:12, mean age=62.9 years). Lower-grade neuroendocrine tumors and neuroendocrine carcinomas were recognized in 5 and 10 patients, respectively. Data were evaluated retrospectively with regard to clinical and pathologic characteristics and outcomes. RESULTS: The median age of the patients with lower-grade NETs was significantly lower than that in patients with NECs (53 yr vs. 68 yr, p=0.03). NETs G1-G2 were significantly smaller than neuroendocrine carcinomas (4.0 cm vs. 6.4 cm, p=0.02). There were no differences between lower-grade NETs and NECs with regard to tumor location, rate of nodal involvement and distant metastases. All the patients underwent open segmental resection of the colon or rectum. Complete resection was achieved in 3 of 5 patients from the lower-grade NET group, and in 5 of 10 patients in the NEC group. Overall survival was significantly better for lower-grade NETs tumors (p=0.005). The median survival was 4.8 months in the NEC group. The median survival in the lower-grade NET group was not achieved after a median follow-up of 69 months. Three-year overall survival was 100% for lower-grade NETs, and only 27% for NECs. CONCLUSION: Lower-grade neuroendocrine tumors seem to exhibit comparable potential for dissemination as neuroendocrine carcinomas, but prognostic implications of metastases are distinct.

Comparison between minimally invasive and open surgical treatment in necrotizing pancreatitis.

BACKGROUND: Minimal access techniques have gained popularity for the management of necrotizing pancreatitis, but only a few studies compared open necrosectomy with a less invasive treatment. The aim of this study was to evaluate the outcomes of minimally invasive treatment for necrotizing pancreatitis in comparison with open necrosectomy. MATERIALS AND METHODS: This retrospective study included 70 patients who underwent minimally invasive intervention or open surgical debridement for necrotizing pancreatitis between January 2007 and December 2014. Data were analyzed for postoperative morbidity and outcome. RESULTS: Of 70 patients, 22 patients underwent primary open necrosectomy and 48 patients were treated with minimally invasive techniques. Percutaneous and endoscopic drainage were successful in 34.9% and 75.0% of patients, respectively. The rates of postoperative new-onset organ failure and intensive care unit stay were significantly lower in the minimally invasive group (25.0% versus 54.5%; P = 0.016, and 29.2% versus 54.5%; P = 0.041, respectively). Gastrointestinal fistulas occurred more frequently after primary open necrosectomy (36.4% versus 10.4%; P = 0.009). Mortality was comparable in both groups (18.6% versus 27.3%; P = 0.420). Mortality for salvage open necrosectomy was similar to that for primary open debridement (28.6% versus 27.3%; P = 0.924). The independent risk factors for major postoperative complications were primary open necrosectomy (P = 0.028) and shorter interval to first intervention (P = 0.020). Mortality was independently associated only with older age (P = 0.009). CONCLUSIONS: Minimally invasive treatment should be preferred over open necrosectomy for initial management of necrotizing pancreatitis.

Walled-off necrosis: safety of watchful waiting.

BACKGROUND: Asymptomatic pancreatic necrosis should be managed conservatively, regardless of its extent. However, late sequelae and safety of non-interventional management in patients with asymptomatic walled-off necrosis remain unclear. AIMS: The purpose of this study was to report the clinical outcome of outpatient expectant management in a cohort of patients with walled-off necrosis who were discharged asymptomatic after an episode of acute pancreatitis. METHODS: Sixteen patients with walled-off necrosis asymptomatic at discharge were identified retrospectively from a single institution. Data were analyzed for the type of complications, their incidence and treatment. RESULTS: Seven of 16 patients (44 %) did not experience any complications during a median follow-up of 17 months. Nine of 16 patients (56 %) became symptomatic or developed complications within a median follow-up of 49 days after discharge. The most common complication was infection of pancreatic necrosis which occurred in 7 of 9 patients. Six of these patients were successfully treated with minimally invasive techniques. In 5 of 7 patients, infection of necrosis was due to oral commensal bacteria. Acute intracavitary hemorrhage and intractable abdominal pain developed in one patient each. There was no mortality in this series. CONCLUSIONS: Outpatient watchful waiting can be used safely in patients with asymptomatic walled-off necrosis, although nearly half of them eventually develop complications which require interventional treatment. Most late infections of pancreatic necrosis are probably due to a blood-borne transmission of oral commensal bacteria.

Combined minimally invasive management of infected pancreatic necrosis: a case report.

Infected necrosis is a potentially fatal complication of necrotizing pancreatitis. Open surgical debridement is the mainstay management of infected pancreatic necrosis. Over the last decade minimally invasive techniques have been increasingly used for the treatment of infected pancreatic necrosis and their results are encouraging. However, the optimal technique of minimal access necrosectomy and the timing of intervention have not been established yet. Patients with septic complications of acute pancreatitis represent a challenging group which requires individualized management often involving numerous techniques. We report a case of a 52-year-old patient in whom 3 minimally invasive techniques were needed for complete recovery.

