Pancreatic ductal adenocarcinoma concomitant with pancreatic metastases of clear-cell renal cell carcinoma: a case report

Background!#!Metastatic spread to the pancreas is a rare event. Renal cell carcinoma represents one possible site of origin of pancreatic metastases. Renal cell carcinoma often metastasizes late and exclusively to the pancreas, suggesting a special role of renal cell carcinoma among primaries metastasizing to the pancreas. Even rarer, renal cell carcinoma may occur simultaneously with pancreatic ductal adenocarcinoma.!##!Case presentation!#!We present the case of a 78-year-old male Caucasian patient with a history of clear-cell renal cell carcinoma treated with oncological left nephrectomy 20 years before. The patient was diagnosed with pancreatic ductal adenocarcinoma by fine-needle aspiration cytology. At our institution, he received neoadjuvant therapy with folic acid, fluorouracil, irinotecan, oxaliplatin for borderline-resectable pancreatic ductal adenocarcinoma, and subsequently underwent total pancreatectomy. Upon resection, pancreatic ductal adenocarcinoma as well as two metachronous metastases of clear-cell renal cell carcinoma occurring simultaneously and cospatially with pancreatic ductal adenocarcinoma were diagnosed in the pancreatic body.!##!Conclusions!#!Renal cell carcinoma metastases of the pancreas are rare and often occur decades after the initial diagnosis of renal cell carcinoma. The combination of renal cell carcinoma metastases and pancreatic ductal adenocarcinoma is even rarer. However, the possibility should be considered by clinicians, radiologists, and pathologists. The special role of renal cell carcinoma as a site of origin of pancreatic metastasis should be further elucidated

Overweight and Obesity Determine the Risk for Gastrointestinal Cancer in a Sex-Dependent Manner: A Retrospective Cohort Study of 287,357 Outpatients in Germany

Cancer represents the second leading cause of death worldwide, implementing a major health care and socioeconomic burden. Overweight and obesity, both of which are dramatically on the rise in both highly and less developed regions worldwide, have been established as modifiable risk factors for the development of various tumor entities including gastrointestinal (GI) cancers such as colorectal or gastric cancer. However, systematic data on an association between excessive body fat and GI cancer development from Germany are missing. Methods: A total of 287,357 adult outpatients with an available BMI value between 2010 and 2019 were identified from the Disease Analyzer database (IQVIA). The main outcome was the association between pre-obesity (BMI 25–30 kg/m2) and obesity (BMI ≥ 30 kg/m2) compared to normal weight (BMI 18.5–25 kg/m2) and the incident of a GI cancer diagnoses (including colon, rectum, stomach, pancreas, and liver cancer). Results: Within the observation period, the proportion of colon cancer patients increased stepwise from 0.5% and 0.64% in normal weight to 0.71% and 0.91% in obese female and male patients, respectively, which was confirmed in multivariable regression models (ORfemale obesity: 1.23; 95% CI: 1.03–1.48; ORmale obesity: 1.43, 95% CI: 1.17–1.74). In contrast, multivariable regression models revealed that obesity was significantly associated with rectal cancer (OR: 1.36, 95% CI: 1.01–1.84) as well as liver cancer (OR: 1.79, 95% CI: 1.17–2.73) in men only. Conclusions: Our data suggest that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner. Since overweight and obesity are modifiable risk factors, the current results may help to establish appropriate prevention and lifestyle programs to reduce both the incidence as well as the high morbidity and mortality of GI tumors in the future

Two-port versus three-port video-assisted thoracoscopic surgery for primary spontaneous pneumothorax: feasibility, postoperative outcome and long-term recurrence rates

