Three-Year Outcomes of a Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

BACKGROUND: We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. METHODS: The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). RESULTS: Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. CONCLUSION: Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).

A Phase II Study of Perioperative Capecitabine plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

LESSONS LEARNED: Perioperative capecitabine and oxaliplatin (CapeOx) therapy showed favorable efficacy with sufficient pathological response. Small sample size limited the statistical power of this result. Perioperative CapeOx therapy showed good feasibility. Further studies with larger sample size are required to validate this novel approach. BACKGROUND: D2 gastrectomy followed by adjuvant S-1 is the standard therapy for patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with GC. METHODS: The eligibility criteria included confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx (AC) after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to the JCGC (≥grade 1b). RESULTS: Thirty-seven pts were enrolled on CapeOx. An R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4-68.2) were demonstrated. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment. Grade 3-4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%). CONCLUSION: Perioperative CapeOx showed good feasibility and favorable efficacy with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations.

[A Case of Resected Combined Pancreatic Mixed Ductal Adenocarcinoma and Neuroendocrine Tumor].

A 63-year-old man was followed-up for diabetes mellitus. During follow-up, computed tomography(CT)showed dilatation of the main pancreatic duct in the tail of the pancreas. Abdominal enhanced CT revealed a 25 mm tumor in the body of the pancreas. Endoscopic ultrasound-fine needle aspiration(EUS-FNA)was performed, and the pathological diagnosis was adenocarcinoma. Therefore, based on the diagnosis of pancreatic body carcinoma, distal pancreatectomy with splenectomy was performed. The postoperative course was uneventful. Histological and immunohistochemical examination revealed that the tumor consisted of a ductal carcinoma and a neuroendocrine component. Therefore, combined pancreatic tumor (fT3N1M0, StageⅡB)was diagnosed. The patient subsequently received postoperative adjuvant chemotherapy(S-1 100mg/ day), and survived without recurrence 6 months after the operation. We report this case of combined pancreatic tumors with a review of the literature.

[A Case of Elderly Advanced Rectal Cancer Treated with Abdominoperineal Resection after 16 Months of Chemoradiotherapy].

An 81-year-old woman underwent preoperative chemoradiotherapy(CRT)for advanced lower rectal cancer with vaginal invasion. However, she refused surgery and received additional radiotherapy. We detected a rectal-vaginal leak, so we performed ileostomy with double orifices and chemotherapy. As the tumor and vaginal leak increased, we performed laparoscopy- assisted abdominoperineal resection and vaginal posterior wall resection after 16 months of CRT. Although adhesion occurred due to inflammation and tumor invasion after the CRT, surgery could be performed safely. Despite the advanced age of the patient, complications did not occur, and no recurrence was observed for 66 month after the surgery. In rectal cancer, operation is usually performed until 6 to 8 weeks after CRT, but in our case, the surgery was performed after a long interval, with good results. Thus, we report the case herein.

[A Case of Advanced Sigmoid Colon Cancer That Was Resected after Chemoradiation Therapy Following Ineffective Chemotherapy].

We report a case of advanced sigmoid colon cancer that was resected after chemoradiation therapy(CRT)following ineffective chemotherapy. A 59-year-old woman harbored a lower abdominal tumor the size of an infant's head and was diagnosed with a huge sigmoid colon cancer with invasion to the urinary bladder and metastases to the para-aortic lymph nodes. The patient received 2 courses of modified FOLFOX6(mFOLFOX6)plus cetuximab therapy, which was assessed as ineffective; She then received CRTwith 50.4 Gy in 28 fractions plus concurrent oral S-1(100mg/day for 28 days). Tumor shrinkage in the primary lesion was achieved after CRT; total pelvic exenteration with the removal of metastatic para-aortic lymph nodes was then performed 5 months after the first diagnosis. This case of locally distant advanced colon cancer in the pelvic cavity coexisting with resectable metastatic lesions suggested that CRTmight contribute to successful local treatment after the failure of preoperative chemotherapy.

