Sami-Alexander Safi

Background: Surgery and the perioperative management for periampullary carcinomas are translated from the more frequent ductal adenocarcinoma of the pancreatic head (hPDAC). After implementation of the pathological circumferential resection margin (CRM), true margin negativity dropped dramatically for hPDAC patients. The frequent infiltration of the mesopancreas (MP) is a causative factor for incomplete resection. It remains unknown if the oncological relevance of the MP remains exclusive for the hPDAC or if it can be translated into the operative management for periampullary carcinomas as well. Material and methods: Patients who received oncological pancreatoduodenectomies (PD) for dCCAs and ACs from 2015 to 2025 at our department were included in this study (n =100). The MP status was retrieved from the histopathological reporting. Results: MP infiltration was evident in 36.4% and 62.2% of the AC and dCCA patients respectively (p = 0.015). Across both tumour entities, mesopancreatic involvement emerged as a marker of significantly worse overall survival (AC: p = 0.002; dCCA: p = 0.013). Conclusion: Distal cholangiocarcinomas presented with a frequent infiltration into the mesopancreas. A positive infiltration status of the MP significantly correlated with incomplete resection status in ampullary carcinoma. In addition, MP infiltration proved to be an adverse prognostic factor for overall survival in periampullary carcinoma patients, underscoring its potential role in perioperative staging and its possible relevance for surgical decision-making. This is the first study revealing insights into the infiltrative prevalence of the MP in periampullary carcinomas. Mesopancreatic involvement may not be exclusive to pancreatic cancer and warrants further investigation in other periampullary malignancies.

Background: Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous tumor entity with a steadily rising incidence, mainly due to advances in imaging and growing diagnostic awareness. In pancreatic ductal adenocarcinoma (PDAC), the mesopancreas (MP) has been identified as a frequent site of microscopic tumor spread and a key determinant of circumferential resection margin (CRM) status, leading to the concept of standardized mesopancreatic excision (MPE). While its oncological relevance in PDAC is increasingly recognized, the role of the mesopancreas in PanNENs remains unclear. This study aimed to systematically evaluate mesopancreatic infiltration in PanNENs and to identify associated clinicopathological predictors. Methods: Consecutive patients undergoing oncological pancreatoduodenectomy, spleen-preserving distal pancreatectomy, or distal splenopancreatectomy for PanNENs and PanNECs were included. The mesopancreas was histopathologically examined for tumor infiltration within CRM assessment. Results: MP infiltration was detected in 60% of patients. It was associated with higher Ki-67 index, larger tumor size, lymph node involvement, venous invasion, and positive CRM status. A Ki-67 index ≥ 5% and tumor size ≥ 21.5 mm were identified as predictors of MP infiltration. Higher T stage predicted reduced overall survival (OS), whereas MP infiltration, lymphatic (L1) and venous (V1) invasion, and Ki-67 ≥ 5% were associated with impaired disease-free survival (DFS). Conclusions: Mesopancreatic infiltration is frequently present in PanNENs and correlates with aggressive tumor characteristics. Given its association with CRM positivity and reduced DFS, consideration of the mesopancreas in staging and surgical strategies appears oncologically justified. Larger studies are required to validate these findings.

Purpose: The mesopancreas (MP), the dorsal area of the pancreas, is infiltrated in the majority of patients with pancreatic ductal adenocarcinoma of the pancreatic head (hPDAC) and is associated with an increased risk of incomplete resection. Current radiographic resectability criteria primarily focus on tumor involvement of major peripancreatic vessels. However, the dorsal resection margin, represented by the mesopancreas, is not explicitly considered in current staging concepts. The aim of this study was therefore to standardize a quantitative radiographic assessment of the mesopancreas and to correlate these findings with histopathology. Methods: Radiographic parameters of the primary tumor and the mesopancreas were evaluated in 173 patients with hPDAC who underwent upfront surgery. Patients were stratified according to NCCN anatomical resectability criteria. Mesopancreatic dimensions (mm) and density (HU) were analyzed on preoperative multidetector computed tomography (MDCT). Nineteen patients served as a reference group. Histopathological evaluation followed the Leeds Pathology Protocol (LEEPP). Results: 124 patients (71.7%) were classified as primary resectable and 49 (28.3%) as borderline resectable. Mesopancreatic infiltration was present in 125 patients (72.3%). Resectability classification was not associated with mesopancreatic infiltration ( p = 0.344; OR 1.5). The median density of the mesopancreas in hPDAC patients was 3 HU. Increased mesopancreatic density correlated with histopathologically confirmed mesopancreatic infiltration ( p = 0.005), with an optimal threshold of −9 HU. In subgroup analysis, this association remained significant in primary resectable patients ( p = 0.021) but not in borderline resectable tumors ( p = 0.780). Additionally, higher mesopancreatic density was associated with poorer disease-free survival in primary resectable patients ( p = 0.040). Conclusion: Increased mesopancreatic density on preoperative MDCT correlated with histopathologically confirmed mesopancreatic tumor infiltration. Radiographic assessment of mesopancreatic density may therefore provide additional information for preoperative risk stratification.

