Schone Handen: als de ene hand de andere wast

Rede, in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht Chirurgie met specifieke aandacht voor het pancreas, aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 25 juni 201

The role of somatostatin receptors in breast and pancreatic cancer

Somatostatin, a hormone which has an inhibitory influence on several physiological processes, is a small peptide consisting of 14 amino-acids, and was first isolated from the hypothalamus of the rat. Soon after, somatostatin was found in numerous other organs, such as the brain, stomach, intestines, pancreas, thyroid, thymus and bronchi, from which it could be extracted. Natural somatostatin has a very short half-life and can only be administered intravenously. The development of several longacting analogues of somatostatin facilitated diagnostic procedures and therapy involving somatostatin and its receptors. One of the first and best known effects of the hormone somatostatin is inhibition of the release of growth hormone by the pituitary gland. Other, mainly inhibitory effects of somatostatin have been described recently, including a direct inhibitory effect on the growth of tumour cells. Somatostatin receptors (SS-R's), present on tumour and pituitary celis, mediate this inhibitory effect as well as release of growth hormone. The analogue octreotide, used in this study, binds to SS-R's on normal and tumour cells. Autoradiography, using '251_ Tyr-octreotide, was utilized to localize receptors for somatostatin in vitro. These receptors were found in several neuroendocrine tumours, as well as in breast carcinomas and islet cell tumours of the pancreas. The aim of this study was to assess the possibility of visualizing SS-R's in vivo, using octreotide labelled with radioactive "'Indium and diethylene-triaminopentaacetic acid (DTPA) as a carrier (octreoscan)

Functional changes after pancreatoduodenectomy: Diagnosis and treatment

Relatively little is known about the gastrointestinal function after recovery of a pancreatoduodenectomy. This review focuses on the functional changes of the stomach, duodenum and pancreas that occur after pancreatoduodenectomy. Although the mortality in relation to pancreatoduodenectomy has decreased over the years, it remains associated with considerable morbidity, which occurs in 40-60% of patients. Physical complaints early after the operation are often caused by motility disorders, in particular delayed gastric emptying, which occurs in up to 40% of patients. During longer follow-up of these patients the occurrence of endocrine and exocrine pancreatic insufficiency becomes more predominant. Diabetes mellitus develops in 20-50% of patients after a pancreatic resection (pancreatogenic diabetes). The main presenting symptoms of exocrine insufficiency are weight loss and steatorrhea. Its presence is suspected on clinical ground and can be supported by fecal elastase-1 measurement. Exocrine insufficiency can be compensated with oral enteric-coated enzyme supplements. The quality of life issue will be addressed as an important outcome measurement after pancreaticoduodenectomy. Furthermore, the functional changes after pancreatoduodenectomy are described in detail with suggestions for diagnosis and treatment

Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract a

Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. Tumour-related deficiencies or disorders should also be corrected. Subsequently, control should be aimed at the tumour growth. Surgery is generally considered as first-line therapy for patients with localized disease, as it can be curative. However, in patients with metastatic disease the role of first-line surgery is not clearly established and other therapies should be considered, such as non-surgical cytoreductive therapies, biotherapy (with somatostatin analogues or interferon-alpha), embolization and chemoembolization of liver metastases, chemotherapy (with single or multiple dose regimens) and peptide receptor-targeted radiotherapy. The delicate balance of the use of the different therapeutical options in patients with endocrine tumours of the gastrointestinal tract and pancreas emphasizes the importance of team approach and team expertise

Mammographic and sonographic spectrum of non-puerperal mastitis

The goal of this study was to explore possible specific mammographic and sonographic features in women with non-puerperal mastitis (NPM), in order to make an accurate diagnosis and prevent unnecessary surgical procedures. From a group of 93 patients with NPM diagnosed between 1987 and 1992, the mammograms of 41, the sonograms and cytology of 47, and the histology of seven patients were retrospectively reviewed. Follow-up was performed on those without histology. In 20 of the 47 patients the inflammation was located subareolarly. In 50% of those with non-subareolar lesions, mammography showed a circumscribed lesion. Sonographically, all patients had an identifiable lesion either well or poorly defined. The majority of the lesions were cystic, but in 23 of 47 cases solid components were seen. Signs of infection in cystic lesions were observed in 25 of 47 cases. Posterior shadowing was not observed. During the follow-up period no breast malignancy was found. It is concluded that NPM has no specific mammographic or sonographic sign. Diagnosis should be made with additional diagnostic assessment, such as FNAB, which was diagnostic in all cases

Neoadjuvant Treatment in Patients With Resectable and Borderline Resectable Pancreatic Cancer

Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients

Pro-inflammatory cytokines affect pancreatic carcinoma cell. Endothelial cell interactions

