[Clinical Evaluation of the Efficacy and Adverse Effects of Nivolumab Treatment for Patients with Advanced Gastric Cancer].

BACKGROUND: Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1(PD-1), was approved for use in the treatment of patients with advanced gastric or gastroesophageal junction cancer who had been previously treated with B2 chemotherapy regimens in Japan. METHODS: We investigated the efficacy of nivolumab therapy in 15 consecutive patients with advanced gastric cancer between October 2017 and December 2018 in our facility. RESULTS: In our study, the 6-month overall survival rate was 67.7%, and the median survival time(MST)was 6.3 months. Immune-related adverse events(irAEs)occurred in the following patients: 2 patients, interstitial pneumonia(13%); 1 patient, myocarditis (6.7%); 1 patient, hypothyroidism(6.7%); and 1 patient, liver dysfunction(6.7%). Of the patients with an absolute lym- phocyte count(ALC)of C2,000/mL at baseline, 33%(4/12)experienced irAEs, while of those with an ALC of >2,000/mL, 67% had irAEs. The 6-month overall survival rate was better in patients with an ALC >1,600/mL(100%, 4/4)than in those with an ALC of C1,600/mL(35%, 4/11). The 6-month overall survival rate of the patients with a neutrophil-to-lymphocyte ratio(NLR)of <4 was 63%, which was better than the 33% rate in those with an NLR of B4. CONCLUSIONS: Nivolumab therapy was a safe and feasible treatment option. The cutoff values of ALC of 2,000/mL for irAEs and of ALC of 1,600/mL and NLR of 4 for prognosis might be effective surrogate markers in nivolumab treatment.

[A Case of Peritoneal Metastasis from an Unresectable Advanced Gastric Cancer with a Good Response to Nivolumab].

A 74-year-old woman presented with abdominal discomfort and was diagnosed with an unresectable advanced gastric cancer(T4aN3aM1, stage Ⅳ)based on a thorough examination. S-1/cisplatin therapy was administered as first-line treatment and paclitaxel/ramucirumab therapy as the second-line treatment. However, because the patient developed a peritoneal dissemination and her lymph node metastasis increased despite these regimens, nivolumab was introduced as a third- line treatment. The CT scan revealed that after the 5 courses of nivolumab, both the peritoneal dissemination and metastatic lymph nodes shrunk; after 12 courses of nivolumab, the peritoneal dissemination almost disappeared. Although nivolumab, an anti-programmed cell death-1(PD-1)antibody, has the possibility to cause immune-related adverse events not seen with conventional chemotherapy, in the present case, these events did not occur and the antitumor effects were maintained for a relatively long period without a decrease in the performance status(PS). We experienced a case of peritoneal metastasis from gastric cancer with a good response to nivolumab. Herein, this case is reported with some literature review.

Is curative gastrectomy justified for gastric cancer with cytology positive as the only stage IV factor?

AIMS: The prognosis of patients with gastric cancer and stage IV factors is poor. However, several recent studies have identified that curative surgery followed by S-1 chemotherapy for cytology positive (CY1) only patients contributed to a better prognosis. This study was designed to compare the prognosis between curative and palliative gastrectomy followed by chemotherapy in CY1 only stage IV gastric cancer. METHODS: Between 2001 and 2016, 1507 patients underwent gastrectomy for gastric cancer. Of these, 51 consecutive patients with only CY1 factor who underwent gastrectomy followed by chemotherapy were enrolled in this study. RESULTS: (1) Twenty three (45%) patients underwent curative D2 or D2+ gastrectomy, and the remaining 28 (55%) patients underwent palliative gastrectomy, followed by S-1 based or another historical recommended chemotherapy postoperatively. (2) Compared with patients undergoing palliative gastrectomy, patients undergoing curative gastrectomy had a significantly better prognosis (P = 0.042; median survival time: curative vs. palliative, 22.6 months vs. 11.8 months) and a lower incidence of recurrences (P = 0.091). Two- and five-year overall survival rates of patients following curative gastrectomy were 48.2% and 18.2%, respectively. A multivariate analysis showed that venous invasion [P = 0.006; hazard ratio (HR), 3.70 (95% CI: 1.27-9.43)] and curative gastrectomy [P < 0.005; HR, 0.28 (95% CI: 0.12-0.87)] were independent prognostic factors. CONCLUSION: Curative gastrectomy followed by chemotherapy might be justified to improve the prognosis of patients with only CY1 Stage IV gastric cancer.