In-situ splitting of the liver before extended resection has gained broad attention. This two-step procedure requires several measures to make an effective and safe procedure. Although the procedure is performed in many institutions, there is no consensus on a uniform technique. The two steps can be divided into different parts and a standardized technique may render the procedure safer and the results will be easier to evaluate. In this paper, we describe a detailed approach to in-situ splitting that allows making both procedures safe, avoids liver necrosis, and is easily reproducible. In the first procedure the portal branches to segments I and IV to VIII are divided, the arterial branches and bile ducts to these segments are preserved and encircled and the parenchyma between segments II/III and IVa/b is divided. This avoids necrosis and bile leaks of segments I and IV and avoids urgent completion operations. In particular, the handling of vital structures close to the dissection line seems important to us. Complete splitting and securing the right and middle hepatic vein will make the second step of this procedure a minimal-risk procedure at a stage where the patient is still recovering from the more demanding first step.

Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p < 0.001) and high cytoplasmic (p < 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4–129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04–3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC.

Background: Even though numerous novel lymph node (LN) classification schemes exist, an extensive comparison of their performance in patients with resected pancreatic ductal adenocarcinoma (PDAC) has not yet been performed. Method: We investigated the prognostic performance and discriminative ability of 25 different LN ratio (LNR) and 27 log odds of metastatic LN (LODDS) classifications by means of Cox regression and C-statistic in 319 patients with resected PDAC. Regression models were adjusted for age, sex, T category, grading, localization, presence of metastatic disease, positivity of resection margins, and neoadjuvant therapy. Results: Both LNR or LODDS as continuous variables were associated with advanced tumor stage, distant metastasis, positive resection margins, and PDAC of the head or corpus. Two distinct LN classifications, one LODDS and one LNR, were found to be superior to the N category in the complete patient collective. However, only the LODDS classification exhibited statistically significant, gradually increasing HRs of their subcategories and at the same time significantly higher discriminative potential in the subgroups of patients with PDAC of the head or corpus and in patients with tumor free resection margins or M0 status, respectively. On this basis, we built a clinically helpful nomogram to estimate the prognosis of patients after radically resected PDAC. Conclusion: One LNR and one LODDS classification scheme were found to out-perform the N category in terms of both prognostic performance and discriminative ability, in distinct patient subgroups, with reference to OS in patients with resected PDAC.

Background: Coronavirus disease 19 (COVID-19) substantially affects cancer patients due to adverse outcomes and disruptions in cancer care. Recent studies have indicated the additional stress and anxiety burden arising from the pandemic and impairing quality of life in this vulnerable group of patients. However, patients with cancer represent a heterogenous group. Therefore, we conducted a study on patients with pancreatic cancer, requiring demanding surgical interventions and chemotherapy regimens due to its aggressive tumor biology, to explore the pandemic’s impact on quality of life within this homogenous cohort. Methods: In a descriptive observational study, the quality of life of patients who had undergone pancreatic surgery for tumor resection at our institution between 2014 and the beginning of the pandemic in March 2020 was assessed. For HRQoL measurement, we used the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), comparing their situation before the pandemic and since its beginning. An additional self-developed questionnaire was applied to assess the life circumstances during the pandemic. Results: Our cohort included 26 patients. Scores from the survey in HRQoL revealed no significant changes over time between before and during the pandemic. A medium deterioration in HRQoL was apparent in social functioning, as well as a small deterioration in role functioning and emotional functioning. Worries concerning a potential impact of COVID-19 on personal health were expressed. Psychological limitations in QoL were mainly attributed to the pandemic, whereas physical limitations in QoL were rather associated with the underlying disease of pancreatic cancer. Conclusion: The COVID-19 pandemic is causing considerable social and emotional distress among pancreatic cancer patients. These patients will benefit from psychological support during the pandemic and beyond. Long-time survivors of pancreatic cancer, such as those included in our cohort, appear to have improved resilience facing the psychosocial challenges of the pandemic. For pancreatic cancer, surgical care is considered the cornerstone of treatment. Prolonged delays in healthcare cause serious damage to mental and physical health. To date, the longer-term clinical consequences are not known and can only be estimated. The potential tragic outcome for the vulnerable group of pancreatic cancer patients highlights the urgency of timely healthcare decisions to be addressed in the future.

Background: Video-assisted thoracoscopic surgery (VATS) with bullectomy and partial pleurectomy (VBPP) is an increasingly used and well-established surgical treatment for primary spontaneous pneumothorax (PSP). However, reports on its effectiveness and long-term outcomes are limited. The aim of this study was to assess and compare long-term recurrence rates following VBPP and chest tube (CT) treatment and to identify potential risk factors for disease recurrence in patients with PSP. Methods: A total of 116 patients treated either by VBPP or CT were included in this study. Long-term recurrence rates and associations between clinical parameters and recurrence of pneumothorax were analyzed. Results: Sixty-two patients (53.4%) underwent VBPP, whereas 54 (46.6%) patients underwent CT treatment only. During a median follow-up period of 76.5 months, VBPP patients experienced a significantly lower recurrence rate compared to CT patients (6/62 vs. 35/54; p < 0.0001). CT treatment (VBPP vs. CT; p < 0.001) and a large initial pneumothorax size (Collins < 4 vs. Collins ≥ 4; p = 0.018) were independent risk factors for pneumothorax recurrence. Conclusion: VBPP is an effective and safe surgical treatment for PSP. Therefore, patients with a large pneumothorax size might benefit from VBPP, as they are at high risk for disease recurrence.