Acinar cell cystadenoma

$\bf Background:$ Von Hippel-Lindau (VHL) disease may occur at various localisations which can be both intraand extrapancreatic as well as challenging to diagnose by medical imaging. $\bf Case$ $\bf Report:$ A positron emission tomography/magnetic resonance imaging in a 40-year old woman was performed to monitor a haemangioblastoma. Additionally, it showed findings which were considered to be a pancreatic neuroendocrine tumour (pNET) and retroumbilical metastasis. The suspected metastasis was laparoscopically resected; however, pathological evaluation did not lead to a clear categorisation. Consequently, the pancreatic head was resected in which a pNET and various acinar cell cystadenomas were found. $\bf Conclusion:$ Diagnostic and therapy of advanced VHL disease can be difficult; if in doubt, a surgical approach may establish clarity

Small bowel obstruction due to a giant Meckel's diverticulum

$\textbf {Background:}$ Meckel’s diverticulum is the most common congenital anomaly of the gastrointestinal tract, with an average length of 3 cm. Complications occur in 6.4% and most commonly include inflammation and gastrointestinal bleeding. Preoperative diagnosis is demanding and achieved in 4%. $\textbf {Case Report:}$ A 34-year-old otherwise healthy patient presented with an acute abdomen due to small bowel obstruction. Computed tomography scan could not identify the underlying cause. Emergency laparotomy was performed, and a torqued giant Meckel’s diverticulum measuring 17 cm was found as the underlying cause for the small bowel obstruction. Resection of the affected ileum segment and ileo-ileal reconstruction were performed. The postoperative course was uneventful. $\textbf {Conclusion:}$ In extremely rare cases, small bowel obstruction in an otherwise healthy patient might be caused by torsion of a symptomatic giant Meckel’s diverticulum

Diagnostic double strike in the emergency room

$\textbf {Background:}$ Pancreatic injuries are rare in cases of blunt abdominal trauma and therefore easily misdiagnosed at time of hospital admission. They are associated with a significantly elevated morbidity and lethality. Bicycle handlebar injuries are the most common cause of pancreatic trauma in children and adolescents. $\textbf {Case presentation:}$ We report two cases of a 23-year-old Caucasian woman and a 15-year-old Caucasian boy who presented to our clinic with a similar history of a bicycle accident on 2 consecutive days. Both suffered from a fall from a bicycle with bicycle handlebar injury 4 and 6 days prior to admission in our clinic. Emergency distal pancreatectomies were performed in both cases. $\textbf {Conclusions:}$ Pancreatic injuries must be highly suspected in bicycle handlebar injuries, even if amylase/lipase levels or ultrasound findings seem unremarkable. The best initial strategies are early computed tomography and a quick referral to a level 1 trauma center. Distal pancreatectomy is the treatment of choice in cases of complete rupture of the pancreatic body

Facing the surgeon's nightmare

$\bf Background$ Postoperative pancreatic fistulas (POPF) grade C represent a rare but feared complication following pancreaticoduodenectomy (PD). They can contribute significantly to postoperative morbidity and mortality. $\bf Methods$ We performed a retrospective chart review for all patients who had undergone pancreatic head resection between 2007 and 2016 to identify those who suffered from POPF grade C according to the updated definition of the International Study Group of Pancreatic Surgery (ISGPS). $\bf Results$ A total of 722 patients underwent PD. Twenty-three patients (3.19%) developed a POPF grade C. Cardiovascular diseases, soft pancreatic texture and main pancreatic duct diameter were identified as risk factors ($\it P$ < .05). Reoperation was necessary in all affected patients on postoperative day 12 $\pm$ 9 on average. Mortality was significantly associated with POPF grade C ($\it P$ < .05) being present in 39.1% (9/23). $\bf Conclusions$ POPF grade C after PD remains a serious complication with a high level of morbidity and mortality. Surgical treatment is the sole curative therapy and thus the treatment of choice

Anti-tumorigenic effects of emodin and its’ homologue BTB14431 on vascularized colonic cancer in a rat model