One-day nasogastric tube decompression after distal gastrectomy: a prospective randomized study.

PURPOSE: Many surgeons in Japan use 1-day nasogastric tube (NGT) decompression after gastrectomy as a standard procedure. This prospective randomized study aimed to define whether 1-day NGT decompression is necessary after distal gastrectomy. METHODS: The subjects were 233 patients with gastric cancer, randomized into two groups immediately after distal gastrectomy: one group received 1-day NGT decompression (NGT group, n = 119) and the other did not (no-NGT group, n = 114). The primary outcome measure was postoperative surgery-related and respiratory complications, whereas secondary measures were the postoperative course to recovery and patient complaints. RESULTS: The incidence of surgery-related complications did not differ significantly between the NGT and no-NGT groups (21.0 and 19.2%, respectively; p = 0.87). The rate of respiratory complications was 6.7% in the NGT group and 7.0% in the no-NGT group (p > 0.99). The time to passage of first flatus and the postoperative hospital stay did not differ between the groups. Twenty-five patients in the NGT group and none in the no-NGT group complained of nasopharyngeal discomfort (p < 0.0001). CONCLUSION: Considering the physical discomfort caused by the NGT, we believe that routine 1-day NGT decompression is unnecessary after distal gastrectomy.

[A Case of Resected Metachronous Cholangiocarcinoma after Pancreaticoduodenectomy].

The patient was a 79-year-old woman, who had undergone pancreaticoduodenectomy(PD)for lower bile duct carcinoma in our hospital(pT3N0H0P0M0, fStage III ). Four years 6 months after the initial operation, abdominal CT revealed left bile duct expansion and hilar bile duct thickening. Therefore, based on the diagnosis of perihilar cholangiocarcinoma originating from the left hilar duct, we performed left lobectomy with caudate lobectomy and biliary tract reconstruction. The surgical specimen showed a tumor in the left hilar bile duct. Histopathological diagnosis of the tumor was a moderately differentiated adenocarcinoma(pT2aN0H0P0M0, fStage II ). Surgical margins were histologically negative. Since the tumor was located away from the anastomosed site of the cholangiojejunostomy, we determined that the tumor was not a recurrence but a metachronous cholangiocarcinoma. The postoperative course was uneventful. The patient survived without recurrence 2 years after the second operation. The possibility of heterochronic biliary carcinomas should be considered during follow-up evaluation. We report this case of metachronous cholangiocarcinoma that occurred 4 years 6 months after PD, with a review of the literature.

[A Case of Advanced Sigmoid Colon Cancer Successfully Resected via Laparoscopic Surgery after Preoperative Chemotherapy].

We report a case of advanced sigmoid colon cancer resected via laparoscopic surgery after preoperative chemotherapy. A- 55-year-old man visited our hospital with diarrhea. CTrevealed a giant tumor in the sigmoid colon, and surrounding lymph node enlargement was also noted. The tumor appeared to be locally advanced; thus, preoperative chemotherapy was started. Due to the possibility of obstruction, we constructed an ileostomy laparoscopically. The tumor was found to be RAS wild, and 4 courses of mFOLFOX6 plus panitumumab were given. Follow-up CTshowed remarkable tumor reduction allowing laparoscopic resection; as such, laparoscopic sigmoidectomy was performed successfully. Chemotherapy with molecular-targeted drugs is a promising method to make laparoscopic surgery possible for advanced colorectal cancer.

[Can Lateral Pelvic Node Dissection Omitted in Rectal Cancer with Suspected Lateral Node Metastasis after Chemoradiotherapy ?]

