Defining distal splenopancreatectomy by the mesopancreas.

BACKGROUND: The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. METHOD: Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. RESULTS: In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). CONCLUSION: While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival.

BACKGROUND: Survival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. METHOD: Clinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. RESULTS: The rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). CONCLUSION: Mesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.

Surgical margin clearance and extended chemotherapy defines survival for synchronous oligometastatic liver lesions of the ductal adenocarcinoma of the pancreas.

BACKGROUND: The role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease. METHODS: Correlation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available. RESULTS: Out of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed. CONCLUSION: This is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results.

Site of relapse of ductal adenocarcinoma of the pancreas affects survival after multimodal therapy.

BACKGROUND: Ductal adenocarcinoma of the pancreas (PDAC) remains one of the most lethal malignancies. To date, no guidelines exists for isolated resectable metachronous disease. It is still unknown, which patients may benefit from relapse surgery. The aim of our study was to compare disease free survival (DFS) and post relapse survival (PRS) in patients with isolated local recurrence, metachronous hepatic or pulmonary metastases. METHODS: Patients with isolated resectable local recurrence, metachronous hepatic or pulmonary metastases were included for survival analyses. PRS of surgically treated patients (local (n = 11), hepatic (n = 6) and pulmonary metastases (n = 9)) was compared to conservatively treated patients (local (n = 17), hepatic (n = 37) and pulmonary metastases (n = 8)). RESULTS: Resected PDAC patients suffering from isolated metachronous hepatic metastases initially had a higher T-stage and venous invasion (V1) compared to the other patients. DFS in the metachronous pulmonary metastases group was longer compared to DFS of the hepatic metastases and local recurrence groups. Surgical resection significantly improved PRS in patients with local recurrence and pulmonary metastases, when compared to patients receiving chemotherapy alone. Very-long term survivors (> 5 years) were detected following secondary resection of local recurrence and 45% of these patients were still alive at the end of our study period. CONCLUSION: Although DFS in PDAC patients suffering from isolated local recurrence was dismal and comparable to that of patients with isolated hepatic metastases, very-long term survivors were present only in this group. These results indicate that a surgical approach for isolated local recurrence, if anatomically possible, should be considered.

Meta-analysis of totally extraperitoneal inguinal hernia repair in patients with previous lower abdominal surgery.

BACKGROUND: Previous lower abdominal surgery is considered a relative contraindication to laparoscopic totally extraperitoneal (TEP) inguinal hernia repair. This was a meta-analysis of studies comparing the feasibility and safety of TEP repair between patients with (PS), and without (NS) a history of lower abdominal surgery. METHODS: A systematic literature search was undertaken for studies comparing the outcome of TEP inguinal hernia repair in patients with, and without previous lower abdominal surgery. Data on postoperative outcomes were extracted and compared by meta-analysis. Odds ratios (ORs) and mean differences with 95 per cent confidence intervals were calculated. RESULTS: Seven comparative cohort studies were identified, involving a total of 1657 procedures (PS 326, NS 1331). There was a statistically significant difference between PS and NS favouring the NS group with regard to both primary outcomes: intraoperative morbidity (OR 2·85, 95 per cent c.i. 1·19 to 6·80; P = 0·02; 7 studies; I2 = 33 per cent), and postoperative morbidity in the multiport subgroup (OR 2·14, 1·28 to 3·58; P = 0·004; 5 studies; I2 = 0 per cent). For the secondary endpoints conversion rate, peritoneal tears, major intraoperative bleeding, postoperative haematoseroma and delay in return to normal activities, there was a statistically significant difference favouring the NS group. CONCLUSION: This study suggests that patients with previous lower abdominal surgery who need hernia repair get less benefit from TEP repair than those with no history of surgery.

[Resuscitation room management for trauma patients]. / Schockraummanagement bei traumatologischen Patienten.