[Validation of the 8th Edition of the UICC TNM Classification for Stage â ¢ Gastric Cancer].

BACKGROUND: The 8th edition of the UICC TNM Classification was released in 2017 and introduced N3a/N3b groupings for gastric cancer. The purpose of this study was to evaluate the validity of the new classification for Stage Ⅲ gastric cancer. PATIENTS AND METHODS: Clinical and pathological data on 388 patients who underwent R0 resection from January 1992 to December 2016 in our institution were retrospectively analyzed. The survival in the 7th and 8th edition stage groupings were compared. Differences in survival according to N classification were also examined in the groups with T4a tumor depth. RESULTS: 1. The 5-year overall survival(OS)probabilities for Stage ⅢA, ⅢB, and ⅢC of 7th edition were 47.6%, 55.0%, and 28.5%(p=0.0003)and the recurrence-free survival(RFS)rates were 81.1%, 79.4%, and 58.7%(p=0.0013), respectively. In contrast, the OS probabilities of the 8th edition were 50.2%, 41.3% and 30.1%(p=0.0009)and the RFS were 81.6%, 70.9% and 50.0%(p=0.0003), respectively. 2. For T4a tumor depth, the OS probabilities of N1, N2, N3a, and N3b were 48.8%, 54.0%, 27.5%, and 25.1%(p=0.0012)and the RFS were 82.7%, 81.2%, 57.0% and 48.7%(p=0.0013), respectively. CONCLUSION: The 8th edition of the UICC TNM classification may provide better accuracy than that of the 7th edition in predicting the prognosis of Stage Ⅲ gastric cancer.

[Laparoscopy and Endoscopy Cooperative Surgery(LECS)-Assisted Open Partial Gastrectomy for a High-Risk Gastrointestinal Stromal Tumor].

Laparoscopy and endoscopy cooperative surgery(LECS)is an excellent surgical procedure to avoid excessive resection of the gastrointestinal wall and maintain its functions. However, LECS for large gastrointestinal stromal tumor(GIST)of> 50mm and/or ulcerative GIST are not recommended because of the oncological risk of peritoneal dissemination. Here, we report a case successfully treated with LECS-assisted open partial gastrectomy for a high-risk GIST with ulceration near the esophago-gastric junction.

[LECS-Assisted Open Partial Gastrectomy for an Ulcerative GIST in an Elderly Patient].

Laparoscopy and endoscopy cooperative surgery(LECS)is an excellent surgical procedure that prevents excessive resection of the gastrointestinal wall and maintains gastrointestinal functions. However, LECS is not recommended for large gastrointestinal stromal tumor(GIST)sized more than 5 cm and/or ulcerative GIST because of the oncological risk of peritoneal dissemination. Here, we report the case of an elderly patient who was successfully treated with LECS-assisted open partial gastrectomy for an ulcerative GIST near the esophagogastric junction.

[A Case of Gastric Remnant Necrosis Following Laparoscopic Distal Gastrectomy for Gastric Cancer Successfully Treated Using a Conservative Approach].

INTRODUCTION: The stomach is an organ considered resistant to ischemia because of the microvascular networks in the stomach wall, and gastric remnant necrosis following gastrectomy is rare. Herein, we report a case of gastric remnant necrosis following gastrectomy successfully treated using a conservative approach. CASE PRESENTATION: An 83-year-old woman underwent laparoscopic distal gastrectomy, D1 plus lymphadenectomy, Billroth Ⅰreconstruction, and suture closure of the esophageal hiatus for early gastric cancer and giant esophageal hiatal hernia. The amylase level of the drainage fluid was abnormally high on postoperative day(POD)3, and contrast-enhanced CT confirmed gastric remnant necrosis. The patient was treated using a conservative approach, as her general condition was stable. Postoperative fluoroscopy on POD 21 revealed contrast media leakage from the gastric remnant; however, adequate drainage was observed. Upper gastrointestinal(GI)endoscopy on POD 23 demonstrated circumferential gastric remnant necrosis, whereas GI endoscopy on POD 52 revealed a decrease in the size of the gastric remnant, proliferation of the granulation tissue, and regeneration of mucosa in the gastric remnant. DISCUSSION: Gastric remnant necrosis following gastrectomy is a rare complication and is associated with poor prognosis. In most cases, total resection of the remnant stomach is warranted. However, for high surgical risk cases, conservative treatment options should be considered based on an assessment of patients' general condition.

