Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015).

BACKGROUND: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. PATIENTS AND METHODS: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. RESULTS: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24-38%)/GS, 26% (18-33%)], but the Kaplan-Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, -50%/-21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. CONCLUSIONS: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

[A Case of Adenocarcinoma of Pancreatic Head of Liver Disfunction after Pancreaticoduodenectomy with Celiac Artery Stenosis Treated by Urgent Median Arcuate Ligament Release].

This patient visited our hospital for the purpose of detailed examination of prostate cancer in his seventies. Abdominal contrast-enhanced computed tomography(CT)revealed a low-density mass of 2 cm in the pancreatic head. He was diagnosed with pancreatic cancer. Pancreaticoduodenectomy was performed after 2 courses of gemcitabine and S-1 therapy were performed as neoadjuvant chemotherapy. An intraoperative clamp test of the gastroduodenal artery showed that the pulsation of the common hepatic artery and the proper hepatic artery was weak but sufficient, so the gastroduodenal artery was cut and the operation was completed as planned. A blood test on the 1st day after the operation showed elevated levels of AST 537 U/L, ALT 616 U/L, and 7 hours later blood sampling showed further increases in AST 1,455 U/L, ALT 1,314 U/L. After a detailed review of the preoperative CT, celiac artery stenosis due to compression of the arcuate ligament was suspected, and urgent median arcuate ligament release was performed on the same day. Dissection of the arcuate ligament significantly improved the pulsation of the common hepatic artery and proper hepatic artery. Postoperatively, hepatic enzymes improved and ISGPS showed Grade B pancreatic juice leakage, but the patient was discharged from the hospital on the 49th postoperative day without any other complications. He took S-1 as adjuvant chemotherapy, and no signs of recurrence have been observed 9 months after the operation.

[A Case of Strangulated Bowel Obstruction after a Laparoscopic Hartmann's Operation for Rectal Cancer].

A 98-year-old woman presented with hematochezia and a circumferential type 2 tumor in the rectum Rb identified on fiberoscopy. We a performed laparoscopic Hartmann's operation and D2 lymphadenectomy for advanced rectal cancer. A sigmoid colostomy was created via the intraperitoneal route. On the postoperative day 12, the patient experienced abdominal pain. Computed tomography showed that the small intestine formed a closed loop in the pelvic space. The patient was diagnosed with a strangulated bowel obstruction of the small intestine for which an emergency exploratory laparotomy was performed. The small intestine, which had passed through a defect between the lifted sigmoid colon and the left abdominal wall, was strangulated by the lifted sigmoid colon. We performed partial resection of the small intestine. The patient died on postoperative day 32 of acute deterioration of aortic valve stenosis. There have been few reports of strangulated bowel obstruction resulting from internal hernia associated with colostomy. These findings demonstrate that it is important to select the appropriate route for colostomy creation in each case.

[A Case of Liver Metastasis Complete Resection for Concurrent Overlapping Cancer of the Transverse Colon and Renal Cell Carcinomas that were Difficult to Differentiate from Hepatocellular Carcinoma].

A 79-year-old man visited the hospital because of constipation. Colonoscopy showed a transverse colon carcinoma. Dynamic CT showed a renal neoplastic lesion and 2 lesions in the liver with early staining and late wash out, and the liver lesions showed ring enhancement on EOB-MRI. The preoperative diagnosis was either transverse colon cancer, renal cell carcinoma, hepatocellular carcinoma, or metastatic liver cancer. The patient underwent partial transverse colon resection, partial right nephrectomy, and partial hepatic resection. Additional to the 2 liver lesions in S6, an intraoperative ultrasound showed 1 tumor in S5; therefore, 3 partial hepatectomies were performed. Histopathological findings revealed that the tumors in S5 and S6 were liver metastases of transverse colon cancer and renal cell carcinoma, respectively. The final diagnosis was transverse colon cancer, pT4a, pN0, pM1, pStage Ⅳa and papillary renal cell carcinoma, pT1a, pN0, pM1, pStage Ⅳ. For 9 months postoperatively, there was no apparent recurrence.

[A Case of Retroperitoneal Leiomyosarcoma Resected Radically by Pancreaticoduodenectomy with Vascular Resection].

