Complete Response to Immune Checkpoint Inhibition in a Platinum Resistant Primary Ovarian Cancer Patient With Lynch Syndrome: A Case Report and Review of the Literature.

BACKGROUND/AIM: Lynch syndrome (LS) is the secondary cause of hereditary ovarian cancer (OC). Germline mutations in the DNA-mismatch repair (MMR) genes cause tumorigenesis and a high immunogenicity. Recent studies showed a promising use of immunotherapy in MMR deficient (MMRd) tumors. This is a case report of a patient with LS-associated OC and a complete response to pembrolizumab. CASE REPORT: A 44-year-old patient was admitted to the hospital with lower abdominal pain. The patient's history showed LS with a germline mutation in the MSH2-gene. Initial diagnostics showed a pelvic tumor mass and a highly elevated cancer antigen 125. After debulking surgery, histopathological findings showed a high-grade serous OC with mutations in the MSH2 and MSH6 genes. Only 5 weeks after operation with no residual tumor mass, a quick and significant intraabdominal progression of the disease was diagnosed. Adjuvant therapy with carboplatin and paclitaxel in a weekly course did not lead to sustainable response. An anti-PD-L1 antibody therapy with pembrolizumab was initiated. After only two courses of therapy, the laboratory results and clinical status of the patient improved tremendously. Shortly after, a complete response was detected, and therapy is still ongoing. The patient remains tumor free for 21 months now. CONCLUSION: The significance of germline compared to somatic mutations has not yet been sufficiently investigated. To our knowledge, this is the first case with complete response to checkpoint inhibition in OC associated with LS. Regarding LS-associated OC, immune checkpoint inhibition is an efficient therapy in tumors nonresponsive to standard therapy.

Angiosarcomas of Primary Gynecologic Origin - A Case Series and Review of the Literature.

BACKGROUND/AIM: Angiosarcoma of primary gynecologic origin is an extremely rare and highly malignant tumor of endothelial origin with a 5-year survival rate of less than 35%. To date, only 61 cases have been described in the literature. The aim of this study was to present more cases and discuss potential therapy options. CASE REPORT: The following case series presents three cases of gynecologic angiosarcomas that were under therapy at the Charité - University medicine of Berlin from June 2014 to February 2018. RESULTS: Two of the cases deal with primary angiosarcomas of the uterus whereas the third case was diagnosed after the suspicion of a recurrence of a poorly differentiated squamous cell carcinoma of the cervix uteri. In case one a 75-year old patient with initial postmenopausal bleeding and a tumor mass of the uterus is described. After surgery a hemangiosarcoma of the uterus was confirmed. After two months the patient presented with a presacral peritoneal sarcomatosis. Chemotherapy of weekly paclitaxel was administered. Case two deals with a patient presenting with abdominal pain. A uterine sarcoma with infiltration of the parametry and angiosarcomatosis peritonei was diagnosed during an emergency laparotomy because of spontaneous peritoneal bleeding. Moreover, osseous metastasis was found. The patient underwent weekly paclitaxel. Due to tumor progression, chemotherapy was changed to doxorubicin and olaratumab and radiotherapy was induced. The patient died 33 months after initial diagnosis. Case three describes a 34-year old patient with suspected local recurrence of cervical cancer with infiltration of the bladder. During TURB an angiosarcoma was found. Following laparoscopy revealed peritoneal metastasis. The patient underwent weekly paclitaxel followed by a paclitaxel and pazopanib maintainance therapy which showed a regression. Due to progression afterwards, chemotherapy was changed to gemcitabine and docetaxel and gemcitabine monotherapy. The patient died 33 months after initial diagnosis. CONCLUSION: Even though there is no evidence on standard treatment of this extremely rare and aggressive tumor entity of the female genital tract the patients showed the longest stability of disease during chemotherapy with weekly paclitaxel.

Transpapillary endopancreatic surgery: decompression of duct system and comparison of greenlight laser with monopolar electrosurgical device in ex vivo and in vivo animal models.

BACKGROUND: Endopancreatic surgery (EPS) is an experimental minimally invasive technique for resection of pancreatic tissue from inside the pancreatic duct, accessed via the duodenum and papilla. It is proposed as an alternative to duodenum-preserving pancreatic head resection in benign diseases such as chronic pancreatitis (CP). This study evaluated the use of EPS for resection of pancreatic duct stenoses. Moreover, greenlight laser (GLL) and monopolar electrosurgical device (MES) were compared as resection tools for EPS. METHODS: The suitability of EPS for resection of stenoses was evaluated in ex vivo bovine pancreas (n = 8). Artificially created stenoses in the pancreatic head were accessed via the duodenal papilla and resected from inside the organ with MES through a rigid endoscope. Furthermore, standardized pancreatic resections were performed in an in vivo porcine model using either GLL (n = 18) or MES (n = 18) to compare blood loss, operating time, and complications. Thermal damage to the surrounding tissue was assessed using a standardized histological classification. RESULTS: Stenosis resection by EPS was feasible in 8/8 bovine pancreases, with a procedure time of 17 (12-24) min. No perforation of the organ occurred. Resection by GLL was associated with reduced blood loss [median 1.7 (interquartile range 0.6-2.6) ml vs. 5.1 (3.8-13.2) ml; p < 0.01] and shorter operating time [109 (81-127) s vs. 390 (337-555) s; p < 0.01] compared with MES. The zone of thermal tissue damage was more extensive when using GLL than with MES [4.12 (3.48-4.89) mm vs. 1.33 (1.09-1.48) mm; p < 0.01]. CONCLUSION: Transduodenal-transpapillary EPS can be used to resect stenoses and decompress the pancreatic duct system. Both GLL and MES are feasible resection methods for EPS. However, GLL showed better hemostatic characteristics than MES in an in vivo porcine model. Safety measures such as temperature control and image-guided navigation should be employed to monitor the resection and tissue heating.

Transduodenal-transpapillary endopancreatic surgery with a rigid resectoscope: experiments on ex vivo, in vivo animal models and human cadavers.

BACKGROUND: Surgery for chronic pancreatitis is afflicted with high morbidity. A novel transduodenal-transpapillary endopancreatic resection (EPR) may provide a less invasive alternative approach. MATERIALS AND METHODS: After laparoscopic duodenotomy the papilla was dilated and accessed with a rigid resectoscope. A resection of pancreatic head tissue was performed from inside the organ. First, the feasibility and resection volume were assessed in bovine pancreas. Bleeding and intraoperative complications were evaluated in an acute in vivo pig model. Finally, the total laparoscopic approach was tested in human cadavers. RESULTS: EPR was feasible in 6/6 bovine and 5/6 porcine pancreases; in one case the papilla could not be located. The resected surface accounted for 30 (23-39)% of the total pancreatic surface and the resection volume was 14.2 (9-25) cm3. In vivo blood loss was minimal [10 (5-20) ml]. The operating time for EPR was 84 (75-110) min in all cadavers. CONCLUSION: The EPR technique is feasible and provides a resection comparable with duodenum-preserving pancreatic head resection (DPPHR). Given the reduced surgical trauma, EPR may emerge as a minimally invasive alternative to DPPHR.