[Evaluated Cases of Anastomotic Recurrence in Colorectal Cancer].

Anastomotic recurrence in 6 colorectal cancer cases during the postoperative surveillance between 2008 and 2015 was evaluated retrospectively. Five cases had undergone DST anastomosis for sigmoidectomy and proctectomy. They had a pathological tendency to have T3 tumor and deeper, positive lymph node metastases and positive lymphatic and vascular invasion. There were 2 cases with the anastomotic recurrence diagnosis 6 to 8 months after the primary tumor resection while 4 resected cases had recurrent tumor depth of T3, though 3 cases were diagnosed 1 year after the primary tumor resection. Anastomotic recurrence should be considered a few months after primary tumor resection.

Short Ballistic Josephson Coupling in Planar Graphene Junctions with Inhomogeneous Carrier Doping.

We report on short ballistic (SB) Josephson coupling in junctions embedded in a planar heterostructure of graphene. Ballistic Josephson coupling is confirmed by the Fabry-Perot-type interference of the junction critical current I_{c}. The product of I_{c} and the normal-state junction resistance R_{N}, normalized by the zero-temperature gap energy Δ_{0} of the superconducting electrodes, turns out to be exceptionally large close to 2, an indication of strong Josephson coupling in the SB junction limit. However, I_{c} shows a temperature dependence that is inconsistent with the conventional short-junction-like behavior based on the standard Kulik-Omel'yanchuk prediction. We argue that this feature stems from the effects of inhomogeneous carrier doping in graphene near the superconducting contacts, although the junction is in fact in the short-junction limit.

Self-expandable Metallic Stents Contribute to Reducing Perioperative Complications in Colorectal Cancer Patients with Acute Obstruction.

BACKGROUND/AIM: The self-expandable metallic stent (SEMS) is an excellent non-invasive tool for emergent bowel obstruction. This study was designed to evaluate the clinical usefulness of the SEMS for avoiding perioperative complications. PATIENTS AND METHODS: We analyzed a total of 47 consecutive patients who had a bowel obstruction due to colorectal cancer at initial diagnosis between 2012 and 2017 from hospital records. RESULTS: Perioperative complications occurred in 30% (14/47) of patients. Univariate and multivariate logistic regression analyses identified an age of more than 75 years [p=0.037, OR=6.84 (95% CI=1.11-41.6)] and the absence of an SEMS treatment [p=0.028, OR=18.5 (95% CI=1.36-250.0)] as independent risk factors for perioperative complications. Pneumonia (12.7% (6/47)) was the most common complication. There were no pneumonia patients (0% (0/15)) who were treated with the SEMS. In contrast to patients with the non-SEMS treatment, 18.7% (6/32) of all patients and 35.7% (5/14) of elderly patients had pneumonia. CONCLUSION: The SEMS is a safe and effective treatment for avoiding perioperative complications, particularly pneumonia, and may be a crucial strategy in elderly patients with acute obstruction due to colorectal cancer.

[A Case of Laparoscopic Distal Gastrectomy after Abdominal Incisional Hernia Repair].

Re-laparotomy with resection of the mesh after abdominal incisional hernia repair may cause recurrence of the hernia and infection of the mesh. In the present study, we performed laparoscopic distal gastrectomy(LDG)for early gastric cancer without the resection of the mesh in such a case. A 82-year-old man who had undergone abdominal vascular replacement, cholecystectomy, abdominal incisional hernia repair with the mesh, sigmoidectomy had local recurrence of gastric cancer after endoscopic submucosal resection. We diagnosed as cStage IA and performed LDG without resection of the mesh. He had no recurrence of hernia nor infection of the mesh. Minimizing damage to the abdominal wall by laparoscopic surgery can prevent them.

