Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma.

PURPOSE: Although gemcitabine-based chemotherapy is most recommended for pancreatic ductal adenocarcinoma (PDAC), its effectiveness is limited because of drug resistance. Given thalidomide's anti-tumor effects in solid tumors, we investigated the effect of avadomide, a novel thalidomide analog, on PDAC and explored its anti-tumor mechanisms. METHODS: PDAC cell lines, including gemcitabine-resistant (GR) clones derived from MiaPaCa2 cells, were used to evaluate the effects of avadomide. An annexin V assay, a cell cycle assay, and western blot analysis were performed to explain the mechanism of avadomide as an anti-tumor reagent. Moreover, we investigated the anti-tumor effect on tumor growth using a subcutaneous xenograft murine model. RESULTS: Avadomide showed anti-tumor effects in human PDAC cell lines. The proportion of apoptotic cells and G0/G1 phase cells after avadomide treatment increased, especially in the GR PDAC clones. Western blot analysis also showed the induction of the apoptotic pathway by inhibiting the NF-κB process and G1 phase cell cycle arrest. The xenograft murine model revealed that the proportion of viable cells in the avadomide-treated group was lower than that in the untreated group. CONCLUSION: Our findings suggest that avadomide could be a novel therapeutic option to overcome gemcitabine resistance in patients with PDAC.

Our experience of repeat laparoscopic liver resection in patients with recurrent hepatocellular carcinoma.

BACKGROUND: Repeat liver resection is an effective treatment approach for patients with recurrent hepatocellular cell carcinoma (HCC). However, the surgical feasibility and oncological significance of repeat laparoscopic liver resection (r-LLR) remain unproven. This study evaluates and compares the clinical outcomes of non-anatomic r-LLR applied towards recurrent HCC, with those of primary LLR (p-LLR) for primary HCC. METHODS: This retrospective study reports 104 patients with HCC, treated with LLR between 2014 and 2018. Twenty eight of these patients underwent r-LLR for recurrent HCC. The clinical and surgical variables were reviewed for all cases. RESULTS: The analysis was limited to non-anatomic resection across both groups (r-LLR: 89% (25/28) vs. p-LLR: 80% (61/76)). There were no statistically significant differences about patient background between the two groups, with the exception of Child-Pugh classification. r-LLR surgical techniques included single-site laparoscopic adhesiolysis (32%, 8/25), Pringle maneuver (8%, 2/25), and crush-clamp method using BiClamp for hepatic parenchymal transection (72%, 18/25). No severe postoperative complications were observed in the r-LLR group. Postoperative hospital stays and procedure-related postoperative survival were similar for both groups. CONCLUSIONS: Non-anatomical r-LLR renders comparable surgical and oncological outcomes. Our data suggest that non-anatomical r-LLR is a safe and feasible therapeutic approach to recurrent HCC.

Successful management of aberrant right hepatic duct during laparoscopic cholecystectomy: a rare case report.

BACKGROUND: Anatomic variants of the biliary tree present challenges to surgical management during laparoscopic cholecystectomy and affect perioperative outcomes. An aberrant right hepatic duct connecting into the cystic duct is a practically important variation because of the susceptibility to serious postoperative refractory bile leakage. We report a successful case of laparoscopic cholecystectomy in the aberrant right hepatic duct of a patient diagnosed with chronic cystitis. CASE PRESENTATION: A 49-year-old man was referred to our department for treatment of chronic cholecystitis. Magnetic resonance cholangiopancreatography indicated that the cystic duct branched from the common bile duct and an aberrant bile duct connected to the cystic duct. Intraoperative cholangiography revealed that the bile duct was not confluent to the major right branch of the intrahepatic bile duct and drained a narrow area. Preoperative magnetic resonance cholangiopancreatography had diagnostic value. Furthermore, intraoperative cholangiography with the Critical View of Safety method was paramount to achieving safe cholecystectomy based on confirmation of the biliary anatomy and the drainage area of the aberrant right hepatic duct. CONCLUSION: We encountered a rare but clinically significant case of laparoscopic cholecystectomy. This case suggests that precise understanding of the anatomy and drainage area of the aberrant right hepatic duct preoperatively and intraoperatively can lead to safe cholecystectomy.

Laparoscopic resection of retroperitoneal paraganglioma behind the Spiegel lobe in a kyphotic patient: A rare case report.

Extra-adrenal paraganglioma is a rare form of neuroendocrine neoplasm capable of catecholamine secretion. The surgical risks associated with the tumor location are compounded in this case of a kyphotic patient. This report presents the successful application of laparoscopy on extra-adrenal paraganglioma located behind the Spiegel lobe in a kyphotic patient. The operation was performed after 1 week of α-blocker administration. The laparoscopic approach, with the patient in the left hemilateral decubitus position on a rotating table, provided optimal access for safe tumor resection after complete hepatic right lobe mobilization. The patient's postoperative course was uneventful. Based on the results, the laparoscopic approach can be a safe and effective method for resecting extra-adrenal paraganglioma in the challenging case of a kyphotic patient.