Resuscitation rooms in central emergency admissions are the first point of contact for potentially severely or multiply injured patients. Here priority is given to the interdisciplinary treatment of these patients, which includes the structured and standardized hospital admission as well as the appropriate initial diagnostics and treatment of potentially life-threatening conditions. The resuscitation room is a central vital link between the prehospital and internal hospital treatment chain. This article describes the core tasks of the resuscitation room team as well as concepts and strategies of initial treatment of severely injured and polytrauma patients.

English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.

Cervical compression due to benign thyroid disorders is not associated with increased postoperative morbidity.

Compressive symptoms due to malignant thyroid disorders and retrosternal goiter have been shown to be associated with increased perioperative morbidity. However, little is known about the risk associated with the surgical management of patients presenting with cervical compressive symptoms secondary to benign thyroid disorders. A retrospective review of data of patients undergoing thyroid surgery in a tertiary referral center was performed. The outcomes of patients with compressive symptoms due to benign thyroid disorders were compared to those of patients without compressive symptoms. 886 patients operated upon between 2005 and 2012 were included for analysis. 284 cases with compressive symptoms (study group) were compared to 602 cases without compressive symptoms (control group). There was no difference in the duration of surgery among both groups (123 vs. 126 min, p = 0.75). There was no significant difference among both groups with regard to postoperative hypocalcemia (1.4 vs. 1.1 %), rate of recurrent laryngeal nerve palsy (6.3 vs. 7.2 %) and postoperative bleeding (2.1 vs. 3.1 %). Compressive symptoms resolved in a significant number of patients following surgery. There was no significant difference in postoperative outcome between patients with and without compressive symptoms. Therefore, cervical compression due to benign thyroid disorders is not associated with increased perioperative morbidity.

[Prognostic Value of Preoperative Anaemia and Perioperative Blood Transfusion in Surgical Treatment of Rectal Cancer]. / Prognostischer Wert präoperativer Anämie und perioperativer Fremdbluttransfusion in der chirurgischen Therapie des Rektumkarzinoms.

INTRODUCTION: There is evidence for the prognostic value of perioperative blood transfusion in the surgical treatment of patients with rectal cancer in the current literature. Also preoperative anaemia seems to have an impact on the outcome of these patients. The aim of this study was to evaluate the impact of preoperative anaemia and perioperative blood transfusion in patients with rectal cancer treated in our hospital. PATIENTS AND METHODS: 208 patients (81 females, 127 males; median age, 67 years) with rectal cancer were included in this retrospective study. All patients received surgical treatment. In 75 % of the patients an anterior rectum resection was performed while 25 % received an abdominoperineal rectum exstirpation. Patients with neoadjuvant treatment were included and statistical analyses were performed. RESULTS: 107 (51.4 %) patients exhibited preoperative anaemia. Patients with neoadjuvant treatment presented with significantly lower preoperative Hb (haemoglobin) values than patients without neoadjuvant treatment (p = 0.022). Patients with preoperative anaemia received significantly more blood transfusions (p = 0.001), had significantly longer hospital stays (p = 0.023) and significantly lower 5-years overall survival (p = 0.005). Blood transfusion was necessary in 82 patients (39.4 %). These patients presented with a significantly higher rate of perioperative complications (p = 0.01) and a lower 5-years overall survival (p = 0.002). In multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor. CONCLUSION: In our study preoperative anaemia and perioperative blood transfusion seems to have an impact on outcome of surgical treatment of patients with rectal cancer. However, in multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor.

Encapsulation status of papillary thyroid microcarcinomas is associated with the risk of lymph node metastases and tumor multifocality.

