[A Case of Primary Adenocarcinoma of the Duodenal Bulb with Laparoscopic Distal Gastrectomy].

A 66-year-old male presented with a torose lesion at the duodenal bulb, detected via endogastroduodenoscopy(EGD) during a medical check-up. It was histopathologically diagnosed as a low-grade adenoma. He was referred to the Department of Gastroenterology for follow-up observation. An endoscopic mucosal resection(EMR)was performed due to the increasing tumor size. The pathological findings of the resected specimen showed a tubular adenoma. The patient was then followed up as an outpatient. Two months later, a follow-up EGD revealed a mass lesion, suspected to be a remnant tumor. A laparoscopic distal gastrectomy, #3, #4sb, #5, #6 dissection, and Billroth Ⅱ+Braun anastomosis reconstruction were performed. Pathological examination showed a tubular adenocarcinoma in adenoma, tub1, with depth M, and no lymph node metastasis. Non-papillary duodenal carcinoma is a rare disease that has no established guidelines for radical surgery and the extent of lymph node dissection. Pancreaticoduodenectomy is often performed in advanced cases. However, due to the increasing number of patients and the risk of complications, limited resection should be considered as an alternative management option.

[Laparoscopic Surgical Treatment of Differentiated Intramucosal Gastric Cancer with Lymph Node Metastasis-A Case Report].

A 78‒year‒old man was admitted to our hospital with the chief complaint of 5 kg weight loss in 6 months. An esophagogastroduodenoscopy revealed a 0‒Ⅱa lesion in the posterior wall of the antrum, and biopsy findings showed a well‒differentiated adenocarcinoma. Endoscopic ultrasonography did not show an obvious invasion of the submucosal layer. Contrast‒ enhanced abdominal computed tomography(CT)revealed an enlargement of the #11p lymph node to approximately 30 mm, and positron emission tomography(PET)‒CT showed an accumulation in the same lymph node. Since no other apparent distant metastases were observed, laparoscopic distal gastrectomy and D2 dissection were performed. The postoperative pathological diagnosis was L, 7×8 mm, 0‒Ⅱa, tub1, pT1a, ly0, v0, pPM0(73 mm), pDM0(35 mm), N2, and pStage ⅡA. We report this case because the successful laparoscopic resection of a differentiated gastric mucosal cancer with lymph node metastasis has been considered to be extremely rare.

[A Case of Long-Term Survival after Multidisciplinary Treatment for Neuroendocrine Carcinoma of the Anal Canal].

A 75-year-old man presented to a local clinic with anal pain, and a palpable anal tumor on was found on digital examination of the rectum. A biopsy led to the diagnosis of neuroendocrine carcinoma. Besides the anal tumor, an right-inguinal lymph node was revealed on computed tomography(CT). Positron emission tomography-CT showed abnormal uptake in the 2 regions. He was diagnosed with lymph node metastases from anal canal carcinoma, and an abdominoperineal resection was performed. The resected specimen included the anal canal tumor with a size of 27×18 mm in diameter. On immunohistochemistry, the anal canal tumor was strongly positive for synaptophysin and positive for chromogranin A, with a Ki- 67 positivity index of 70%. After the surgery, he was administered chemotherapy with 4 courses of cisplatin and CPT-11. One year after the surgery, CT revealed lymph node recurrence. Therefore, cisplatin and CPT-11 therapy was repeated. After 11 courses of the cisplatin and CPT-11 treatment, tumor regrowth was still detected. The treatment protocol was changed to an amrubicin monotherapy regimen. However, the patient's general condition worsened after the therapies, and he died 38 months after the surgery.

[A Case of Long-Term Survival after Chemotherapy for Gastric Cancer with Peritoneal Dissemination].

The patient was a 58-year-old man who had undergone wide gastrectomy for gastric ulcer at 22 years of age. Endoscopic examination revealed an advanced type 3 gastric cancer in the anastomotic region. We performed total gastrectomy and D1 lymph node dissection because of the bleeding from the tumor, although peritoneal dissemination was found during the surgery. A post-operative pathological diagnosis of gastric cancer pT4b(SI, abdominal wall)N0M1(PER), pStage Ⅳ, was made. After the surgery, he was administered chemotherapy with S-1 and cisplatin. After 9 courses of the treatment, the treatment protocol was changed to an S-1 therapy regimen because of general fatigue. Four years and 8 months after the surgery, the tumor marker had increased, and CT scans revealed a dissemination nodule at the left back side of the bladder. Therefore, PTX plus Rmab therapy was administered as a second-line chemotherapy. Treatment with PTX plus Rmab resulted in tumor reduction, with an improvement of the QOL of the patient; partial response was maintained for 12 months. After 16 courses of the PTX plus Rmab treatment, tumor regrowth was detected. The treatment protocol was changed again to a nivolumab regimen. After 4 courses, the tumor marker was normalized, and CT scans revealed that the peritoneal dissemination had shrunk. Although the prognosis of gastric cancer with dissemination is very poor, it is possible to prolong survival with chemotherapy.

