Current Therapy of Cryptoglandular Anal Fistula: Gold Standards and Alternative Methods. / Therapie der kryptograndulären Analfisteln: aktuelle Goldstandards und Alternativen.

Cryptoglandular anal fistulas are one of the most common colorectal diseases and occur with an incidence of about 20/100,000. Anal fistulas are defined as an inflammatory junction between the anal canal and the perianal skin. They develop from an abscess or chronic infection of the anorectum. Surgical treatment of the disease is the method of choice. Even when treating an acute abscess, its cause should be sought at the same time. If there is a connection to the anal canal without affecting relevant parts of the sphincter muscles, primary fistulotomy should be performed. If larger parts of the sphincter muscle are involved, the insertion of a seton drain is usually useful. There are essentially two recommendations for the elective treatment of cryptoglandular anal fistulas. Distal fistulas should be excised, with the proviso that as little sphincter muscle as possible is sacrificed. In the case of highly proximally located and complex fistulas, sphincter-preserving surgical techniques should be used. In this case, the method of choice is the mucosal or advancement flap. Alternatively, clips, fibrin injections, fistula plugs, fistula ligatures, or laser-based procedures are described in the literature. In the case of intermediate fistulas, a fistulectomy with primary sphincter reconstruction can be useful. Every operation is carried out as a compromise between definitive healing of the fistula and a potential risk to the patient's continence. It is often difficult to make a reliable prognosis about the continence function to be expected postoperatively. In addition to the fistula morphology, particular attention should be paid to whether previous proctological operations have already been performed, the gender of the patient, and whether there are pre-existing sphincter dysfunctions. Since the surgeon's expertise plays a decisive role in the success of the treatment, the procedure should be carried out in a specialist proctological centre, especially in the case of complex fistulas or in the case of a condition after previous operations. In addition to the classic procedures, such as fistulectomy or the plastic fistula closure, this article examines alternative methods and their areas of application.

Proposal of an algorithm for the management of rectally inserted foreign bodies: a surgical single-center experience with review of the literature.

BACKGROUND: Retained rectal foreign bodies (RFBs) are uncommon clinical findings. Although the management of RFBs is rarely reported in the literature, clinicians regularly face this issue. To date, there is no standardized management of RFBs. The aim of the present study was to evaluate our own data and subsequently develop a treatment algorithm. METHODS: All consecutive patients who presented between January 2006 and December 2019 with rectally inserted RFBs at the emergency department of the Klinikum Stuttgart, Germany, were retrospectively identified. Clinicopathologic features, management, complications, and outcomes were assessed. Based on this experience, a treatment algorithm was developed. RESULTS: A total of 69 presentations with rectally inserted RFBs were documented in 57 patients. In 23/69 cases (33.3%), the RFB was removed transanally by the emergency physician either digitally (n = 14) or with the help of a rigid rectoscope (n = 8) or a colonoscope (n = 1). In 46/69 cases (66.7%), the RFB was removed in the operation theater under general anesthesia with muscle relaxation. Among these, 11/46 patients (23.9%) underwent abdominal surgery, either for manual extraction of the RFB (n = 9) or to exclude a bowel perforation (n = 2). Surgical complications occurred in 3/11 patients. One patient with rectal perforation developed pelvic sepsis and underwent abdominoperineal extirpation in the further clinical course. CONCLUSION: The management of RFBs can be challenging and includes a wide range of options from removal without further intervention to abdominoperineal extirpation in cases of pelvic sepsis. Whenever possible, RFBs should obligatorily be managed in specialized colorectal centers following a clear treatment algorithm.

Preoperative versus pathological staging of rectal cancer-challenging the indication of neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by surgery is recommended for patients with diagnosed rectal cancer UICC stage II/III. The present study aimed to evaluate the accuracy of preoperative staging with focus on tumor infiltration depth and lymph node status challenging the indication of neoadjuvant CRT. METHOD: All consecutive rectal cancer patients who underwent surgical resection without neoadjuvant CRT at the Klinikum Stuttgart, Germany, between January 2015 and December 2018, were included into the study. Clinicopathologic features focusing on preoperative tumor staging and histological outcome were assessed. RESULTS: A total of 100/162 patients (61.7%) underwent primary surgical rectal resection with curative intent. Among these patients, 54/100 had a correct preoperative T-staging, while 34 were overstaged and 12 understaged. With regard to the nodal status, 68 were accurately staged, while 28 were overstaged and 4 understaged. Only 4/40 perirectal lymph nodes of more than 5 mm in diameter in preoperative MRI histologically revealed to be metastasis. CONCLUSION: For patients without neoadjuvant CRT, a tendency to preoperative overstaging was observed. Lymph node size alone did not reliably predict metastasis. According to current guidelines, 21/62 (33.9%) of these patients would have been overtreated by using CRT. On the background of relevant side effects, complications, and the limited benefit of CRT on overall survival, we suggest that primary surgical resection should be recommended more liberally for stages II and III rectal cancer.