The management of papillary microcarcinoma (PMC) of the thyroid is controversial, especially after partial thyroid resection for benign thyroid disease. In order to detect prognostic factors for PMC, we analyzed 116 patients with PMC for encapsulation status and lymph node metastases. Between 10/1992 and 12/2010, 116 patients with PMC have been operated in our department (87 females, 29 males, median age 49 years). Eighty per cent of PMCs were diagnosed postoperatively. Seventy-six patients (66%) received a more extended resection with either thyroidectomy, near total thyroidectomy, or Dunhill operation either primarily or after completion operation, whereas 40 patients (34%) had only partial resection. Fifty patients (43%) received radioiodine (RIA) ablation. Lymph node metastases were found in 21 patients (18%). Univariate analysis showed four risk factors to be significantly associated with the risk of lymph node metastasis (p<0.05): male gender, younger age, age group<50 years and nonencapsulation of the tumor. Multivariate analysis demonstrated statistical significance for gender and tumor capsulation status. The tumor capsulation status also correlated with tumor multifocality. Our data show that the risk of lymph node metastases is significantly higher in partially or nonencapsulated PMC than in encapsulated specimens. We therefore suggest that the WHO classification should be extended to a compulsory notification of the encapsulation status in PMC.

[Neuroendocrine neoplasms of the distal jejunum and ileum]. / Neuroendokrine Neoplasien des distalen Jejunums und Ileums.

Neuroendocrine neoplasms (NEN) of the distal jejunum and ileum derive from serotonin-producing enterochromaffin (EC) cells. Due to their low proliferation rate and their infiltrative growth, they are often discovered at an advanced disease stage when metastasis has already occurred. The biology of these tumours is different from other NEN of the digestive tract. In order to standardise and improve diagnosis and therapy, the guidelines for the diagnosis and clinical management of jejuno-ileal NEN as well as for the management of patients with liver and other distant metastases from NEN were revised by the European Neuroendocrine Tumour Society (ENETS) in 2012. This review focuses on aspects relevant for surgical pathology.

[How radical should the surgical therapy for gastric/cardia cancer be?]. / Wie radikal sollte ein Magen- bzw. Kardiakarzinom operiert werden?

With the exception of tumours limited to the mucosa, surgical resection of the primary tumour and its local lymph node metastases still remains the sole option for a curative therapy for potentially resectable gastric cancer, as long as a complete tumour resection (R0 resection) can be performed. In this context, the extent of surgical radicality has been discussed over the last years, especially based on the following aspects: 1. extent of lymphadenectomy/need for splenectomy; 2. subtotal versus total gastrectomy; 3. surgical therapy for cardia cancer; 4. operative approach in cT4-tumours; 5. laparoscopic versus open surgery. Based on the recent study results as well as the current guidelines, this review will discuss these specific issues and gives an insight about the recommended surgical radicality in gastric cancer.

In situ liver transection with portal vein ligation for rapid growth of the future liver remnant in two-stage liver resection.

BACKGROUND: Portal vein embolization (PVE) has become a standard procedure to increase the future liver remnant (FLR) and enable curative resection of initially unresectable liver tumours. This study investigated the safety and feasibility of a new two-stage liver resection technique that uses in situ liver transection (ISLT) and portal vein ligation before completion hepatectomy. METHODS: A consecutive series of patients undergoing ISLT and extended right hepatectomy between 2009 and 2011 were compared with consecutive patients undergoing extended right hepatectomy after PVE. All patients had initially unresectable primary or secondary liver tumours, owing to an insufficient FLR (liver segments II/III). RESULTS: Fifteen patients who had PVE and seven who underwent ISLT before extended right hepatectomy were evaluated. ISLT induced rapid growth of the FLR within 3 days, particularly after insufficient PVE, from a mean(s.d.) of 293(58) ml to 477(85) ml, corresponding to a volume increase of 63(29) per cent. All patients who had ISLT underwent completion extended right hepatectomy within 8 days (range 4-8 days). CONCLUSION: ISLT is an effective and reliable technique to induce rapid growth of the FLR, even in patients with insufficient volume increase after PVE.

Coincidence of primary hyperparathyroidism and nonmedullary thyroid carcinoma.