Sister Mary Joseph nodule: a tip of an iceberg.

A Sister Mary Joseph nodule represents a cutaneous metastasis into the umbilicus. This clinical sign of intra-abdominal malignancy is frequently overlooked or misinterpreted by both patients and their physicians. We report 4 patients with a Sister Mary Joseph nodule. The umbilical metastases appeared sonographically as hypoechoic masses with irregular margins and small internal hyperechoic foci. Further evaluation revealed disseminated malignancy, and the umbilical nodule was just "a tip of an iceberg."

Minimally invasive treatment of infected pancreatic necrosis.

Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis.

Parenchyma-Sparing Pancreatic Resections: With or Without a Pancreaticojejunostomy?

BACKGROUND/AIM: Parenchyma-sparing pancreatic resections are used in low-grade malignant tumors, but result in a high incidence of pancreatic fistula. Pancreaticojejunostomy to the site of resection might decrease the risk of pancreatic fistula. The purpose of this study was to evaluate the influence of pancreaticojejunostomy on the outcomes of parenchyma-sparing resections. METHODOLOGY: The study group consisted of 21 patients (M/F = 4:17, mean age = 47 years). Local tumor resection with a pancreaticojejunostomy was performed in 11 patients and enucleation in 10 patients. Both groups were compared retrospectively with regard to perioperative variables. RESULTS: The operative time was significantly shorter in the enucleation group (median 180 min vs. 222 min, P = 0.005). The overall surgical morbidity was similar in both groups (81% vs. 70%, P = 0.64). The rate of clinically significant pancreatic fistula (64% vs. 40%, P = 0.39), hemorrhagic complications (27% vs. 10%, P = 0.59) and wound infection (18% vs. 40%, P = 0.36) were comparable in both groups. One patient died after central pancreatectomy. There were no new-onset cases of diabetes mellitus postoperatively. CONCLUSIONS: Local resection combined with pancreaticojejunostomy is an option to avoid extensive resection of the pancreatic parenchyma, but is still associated with a high incidence of pancreatic fistula which is comparable to that after enucleation.

Ultrasound-guided percutaneous drainage of infected pancreatic necrosis.

BACKGROUND: The role of percutaneous drainage in the management of infected pancreatic necrosis remains controversial, and ultrasound-guided technique is rarely used for this indication. The purpose of this study was to evaluate the safety and efficacy of sonographically guided percutaneous catheter drainage for infected pancreatic necrosis. METHODS: The patient group consisted of 16 men and 2 women. The mean age of the patients was 47 years. The median computed tomography severity index of acute pancreatitis was 10 points. Percutaneous catheter drainage was performed under sonographic guidance using preferably retroperitoneal approach, and transperitoneal access in selected cases. The medical records and imaging scans were reviewed retrospectively for each patient. RESULTS: Percutaneous catheter drainage resulted in a complete resolution of infected pancreatic necrosis in 6 of 18 patients (33 %). Twelve of 18 patients who were initially managed with PCD required eventually necrosectomy (67 %). The most common reason for crossover to surgical intervention was persistent sepsis (n = 7). Open necrosectomy was performed in 4 of these patients, and 3 patients underwent successful minimally invasive retroperitoneal necrosectomy. Five patients required conversion to open surgery because of procedure-related complications. In 3 cases, there was leakage of the necrotic material into the peritoneal cavity. Two other patients experienced hemorrhagic complications. Overall mortality rate was 17 %. The size of the largest necrotic collection in patients who were successfully treated with percutaneous drainage decreased by a median of 76 % shortly after the procedure, whereas it decreased only by a median of 16 % in cases of failure of percutaneous drainage. CONCLUSIONS: Ultrasound-guided percutaneous catheter drainage used in infected pancreatic necrosis is a technique with acceptably low morbidity and mortality that may be the definitive treatment or a bridge management to necrosectomy. A negligible decrease in size of the necrotic collection predicts failure of percutaneous drainage.

The effect of slaughter season on the Fatty Acid profile in four types of fat deposits in crossbred beef bulls.

The objective of this study was to determine the effect of slaughter season on the fatty acid profile in four types of fat deposits in crossbred (Polish Holstein Friesian Black-and-White×Limousine) beef bulls. The percentage share of fatty acids was determined by gas chromatography and were divided into the following categories of fatty acids: saturated (SFAs), unsaturated (UFAs), monounsaturated (MUFAs), polyunsaturated (PUFAs), desirable hypocholesterolemic (DFAs) and undesirable hypercholesterolemic (OFAs), n-3 and n-6. Perinephric fat was characterized by the highest SFA concentrations (59.89%), and subcutaneous fat had the highest MUFA content (50.63%). Intramuscular fat was marked by a high percentage share of PUFAs and the highest PUFA/SFA ratio. The slaughter season had a significant effect on the levels of C18:3, C20:4 (p≤0.01) and conjugated linoleic acid (p≤0.05). There was an interaction between the slaughter season and fat type for the content of C20:4 (p≤0.01) and C20:5 (p≤0.05). The results of this study show that beef from cattle slaughtered in the summer season has a higher nutritional value and more health-promoting properties.