[A Case of HER2-Positive Gastric Cancer with Multiple Liver Metastases Treated with Curative Conversion Therapy after Chemotherapy].

A 66-year-old man underwent chemotherapy with S-1 plus cisplatin plus trastuzumab to treat advanced gastric cancer that was diagnosed as cStage Ⅳ adenocarcinoma(T3N1M1[P0, CYX, H1]). After 8 courses, liver metastases were absent on contrast-enhanced MRI. The patient underwent a laparoscopic distal gastrectomy with D2 lymphadenectomy. The gross appearance of the surgically resected specimen showed a shrunk gastric tumor measuring 1 mm. The postoperative course was uneventful, and the patient has been well, receiving maintenance chemotherapy of S-1 plus trastuzumab without evidence of recurrence for 15 months following the operation. Conversion surgery following chemotherapy might be an effective treatment for patients with advanced gastric cancer; however, further studies are needed to establish this treatment strategy.

[A Case of Hypophysitis Due to Immune Check Point Inhibitor Treatment].

The patient was a man in his 70s with bone metastasis from renal cell carcinoma who had received immune checkpoint inhibitors(ICI)therapy. After 2 courses of chemotherapy, he was admitted to our hospital with diverticulitis. His diverticulitis could be treated with antibiotics, but he presented with severe hyponatremia and consciousness disorder during hospitalization. Brain MRI showed pituitary swelling, and his serum TSH, ACTH, cortisol levels decreased. We therefore diagnosed him with hypopituitarism due to ICIs. Hydrocortisone improved his hyponatremia and consciousness disorder. Endocrine stimulation tests revealed no reaction of ACTH, and low-level reactions of TSH, LH and FSH, ICIs cause many types of immune- related adverse events(irAEs). The indications for ICI therapy are expanding; thus, we can expect to experience more cases of serious irAEs in association with ICI treatment. Further studies should be performed to improve our understanding of irAEs.

[A 3mm Gastric Neuroendocrine Tumor That Metastasized to a Lymph Node].

A 46-year-old man underwent a medical check-up and gastrointestinal endoscopy, which revealed a brown lesion at the greater curvature of the gastric body. Biopsy was performed, and a gastric neuroendocrine tumor(NET)was diagnosed. The serum levels of gastrin and other tumor markers were not elevated. The preoperative diagnosis was Rindi type Ⅲ gastric NET, and laparoscopic distal gastrectomy with D1 plus lymph node dissection was performed. Histological examination showed that the resected specimen was positive for chromogranin A, CD56, and synaptophysin, which was consistent with the findings of NET. Even though the tumor diameter was only 3 mm, a metastatic #4d lymph node was found. This case suggests that Rindi type Ⅲ gastric NET has high malignant potential, and gastrectomy with lymph node dissection is necessary, regardless of tumor size.

[A Case of Appendiceal Adenocarcinoma with Vesico-Appendiceal Fistula Treated by Additional Laparoscopic Excision].

A 40-year-old woman was admitted to our hospital with the chief complaint of miction pain. MRI showed fundal wall thickening of the bladder in contact with the appendix. Under cystoscopy, redness of the mucous membrane was found in the posterior wall of the bladder. Therefore, laparo-appendectomy with partial cystectomy was performed. Microscopically, adenocarcinoma cells were observed in the lumen of the appendix, invading the wall of the urinary bladder at the fundus of the appendix. We performed laparo-ileocecal resection for a regional lymphadenectomy. Thus, the patient was diagnosed with adenocarcinoma of the appendix[V, type 3, 16×7 mm, tub2, pT4b(SI, urinary bladder), int, INF b, ly0, v0, pN0, cM0, pStage Ⅱ]. The patient has been receiving adjuvant chemotherapy using capecitabine for 6 months. There was no evidence of recurrence after 9 months of follow-up.

Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma.

AIM: To elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Tumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker. RESULTS: In total, 48.5% (66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors (median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade (P = 0.0290), preoperative CA19-9 level (P = 0.0060), epithelial cell adhesion molecule (EpCAM) expression (P = 0.0235), and the triple-positive expression of CD44/CD24/EpCAM (P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4 (P = 0.0091), high preoperative serum SPan-1 level (P = 0.0034), R1/2 (P < 0.0001), positive expression of DCLK1 (P < 0.0001) or CD44 (P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio (OR) = 2.019, 95% confidence interval (CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression (OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors. CONCLUSION: DCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

Analysis of the origin of anaplastic pancreatic cancer and the mechanism of its dedifferentiation.

