Johannes Lemke

Brain metastasis in pancreatic cancer.

Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreatic cancer were identified. In three patients brain metastases were the first manifestation of pancreatic cancer. All other patients developed brain metastases during their clinical course. In most cases, the disease progressed rapidly and the patients died within weeks or months. However, two patients showed long-term survival. Of note, both patients received resection of the pancreatic cancer as well as curative resection of the metachronous brain metastases. Brain metastases in pancreatic cancer are a rare condition and usually predict a very poor prognosis. However, there is evidence that resection of brain metastases of pancreatic cancer can be immensely beneficial to patient’s survival, even with the chance for cure. Therefore, a surgical approach in metastatic pancreatic cancer should be considered in selective cases.

Quality of Life After Sphincter-Preserving Rectal Cancer Resection

BACKGROUND With an increasing number of cancer survivors quality of life (QoL) becomes more and more important in the treatment of rectal cancer (RC). QoL after sphincter-preserving anterior resection (AR), however, was found nonsuperior to abdominoperineal resection. The aim of our study was to evaluate QoL after AR compared with colon cancer patients after right hemicolectomy (CC) and healthy lay persons without history of cancer (HL) in long-term follow-up. PATIENTS AND METHODS Consecutive alive RC patients (n = 293) who received an AR between 1998 and 2008 were included. CC patients (n = 201) and HL of the same age were used as a surgical and a nonsurgical control group, respectively. QoL was assessed using European Organization of Research and Treatment of Cancer questionnaires QLQ-C 30 and -CR 38. RESULTS Questionnaires from 116 RC patients, 105 CC patients, and 103 HL were evaluable with a median time after surgery of 5 years. The global health status did not differ. Social functioning, future perspectives, and financial difficulties tended to poorer scores in the cancer groups. Physical functioning was better in RC and CC patients compared with HL. Defecation problems and diarrhea were more frequent in RC patients (P < .05). An additional open question revealed a median stool frequency of 3, 2, and 1 per day for RC, CC, and HL, respectively. Defecation problems were more frequent in RC patients who received radiation therapy (P < .05). CONCLUSION Diarrhea and defecation problems impaired QoL after AR for RC, which was worsened after radiation therapy. To improve QoL of RC patients in the future, physicians have to focus on minimization of gastrointestinal side effects while optimizing surgical reconstruction.

CDK9 is a prognostic marker and therapeutic target in pancreatic cancer

Despite recent advances in diagnosis and therapy, prognosis of pancreatic cancer still remains very poor. Besides valid prognostic markers, novel therapeutic approaches are urgently needed. The family of cyclin-dependent kinases comprises 20 kinases which contribute to malignancy by promoting proliferation, migration, invasion, and apoptotic resistance of cancer cells. In this work, we investigated the role of CDK9 in pancreatic cancer. Immunohistochemical analysis of CDK9 expression in tumor and normal tissue of pancreatic cancer patients revealed an overexpression of CDK9 in pancreatic cancer tissue. In addition, high CDK9 expression in tumor tissue is associated with significantly shortened survival, especially in well-differentiated tumors. Moreover, the therapeutic potential of selective CDK9 inhibition on pancreatic cancer cells was evaluated by analysis of cell viability, long-term survival, and induction of apoptosis and characterized by western blotting and flow cytometry. Pharmacological CDK9 inhibition by SNS-032 drastically reduced cell viability in pancreatic cancer cells and potently suppressed long-term survival. Analyzing the mechanism of action revealed that CDK9 inhibition induced apoptosis and cell cycle arrest in a time-dependent manner by suppression of anti-apoptotic proteins. Furthermore, CDK9 inhibition potently enhances the therapeutic effect of chemotherapeutics in pancreatic cancer cells. In conclusion, we identified CDK9 as a negative prognostic marker in pancreatic cancer. Furthermore, pharmacological CDK9 inhibition is a novel and promising therapeutic approach for pancreatic cancer.

CK1α overexpression correlates with poor survival in colorectal cancer

BackgroundColorectal cancer (CRC) is the fourth leading cause of cancer related deaths worldwide and prognosis in advanced tumor stage still remains poor. Since CK1 isoforms have been reported to be deregulated in several tumor entities CK1 has emerged as a novel drug target in cancer therapy. In this study we set out to investigate whether CK1α might have the potential to serve as prognostic marker.MethodsCK1α RNA and protein expression levels in healthy and tumor tissue of CRC patients were analyzed using quantitative real-time PCR and Western Blot analysis, respectively. Prognostic relevance was investigated by correlating obtained CK1α expression levels with patients’ survival rate generating Kaplan-Meier survival plots.ResultsIt could be shown that CK1α is overexpressed in colorectal tumor tissue compared to normal tissue and CK1α overexpression in tumor tissue correlates with poor survival in CRC patients. Results become more significant when only considering patients with high-grade tumors, as well as patients assigned to UICC II and UICC III stage. Furthermore, Cox regression analysis revealed that CK1α is an independent prognostic factor. In addition, tumors expressing decreased levels of the kinase reveal positive effects on overall survival when localized in the right colon compared to those in the left side.ConclusionIn summary, this study provides evidence for the first time that CK1α RNA levels might serve as prognostic marker for CRC.

Challenging the limits in pancreatic surgery: A case report

Highlights • Despite the great progress remains challenging in many cases due to proximity of main vascular structures.• This unique cases demonstrates the complex surgical procedure of a partial pancreaticoduodenectomy in combination with a mesenterico-caval shunt.• Autoimmune pancreatitis is a relevant differential diagnosis of pancreatic conditions which may require complex surgical approaches.

Ectopic spleen and liver hemangioma mimicking metastatic pancreatic neuroendocrine tumor.

Highlights • IPAS (intrapancreatic accessory spleen) can mimic pancreatic neuroendocrine tumors in nuclear imaging, such as Dotatate PET-CT, due to somatostatine-receptor positivity of intrasplenic lymphocytes.• Non-invasive differentiation between intrapancreatic accessory spleens and pancreatic neuroendocrine tumors can be provided by using 99mTc-sulphur-colloid or 99mTc-tagged heat-damaged RBC Scintigraphy.• Extended preoperative radiological and nuclear medical examinations play a key role in properly differentiating suspect intrapancreatic lesions from intrapancreatic accessory spleens and prevent patients from unnecessary surgery.• We consider intrapancreatic accessory spleens a relevant differential diagnosis in patients with suspected pancreatic neuroendocrine tumors of the pancreatic tail, which should be taken into account before surgery is provided.

Laparoscopic splenectomy of a wandering spleen with coincidental enormous splenomegaly.

Ectopy of the spleen also referred to as wandering spleen is a rare condition and preferentially treated by laparoscopic splenopexy. However, in complicated cases with torsion and consecutive infarction of the spleen splenectomy is required. Performing the splenectomy of a wandering spleen laparoscopically has already been reported as a save therapeutic option. However, open splenectomy is usually preferred in case of massive splenomegaly for both, wandering and regular localized spleen. In this case report we describe a laparoscopic technique as alternative for conventional splenectomy in the case of a huge wandering spleen.