The incidence of primary hyperparathyroidism (pHPT) combined with nonmedullary thyroid carcinoma (NMTC) has been reported between 2-13%. To date, it remains controversial whether these 2 pathologies occur coincidental or are caused by specific risk factors or genetic changes. The aim of this study was to evaluate the clinical and histological characteristics of NMTC associated with pHPT. We reviewed prospective database records of 1 464 unselected, consecutive patients who were treated for pHPT in our institution between 1986 and 2012 and identified 41 NMTC (2.8%). The collective consisted of 35 papillary (PTC) and 6 follicular (FTC) thyroid carcinomas. Our collective of 41 NMTC including 34 single adenomas and 7 multiglandular diseases consisted of 33 females and 8 males. Patients with FTC demonstrated significant lower preoperative PTH levels compared to PTC. Interestingly, NMTC were predominantly located on the right side. FTC had significant larger tumors as well as demonstrated increased extrathyroidal growth and lymph node metastases. In 71% pHPT and NMTC were diagnosed synchronously. The comorbidity of pHPT and NMTC occurs in about 3%. As pHPT is often operated by a focal minimally invasive approach, we advocate a mandatory preoperative thyroid ultrasound for all patients with pHPT to be able to identify synchronous thyroid disease.

[Hepatic cholestasis resulting from a long-standing enterothorax: a case report]. / Langjähriger Enterothorax als ungewöhnliche Ursache einer Cholestase: ein Fallbericht.

BACKGROUND: Due to the lack of symptoms an enterothorax frequently remains undetected in adults. Most symptomatic patients complain about bowel obstruction and a surgical repair of the diaphragmatic defect, particularly with a mesh, is mandatory. METHODS: This report presents the case of a 72-year-old female patient with a history of an upside-down stomach presenting with a painless jaundice and signs of liver cirrhosis. CLINICAL COURSE: The preoperative work-up revealed an enterothorax with compression of the main bile duct. Explorative laparotomy showed a liver cirrhosis with distinct intrahepatic cholestasis, a hydropic gallbladder and confirmed a right-sided diaphragmatic defect with an enterothorax. After reposition of the intestine, a cholecystectomy, bile duct revision and the closure of the diaphragmatic defect using a mesh were performed. CONCLUSION: Diaphragmatic defects are the basis for the formation of an enterothorax which may be associated with a complicated clinical course. Therefore, in cases of coincidental diagnosis, even in asymptomatic patients, surgical repair should be performed in order to prevent serious complications as presented in this case.

[Stem cell-induced liver regeneration]. / Stammzell-induzierte Leberregeneration.

BACKGROUND: The liver has an excellent regenerative capacity after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSC) to participate in liver regeneration. Here we report our experience with portal vein embolisation (PVE) and CD133+ BMSC administration to the liver, compared with PVE alone, to augment hepatic regeneration in patients with critically low FLRV or impaired liver function. PATIENTS AND METHODS: Eleven patients underwent PVE of liver segments I and IV-VIII to stimulate hepatic regeneration prior to extended right hepatectomy. In these 11 patients with a FLRV below 25% and/or limited quality of hepatic parenchyma, PVE alone did not promise adequate proliferation. These patients underwent additional BMSC administration to segments II and III. Two radiologists blinded to patients' identity and each other's results measured liver and tumour volumes with helical computed tomography. Absolute, relative and daily FLRV gains were compared with a group of patients that underwent PVE alone. RESULTS: The increase of the mean absolute FLRV after PVE with BMSC application from 239.3 mL±103.5 (standard deviation) to 417.1 mL±150.4 was significantly higher than that from 286.3 mL±77.1 to 395.9 mL±94.1 after PVE alone (p<0.05). Also the relative gain of FLRV in this group (77.3%±38.2%) was significantly higher than that after PVE alone (39.1%±20.4%) (P=0.039). In addition, the daily hepatic growth rate after PVE and BMSC application (9.5±4.3 mL/d) was significantly superior to that after PVE alone (4.1±1.9 mL/d) (p=0.03). Time to surgery was 27 days±11 in this group and 45 days±21 after PVE alone (p=0.02). Short- and long-term survival were not negatively influenced by the shorter waiting period. CONCLUSION: In patients with malignant liver lesions, the combination of PVE with CD133+ BMSC administration substantially increased hepatic regeneration compared with PVE alone. This procedure bears the potential to allow the safe resection of patients with a curative intention that would otherwise carry the risk post-operative liver failure.