A 54-year-old woman visited to a doctor nearby medical clinic complaining of loss of appetite. She was diagnosed with right hydronephrosis on abdominal ultrasonography, and referred to our hospital for further examination. Contrast abdominal computed tomography(CT)revealed that a 6.2 cm tumor with a contrast-enhancing effect inside in the retroperitoneum near the lower pole of the right kidney. She was diagnosed with hydronephrosis due to infiltration of the right kidney of a retroperitoneal tumor. The tumor was suspected of invading the duodenum and inferior vena cava, but no obvious lymph node or distant metastasis was observed. Abdominal MRI revealed a tumor showed hyperintensity on T2-weighted and diffusion-weighted images. We performed pancreaticoduodenectomy with inferior vena cava resection and right nephrectomy. The pathological diagnosis was leiomyosarcoma originating from retroperitoneum and pT2, pN0, pM0, pStage ⅢA. The postoperative course was good, and she was discharged 10 days after the operation. Thoracoabdominal CT showed a tumor 4 cm at the hepatic hilum three months after surgery, and EOB-MRI showed many tumors other than the same site, so multiple liver metastases were diagnosed as recurrence. Doxorubicin has been started and is still being treated.

[A Resected Case of Adeno-Squamous Carcinoma of Gallbladder with Liver Invasions].

A patient was 70-year-old female. Because unknown fever following operation of left knee in December 20XX-1, abdominal simple CT was performed, diagnosed as cholecystitis and liver abscesses. However, her unknown fever did not improve with antibiotics therapy. Abdominal enhanced CT and MRI revealed to gallbladder cancer with liver invasion and metastases. These lesions were relatively localized in liver S4a/S5 and gallbladder, hepatoduodenal mesentery. Because unknown fever was exhausting, cholecystectomy, S4a+S5 hepatectomy with extrahepatic bile duct resection and lymph node dissemination were performed in January 20XX+1. In these pathological findings, there were moderate to poorly differentiated adenocarcinoma with squamous cell differentiation in almost area of gallbladder, diagnosed as adeno-squamous carcinoma with liver invasion and metastasis(pT3a[SI][H-inf], int, INF-ß, ly1, v3, pn1, pN1, pM1, pStage ⅣB). One months after operation, abdominal CT revealed multiple liver metastatic recurrences. She died 7 months after operation. Although gallbladder adeno-squamous carcinoma has a poor prognosis, these many cases had a tendency to local infiltration accompanied with tumor fever. If curative resection might be obtained and the symptoms might be improved, aggressive resection should be performed.

[A Case of Mesh Infection Due to Transverse Colon Cancer].

A 69-year-old female underwent a mesh repair for an abdominal incisional hernia 4 years previously in our hospital. She visited local hospital for abdominal pain and fever. Abdominal CT showed a localizes abscess formation above the mesh, then she was taken to our hospital. We suspected mesh infection and performed emergent mesh removal. After the operation, we examined for her anemia. Her colonoscopy and CT findings pointed to transverse colon cancer. We performed right hemicolectomy, and final diagnosis was transverse colon cancer pT4aN0M0, pStage Ⅱb. She underwent adjuvant chemotherapy, and 9 months after surgery, no recurrence was found.

[A Case of Laparoscopic Assisted Resection for Small Intestinal Cancer Diagnosed Preoperatively].

A 50-year-old woman was admitted to our hospital due to intermittent epigastric pain and vomiting for 2 months. Contrast enhanced CT scan showed stenosis in the upper jejunum. She was diagnosed with small intestinal ileus. A small enteroscopy revealed a peripheral type 2 lesion in the upper jejunum, approximately 10 cm from the Treitz's ligament. Upon biopsy, she was diagnosed with a well-differentiated adenocarcinoma. A laparoscope-assisted extracorporeal operation was performed due to the ease of raising the umbilical wound. Swollen lymph nodes were found in the mesentery. A surgical margin of 5 cm on the oral side and 20 cm on the anal side was secured. We performed partial resection of the small intestine, including the mesentery with the enlarged lymph nodes. The histopathological diagnosis was a Type 2, 3×2 cm, tub2, pT4aN1aM0, pStage Ⅲb small intestinal cancer. Due to the development of small intestinal ileus, the small bowel cancer was diagnosed preoperatively. Hence, it was slightly we will report including the literature consideration of.

[Hyperprogressive Disease during Treatment with Nivolumab for Recurrence of Gastric Cancer].