OBJECTIVES: The potential role of surgery-induced pro-inflammatory\n cytokines on the development of tumor recurrence in pancreatic cancer was\n investigated. MAIN OUTCOME MEASURES: The adhesion of 3 human pancreatic\n carcinoma cell lines, PanC1, MiaPaCa and BxPC3 to monolayers of\n microvascular endothelial cells after pre-incubation with 0.1 or 10 ng/mL\n IL-1beta, TNF-alpha or IL-6 was assessed in a reproducible human in vitro\n assay. Untreated monolayers served as controls. RESULTS: Pre-incubation of\n microvascular endothelial cells with IL-1beta or TNF-alpha, but not IL-6,\n increased adhesion of all three tumor cell lines as compared to adhesion\n in the control group. Maximally stimulated adhesion for PanC1 reached\n 159%, for MiaPaCa 204% and for BxPC3 155% (all vs. the control, P<0.001).\n Pre-incubation of microvascular endothelial cells with IL-1beta or\n TNF-alpha resulted in a significant up-regulation of E-selectin, ICAM-1\n and VCAM-1 expression. The addition of anti-E-selectin, anti-ICAM-1 or\n anti-VCAM-1 monoclonal antibodies did not decrease adhesion to\n microvascular endothelial cells pre-incubated with IL-1beta. Therefore,\n enhanced tumor cell binding seems to be independent of these adhesion\n molecules. CONCLUSIONS: Pro-inflammatory cytokines derived from surgical\n trauma may enhance tumor cell adhesion to microvascular endothelial cells\n and thus bring about more successful tumor cell implantation resulting in\n an increased risk of metastasis formation

Current evidence of nutritional therapy in pancreatoduodenectomy: Systematic review of randomized controlled trials

Aim: Evidence of nutritional therapies in pancreatoduodenectomy (PD) has been shown. However, few studies focus on the association between different nutritional therapies and outcomes. The aim of this review was to summarize the current evidence of nutritional therapies such as enteral nutrition (EN), immunonutrition, and synbiotics on postoperative outcomes after PD. Methods: A systematic literature search of Embase, Medline Ovid, and Cochrane CENTRAL was done to summarize the available evidence, including randomized controlled trials, meta‐analyses and reviews, regarding nutritional therapy in PD. Results: A total of 20 randomized controlled trials were included in this review. Safety and tolerability of EN in PD was shown. Giving postoperative EN can shorten length of stay compared to parenteral nutrition; however, the effect of EN on postoperative complications remains controversial. Postoperative EN should be given only on selective indications rather than routinely used, and preoperative EN is indicated only in patients with severe malnutrition. Giving preoperative immunonutrition is considered to reduce the incidence of infectious complications; however, evidence level is moderate and recommendation grade is weak. The beneficial effect of perioperative synbiotics on postoperative infectious complications is limited. Furthermore, the effectiveness of other nutritional supplements remains unclear. Conclusion: Recently, evidence of enhanced recovery after surgery (ERAS) in PD has been increasing. Early oral intake with systematic nutritional support is an important aspect of the ERAS concept. Future well‐designed studies should investigate the impact of systematic nutritional therapies on outcomes following PD

Reduction of peritoneal trauma by using nonsurgical gauze leads to less implantation metastasis of spilled tumor cells

OBJECTIVES: To evaluate whether infliction of peritoneal trauma would promote tumor cell adherence to damaged peritoneal surfaces; to investigate whether peritoneal damage could promote tumor growth of extraperitoneal tumors; and to evaluate whether the amount of trauma correlated with the degree of tumor cell adherence and local and distant tumor growth. BACKGROUND DATA: After potentially curative resection of colorectal carcinoma, the most common site for recurrence is locoregional. We previously demonstrated that surgical trauma induces a cascade of events leading to adhesion formation. The same mechanisms may be responsible for improved tumor cell adherence and growth facilitation in early local recurrence. METHODS: A reproducible rat model was used in which peritoneal damage was inflicted by standardized rubbing of the peritoneum with surgical gauzes of different texture. In the first experiment, tumor cell adherence and growth at traumatized and nontraumatized peritoneal sites were assessed semiquantitatively 3 weeks after perioperative intra-abdominal injection of CC-531 tumor cells. In the second experiment, the effect of peritoneal trauma on ectopic tumor growth was investigated (CC-531 implanted under the renal capsule). In the final experiment, we evaluated how soon after peritoneal traumatization tumor cell adhesion and growth-promoting factors were active and whether they could be passively transferred to naive nontraumatized abdominal cavities. RESULTS: A significant correlation between the amount of peritoneal trauma and the degree of tumor take at damaged peritoneal surfaces was found (p < or = 0.018). Tumor take at remote peritoneal sites not directly traumatized was also significantly higher after severe trauma than after moderate trauma of the peritoneum (p < or = 0.005). In addition, a significant correlation between the degree of peritoneal trauma and the growth of ectopic tumors under the renal capsule was observed (p < or = 0.009). The final experiment demonstrated that within a few hours after infliction of peritoneal trauma, tumor growth-promoting effects could be passively transferred to naive recipients. CONCLUSIONS: Surgical trauma is an important factor in the promotion of local recurrence. The enhancing effect of trauma is not restricted to the inflicted site but rather has a generalized character. Avoidance of unnecessary surgical trauma by using gentle techniques and materials is therefore indicated