To elucidate ideal strategy of treatment for advanced lower rectal cancer, we investigated 11 patients with clinically suspected lateral pelvic node(LPN)metastasis among 36 patients who received neoadjuvant chemoradiation therapy(NCRT). Nodal metastasis was diagnosed as positive when the major axis of a lymph node was over 7mm in computed tomography(CT). Both tumor and nodal downstaging were observed in CT after NCRT; pathological complete response and ypN0 was obtained in 2(18.2%)and 6(54.5%)cases, respectively, and positive LPN was observed only in 2 cases. All of 4 cases who were diagnosed as ycN0 in CT after chemoradiation were confirmed as ypN0. Extended examination with 36 patients who underwent NCRT showed that 85% of 21 ycN0-cases were confirmed to be ypN0. As a conclusion, NCRT for lower rectal cancer with suspected LPN metastasis was highly effective, and omitting lateral node dissection when all nodes turned to be less than 7mm on CT, can be a hopeful option.

[A Case of an IgG4-Related Inflammatory Pseudotumor of the Liver Showing Enlargement That Was Difficult to Differentiate from Hepatic Cancer].

A 60-year-old man was admitted for a liver mass(S3), which rapidly increased in size during intraductal papillary mucinous neoplasm(IPMN)follow-up. Although EOB-MRIwas performed, the mass could not be accurately diagnosed as hepatic cancer. Thus, we performed a lateral segmentectomy. In the resected specimen, a solid tumor mass was clearly bound in segment 3 of the liver. Since histopathology revealed no malignant cells and many IgG4-positive cells, we confirmed the diagnosis as IgG4-related inflammatory pseudotumor of the liver. IgG4-related diseases occur in various organs in the body, and they are known to associate with autoimmune pancreatitis and sclerosing cholangitis, but an IgG4-related inflammatory pseudotumor of the liver is a rare disease. It is often difficult to distinguish from hepatic cancer and surgical resection is performed.

[A Case of Xanthogranulomatous Cholecystitis That Changed Over Time and Was Difficult to Distinguish from Advanced Gallbladder Cancer].

A 70-year-old man was referred because of suspected gallbladder cancer and gallstones. Contrast-enhanced CT, EOB-MRI and PET-CT could not completely rule out gallbladder cancer. The patient preferred follow-up without surgery. At 4 months after initial examination, the gallbladder wall thickening showed improvement, but appeared worse at 9 months after initial examination. Therefore, we decided to perform surgery. Since malignant findings were not observed on rapid intraoperative pathology, we performed a cholecystectomy and right hemicolectomy because of inflammation in the transverse colon. Pathological examination diagnosed xanthogranulomatous cholecystitis. The imaging appearance of xanthogranulomatous cholecystitis varies, and also changes over time, making it difficult to distinguish from advanced gallbladder cancer. We experienced a case of xanthogranulomatous cholecystitis that changed over time, and report this case with a review of the literature.

Usability of elective laparoscopic sigmoidectomy and feasibility of single-incision laparoscopic surgery for sigmoid volvulus: report of three cases.

A therapeutic guideline for sigmoid volvulus (SV) has not been established, and the most recommended surgical procedure for SV has not been determined. Our objective is to assess the usability of elective laparoscopic sigmoidectomy and the feasibility of single-incision laparoscopic surgery for SV following endoscopic reduction. SV typically affects the elderly and accounts for 1% to 7% of intestinal obstructions in Western countries. We report on 3 patients with SV who underwent elective laparoscopic sigmoidectomy following endoscopic reduction, and we first describe single-port surgery for SV. We discuss the 3 patients (a 79-year-old male, an 88-year-old female, and a 67-year-old female) with SV who underwent elective laparoscopic sigmoidectomy following endoscopic reduction. All 3 patients underwent laparoscopic sigmoidectomy, and 2 patients underwent single-port laparoscopic surgery without complications. Recurrence of volvulus was not seen during the course of 12 to 24 months. In experienced hands, elective laparoscopic sigmoidectomy after colonoscopic detorsion is a valuable alternative, and single-port surgery is also feasible.

[The Implications of Primary Tumor Resection during Recent Chemotherapy of Unresectable Colon Cancer].