The transverse coloplasty pouch is technically easy and safe and improves functional outcomes after low rectal cancer resection-a single center experience with 397 patients.

BACKGROUND: Following resection for low rectal cancer, numerous patients suffer from frequent bowel movements, fecal urgency, and incontinence. Although there is good evidence that colonic J-pouch reconstruction, side-to-end anastomosis, or a transverse coloplasty pouch (TCP) improves functional outcome, many surgeons still prefer straight coloanal anastomosis because it is technically easier and lacks the risk of pouch-associated complications. The present single-center study aimed to evaluate the practicability of TCPs in routine clinical practice as well as pouch-related complications. METHOD: All consecutive patients who underwent low anterior rectal resection with restoration of bowel continuity for cancer during the period September 2008 to June 2018 were included. A TCP in combination with a diverting ileostomy was defined as the hospital standard. The feasibility and safety of TCPs were assessed in a retrospective single-center study. RESULTS: A total of 397 patients were included in the study. A total of 328/397 patients underwent TCP construction (82.6%). Two pouch-related surgical complications occurred (0.6%); one case of pouch-related stenosis and one case of sutural insufficiency. Overall, leakage of the coloanal anastomosis was reported in 14.1% of patients with a TCP and in 18.8% of patients without a pouch (p=0.252). Diverting ileostomy was applied in 378/397 patients (95.2%). The 30-day mortality was 0.25%. CONCLUSION: The present study is by far the largest single-center experience with TCP construction for low rectal cancer resection. The study shows that a TCP is technically applicable in the vast majority of cases (82.6%). Pouch-associated surgical complications are sporadic events. In our opinion, the TCP can be considered an alternative to J-pouch construction after low anterior rectal resection.

Hedgehog signaling promotes angiogenesis directly and indirectly in pancreatic cancer.

INTRODUCTION: The inhibition of Hedgehog (Hh) signaling in pancreatic ductal adenocarcinoma (PDAC) reduces desmoplasia and promotes increased vascularity. In contrast to these findings, the Hh ligand Sonic Hedgehog (SHH) is a potent proangiogenic factor in non-tumor models. The aim of this study was to determine the molecular mechanisms by which SHH affects the tumor stroma and angiogenesis. METHODS: Mice bearing three different xenografted human PDAC (n = 5/group) were treated with neutralizing antibodies to SHH. After treatment for 7 days, tumors were evaluated and the expression of 38 pro- and antiangiogenic factors was assessed in the tumor cells and their stroma. The effect of SHH on the regulation of pro- and antiangiogenic factors in fibroblasts and its impact on endothelial cells was then further assessed in in vitro model systems. RESULTS: Inhibition of SHH affected tumor growth, stromal content, and vascularity. Its effect on the Hh signaling pathway was restricted to the stromal compartment of the three cancers. SHH-stimulated angiogenesis indirectly through the reduction of antiangiogenic THBS2 and TIMP2 in stromal cells. An additional direct effect of SHH on endothelial cells depended on the presence of VEGF. CONCLUSION: Inhibition of Hh signaling reduces tumor vascularity, suggesting that Hh plays a role in the maintenance or formation of the tumor vasculature. Whether the reduction in tumor growth and viability seen in the epithelium is a direct consequence of Hh pathway inhibition, or indirectly caused by its effect on the stroma and vasculature, remains to be evaluated.

A new storage solution for the hypothermic preservation of corneal grafts: an experimental study.