[Improvement of Pain Control after Dealing with Chemical Coping-A Case of Local Recurrence of Rectal Cancer].

A 57-year-old female underwent abdominoperineal resection for rectal cancer. Although she received postoperative adjuvant chemotherapy, she had presacral recurrence with pain 26 months postoperatively. We provided palliative care in parallel with systemic chemotherapy, but she had difficulty controlling pain despite using high-dose opioids at 43 months after surgery. Multimodal therapy contributed to a reduction in opioid use for a brief time. Nevertheless, she required high-dose opioid therapy again at 50 months after the procedure. Since she used a rescue dose for relieving anticipatory anxiety for pain, we estimated that she developed chemical coping. After we tried analgesic adjuvant therapy and psychotherapy, her opioid use was reduced. For 10 months afterward, her disease worsened with time, but her pain was well-controlled. In cases where it is difficult to control pain, protection against exacerbation or opioid dose escalation should be considered. Furthermore, psychological contexts, including chemical coping, should also be considered. It may lead to the use of a proper dose of opioids and improve quality of life for patients.

[Examination of Patients with Malignant Obstruction Treated with Chemotherapy after Ileo/Coleostomy].

Management for obstructive cancer of the colon diverges into many ways. The aim of this study was to evaluate the treatment course of patients with malignant obstruction after ileo/coleostomy. Thirty-six patients with malignant obstruction who underwent ileo/coleostomy in our hospital from May 2012 to January 2016were enrolled in the study. Clinical outcomes were the period before treatment initiation, chemotherapy, radiotherapy, primary lesion resection, and death, and these were retrospectively analyzed. Although 9 stomal complications occurred, no case experienced a delayed treatment start. However, patients with perioperative complications, sepsis due to the tumor, pneumonia, cerebral infractions, and ileus needed a long recovery period before treatment initiation. Patients who need ileo/coleostomy must be considered for performance status and ways to decrease perioperative complications to prevent stomal complications from chemo/radiotherapy.

[Examination of the Usefulness of Palliative Self-Expanding Metallic Stents in Patients with Malignant Colorectal Obstruction].

Self-expanding metallic stents (SEMS) are a useful palliative option in malignant colorectal obstruction. The aim of this study was to evaluate the clinical outcomes of SEMS used for palliation. Patients with malignant colorectal obstruction who underwent SEMS insertion in our hospital from April 2014 to March 2015 were enrolled in the study. Clinical outcomes and complications of palliative SEMS insertion were retrospectively analyzed. Nine patients were enrolled in the palliative SEMS group. The success rate was 100%, while the complication rate was 11%. Successful SEMS insertion may enable oral intake in a few days, but 3 patients required up to several weeks to resume oral intake. Palliative SEMS are effective and beneficial for malignant colorectal obstruction.

[A Case of Disseminated Carcinomatosis of the Bone Marrow with Disseminated Intravascular Coagulation Caused by Cecal Cancer Successfully Treated with mFOLFOX6].

Disseminated carcinomatosis of the bone marrow is often accompanied by disseminated intravascular coagulation syndrome (DIC). This condition is rarely caused by colorectal cancer, and there are no established therapies. OUR CASE: A 66-year-old woman was admitted to our hospital because of DIC. She had been diagnosed with cecal cancer and multiple metastases of the lymph nodes, liver, and bone. She was diagnosed with disseminated carcinomatosis of the bone marrow and treated with systemic chemotherapy by modified FOLFOX6 (mFOLFOX6). Subsequently, the DIC rapidly resolved, and she was discharged from the hospital.

[A Case of Invasive Ductal Carcinoma in the Fat Replacement of the Pancreatic Body and Tail].

A 56 year-old woman with obesity (BMI3 2) and diabetes mellitus was diagnosed with right renal cell carcinoma. She underwent right nephrectomy 1 year ago. Seven months after surgery, CT revealed a rapidly growing mass near the spleen. The mass showed slight accumulation of FDG (SUVmax=2.4) on PET-CT. Since the lesion grew rapidly and was not enhanced in the early phase of enhanced CT, we diagnosed pancreatic cancer. Distal pancreatectomy and splenectomy were performed. The final pathological diagnosis was invasive ductal carcinoma in the fat replacement of the pancreatic body and tail. Postoperatively, the patient had no complications such as pancreatic fistula or aggravation of glucose intolerance. She received postoperative chemotherapy with gemcitabine. Since she developed pulmonary artery thrombosis, postoperative chemotherapy was interrupted after 8 courses. Thirty-two months after the surgery, she was still living without any recurrence. Acinar cells were absent in the fat replacement of the pancreas, but the pancreatic duct cells were still present. There was carcinoma in situ in the main pancreatic duct surrounding chronic inflammation. Fat replacement itself could be potentially precursor of the pancreatic cancer.