Background!#!Two-port VATS (2-P-VATS) and three-port VATS (3-P-VATS) are well-established techniques for surgical therapy of primary spontaneous pneumothorax (PSP). However, comparisons of both techniques in terms of postoperative outcome and recurrence are limited.!##!Methods!#!From January 2010 to March 2020, we retrospectively reviewed data of 58 PSP patients who underwent VATS in our institution. For statistical analysis, categorical and continuous variables were compared by chi-square test or Fisher's exact test and the Student´s t-test, respectively. Twenty-eight patients underwent 2-P-VATS and 30 were treated with 3-P-VATS. Operation time, length of hospital stay (LOS), total dose of analgesics per stay (opioids and non-opioids), duration of chest tube drainage, pleurectomy volume (PV), postoperative complications and recurrence rates were compared between both groups.!##!Results!#!Clinical and surgical characteristics including mean age, gender, Body-Mass-Index (BMI), pneumothorax size, smoking behaviour, history of contralateral pneumothorax, side of pneumothorax, pleurectomy volume and number of resected segments were similar in both groups. The mean operation time, LOS and total postoperative opioid and non-opioid dose was significantly higher in the 3-P-VATS group compared with the 2-P-VATS group. Despite not being statistically significant, duration of chest tube was longer in the 3-P-VATS group compared with the 2-P-VATS group. In terms of postoperative complications, the occurrence of hemothorax was significantly higher in the 3-P-VATS group (3-P-VATS vs. 2-P-VATS; p = 0.001). During a median follow-up period of 61.6 months, there was no significant statistical difference in recurrence rates in both groups (2/28 (16.7%) vs. 5/30 (7.1%); p = 0.274).!##!Conclusion!#!Our data demonstrate that 2-P-VATS is safer and effective. It is associated with reduced length of hospital stay and decreased postoperative pain resulting in less analgesic use

Socioeconomic Impact of Recurrent Primary Spontaneous Pneumothorax: Should Video-Assisted Thoracoscopic Surgery Be Considered at First Episode of Primary Spontaneous Pneumothorax?

Background: Current guidelines recommend video-assisted thoracoscopic surgery (VATS) for recurrent primary spontaneous pneumothorax (PSP) and for cases with persistent air leak after chest tube treatment. The socioeconomic impact of recurrent PSP on the healthcare system is insufficiently reported. Methods: Ninety-six patients treated for PSP between 01/2010 and 01/2020 were included. Forty-eight patients underwent primary VATS, while the second group received chest tube (CT) treatment only. Length of hospital stay (LOS), duration of chest tube, prolonged air leak, postoperative complications, recurrences and treatment costs were analyzed. Results: Prolonged air leaks were evident in 12.5% and 22.9% patients of the VATS and CT group, respectively. Ten (20.8%) patients in the CT group underwent VATS for persistent air leakage. During follow-up, the VATS group recurred at 8.3% compared to 52.1% in the CT group. The total cost of treatment per patient, including treatment cost due to recurrence, was EUR 1.501 in the VATS group and EUR 2.233 in the CT group. Conclusions: Primary treatment of PSP by CT is associated with an increased socioeconomic burden for patients and the healthcare system due to high recurrence rates. This burden may be reduced if VATS is considered at the first episode of PSP

Does Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy for Primary Spontaneous Pneumothorax Impair Health-Related Quality of Life and Pulmonary Function?

Background: Video-assisted thoracoscopic surgery (VATS) with partial pleurectomy is an established treatment for primary spontaneous pneumothorax (PSP). However, postoperative pulmonary function and health-related quality of life (HR-QoL) after VATS–bullectomy with partial pleurectomy (VBPP) have not been elucidated. Methods: Eligible patients were assessed for HR-QoL using the Short-Form 36 (SF-36) health survey. Pulmonary function (PF) was evaluated by spirometry. We compared the results of the VBPP cohort with the German national norms, and with a similar cohort of patients successfully treated by chest tube (CT) only. Results: A total of 25 VBPP patients completed the SF-36 health survey, of whom 15 presented for PF assessment. Between the VBPP and CT groups, the mean forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratio were not statistically significantly different. However, in both groups, FVC, FEV1, and FEV1/FVC were above the lower limit of normal (LLN), suggesting no restrictive or obstructive patterns. Compared with the sex- and age-matched normal German population, patients who underwent VBPP displayed a similar physical component summary score and a significantly decreased mental component summary score. Interestingly, comparison of the SF-36 domains between the VBPP and CT groups showed no statistical difference. Conclusion: VBPP is a suitable surgical treatment for PSP, with no apparent adverse impacts on pulmonary or physical function. However, psychological distress and measures to counteract its impact should be considered

Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head

Background: Survival of patients with adenocarcinoma of the pancreas (PDAC) is poor and has remained almost unchanged over the past decades. The genomic landscape of PDAC has been characterized in recent years. The aim of this study was to identify a genetic profile as a possible predictor of prolonged survival in order to tailor therapy for PDAC patients. Methods: Panel next generation sequencing (NGS) and immunohistochemistry (IHC) were performed on paraffin-embedded tumor tissues from curatively treated PDAC patients. Tumor slides were re-evaluated with a focus on the histomorphology. Patients were subgrouped according to short and long overall (4 years) and disease-free (2 years) survival. Results: Thirty-nine patients were included in the study. Clinicopathological staging variables as well as the histomorphological subgroups were homogenously distributed between short- and long-term overall and disease-free survivors. In survival analysis, patients with the KRAS G12D mutation and patients with TP53 nonsense and splice-site mutations had a significantly worse overall survival (OS) and disease-free survival (DFS). Patients with long-term OS and DFS showed no KRAS G12D, no TP53 nonsense or splice-site mutations. Rare Q61H/D57N KRAS mutations were only found in long-term survivors. The allele frequency rate of KRAS and TP53 mutations in tumor cells was significantly higher in short-term disease-free survivors and overall survivors, respectively. Conclusions: NGS of PDAC revealed significant differences in survival outcome in a patient collective with homogenously distributed clinicopathological variables. Further multi-institutional studies are warranted to identify more long-term survivors to detect genetic differences suitable for targeted therapy

Neoadjuvant Treatment Lowers the Risk of Mesopancreatic Fat Infiltration and Local Recurrence in Patients with Pancreatic Cancer

Background: Survival following surgical treatment of ductal adenocarcinoma of the pancreas (PDAC) remains poor. The recent implementation of the circumferential resection margin (CRM) into standard histopathological evaluation lead to a significant reduction in R0 rates. Mesopancreatic fat infiltration is present in ~80% of PDAC patients at the time of primary surgery and recently, mesopancreatic excision (MPE) was correlated to complete resection. To attain an even higher rate of R0(CRM−) resections in the future, neoadjuvant therapy in patients with a progressive disease seems a promising tool. We analyzed radiographic and histopathological treatment response and mesopancreatic tumor infiltration in patients who received neoadjuvant therapy prior to MPE. The aim of our study was to evaluate the need for MPE following neoadjuvant therapy and if multi-detector computed tomographically (MDCT) evaluated treatment response correlates with mesopancreatic (MP) infiltration. Method: Radiographic, clinicopathological and survival parameters of 27 consecutive patients who underwent neoadjuvant therapy prior to MPE were evaluated. The mesopancreatic fat tissue was histopathologically analyzed and the 1 mm-rule (CRM) was applied. Results: In the study collective, both the rate of R0 resection R0(CRM−) and the rate of mesopancreatic fat infiltration was 62.9%. Patients with MP infiltration showed a lower tumor response. Surgical resection status was dependent on MP infiltration and tumor response status. Patients with MDCT-predicted tumor response were less prone to MP infiltration. When compared to patients after upfront surgery, MP infiltration and local recurrence rate was significantly lower after neoadjuvant treatment. Conclusion: MPE remains warranted after neoadjuvant therapy. Mesopancreatic fat invasion was still evident in the majority of our patients following neoadjuvant treatment. MDCT-predicted tumor response did not exclude mesopancreatic fat infiltration

Down-regulation of CDH1 is associated with expression of SNAI1 in colorectal adenomas.

Down-regulation of E-cadherin (CDH1) and epithelial-mesenchymal transition (EMT) are considered critical events for invasion and metastasis of colorectal carcinoma. Here we tested whether the important regulators of E-cadherin expression SNAI1 and TWIST1 are already detectable in human colorectal adenomas.RNA was extracted from a set of randomly selected formalin-fixed and paraffin-embedded (FFPE) colorectal adenomas (n = 41) and normal colon mucosa (n = 10). Subsequently mRNA expression of CDH1, CDH2, SNAI1 and TWIST1 was analysed by quantitative RT-PCR analysis. CDH1 as well as SNAI1 protein expression were assessed by immunohistochemistry (IHC).SNAI1 mRNA was expressed in 78% (n = 32/41), TWIST1 mRNA in 41% (n = 17/41) and CDH2 mRNA in 41% (n = 17/41) of the colorectal adenoma tissue, while normal colon mucosa was negative for these transcription factors. We found a significant correlation between reduced CDH1 and the presence of SNAI1 mRNA expression and for combined SNAI1 and TWIST1 mRNA expression, respectively. A correlation between CDH2 mRNA expression and reduced CDH1 expression was not observed. We confirmed the relationship between SNAI1 expression and reduced E-cadherin expression on the protein level via IHC.Our data show that SNAI1 and Twist1 are already expressed in benign precursor lesions of colorectal cancer and that SNAI1 expression was significantly correlated with lower expression of CDH1. Whether these findings reflect true EMT and/or are a sign of a more aggressive biology need to be investigated in further studies