In this experimental study we used for the first time Tiprotec® as a solution for corneal preservation and cold storage. We compared the resultant endothelial cell morphology and viability with this obtained after preservation of the ex-vivo corneas with both usual standard techniques: conventional cold storage (using Eusol-C) and organ culture. This prospective, in vitro, 3-armed parallel study was performed with the use of 90 porcine corneas (examined for their endothelial quality and transparency) randomly selected for preservation in three storage methods (each 30 corneas): organ culture, standard cold storage (Eusol-C) and experimental cold storage (Tiprotec®) Endothelium cell quantity and quality as well as corneal opacification were assessed. The degree of endothelial transparency was significantly reduced over time with all preservation media, without any significant difference among the three groups at any point of time. A reduction in endothelial cell density was also observed with all three preservation media after 30 days of storage without statistically significant differences between groups. The number of hexagonal and pentagonal endothelium cells was significantly reduced overtime in all media with significantly more hexagonal and pentagonal in the organ culture group compared to the cold storage groups. We could show that the cryopreservation medium Tiprotec®, used until now for the preservation of vascular grafts, was of similar quality compared to the medium Eusol-C for the hypothermic storage of corneal tissue for an extended period of time up to 30 days. In comparison to organic culture with culture medium KII, both Tiprotec® and Eusol-C were found less effective in preserving endothelial cell quality, as assessed by the morphometric analysis, and viability, as assessed by the degree of vacuolization at least up to the 30th day of storage. However, both, Tiprotec®- and Eusol-C-preserved corneas demonstrated a certain capacity to recover after their submission in organ culture.

Pylorus drainage procedures in thoracoabdominal esophagectomy - a single-center experience and review of the literature.

BACKGROUND: Pylorotomy and pyloroplasty in thoracoabdominal esophagectomy are routinely performed in many high-volume centers to prevent delayed gastric emptying (DGE) due to truncal vagotomy. Currently, controversy remains regarding the need for these practices. The present study aimed to determine the value and role of pyloric drainage procedures in esophagectomy with gastric replacement. METHODS: A retrospective review of prospectively collected data was performed for all consecutive patients who underwent thoracoabdominal resection of the esophagus between January 2009 and December 2016 at the Katharinenhospital in Stuttgart, Germany. Clinicopathologic features and surgical outcomes were evaluated with a focus on postoperative nutrition and gastric emptying. RESULTS: The study group included 170 patients who underwent thoracoabdominal esophageal resection with a gastric conduit using the Ivor Lewis approach. The median age of the patients was 64 years. Most patients were male (81%), and most suffered from adenocarcinoma of the esophagus (75%). The median hospital stay was 20 days, and the 30-day hospital death rate was 2.9%. According to the department standard, pylorotomy, pyloroplasty, or other pyloric drainage procedures were not performed in any of the patients. Overall, 28/170 patients showed clinical signs of DGE (16.5%). CONCLUSIONS: In the literature, the rate of DGE after thoracoabdominal esophagectomy is reported to be approximately 15%, even with the use of pyloric drainage procedures. This rate is comparable to that reported in the present series in which no pyloric drainage procedures were performed. Therefore, we believe that pyloric drainage procedures may be unwarranted in thoracoabdominal esophagectomy. However, future randomized trials are needed to ultimately confirm this supposition.

Successful ablation of lymph nodes using irreversible electroporation (IRE) in a porcine survival model.

BACKGROUND: Irreversible electroporation (IRE), a nonthermal injury ablation technique, has been shown to be effective and safe in various organs, such as in the kidney, liver, prostate, or in pancreas. In contrast to radiofrequency or microwave ablation, IRE is also effective in the neighborhood of major vessels. Many human cancers reveal lymphatic spread. The present study aimed to evaluate technical feasibility and safety of IRE in lymphatic tissue. To our knowledge, this is the first report showing successful IRE of lymph nodes in a standardized porcine survival model. METHODS: A total of ten pigs were divided into two study groups. Five animals received ECG-gated IRE of mesenteric lymph nodes of the small bowel and were sacrificed 2 h after ablation. Another five animals were followed up for 7 days. Clinical parameters, laboratory and abdominal imaging by contrast-enhanced computed tomography, as well as histology were obtained from all animals at different time points. RESULTS: During and after IRE ablation, no cardiocirculatory side effects were noted in any of the animals. In the acute phase experiments, no damage to adjacent organs and no thermal injuries were seen following IRE. One hundred twenty minutes after ablation, no significant laboratory changes were observed. In the survival group, all animals recovered quickly and showed normal activity and feeding habits indicating a minimal pain level. Seven days after IRE ablation, a significant increase in white blood cell count was observed, while creatinine, urea, or hemoglobin remained unchanged. Computed tomography revealed a hypodense lesion following IRE already at 2 h. Histopathology showed coagulation necrosis of the treated lymph nodes with preservation of the lymph node capsule. CONCLUSIONS: This porcine survival model shows that IRE can safely and effectively be performed in lymph nodes. Thus, IRE might display a novel approach for therapy of lymph node metastasis. Further clinical studies are needed to evaluate the oncologic outcome of IRE ablation in lymph node metastasis.