[A Case of Thyroid Metastasis from Rectal Cancer].

The patient was a 68-year-old man who underwent Hartmann's procedure for a fistula due to rectal cancer in August 2012. The cancer was tub2>tub1, pSE, pN2, pH2, pM1(intrapulmonary metastasis), stage IV. The patient received 5 courses of FOLFOX and bevacizumab as adjuvant chemotherapy. In December 2012, the patient was seen by Otolaryngology for hoarseness. A neck examination revealed induration of the left lobe of the thyroid, and FNA biopsy strongly suggested metastasis of rectal cancer to the thyroid. FDG-PET was performed and revealed extensive accumulation of FDG at the same site. The patient was diagnosed with thyroid metastasis of rectal cancer and underwent a left thyroid lobectomy and lymph node dissection in January 2013. Histopathology confirmed the thyroid metastasis of rectal cancer. Thyroid metastasis of rectal cancer is extremely rare: there are 11 such cases in the Japanese literature, including the case encountered by the current authors. This case is reported here, along with a discussion of some of the literature.

[Surgical Technique for Lesser Curvature Lymph Node Dissection in Laparoscopic Distal Gastrectomy].

INTRODUCTION: Lesser curvature lymph node dissection is often performed at the end of the procedure in laparoscopic distal gastrectomy. In obese patients, it can be difficult to secure a visual field, and bleeding or injury of the remnant stomach may occur. SURGICAL TECHNIQUE: After separating the duodenum using an automated suturing instrument, the stomach is rolled under the left diaphragm. An assistant holds the gastric angle near the lesser curvature with forceps in the right hand, and pulls the stomach cephalad toward the left side of the patient. As a result, the region from the esophagogastric junction to the gastric angle is aligned, enabling use of an ultrasonically activated scalpel from the right side of the operator. Dissection is performed from around the posterior wall of the esophagogastric junction to the gastric angle. After dissecting the posterior wall as much as possible, dissection of the anterior wall is performed to complete the lesser curvature procedure. CONCLUSION: This technique enables safe and reliable dissection of the lesser curvature while avoiding bleeding and damage to the stomach wall.

[Modified NEWS as a Safe and Inventive Approach for Gastrointestinal Stromal Tumor near the Esophagogastric Junction].

Laparoscopy and endoscopy cooperative surgery(LECS)is an excellent surgical procedure that utilizes the advantages of both methods. Furthermore, non-exposed endoscopic wall-inversion surgery(NEWS)is a more promising procedure that enables avoidance of tumor exposure of and dissemination to the abdominal cavity. However, NEWS has the potential risk of postoperative ulceration, leading to delayed perforation because of mucosal defect. We invented a modified NEWS, which was a safe procedure, by including the all-layer suture to close the mucosal defect. We present a case of gastrointestinal stromal tumor(GIST)near the esophagogastric junction, which was treated with modified NEWS.

[Better Effects of Inventive Nutritional Approaches for Chemotherapy and Conversion Surgery in Stage â £ Gastric Cancer].

The REGATTA trial revealed that chemotherapy is the standard strategy for gastric cancer patients with Stage Ⅳ factors. However, some recent studies have identified the prognostic effect of conversion surgery after complete response to Stage Ⅳ factors during chemotherapy. Here, we report a case with Stage Ⅳ factors successfully treated via intensive chemotherapy and conversion surgery without any adverse events and complications, using preoperative parenteral hyper-nutrition and postoperative enteral nutrition. Nutrition might be the key strategy during the treatment of gastric cancer patients with Stage Ⅳ factors.

[A Case of GIST with Extensive Peritoneal Dissemination Controlled over Long-Term by Low-Dose, Intermittent Administration of Imatinib after Weight Loss Surgery].