A man in his 60s with a large Type 3 gastric cancer presented with the chief complaint of epicardial discomfort. We decided to perform laparoscopy. The patient was diagnosed with cT4aN2M1(CY1), cStage Ⅳ disease and was treated with XP(capecitabine plus cisplatin[CDDP])plus trastuzumab(HER). After chemotherapy, CY0 was confirmed using laparoscopy. The patient underwent total gastrectomy and D2 lymph node dissection. Histopathological examination revealed ypT4aN3M0, ypStage ⅢC disease. Therefore, adjuvant treatment with XP plus HER was continued. Four months after surgery, liver, lung, and # 16b1latLN metastases were observed on CT. The metastatic foci were observed even after 3 courses of ramucirumab plus paclitaxel. Nivolumab was administered as the third-line treatment; after 3 courses, the liver metastasis increased markedly. Hence, our final diagnosis was hyperprogressive disease(HPD).

[Bilateral Multiple Liver Metastases after Pancreatoduodenectomy for a Duodenal Neuroendocrine Tumor-A Case Report].

The patient was a 79-year-old woman. In January 20XX, upper gastrointestinal endoscopy revealed a duodenal tumor with bleeding and ulceration. This tumor was diagnosed as a duodenal neuroendocrine tumor(NET)based on biopsy findings. In March 20XX, the patient underwent pancreatoduodenectomy with lymph node dissemination. Based on these pathological findings, the tumor was diagnosed as a duodenal NET(G2)with a lymph node metastasis(T2, N1, M0, Stage Ⅲ). Twenty months after the operation, abdominal CT revealed multiple liver metastases(S4, S7, and S8). After this recurrence, she underwent the subcutaneous somatostatin analogue injection therapy every 28 days, and transarterial chemoembolization( TACE)when these recurrent tumors showed remarkable regrowth, once a year, accounting for her age. She has maintained good disease control for 5 years.

[Resection of the Acinar Cell Carcinoma of the Pancreas with Lymph Node Recurrence along the Lesser Curvature of the Stomach-A Case Report].

A 78-year-old woman had undergone subtotal stomach-preserving pancreatoduodenectomy for acinar cell carcinoma (ACC)of the pancreatic head approximately 2 years before presentation, and the pathological diagnosis had been pT2pN0pM0, fStageⅠB(JPS 7th). Adjuvant chemotherapy was discontinued after 3 months because of side effects. Contrast- enhanced CT and PET-CT 2 years postoperatively revealed a tumor measuring 2 cm with a high concentration of FDG in the minor curvature of the stomach. During laparotomy, a 3 cm large lymph node was palpated in the minor curvature of the stomach, and a small lymph node was found adjacently. We diagnosed the patient with multiple lymph node recurrences and performed gastric lymph node dissection of the minor curvature. The pathological diagnosis was a single 2 cm large ACC lymph node metastasis. The patient did not consent to postoperative adjuvant chemotherapy and showed no recurrence for 1 year and 7 months postoperatively. Pancreatic ACC is a rare pancreatic tumor, and its clinicopathologic features are still largely unknown. In recent years, there have been reports of active resection or long-term survival with anti-cancer drug treatment even in recurrent cases, such as the present case. However, the indication and method of anti-cancer treatment are unclear and might need the accumulation of many more cases.

[A Case of Mature Teratoma in the Hepatoduodenal Ligament].

A 60's woman was admitted to our hospital because of palpitations that occurred with exertion. Coronary angiography computed tomography(CT)of suspected angina detected a tumor in the pancreatic head region. Abdominal CT showed a poorly enhanced 40×32 mm solid tumor in the hepatoduodenal ligament that contained a fatty component and calcification. During surgery, the tumor was located in the hepatoduodenal ligament, adhered to the pancreatic head, common hepatic artery, gastroduodenal artery, portal vein and common bile duct. However, the tumor was resected by preserving them. The tumor contained stratified squamous epithelium, a sebaceous gland, nerve, a pancreatic gland, and an adrenal gland. The histological diagnosis was a mature cystic teratoma. The patient showed no recurrence in 2 years and 10 months post-surgery. Mature teratomas in the hepatoduodenal ligament are extremely rare. Some reports showed that combined resection was performed when the tumor was in contact with the common bile duct, portal vein, and arteries. However, in our case, the tumor was removed relatively safely without combined resection.