Electrochemical Effects after Transarterial Chemoembolization in Combination with Percutaneous Irreversible Electroporation: Observations in an Acute Porcine Liver Model.

PURPOSE: To evaluate the effects of combined use of transarterial chemoembolization and irreversible electroporation (IRE) for focal tissue ablation in an acute porcine liver model. MATERIALS AND METHODS: Two established interventional techniques were combined: IRE with zones of irreversible and reversible electroporation and chemoembolization with microspheres, iodized oil, and doxorubicin. IRE was performed before chemoembolization in two pigs (pigs 1 and 2; IRE/chemoembolization group), chemoembolization was performed before IRE in two pigs (pigs 3 and 4; chemoembolization/IRE group), and only IRE was performed in two pigs (pigs 5 and 6). Five study groups were defined: IRE/chemoembolization (pigs 1 and 2), chemoembolization/IRE (pigs 3 and 4), IRE only (pigs 5 and 6), chemoembolization only (tissue outside the IRE zones in pigs 1-4), and control (untreated liver tissue outside the IRE zones in pigs 5 and 6). Animals were euthanized 2 hours after intervention. Size and shape of IRE zones on contrast-enhanced computed tomography, cell death on light microscopy, and doxorubicin tissue concentrations on chromatography and fluorescence microscopy were analyzed. RESULTS: Size and shape of IRE zones were not significantly different (eg, P = .067 for volume). A histologic marker for irreversible cell death was positive in IRE/chemoembolization, chemoembolization/IRE, and IRE groups only in the macroscopically visible IRE zones. Doxorubicin tissue concentrations were not significantly different (P = .873). However, in the reversible electroporation (RE) zones, broad areas with intense intranuclear doxorubicin accumulation were observed in IRE/chemoembolization but not in chemoembolization/IRE and chemoembolization groups. CONCLUSIONS: IRE before chemoembolization enhances the intranuclear accumulation of doxorubicin in the RE zone.

Surgical ampullectomy: an underestimated operation in the era of endoscopy.

INTRODUCTION: Benign neoplastic, inflammatory or functional pathologies of the ampulla of Vater are mainly treated by primary endoscopic interventions. Consequently, transduodenal surgical ampullectomy (TSA) has been abandoned in many centres, although it represents an important tool not only after unsuccessful endoscopic treatment. The aim of the study was to analyse TSA for benign lesions of the ampulla of Vater. PATIENTS AND METHODS: All patients who underwent TSA between 2001 and 2014 were included. Patients were analysed in terms of indications, postoperative morbidity and mortality as well as long-term success. RESULTS: Eighty-three patients underwent TSA. Indications included adenomas in 44 and inflammatory stenosis in 39 patients. 96% of the patients had undergone endoscopic therapeutic approaches prior to TSA (median no. of interventions n = 3). Postoperative morbidity occurred in 20 patients (24%). There was one procedure-associated death (mortality 1.2%). The mean follow-up was 54 months. Long-term overall success rate for TSA was 83.6%. After TSA for ampullary adenoma, the recurrence rate was 4.5%. CONCLUSION: TSA is an underestimated surgical procedure, which can be performed safely with high long-term efficacy. It can be implemented in clinical algorithms for patients with benign pathologies of the ampulla of Vater, particularly after unsuccessful endoscopic treatment.

Fluid collection after distal pancreatectomy: a frequent finding.