Retroperitoneal minimally invasive pancreatic necrosectomy using single-port access.

Infected pancreatic necrosis is a life-threatening complication of acute pancreatitis that has been traditionally managed with open surgical debridement. Over the last decade, minimally invasive techniques have been increasingly used for the treatment of infected pancreatic necrosis and their results are encouraging. Percutaneous retroperitoneal pancreatic necrosectomy is one of the minimally invasive approaches used for debridement of pancreatic necrosis. We report our technique of retroperitoneoscopic necrosectomy using a single-port access.

The Effect of Body Energy Reserve Mobilization on the Fatty Acid Profile of Milk in High-yielding Cows.

We investigated the effect of the amount of body condition loss in the dry period and early lactation in 42 high-yielding Holstein-Friesian cows on milk yield and the share of fatty acids in milk fat. Energy reserves were estimated based on the body condition scoring (BCS) and backfat thickness (BFT). Milk yield and milk composition were determined over 305-d lactation. From d 6 to 60 of lactation, the concentrations of 43 fatty acids in milk fat were determined by gas chromatography. Cows were categorized based on body condition loss from the beginning of the dry period to the lowest point of the BCS curve in early lactation into three groups: low condition loss group (L) ≤0.5 points (n = 14); moderate condition loss group (M) 0.75 to 1.0 points (n = 16) and high condition loss group (H) >1.0 points (n = 12). Cows whose body energy reserves were mobilized at 0.8 BCS and 11 mm BFT, produced 12,987 kg ECM over 305-d lactation, i.e. 1,429 kg ECM more than cows whose BCS and BFT decreased by 0.3 and 5 mm, respectively. In group H, milk yield reached 12,818 kg ECM at body fat reserve mobilization of 1.3 BCS and 17 mm BFT. High mobilization of body fat reserves led to a significant (approx. 5%) increase in the concentrations of monounsaturated fatty acids-MUFA (mostly C18:1 cis-9, followed by C18:1 trans-11), a significant decrease in the levels of fatty acids adversely affecting human health, and a drop in the content of linoleic acid, arachidonic acid and docosahexaenoic acid in milk fat. In successive weeks of lactation, an improved energy balance contributed to a decrease in the concentrations of unsaturated fatty acids (UFA) and an increase in the conjugated linoleic acid (CLA) content of milk fat.

Optimizing management of pancreaticopleural fistulas.

AIM: To evaluate the management of pancreaticopleural fistulas involving early endoscopic instrumentation of the pancreatic duct. METHODS: Eight patients with a spontaneous pancreaticopleural fistula underwent endoscopic retrograde cholangiopancreatography (ERCP) with an intention to stent the site of a ductal disruption as the primary treatment. Imaging features and management were evaluated retrospectively and compared with outcome. RESULTS: In one case, the stent bridged the site of a ductal disruption. The fistula in this patient closed within 3 wk. The main pancreatic duct in this case appeared normal, except for a leak located in the body of the pancreas. In another patient, the papilla of Vater could not be found and cannulation of the pancreatic duct failed. This patient underwent surgical treatment. In the remaining 6 cases, it was impossible to insert a stent into the main pancreatic duct properly so as to cover the site of leakage or traverse a stenosis situated downstream to the fistula. The placement of the stent failed because intraductal stones (n = 2) and ductal strictures (n = 2) precluded its passage or the stent was too short to reach the fistula located in the distal part of the pancreas (n = 2). In 3 out of these 6 patients, the pancreaticopleural fistula closed on further medical treatment. In these cases, the main pancreatic duct was normal or only mildly dilated, and there was a leakage at the body/tail of the pancreas. In one of these 3 patients, additional percutaneous drainage of the peripancreatic fluid collections allowed better control of the leakage and facilitated resolution of the fistula. The remaining 3 patients had a tight stenosis of the main pancreatic duct resistible to dilatation and the stent could not be inserted across the stenosis. Subsequent conservative treatment proved unsuccessful in these patients. After a failed therapeutic ERCP, 3 patients in our series developed superinfection of the pleural or peripancreatic fluid collections. Four out of 8 patients in our series required subsequent surgery due to a failed non-operative treatment. Distal pancreatectomy with splenectomy was performed in 3 cases. In one case, only external drainage of the pancreatic pseudocyst was done because of diffuse peripancreatic inflammatory infiltration precluding safe dissection. There were no perioperative mortalities. There was no recurrence of a pancreaticopleural fistula in any of the patients. CONCLUSION: Optimal management of pancreaticopleural fistulas requires appropriate patient selection that should be based on the underlying pancreatic duct abnormalities.