[A Case of Appendix Torsion with Low-Grade Appendiceal Mucinous Neoplasm].

An 84-year-old woman with a chief complaint of right lower abdominal pain was admitted to our hospital in November 20XX. Abdominal CT scan revealed a 9.6×4.1 cm diameter low density area proximal to the 13 mm diameter appendix, which led to perforated appendicitis with a huge abscess. The patient underwent an open appendectomy with partial cecum resection. The appendix was found to be twisted by 540°. The pathological diagnosis was low-grade appendiceal mucinous neoplasm(LAMN). Recent research has found that the use of laparoscopic surgery for the treatment of LAMN has been increasing. Appropriate surgical intervention should be considered for LAMN because it is a borderline malignancy. Careful treatment with laparoscopic surgery might be considered as one of the treatment options for LAMN. We hope to accumulate more cases of LAMN to confirm our results.

[A Case of Intestinal Obstruction Caused by Peritoneal Metastatic Recurrence One Year after Radical Operation for Pancreatic Cancer].

In December 20XX-1, abdominal enhanced CT of a 73-year-old female patient showed a 28mm-in-diameter pancreatic tail cancer with splenic venous invasion. She underwent neoadjuvant GEM/TS-1 combination chemotherapy but abandoned this chemotherapy due to melena and exanthema. She underwent a distal pancreatectomy with lymph node dissemination. In these pathological findings, the tumor was diagnosed as a pancreatic tail cancer with splenic venous invasion(T3, N0, M0, Stage ⅡA). She underwent adjuvant GEM chemotherapy, but she abandoned this chemotherapy due to exanthema and was managed with observation. In September 20XX, she had a postoperative bowel obstruction and was treated with natural light. However, she had a postoperative bowel obstruction again in July, 20XX+1. Fluoroscopic images revealed stenosis in the intestine located 170 cm from the nasal cavity. She underwent open surgery to manage the bowel obstruction. There was a peritoneal tumor with adhesion to each intestine serosa in 3 areas located 80 cm, 100 cm, and 150 cm from the Treitz ligament. Therefore, she underwent a small intestine resection and anastomosis 70 cm to 110 cm from the Treitz ligament. Pathological findings showed that there was a 3mm-in-diameter adenocarcinoma in this peritoneal tumor. In these findings, this final diagnosis was an adhesive intestinal obstruction caused by peritoneal metastasis. Curative resection for single peritoneal recurrent metastasis might be useful for prognosis prolongation.

[A Case of Unresectable Advanced Esophageal Cancer Treated with Chemoradiotherapy Resulting in Complete Response].

A70s man was admitted to our hospital complaining of chest discomfort. Endoscopic examination showed mucosal erythema and irregularity and an area unstained by iodine in the middle esophagus 21 to 41 cm from the incisors. The biopsy specimen showed moderately differentiated squamous cell carcinoma. An abdominal computed tomographic(CT)scan revealed swelling of the lymph nodes along the celiac artery and abdominal aorta. The patient was diagnosed with unresectable advanced esophageal cancer(cT2N4M0, cStage Ⅳa). Systemic chemotherapy was initiated using a regimen of 5-FU and cisplatin(FP). After 2 courses of chemotherapy, an abdominal CT scan showed reduction of the lymph node swelling along the abdominal aorta, but the lymph node swelling remained along the celiac artery. Therefore, chemoradiotherapy(CRT; FP plus RT 60 Gy/30 Fr at the main tumor and the swelling of lymph nodes along the celiac artery)was administered. An abdominal CT scan showed reduced swelling of the lymph nodes along the abdominal aorta and the celiac artery after CRT. In addition, FP chemotherapy was also administered. APET -CT scan showed no increased FDG up take in the main tumor and swollen lymph nodes after 2 courses of chemotherapy. The complete response(CR)has been maintained for 30 months without therapy.

[XELIRI plus Bmab Therapy as a Secondary Treatment for Recurrent Colorectal Cancer with Long-Term Survival].