Bone Mineral Density Is a Predictor of Mortality in Female Patients with Cholangiocellular Carcinoma Undergoing Palliative Treatment

Background: Cholangiocellular adenocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts. Its general prognosis is poor as therapeutic options are limited. Many patients present with advanced stages of disease, and palliative chemotherapy remains the only treatment option. Prognostic markers to assess the outcome of chemotherapeutic treatment in CCA are limited. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients with advanced CCA. Patients and Methods: We included 75 patients with advanced CCA that were treated at our academic tumor center. Prior to treatment, bone mineral density was analyzed at the first lumbar vertebra using routine CT scans in the venous phase and the local PACS (IntelliSpace PACS, Philips, Amsterdam, The Netherlands). Results: BMD was not significantly different between male and female patients but decreased with age. Patients with BMD above 167 HU have a significantly improved overall survival (474 days vs. 254 days; log-rank X2(1) = 6.090; p = 0.014). The prognostic value of BMD was confirmed using univariate (HR 2.313 (95%CI: 1.170–4.575); p = 0.016) and multivariate (HR 4.143 (95%CI: 1.197–14.343); p = 0.025) Cox regression analyses. Subgroup analysis revealed that the prognostic value of BMD was only present in female patients and not in male patients, suggesting sex-specific differences. Conclusions: Our data suggest that BMD is a valuable, easily accessible, and independent prognostic marker for overall survival in patients with advanced CCA. Furthermore, subgroup analysis showed the sex specificity of this marker, which demonstrated relevance only in female patients

Sarcopenia and Myosteatosis as Prognostic Markers in Patients with Advanced Cholangiocarcinoma Undergoing Palliative Treatment

Background: Cholangiocarcinoma (CCA) represents the second most common primary liver cancer and is characterized by a very poor outcome, but reliable prognostic markers are largely missing. Sarcopenia, the progressive loss of muscle mass and strength, as well as myosteatosis have been associated with an unfavorable outcome in several clinical conditions, including cancer. Here, we evaluated the prognostic relevance of sarcopenia and myosteatosis using routine abdominal CT (computed tomography) scans in advanced stage CCA patients undergoing palliative treatment. Methods: Routine abdominal CT scans were used to assess the skeletal muscle and the psoas muscle index (L3SMI/L3PMI) at the level of the third lumbar vertebra as radiological indices for sarcopenia as well as the mean skeletal muscle attenuation (MMA) as a surrogate for myosteatosis. Results were correlated with clinical data and outcomes. Results: Using a calculated optimal cut-off value of 71.95 mm2/cm, CCA patients with an L3SMI value below this cut-off showed a significantly reduced median overall survival (OS) of only 250 days compared to 450 days in patients with a higher L3SMI. Moreover, the median OS of CCA patients with an L3PMI above 6345 mm2/cm was 552 days compared to 252 days in patients with a lower L3PMI. Finally, CCA patients with an MMA above 30.51 Hounsfield Units survived significantly longer (median OS: 430 days) compared to patients with an MMA value below this ideal cut-off (median OS: 215 days). The prognostic relevance of L3SMI, L3PMI, and MMA was confirmed in uni- and multivariate Cox regression analyses. Conclusion: Routine abdominal CT scans represent a unique opportunity to evaluate sarcopenia as well as myosteatosis in advanced CCA patients. We identified the L3SMI/L3PMI as well as the MMA as negative prognostic factors in CCA patients undergoing palliative therapy, arguing that the “opportunistic” evaluation of these parameters might yield important clinical information in daily routine