[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.

Two-surgeon technique for liver transection using precoagulation by a soft-coagulation system and ultrasonic dissection.

BACKGROUND/AIMS: A soft-coagulation system (SCS) was introduced as an effective device to reduce blood loss in hepatectomy. Here we evaluated the efficacy of a two-surgeon technique using precoagulation by an SCS and the Cavitron Ultrasonic Surgical Aspirator (CUSA) for liver transection. METHODOLOGY: The 163 patients with liver tumors were divided into two groups (conventional group and two-surgeon group). Liver transection was conducted using saline-coupled bipolar electrocautery and CUSA in 102 patients (conventional group). In 61 patients (the two-surgeon group), a two-surgeon technique using precoagulation by an SCS and CUSA for liver resection was performed. RESULTS: The median blood loss was significantly less in the two-surgeon group compared to the conventional group (354.8 mL vs. 557.8 mL, respec tively: p = 0.0011). The postoperative hospital stay was significantly shorter in the two-surgeon group compared to the conventional group (12.7 days vs. 15.5 days, p = 0.0035). CONCLUSIONS: The two-surgeon technique using precoagulation by an SCS and CUSA was significantly reduced blood loss during liver transection, and associated with low morbidity and mortality. This technique may be useful for many hepatobiliary surgeons.

[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.

Prognostic indicator for the resection of liver metastasis of colorectal cancer.

PURPOSE: We investigated the predictive indicator for a good prognosis of surgical resection for liver metastasis of colorectal cancer. METHOD: Between 1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for liver metastasis of colorectal cancer. The clinical, pathological, and outcome parameters affecting their prognoses were analyzed. The extent of the liver metastases was subdivided according to the Japanese Classification of Colorectal Carcinoma (JCCRC), and the patients were classified into different grades based on the JCCRC classification and the status of the nodal involvement of the primary tumor. RESULT: The median survival time (MST) of the 117 patients was 58 months, and the actuarial survival rates at 1, 3, and 5 years were 92.3, 60.0, and 46.1 %, respectively. A multivariate analysis revealed that the JCCRC Grade classification was an independent prognostic indicator (Grade A vs. B vs. C: MST, 72 vs. 41 vs. 23 months; 5-year survival, 59.0 vs. 38.6 vs. 0 %: p < 0.0001). CONCLUSION: Our findings indicate that the JCCRC Grade classification for liver metastasis of colorectal cancer is a significant prognostic indicator and may be useful for making decisions regarding the treatment of liver metastasis.

[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.

IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer.

BACKGROUND: The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated. METHODS: Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed. RESULTS: Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001). CONCLUSION: IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer.

MUC1 and HER2 might be associated with invasive phenotype of intraductal papillary mucinous neoplasm.

BACKGROUND/AIMS: The purpose of this study was to clarify the biomarkers which distinguish invasive Intraductal papillary mucinous neoplasms (IPMNs) from noninvasive IPMNs. METHODOLOGY: In tumor specimens from sixty patients with IPMNs (42 noninvasive IPMNs and 18 invasive IPMNs) who underwent surgical resection at our institute, we analyzed the correlation between the immunohistochemical expression level of MUC1, MUC2, MUC4, MUC5AC, p53, VEGFR2, HER2, and HER3. RESULTS: The 5-year survival rate was 100% in noninvasive IPMNs, while that of invasive IPMNs was only 36.5%. MUC1, MUC4, HER2 and HER3 were significantly associated with invasive IPMNs in univariate analysis. Multivariate analysis revealed that MUC1 and HER2 were significantly associated with invasive IPMNs. The 5-year survival of IPMN patients with either MUC1-positive and/or HER2-positive (54.5%) is significantly poorer than that of IPMN patients with MUC1 negative and HER2 negative (100%). CONCLUSIONS: MUC1 and HER2 might be closely associated with invasive phenotype of IPMNs.

Hypoxia stimulates the EMT of gastric cancer cells through autocrine TGFß signaling.