BACKGROUND: We researched the origin and progression of anaplastic pancreatic cancer (APC) from the viewpoints of cell lineage, epithelial-mesenchymal transition (EMT) and cancer stem-like cells (CSC). METHODS: Using specimens from patients with APC and differentiated pancreatic ductal adenocarcinoma (PDAC), expression of sex-determining region Y-box 9 (SOX9), E-cadherin, vimentin, ZEB1, Snail, N-cadherin, CD24 and CD44 was estimated using immunohistochemistry. RESULTS: Almost all cases were positive for SOX9 expression. APC cases were negative, but many PDAC cases were positive for the expression of E-cadherin. A much higher number of APC cases than PDAC cases were positive for the expression of other EMT related proteins and for the expression of CSC related proteins. The ductal cancerous component of APC accounted for an average of 12% of the cancerous lesion and the expression of each marker in this component was similar to that of PDAC cases. CONCLUSIONS: Anaplastic pancreatic cancer had pancreatic duct cell like features and might gain dedifferentiate components through EMT and the acquisition of CSC properties.

[Multidisciplinary Therapy for Advanced Gastric Cancer with Liver and Brain Metastases].

A 68-year-old man was admitted to our hospital. He was diagnosed with advanced gastric cancer with multiple liver metastases. The primary tumor was treated with distal gastrectomy with D2 dissection and anti-cancer agents, and then he was scheduled for a 2-stage hepatic resection. After surgery, the liver metastases disappeared, and he was diagnosed with a CR. However he complained of dizziness and was diagnosed with metachronous brain matastasis. Multidisciplinary treatment including resection and radiotherapy was administerd and he survived for 5 years after diagnosis.

[A Case of Laparoscopic Gastrectomy in a Patient with Refractory Vasospastic Angina].

We report a case of laparoscopic gastrectomy in a patient with refractory vasospastic angina. An 83-year-old man received 2 types of oral coronary vasodilators but complained of chest pain about twice a week thereafter. He was diagnosed with refractory vasospastic angina. Upper gastrointestinal endoscopy was performed for tarry stools and revealed a type 2 tumor in the anglar posterior wall. CT revealed no lymph node swelling or metastasis. Laparoscopic gastrectomy was performed, and intravenous administration of coronary vasodilators was started before the operation. During the operation, coronary spasm could be prevented while being careful not to induce circulation change, bleeding, or traction of the peritoneum. Many cases of coronary spasm-related angina in the absence of a history of angina have been reported during non-cardiac operations. In such cases, careful coronary spasm is necessary.

[A Case of Cecal Cancer with Multiple Cutaneous Metastases].

We encountered a case of cutaneous metastases from colorectal carcinoma. A 63-year-old woman underwent laparoscopic-assisted ileocecal resection for cecal cancer. Computed tomography (CT) showed multiple liver metastases. The tumor was diagnosed as a well-differentiated adenocarcinoma and was staged as pSE, pN1, sH2, ly1, v1, CP0cM0, fStage Ⅳ. She was treated with 33 courses of the 5-fluorouracil, Leucovorin, and irinotecan (FOLFIRI) regimen and 15 courses of the 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab regimen. Thirty-four months after resection, multiple cutaneous tumors were noted, predominantly on the lower abdomen, and we resected 2 of them. Histologically, the specimens were diagnosed as well-differentiated adenocarcinoma, which was similar to that of cecal carcinoma. After 1 course of regorafenib, she died 3 years after the primary surgical resection.

[The usefulness of intraoperative Doppler echo and laparoscopic echo in laparoscopic colectomy].

Laparoscopic surgery has been increasingly performed in colon cancer patients; it has also been adapted for cases of advanced colorectal cancer. While performing an operation for rectosigmoid colon cancer, preservation of the left colic artery and prompt and accurate detection of the branch of the left colic artery from the inferior mesenteric artery is important. Detecting the left colon arterial bifurcation takes time, especially because of the presence of mesenteric fat, which is observed in many cases. In addition, in cases in which preoperative enhanced computed tomography (CT) cannot be performed, the surgery is sometimes performed without knowing the traveling vessel. As palpation is impossible, it is impossible to tactile running of the arteries as laparotomy in laparoscopic surgery. With endoscopic echo or Doppler echo, real-time identification of the blood vessels during surgery is possible without being invasive. It would be in laparoscopic surgery impossible palpation, and the combined use of intraoperative echo in ensuring the safety to be useful.

[A case of palliative resection resulting in improvement in quality of life in a patient with colon cancer and simultaneous ovarian metastasis].

A 72-year-old woman was admitted for investigation of lower abdominal bloating and melena. She was diagnosed with rectal cancer with ascites, multiple liver metastases, and large bilateral ovarian metastases. The patient underwent bilateral oophorectomy for the ovarian tumors and a Hartmann procedure for rectal cancer. The ovarian lesions were diagnosed as ovarian metastasis of colorectal cancer by histological analysis. Ascites and lower abdominal bloating resolved after the intervention. At 11 months after surgery, the patient is alive and well. Ovarian metastasis from colorectal cancer is relatively rare and associated with poor prognosis. Radical intervention is generally not possible in the presence of metastases, but in the present case, the ovarian tumors were large. It is often difficult to determine the optimal type of invasive surgery, although excision of the lesion may provide palliative relief. In this case, the patient's quality of life improved following palliative resection of the primary colon cancer and ovarian metastases.