BACKGROUND: Fluid collections (FC) at the resection margin of the pancreatic stump after distal pancreatectomy (DP) are common radiological findings in follow-up scans. No recommendations exist regarding the management of such findings. The aim was to characterise incidence, risk factors, clinical impact and therapy of FC. METHOD: Data of 209 patients who underwent DP between 07/2009 and 06/2011 were prospectively collected and analysed, regarding follow-up CT or MRI scan findings of FC at the resection margin. FC was defined as a cyst-like lesion >1 cm in diameter. RESULTS: A follow-up with at least two cross-sectional images was available in 159/209 patients. In the first postoperative control, 68 patients showed an FC (43%). FC size was classified as <5 cm (n = 38 pat.), 5-10 cm (n = 24 pat.) and >10 cm (n = 6 pat.). 20 patients (30%) showed clinical symptoms. Six patients (9%) required specific treatment, all other FC showed spontaneous regression. No correlation with stump closure techniques or preceding postoperative pancreatic fistula was found (4/68 patients, 6%). Multivariate analysis revealed standard resections as the only significant factor for FC. CONCLUSIONS: FCs at the resection margin after DP are frequent and harmless findings. Therapeutic interventions are required in only 9% of all FC patients.

Main-duct Intraductal Papillary Mucinous Neoplasm: High Cancer Risk in Duct Diameter of 5 to 9 mm.

OBJECTIVE: The 2012 international consensus guidelines for the management of intraductal papillary mucinous neoplasms (IPMN) recommend surgical treatment in main-duct IPMN patients with a main pancreatic duct (MPD) diameter of ≥10 mm. Aim of the present study was to analyze cancer risk in patients with an MPD diameter of less than 10 mm. METHODS: All consecutive patients (prospective data protocol) with histological proof of IPMN who underwent surgery between January 2004 and December 2013 were included in the study. Clinical characteristics, particularly preoperative imaging with regard to morphology of the MPD, were correlated with final histopathology. RESULTS: Among a total of 605 patients who underwent surgery for IPMN, there were 320 patients with MPD involvement, 238 patients with mixed-type IPMN, and 82 patients with main-duct IPMN alone. The total malignancy rate including high-grade dysplasia and invasive carcinoma in IPMNs with MPD involvement was 68%. When the MPD diameter was 5 to 9 mm, malignancy rate was 59%, whereas in MPD diameter more than 10 mm, it was 73%. No statistical correlations were observed between MPD diameter and clinical and/or IPMN features such as age, cyst location, mural nodules, serum tumor markers, or bilirubin. CONCLUSIONS: Main-duct IPMNs with a MPD between 5 and 9 mm already bear a significant risk of malignancy. Therefore, surgical treatment is clearly indicated in patients with a MPD diameter of ≥5 mm and the 2012 guidelines should be discussed and adapted with regard to this topic.

Pancreatic intraductal papillary mucinous neoplasm--where is the challenge?

Cystic lesions of the pancreas are increasingly recognized due to the widespread use of modern abdominal imaging technologies. The majority of these lesions display pseudocysts and mucinous cystic neoplasms. In contrast to pseudocysts, it is well established that mucinous cystic neoplasms of the pancreas exhibit a significant potential for malignant transformation over time. Among mucinous cystic tumors, the most frequently observed entity is pancreatic intraductal papillary mucinous neoplasm (IPMN). IPMNs are characterized by cystic dilation of pancreatic ducts and the production of mucus and by an adenoma-carcinoma sequence eventually culminating in invasive carcinoma in some patients. Due to the high risk of harboring malignancy, there is international consensus that IPMNs with involvement of the main pancreatic duct should be recommended for surgical resection. To date, the indication for surgery of branch-duct IPMNs is controversially discussed because of the overall lower risk of malignant transformation compared to main-duct IPMNs. Particularly for small and asymptomatic side-branch IPMNs, the indication for surgical resection remains challenging. In addition to the international consensus guidelines, a number of potential preoperative features predicting malignant transformation have been discussed recently. Moreover, novel surgical pancreatic parenchyma-sparing techniques such as enucleations or segmental pancreatic resections have been reported in order to treat IPMNs. The present article aims to demonstrate the current scientific knowledge in this field and to highlight the current controversy.

Emergency pancreatic surgery--demanding and dangerous.