A 71-year-old woman complained of melena, and laparoscopic right hemicolectomy was performed for advanced colorec- tal cancer. Pathological examination revealed pStage Ⅲa(RAS-positive)disease. After the operation, UFT/LV was administered. However, peritoneal recurrence was confirmed. We changed the chemotherapeutic regimen to CapeOX plus Bmab and capecitabine plus Bmab. After 5 years and 9 months, pulmonary metastasis was observed. Therefore, we again changed the chemotherapeutic regimen to biweekly XELIRI plus Bmab. After 43 courses, the patient had stable disease. During biweekly XELIRI plus Bmab therapy, Grade 4 neutropenia occurred, so we reduced the CPT-11 dose by 20%. After dose reduction the patient experienced no more Grade 3/4 adverse events. We experienced a case of colorectal cancer wherein biweekly XELIRI plus Bmab therapy contributed to disease control as second-line treatment.

[Long-Term Survival after Palliative Surgery for Advanced Gastric Cancer with Bone Marrow Metastasis-A Case Report].

A 57-year-old woman was diagnosed with advanced gastric cancer with bone marrow metastasis(cT4aN1pM1[MAR], pStage Ⅳ). After 18 courses of S-1 and cisplatin and 18 courses of ramucirumab and paclitaxel, the chemotherapy was stopped because of stenosis. We performed endoscopic metallic stent placement, but stenosis reappeared after a month. Subsequently, distal gastrectomy was performed as a palliative surgery. She had no complications and improved appetite, therefore, she resumed chemotherapy after 3 postoperative months and continued for 4 years and 9 months from the first visit. In general, gastric cancer with bone marrow metastasis has a poor prognosis, however, in this case, long-term survival was achieved with palliative surgery.

Comparison of Adverse Events and Outcomes Between Patients With and Without Drain Insertion After Hepatectomy: A Propensity Score-Matched, Multicenter, Prospective Observational Cohort Study in Japan (CSGO-HBP-001).

BACKGROUND: Adverse events (AEs) after hepatectomy (Hx) have decreased. The aim of this study was to assess the safety of Hx and to identify the risks and benefits of drain insertion. METHODS: From 2010 to 2012, a multicenter, prospective cohort study was conducted in consecutive patients who underwent Hx. Patients who were scheduled to undergo Hx with neither reconstruction of the biliary tract nor concomitant resection of other organs were excluded. AEs were graded based on the Clavien-Dindo classification. Univariate analysis was performed to identify the risks and benefits in all cases and in selected cases matched by propensity score. RESULTS: This study included 197 patients. AEs occurred in 20 (10.1%). In all cases, no difference in the rate of AE was observed between those with and without drain insertion. Postoperative hospital stay in the group with drains (n = 132) was statistically longer than that in the group without drains (n = 65) (17.7 vs. 11.5 days, P = 0.001). In patients without AE (n = 177), hospital stay in the group with drains was statistically longer than that in the group without drains (14.1 vs. 11.3 days, P < 0.001). In propensity score-matched cases (41 cases in each group), postoperative hospital stay in the group with drains was also statistically longer than that in the group without drains (17.3 vs. 11.4 days, P = 0.003). CONCLUSION: Drain insertion after hepatectomy may lead to longer hospital stay in patients with and without AE.

[A Case of Hyperammonemia Induced by Chemotherapy with 5-Fluorouracil for Metastatic Colon Cancer].

Systemic chemotherapy based on 5-fluorouracil(5-FU)is a standard treatment for unresectable or recurrent colon cancers. Here, we report a case of hyperammonemia induced by chemotherapy using 5-FU for metastatic colon cancer. An 84-yearold male patient with past histories of liver cirrhosis related to hepatitis C virus and renal dysfunction underwent an operation for the rectosigmoid colon cancer 8 years ago. Three years after that operation, a local recurrence of the colon cancer was diagnosed, and chemotherapy using sLV5FU2 was initiated. The recurrence lesion reduced markedly by this chemotherapy, which was ceased 2 years ago. Two years after the cessation the recurrent tumor had been enlarged, and the chemotherapy using the same drugs at the same dose was performed. On the treatment day 3, he was emergently transported to our hospital due to the disturbance of consciousness. Since laboratory tests showed the high concentration of plasma ammonia and the progressed renal dysfunction with no other definite cause of obnubilation, he was diagnosed as the hyperammonemia induced by 5-FU. He was treated by administrating the branched-chain amino acids solutions combined with fluid therapy, which quickly recovered him from the encephalopathy. He is followed up without any chemotherapy because of his high age. When a patient treated with the chemotherapy using 5-FU is sent with the disturbance of consciousness, we should take hyperammonemia into consideration, especially when he or she has the hepatic or renal dysfunction.