Classification of parathyroid cancer.

PURPOSE: Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 ("Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer," Ann Surg Oncol 2010;17:2156-74) derived from a retrospective literature review of 330 patients. METHODS: This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone; high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver-operating characteristic (ROC) analysis. RESULTS: Follow-up ranged 2-347 months (mean 76 months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6; 95% confidence interval 2.4-38.4; P < 0.0001), with significantly lower 5-year disease-free survival (χ(2) = 8.7; P < 0.005 for n = 45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P < 0.05 between each class). CONCLUSIONS: This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.

Losses at chromosome 4q are associated with poor survival in operable ductal pancreatic adenocarcinoma.

Here we tested the prognostic impact of genomic alterations in operable localized pancreatic ductal adenocarcinoma (PDAC). Fifty-two formalin-fixed and paraffin-embedded primary PDAC were laser micro-dissected and were investigated by comparative genomic hybridization after whole genome amplification using an adapter-linker PCR. Chromosomal gains and losses were correlated to clinico-pathological parameters and clinical follow-up data. The most frequent aberration was loss on chromosome 17p (65%) while the most frequent gains were detected at 2q (41%) and 8q (41%), respectively. The concomitant occurrence of losses at 9p and 17p was found to be statistically significant. Higher rates of chromosomal losses were associated with a more advanced primary tumor stage and losses at 9p and 18q were significantly associated with presence of lymphatic metastasis (chi-square: p = 0.03, p = 0.05, respectively). Deletions on chromosome 4 were of prognostic significance for overall survival and tumor recurrence (Cox-multivariate analysis: p = 0.026 and p = 0.021, respectively). In conclusion our data suggest the common alterations at chromosome 8q, 9p, 17p and 18q as well as the prognostic relevant deletions on chromosome 4q as relevant for PDAC progression. Our comprehensive data from 52 PDAC should provide a basis for future studies with a higher resolution to discover the relevant genes located within the chromosomal aberrations identified.

Loss of PTEN expression in neuroendocrine pancreatic tumors.

PTEN (phosphatase and tensin homologue deleted from chromosome 10) is a well established tumor suppressor gene, which was cloned to chromosome 10q23. PTEN plays an important role in controlling cell growth, apoptosis, cell adhesion, and cell migration. In various studies, a genetic change as well as loss of PTEN expression by different carcinomas has been described. To date, the role of PTEN as a differentiation marker for neuroendocrine tumors (NET) and for the loss of PTEN expression is still unknown. It is assumed that loss of PTEN expression is important for tumor progression of NETs. We hypothesize that PTEN might be used as a new prognostic marker. We report 38 patients with a NET of the pancreas. Tumor tissues were surgically resected, fixed in formalin, and embedded in paraffin. PTEN expression was evaluated by immunohistochemistry and was correlated with several clinical and pathological parameters of each individual tumor. After evaluation of our immunohistochemistry data using a modified Remmele Score, a widely accepted method for categorizing staining results for reports and statistical evaluation, staining results of PTEN expression were correlated with the clinical and pathological parameters of each individual tumor. Our data demonstrates a significant difference in survival with existence of lymph node or distant metastases. Negative patients show a significant better survival compared with positive patients. Furthermore, we show a significant difference between PTEN expression and WHO or TNM classification. Taken together, our data shows a positive correlation between WHO classification and the new TNM classification of NETs, and loss of PTEN expression as well as survival. These results strongly implicate that PTEN might be helpful as a new prognostic factor.