BACKGROUND: Elective pancreatic surgery can be carried out with mortality rates below 5% in specialized centers today. Only few data exist on pancreatic resections in emergency situations. The aim of the study was to characterize indications, procedures, and outcome of emergency pancreatic surgery in a tertiary center. METHODS: Prospectively collected data of all patients undergoing pancreatic operations at the authors' institution between October 2001 and December 2012 were analyzed regarding primary emergency operations in terms of indications, procedures, perioperative complications, and outcome. Emergency operations after preceding resections were excluded from the analysis. RESULTS: Twenty-three emergency operations were performed during the observation period. Indications were duodenal perforation (n = 8), upper GI bleeding (n = 6), complicated pseudocysts (n = 3), bile duct perforation (n = 2), pancreatic bleeding after blunt abdominal trauma (n = 1), pancreatic stent perforation (n = 1), necrotizing cholecystitis (n = 1), and ileus (n = 1). Procedures included partial and total duodeno-pancreatectomy (n = 15), cystojejunostomy (n = 2), distal pancreatectomy (n = 4), reconstruction of the ampulla Vateri (n = 1), and duodenectomy (n = 1). Median intraoperative blood loss was 750 (200-2500) ml and OP time 4.25 (1.75-9.25) h. Mean ICU stay was 21.3 (1-80) days with an overall surgical morbidity of 52.2%. Overall in-hospital mortality was 34.8% (8/23 pat.). CONCLUSIONS: Emergency pancreatic operations are infrequent and mainly performed due to duodenal perforation or bleeding; blunt abdominal trauma is rarely leading to emergency pancreas resections. They are associated with an increased morbidity and mortality and require a high level of surgical as well as interdisciplinary experience. Perioperative anesthesiological care and interventional radiological complication management are essential to improve outcome in this selective patient collective.

Pancreatic main-duct involvement in branch-duct IPMNs: an underestimated risk.

OBJECTIVES: This study aimed to analyze a large single-center population of resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas with respect to risk factors of malignant transformation. BACKGROUND: There is international consensus that main-duct (MD) as well as mixed-type IPMNs should be treated surgically due to a high risk of malignancy. In contrast, there is an ongoing controversy about surgery of branch-duct type IPMN (BD-IPMN). METHODS: All consecutive patients who underwent surgery for IPMN between January 2004 and December 2012 were included. Clinical characteristics and preoperative imaging were correlated with histopathological features. RESULTS: A total of 512 patients underwent pancreatic surgery and had a histological proof of IPMN. According to preoperative imaging, 74 patients had MD-IPMN (14%), 205 mixed-type (40%), and 233 suspected BD-IPMN (46%). On histopathology, 162 of 512 patients revealed low-grade, 105 moderate, and 52 high-grade dysplasia. One hundred ninety-three IPMN patients (38%) suffered from invasive carcinoma. Among invasive IPMNs, the majority (58%) were mixed-type lesions according to preoperative imaging. Of 141 Sendai negative BD-IPMNs, a malignancy rate of 18% (high-grade dysplasia and invasive carcinoma) was found. Most interesting, 29% of suspected BD-IPMNs (67/233) revealed histological involvement of the main pancreatic duct not evident in preoperative imaging. CONCLUSIONS: All subtypes of IPMNs display a relevant risk for malignant transformation. By abdominal imaging, many IPMNs are misclassified as BD-IPMNs but reveal mixed-type lesions in histopathology. Because currently available preoperative diagnostics are not sufficient to reliably diagnose BD-IPMNs, surgical resection for suspected small branch-duct IPMN should be considered in patients fit for surgery.

Specific CT 3D rendering of the treatment zone after Irreversible Electroporation (IRE) in a pig liver model: the "Chebyshev Center Concept" to define the maximum treatable tumor size.

BACKGROUND: Size and shape of the treatment zone after Irreversible electroporation (IRE) can be difficult to depict due to the use of multiple applicators with complex spatial configuration. Exact geometrical definition of the treatment zone, however, is mandatory for acute treatment control since incomplete tumor coverage results in limited oncological outcome. In this study, the "Chebyshev Center Concept" was introduced for CT 3d rendering to assess size and position of the maximum treatable tumor at a specific safety margin. METHODS: In seven pig livers, three different IRE protocols were applied to create treatment zones of different size and shape: Protocol 1 (n = 5 IREs), Protocol 2 (n = 5 IREs), and Protocol 3 (n = 5 IREs). Contrast-enhanced CT was used to assess the treatment zones. Technique A consisted of a semi-automated software prototype for CT 3d rendering with the "Chebyshev Center Concept" implemented (the "Chebyshev Center" is the center of the largest inscribed sphere within the treatment zone) with automated definition of parameters for size, shape and position. Technique B consisted of standard CT 3d analysis with manual definition of the same parameters but position. RESULTS: For Protocol 1 and 2, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were not significantly different between Technique A and B. For Protocol 3, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were significantly smaller for Technique A compared with Technique B (41.1 ± 13.1 mm versus 53.8 ± 1.1 mm and 39.0 ± 8.4 mm versus 53.8 ± 1.1 mm; p < 0.05 and p < 0.01). For Protocol 1, 2 and 3, sphericity of the treatment zone was significantly larger for Technique A compared with B. CONCLUSIONS: Regarding size and shape of the treatment zone after IRE, CT 3d rendering with the "Chebyshev Center Concept" implemented provides significantly different results compared with standard CT 3d analysis. Since the latter overestimates the size of the treatment zone, the "Chebyshev Center Concept" could be used for a more objective acute treatment control.

CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy.

PURPOSE: In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences. METHODS: Of a total of 1,626 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels. RESULTS: The more that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus ≥4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels ≥1,000 U/ml. CA19-9 increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient ≤0.135). CONCLUSIONS: In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and perioperative therapy.

Irreversible electroporation of the pig kidney with involvement of the renal pelvis: technical aspects, clinical outcome, and three-dimensional CT rendering for assessment of the treatment zone.

PURPOSE: To analyze irreversible electroporation (IRE) of the pig kidney with involvement of the renal pelvis. MATERIALS AND METHODS: IRE of renal tissue including the pelvis was performed in 10 kidneys in five pigs. Three study groups were defined: group I (two applicators with parallel configuration; n = 11), group II (three applicators with triangular configuration; n = 2), and group III (six applicators with complex configuration; n = 3). After IRE and before euthanasia, pigs underwent contrast-enhanced computed tomography (CT). Technical aspects (radial distance of applicators, resulting mean current), clinical outcome (complications, blood samples), and three-dimensional CT rendering for assessment of the treatment zone (short axis, circularity) were assessed. RESULTS: Radial distances of applicators were 14.3 mm ± 2.8 in group I, 12.3 mm ± 1.9 in group II, and 16.4 mm ± 3.5 in group III. Resulting mean currents were 25.7 A ± 6.5 in group I, 27.0 A ± 7.1 in group II, and 39.4 A ± 8.9 in group III. In group III, two perirenal hematomas were identified. There was no damage to the renal pelvis. During IRE, clinical blood parameters and cardiovascular markers did not change significantly. Short axis measurements were 20.6 mm ± 3.6 in group I, 31.9 mm ± 8.2 in group II, and 39.3 mm ± 2.4 in group III (P < .01 between groups). Circularity scores were 0.8 ± 0.2 in group I, 0.7 ± 0.1 in group II, and 0.7 ± 0.1 in group III, with a score of 1 indicating perfect roundness (P value not significant). CONCLUSIONS: IRE of the pig kidney with involvement of the renal pelvis is feasible and safe. Size but not shape of the treatment zone is significantly affected by applicator configuration.

Small (Sendai negative) branch-duct IPMNs: not harmless.

OBJECTIVE: The aim of this study was to evaluate existing management guidelines for branch-duct intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: According to current treatment guidelines (Sendai criteria), patients with asymptomatic branch-duct type IPMNs of the pancreas less than 3 cm in diameter without suspicious features in preoperative imaging should undergo conservative treatment with yearly follow-up examinations. Nevertheless, the risk of harboring malignancy or invasive cancer remains a significant matter of consequence. METHODS: All patients who were surgically resected for branch-duct IPMNs between January 2004 and July 2010 at the University Clinic of Heidelberg were analyzed. Clinical characteristics of the patients and preoperative imaging were examined with regard to the size of the lesions, presence of mural nodules, thickening of the wall, dilation of the main pancreatic duct, and tumor markers. Results were correlated with histopathological features and were discussed with regard to the literature. RESULTS: Among a total of 287 consecutively resected IPMNs, 123 branch-duct IPMNs were identified analyzing preoperative imaging. Some 69 branch-duct IPMNs were less than 3 cm in size, without mural nodules, thickening of the wall, or other features characteristic for malignancy ("Sendai negative"). Of all the Sendai negative branch-duct IPMNs, 24.6% (17/69) showed malignant features (invasive carcinoma or carcinoma in situ) upon histological examination of the surgical specimen. CONCLUSIONS: Although many branch-duct IPMNs are small and asymptomatic, they harbor a significant risk of malignancy. We believe that both main-duct and branch-duct IPMNs represent premalignant lesions. This should be taken into account for adequate therapeutic management. With regard to these results, the current Sendai criteria for branch-duct IPMNs need to be adjusted.