A 67-year-old man presented with abdominal pain and fever. Many abdominal tumors were detected by enhanced computed tomography(CT). The largest tumor, measuring 20 cm, had perforated the ileum and formed an abscess. Emergency surgery was performed to remove multiple tumors in the peritoneal cavity as much as possible. Immunostaining showed c-kit and CD34 positivity, and the tumors were diagnosed as gastrointestinal stromal tumor(GIST). During postoperative imatinib therapy for the residual tumor, low-dose intermittent administration was required due to side effects, but the disease was controlled for over 91months. For advanced GIST with peritoneal dissemination, 200mg/day imatinib or intermittent administration after volume reduction surgery might be effective depending on the patient's general condition.

Ectopic gastrointestinal variceal bleeding with portal hypertension.

Massive gastrointestinal bleeding from gastrointestinal varices is one of the most serious complications in patients with portal hypertension. However, if no bleeding point can be detected by endoscopy in the predilection sites of gastrointestinal varices, such as the esophagus and stomach, ectopic gastrointestinal variceal bleeding should be considered as a differential diagnosis. Herein, we report a case of ectopic ileal variceal bleeding in a 57-year-old woman, which was successfully diagnosed by multi-detector row CT (MDCT) and angiography and treated by segmental ileum resection. To date, there have been no consensus for the treatment of ectopic ileal variceal bleeding. This review was designed to clarify the clinical characteristics of patients with ectopic ileal variceal and discuss possible treatment strategies. From the PubMed database and our own database, we reviewed 21 consecutive cases of ileal variceal bleeding diagnosed from 1982 to 2017. MDCT and angiography is useful for the rapid examination and surgical resection of an affected lesion and is a safe and effective treatment strategy to avoid further bleeding.

[A Case of Resection for Metastatic Osseous Tumor from Rectal Cancer].

A 67-year-old male was referred to our hospital for further investigation of fecal occult blood. We diagnosed him with rectal cancer with osseous metastasis. Chemo-and radiation therapy were administered following resection of the rectal cancer. There were no other lesions except for the osseous metastasis remaining after these interventions. The osseous lesion was then resected. There have no signs of recurrence for 1 year and 9 months since the last operation. We report a case of successful resection of osseous metastasis from rectal cancer.

[A Case of QOL Improvement after Intestinal Stenosis Due to Peritoneal Dissemination of Gastric Cancer in Elderly Patients].

Nearly 70% of gastric cancer recurrences occur as peritoneal dissemination. Most of the treatment for recurrence of gastric cancer dissemination is chemotherapy; depending on the symptoms and the site of recurrence, palliative bypass surgery may be performed. Intensive treatment is often difficult for elderly patients over 85-years-old. This case was a 91-year-old female who underwent total gastrectomy for gastric cancer(signet-ring cell carcinoma)7years prior. Two years ago, a stenosis due to recurrence was revealed in the small intestine and bypass surgery was performed. At that time, she was 89-years-old, and chemotherapy was continued for 1 year. Six months ago, recurrence was revealed in the esophago-jejuno anastomosis. Since the stenosis was severe, it was possible to resume oral reconstitution by inserting a metallic stent. Chemotherapy(S-1)is currently ongoing. There are few reports of long-term treatment for recurrence of gastric cancer peritoneal dissemination in elderly people over 80 years of age. This report is a case of long-term survival involving multidisciplinary treatments, which improved the quality of life(QOL)over the age of 90 years.

A case of a horseshoe appendix.

Anomalies of the appendix are extremely rare, and a horseshoe appendix is even rarer. A literature search has revealed only five reported cases. In this report, we present a case of a horseshoe appendix.A 78-year-old man was referred for further examination following a positive fecal occult blood test. A mass in his ascending colon was detected on colonoscopy, while computed tomography showed that it was connected to the appendix. Tumor invasion derived from the ascending colon or appendix was suspected. We diagnosed ascending colon cancer prior to laparoscopic ileocecal resection. Macroscopic findings showed that the appendix connected to the back side of the mass, while microscopic findings showed that the mucosa and submucosa were continuous from the appendiceal orifice in the cecum to the other orifice in the ascending colon, where a type 1 tumor was observed on the orifice. We eventually diagnosed the patient with tubulovillous adenoma and a horseshoe appendix.A horseshoe appendix communicates with the colon at both ends and is supplied by a single fan-shaped mesentery. Cases are classified by the disposal of the mesentery and the location of the orifice. Anatomical anomalies should be considered despite the rarity of horseshoe appendices.