Objective: New drugs for cancer treatment are being sought worldwide. Therapeutic agents derived from natural substances can provide cost-efficient options. We evaluated the effect of emodin, an active natural anthraquinone derivate, and it’s in-silico homologue the novel substance BTB14431 in vivo. Method: CC-531 colon cancer cells were implanted intraperitoneal (ip) and subcutaneous (sc) in 100 WAG/Rij rats. 28 days after tumor cell implantation, solid cancers were treated for 7 days by varying doses of BTB14431 (0.3 mg/kg body weight; 1.7 mg/kg) or emodin (2.5 mg/kg; 5 mg/kg). Treatment was applied either via an intravenous (iv) port catheter or by ip injection. Saline solution served as control. 21 days after final dose all animals were euthanized and ip tumor weight, sc tumor weight and animal body weight (bw) were determined by autopsy. Significant lower total tumor weight occurred after iv treatment with low dose BTB14431 (6.8 g; 90% confidence interval (CI) 5.3 - 8.2 g; p $\leq$ 0.01) and also low and high concentrations of emodin (9.4 g; CI 7.9 - 10.7 g; p $\leq$ 0.01 and 8.3 g; CI 7.6 - 9.3; p $\leq$ 0.01). Iv treatment by high dose BTB14431 did not lead to a decline in tumor weight. High dose ip treatment by emodin led to a lower overall (11.1 g; CI 10.1 – 13.8 g; p $\leq$ 0.01) and ip tumor weight (8.6 g; CI 6 – 10.4 g; p $\leq$ 0.01). Sc tumor weight was not affected. All other ip treatments did not result in changes of combined, ip or sc tumor weight. Bw decreased during iv treatment in all animals and increased after treatment was completed. Regain of bw was stronger in animals receiving low dose emodin. Conclusion: Our study shows promising anti-cancer properties of BTB14431 and supports the evidence regarding emodin as a natural antitumorigenic agent. Optimal dosing of iv emodin and especially BTB 14431 for maximal efficacy remains unclear and should be a subject of further research

Recurrence of pancreatic ductal adenocarcinoma after complete histopathological remission caused by FOLFIRINOX

We previously reported 2 cases of pathologic complete response (pCR) of a pancreatic cancer (PC) following neoadjuvant FOLFIRINOX treatment. We now complete our report by a follow-up on both patients. Patient 1 achieved a disease-free survival of 12 months after initial resection until she developed a singular hepatic metastasis. Treatment by FOLFIRINOX and complete removal of the metastasis by atypical liver resection after 6 months allowed for another 12 months of disease control. After intra-abdominal tumor recurrence and development of intracerebral metastases, the patient died 34 months after primary diagnosis. Patient 2 developed hepatic tumor recurrence only 3 months after initial resection. However, treatment by FOLFIRINOX led to a stable disease for 27 months after resection and was followed by atypical liver resection of multiple segments. Six months later, another hepatic recurrence was suspected. Via next-generation sequencing (NGS) of the tumor genome, a deleterious mutation in the ataxia telangiectasia-mutated ($\it ATM$) gene, causing a $\it BRCA$ness, was detected. After initial treatment by FOLFOX, maintenance therapy with the poly-ADP-ribose-polymerase (PARP) inhibitor olaparib was initiated. The patient is now alive for 54 months after initial diagnosis of metastasized pancreatic adenocarcinoma. Tumor recurrence is possible even after pCR of PC and remains challenging. In case of multifocal tumor recurrence, chemotherapy remains the standard treatment. Recently, genetic sequencing allows individualized treatments. In selected cases, highly specialized teams can offer a variety of therapeutic options leading to previously unseen clinical courses

Pathologic complete response of pancreatic cancer following neoadjuvant FOLFIRINOX treatment in hepatic metastasized pancreatic cancer

$\textit {Introduction:}$ Pancreatic cancer is a lethal disease and often asymptomatic. Therefore, it is most often diagnosed at an advanced stage. The standard approach in a metastasized tumor stage is palliative chemotherapy. However, the prognosis remains extremely poor. $\textit {Case Report:}$ We present the case of a patient who was diagnosed with a cancer of the head of the pancreas with hepatic metastases. After receiving palliative intended chemotherapy with the FOLFIRINOX regimen, staging computed tomography revealed the disappearance of the liver metastases and local resectability of the pancreatic head tumor. The patient underwent an uneventful Whipple's procedure. Surprisingly, pathohistological investigation revealed a complete pathological response. $\textit {Conclusion:}$ Pathological complete response after FOLFIRINOX treatment in hepatic metastasized pancreatic cancer is extremely rare. It enables surgical resection and increases the survival rate significantly

Ergebnisse des Limberg-Plastik-Verfahrens bei akuten und chronischen Pilonidalabszessen