Epithelial mesenchymal transition (EMT) is considered to be correlated with malignancy of cancer cells and responsible for cancer invasion and metastasis. We previously reported that distant metastasis was associated with hypoxia in gastric cancer. We therefore investigated the effect of hypoxic condition on EMT of gastric cancer cells. Gastric cancer cells were cultured in normoxia (21% O2) or hypoxia (1% O2) for 24 h. EMT was evaluated as the percentage of spindle-shaped cells in total cells. Effect of transforming growth factor ß1 (TGFß1) or tyrosine kinase inhibitors on the EMT was evaluated. The expression level of TGFß1 and TGFßR was evaluated by real time RT-PCR. The TGFß1 production from cancer cells was measured by ELISA. Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of OCUM-2M cells. The expression level of TGFß1 mRNA under hypoxia was significantly higher than that under normoxia in all of three cell lines. The expression level of TGFßR mRNA was significantly increased by hypoxia in OCUM-2MD3 cells, but not in OCUM-2M cells. TGFßR inhibitor, SB431542 or Ki26894, significantly suppressed EMT of OCUM-2MD3 and OCUM-12. TGFß1 production from OCUM-2MD3 and OCUM-12 cells was significantly increased under hypoxia in comparison with that under normoxia. These findings might suggest that hypoxia stimulates the EMT of gastric cancer cells via autocrine TGFß/TGFßR signaling.

Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary tract cancer treated with gemcitabine alone.

BACKGROUND: Gemcitabine is a pyrimidine nucleoside analog that is a commonly used chemotherapeutic agent for unresectable or recurrent biliary tract cancer (BTC). Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of gemcitabine efficacy, mostly in pancreatic cancer. The aim of this study is to clarify which biomarker is the most reliable among hENT1, dCK, and RRM1 to predict survival in patients with advanced BTC treated with gemcitabine alone. METHODS: The analysis was performed on samples from 28 patients with unresectable or recurrent BTC who were treated with gemcitabine alone as first-line therapy. The starting date of overall survival (OS) and progression-free survival (PFS) was defined as the date of first treatment with gemcitabine. Intratumoral hENT1, dCK, and RRM1 expressions were examined by immunohistochemistry. RESULTS: The expressions of hENT1, dCK, and RRM1 had no significant relationships with age, gender, primary tumor site, recurrence/unresectable, or histological type. Among the three molecules, only hENT1 expression was a significant factor affecting OS and PFS in univariate analysis; OS was 11.4 months for high hENT1 expression versus 5.7 months for low, P = 0.0057; PFS was 7.7 months for high versus 2.5 months for low, P = 0.0065. Multivariate analyses also identified hENT1 expression as an independent predictive factor for OS. CONCLUSIONS: hENT1 is the most reliable predictive marker of survival in patients with advanced BTC treated with gemcitabine.

SPan-1 is a useful prognostic marker for patients with stage IV gastric cancer who underwent palliative gastrectomy: a retrospective multivariate study.

BACKGROUND: We retrospectively investigated prognostic factors to be used in selecting the patients with stage IV gastric cancer (GC) who have an unfavorable prognosis after palliative gastrectomy. METHODS: A total of 146 GC patients at stage IV who had undergone palliative gastrectomy were enrolled. Various clinicopathological parameters were evaluated for prognosis. RESULTS: Surgical morbidity and hospital mortality occurred in 35 (23.9 %) and 4 (2.7 %) patients, respectively. The overall 5-year survival rate and the median survival time were 11.2 % and 13.2 months, respectively. Of the 146 patients, 64 had uncomfortable symptoms associated with GC and 76 had no such symptoms. Of the 64 patients with uncomfortable symptoms, 60 (93.7 %) experienced relief of these symptoms after palliative surgery. Multivariate analysis for patients without uncomfortable symptoms associated with GC revealed that the number of incurable factors and serum SPan-1 level were independent prognostic factors. CONCLUSIONS: Patients with stage IV GC who had multiple incurable factors and a high level of serum SPan-1 might not be candidates for palliative gastrectomy for the purpose of prognostic benefit.