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.

Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

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.

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.

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.

Technical validation of a new microfluidic device for enrichment of CTCs from large volumes of blood by using buffy coats to mimic diagnostic leukapheresis products.

Diagnostic leukapheresis (DLA) enables to sample larger blood volumes and increases the detection of circulating tumor cells (CTC) significantly. Nevertheless, the high excess of white blood cells (WBC) of DLA products remains a major challenge for further downstream CTC enrichment and detection. To address this problem, we tested the performance of two label-free CTC technologies for processing DLA products. For the testing purposes, we established ficollized buffy coats (BC) with a WBC composition similar to patient-derived DLA products. The mimicking-DLA samples (with up to 400 × 106 WBCs) were spiked with three different tumor cell lines and processed with two versions of a spiral microfluidic chip for label-free CTC enrichment: the commercially available ClearCell FR1 biochip and a customized DLA biochip based on a similar enrichment principle, but designed for higher throughput of cells. While the samples processed with FR1 chip displayed with increasing cell load significantly higher WBC backgrounds and decreasing cell recovery, the recovery rates of the customized DLA chip were stable, even if challenged with up to 400 × 106 WBCs (corresponding to around 120 mL peripheral blood or 10% of a DLA product). These results indicate that the further up-scalable DLA biochip has potential to process complete DLA products from 2.5 L of peripheral blood in an affordable way to enable high-volume CTC-based liquid biopsies.

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.

Analysis of DNA methylation in single circulating tumor cells.

Direct analysis of circulating tumor cells (CTCs) can inform on molecular mechanisms underlying systemic spread. Here we investigated promoter methylation of three genes regulating epithelial-to-mesenchymal transition (EMT), a key mechanism enabling epithelial tumor cells to disseminate and metastasize. For this, we developed a single-cell protocol based on agarose-embedded bisulfite treatment, which allows investigating DNA methylation of multiple loci via a multiplex PCR (multiplexed-scAEBS). We established our assay for the simultaneous analysis of three EMT-associated genes miR-200c/141, miR-200b/a/429 and CDH1 in single cells. The assay was validated in solitary cells of GM14667, MDA-MB-231 and MCF-7 cell lines, achieving a DNA amplification efficiency of 70% with methylation patterns identical to the respective bulk DNA. Then we applied multiplexed-scAEBS to 159 single CTCs from 11 patients with metastatic breast and six with metastatic castration-resistant prostate cancer, isolated via CellSearch (EpCAMpos/CKpos/CD45neg/DAPIpos) and subsequent FACS sorting. In contrast to CD45pos white blood cells isolated and processed by the identical approach, we observed in the isolated CTCs methylation patterns resembling more those of epithelial-like cells. Methylation at the promoter of microRNA-200 family was significantly higher in prostate CTCs. Data from our single-cell analysis revealed an epigenetic heterogeneity among CTCs and indicates tumor-specific active epigenetic regulation of EMT-associated genes during blood-borne dissemination.

[Resection for advanced pancreatic cancer following multimodal therapy]. / Resektion beim fortgeschrittenen Pankreaskarzinom nach multimodaler Vorbehandlung.

Pancreatic cancer patients presenting with borderline resectable or locally advanced unresectable tumors remain a therapeutic challenge. Despite the lack of high quality randomized controlled trials, perioperative neoadjuvant treatment strategies are often employed for this group of patients. At present the FOLFIRINOX regimen, which was established in the palliative setting, is the backbone of neoadjuvant therapy, whereas local ablative treatment, such as stereotactic irradiation and irreversible electroporation are currently under investigation. Resection after modern multimodal neoadjuvant therapy follows the same principles and guidelines as upfront surgery specifically regarding the extent of resection, e.g. lymphadenectomy, vascular resection and multivisceral resection. Because it is still exceedingly difficult to predict tumor response after neoadjuvant therapy, a special treatment approach is necessary. In the case of localized stable disease following neoadjuvant therapy, aggressive surgical exploration with serial frozen sections at critical (vascular) margins might be necessary to minimize the risk of debulking procedures and maximize the chance of a curative resection. A multidisciplinary and individualized approach is mandatory in this challenging group of 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.

[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.

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.

[Multimodal treatment of esophageal carcinoma]. / Multimodale Therapie des Ösophaguskarzinoms.

Despite major progress in clinical diagnostics and therapy, esophageal carcinoma represents a tumor entity with limited prognosis. In case of carcinoma restricted to mucosa endoscopic resection has developed into an important therapeutic method. Surgical resection represents the standard procedure for patients with locally limited (cT1/T2, N0) and advanced carcinoma (cT3, T4, Nx). In multimodal therapy neoadjuvant treatment concepts with chemotherapy or radiochemotherapy for patients with locally advanced tumors are well established. In case of metastatic disease palliative radio- and chemotherapy represent a treatment concept, however therapy efficiency is very limited. This review reflects the current status of multimodal therapy.

[Multimodal management in soft tissue sarcoma of the trunk and extremities]. / Multimodales Management bei Weichteilsarkomen des Stammes und der Extremitäten.

Soft tissue sarcoma (STS) is a rare, extremely heterogeneous group of malignant tumors of mesodermal origin. With an incidence of 1-5 per 100,000/year they account for only 1 % of all human malignancies. The STSs occur predominantly in the lower extremities and the trunk. To date 100 different histopathological subentities can be defined. The prognosis varies substantially depending on the localization and histology. Whereas local recurrence rates and overall survival of sarcomas of the extremities have benefited from the introduction of multimodal therapies, only marginal progress has been made in the management of trunk STSs. This manuscript gives an overview of preoperative diagnostics, pathology and neoadjuvant as well as adjuvant therapeutic options for soft tissue sarcoma.

[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.

[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.