$\bf Hintergrund$ In der Behandlung des Sinus pilonidalis werden unterschiedliche Therapiealgorithmen für den akuten sowie den chronischen Sinus pilonidalis empfohlen. Während sich beim chronischen Sinus pilonidalis ein einzeitiges Vorgehen als Exzision oder plastische Rekonstruktion nach Limberg oder Karydakis anbietet, ist die empfohlene Vorgehensweise beim akuten Pilonidalabszess zweizeitig. Ziel dieser Studie war es, die Ergebnisse der einzeitigen Operation mit Limberg-Plastik bei akutem Pilonidalabszess und chronischem Sinus pilonidalis bezogen auf Rezidive, Wundheilungsstörungen, stationärer Liegedauer sowie Patientenzufriedenheit zu vergleichen. $\bf Methoden$ Von 2009 bis 2014 wurden 39 Patienten in die prospektive Beobachtungsstudie eingeschlossen. 21 Patienten mit akutem Pilonidalabszess, 18 mit chronischem Sinus pilonidalis. Alle Patienten wurden einzeitig mittels Limberg-Rautenplastik operativ behandelt. Die Gruppen wurden in Bezug auf postoperative Komplikationsrate und Rezidivhäufigkeit miteinander verglichen. $\bf Ergebnisse$ Beide Gruppen waren im Wesentlichen vergleichbar. Die Analyse der postoperativen Ergebnisse zeigte eine vergleichbare Rate an Wundheilungsstörungen (10 % vs. 17 %, $\it p$ = 0,647). In der Gruppe des akut abszedierten Sinus trat kein Rezidiv im Beobachtungszeitraum auf, während sich in der chronischen Gruppe 2 (11 %) Rezidive zeigten ($\it p$ = 0,206). $\bf Diskussion$ Die Ergebnisse der Limberg-Plastik als einzeitige Therapie des Pilonidalabszesses sind mit denen beim chronischen Sinus pilonidalis vergleichbar. Es zeigt sich ein Trend zu einem geringeren Rezidivrisiko. Der Einsatz der Limberg-Plastik scheint daher auch in der akuten Infektsituation eine adäquate Therapieoption.$\bf Background$ A number of different treatment algorithms are recommended for the treatment of an acute pilonidal abscess and a chronic pilonidal sinus. While a 1-stage surgical procedure using excision or plastic reconstruction according to Limberg or Karydakis is suggested for chronic pilonidal sinus, a 2‑stage procedure is recommended for an acute pilonidal abscess. The aim of this study was to compare the results of the 1‑stage surgery with plastic reconstruction according to Limberg for acute pilonidal abscess and chronic pilonidal sinus in terms of recurrence, disorders of wound healing, inpatient length of stay and patient satisfaction. $\bf Methods$ From 2009 to 2014 a total of 39 patients were included in this prospective observational study: 21 patients with acute pilonidal abscess and 18 patients with chronic pilonidal sinus. All patients were surgically treated with a 1‑stage procedure using the Limberg flap method. The groups were compared in terms of postoperative complication rates and frequency of recurrence. $\bf Results$ Both groups were basically comparable with respect to demographic characteristics and risk factor profiles. Analysis of the postoperative results showed a comparable rate of postoperative wound healing disorders (10% vs. 17%, $\it p$ = 0.647). In the group with acute pilonidal abscesses there was no recurrence during the observational period, while in the chronic pilonidal sinus group there were 2 (11%) recurrences ($\it p$ = 0.206). $\bf Conclusion$ The results of the Limberg flap procedure regarding acute pilonidal abscesses were comparable to those of chronic pilonidal sinus. The results of this study show a trend to a lower risk of recurrence. The use of the Limberg flaps therefore also seems to be an adequate treatment option in an acute infection situation

Substance GP-2250 as a new therapeutic agent for malignant peritoneal mesothelioma

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options

GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-κ\kappaB pathway in pancreatic cancer cells

GP-2250, a novel anticancer agent, severely limits the energy metabolism, as demonstrated by the inhibition of hexokinase 2 and glyceraldehyde-3-phosphate dehydrogenase and a decrease of ATP. Rescue experiments with supplementary pyruvate or oxaloacetate demonstrated that a TCA cycle deficit largely contributed to cytotoxicity. Activation of the energy-deficit sensor, AMP-dependent protein kinase, was associated with increased phosphorylation of acetyl-CoA carboxylase and Raptor, pointing to a possible deficit in the synthesis of fatty acids and proteins as essential cell components. Binding of p65 to DNA was dose-dependently reduced in nuclear lysates. A transcriptional deficit of NF-$\kappa$B (nuclear factor kappa-light-chain-enhancer of activated B cells) was substantiated by the downregulation of cyclin D1 and of the anti-apoptotic Bcl2, in line with reduction in tumour cell proliferation and induction of apoptosis, respectively. The upregulation of p53 concomitant with an excess of ROS supported apoptosis. Thus, the anticancer activity of GP-2250 is a result of disruption of energy metabolism and inhibition of tumour promotion by NF-$\kappa$B