Some patients with unresectable colorectal cancer can be treated by chemotherapy leaving the primary tumor unresected, but indications and implications of a later resection of the primary tumor (RPT) are often controversial. We investigated 5 patients whose primary tumors were resected during chemotherapy, either panitumumab or bevacizumab. The median age of these patients was 63 years and all were men. The unresectable disease was liver metastases in 4 patients and a primary tumor in 2 patients. A diverting stoma was constructed before initiation of chemotherapy in 2 patients. The median interval until RPT was 8.3 months and the reasons for resection were the appearance of obstructive symptoms in 3 patients and a desire for stoma closure in 2 patients. The size of the primary tumor had decreased until RPT in all patients. RPT was performed successfully in all patients, but 2 of the 3 operations that were initiated laparoscopically had to be converted to open surgery. Intensive chemotherapy was resumed in all patients and median survival after RPT was 19 months, including a patient whose liver metastasis was also resected later. RPT can relieve obstructive symptoms and close stomas. Because intensive chemotherapy is still possible and a lengthy survival can be expected after RPT, it should be considered not merely as a palliative option but also as a treatment strategy.

[Resected Focal Nodular Hyperplasia That Was Difficult to Differentiate from Hepatocellular Carcinoma--A Case Report].

We report a case of a 62-year-old woman with a growing liver tumor that was difficult to differentiate from hepatocellular carcinoma (HCC). Abdominal CT revealed a hypervascular tumor (36 mm in diameter) in segment 3 of the liver that showed early enhancement and which had grown from 30 mm to 36 mm over the previous year. A fatty liver and gallstones were also detected. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor on both T1- and T2-weighted images, and EOB-MRI revealed a mass that showed high signal intensity in the hepatobiliary phase. The imaging findings were not typical for HCC; however, the possibility of malignancy could not be ruled out due to the enlargement of the mass. Therefore, in February 2015, we performed a laparoscopic left lateral segmentectomy with cholecystectomy. After a good postoperative course, the patient was discharged from the hospital 11 days after surgery. Histological assessment revealed the tumor was focal nodular hyperplasia (FNH).

[Adjuvant therapy with WT1 peptide-pulsed dendritic cell therapy in combination with TS-1 for pancreatic cancer with positive peritoneal cytology after curative operation].

A 66-year-old woman was diagnosed with pancreatic tail cancer, and she was referred to our hospital. Abdominal computed tomography(CT)revealed a tumor(2.5 cm in diameter)in the pancreatic tail, with invasion to the spleen and splenic vein. In February 2013, we performed distal pancreatectomy with splenectomy, left adrenal gland resection, and D2 lymph node dissection. Diagnostic peritoneal lavage cytology during surgery was positive; however, we performed curative resection because there were no signs of peritoneal dissemination and distant metastasis. The patient was discharged from the hospital 23 days after the operation, with good postoperative course. Histological diagnosis was pancreatic tail cancer, pT4N0H0P0M(-) fStage IVa. Subsequently, the patient received postoperative adjuvant chemotherapy(TS-1: 100mg/day, 4 courses)combined with Wilms'tumor 1(WT1)peptide-pulsed dendritic cell therapy. No serious adverse events occurred during the postoperative adjuvant therapy. The patient remains alive without recurrence 16 months after the operation.

Enantioselective insertion of a carbenoid carbon into a C-C bond to expand cyclobutanols to cyclopentanols.

When a carbenoid species generated from a tosylhydrazone is reacted with a cyclobutanol in the presence of a chiral rhodium catalyst, a C-C single bond of the cyclobutanol is cleaved, and the carbenoid carbon is inserted therein to furnish a ring-expanded cyclopentanol in an enantioselective manner.

[A case of curatively resected advanced intrahepatic cholangiocellular carcinoma through effective response to neoadjuvant chemotherapy].

A 67-year-old-man came to our hospital for further evaluation of a liver tumor detected by abdominal ultrasonography at another hospital. Abdominal computed tomography showed a tumor (8 cm in diameter)in the left lobe of the liver, with invasion of the left and middle hepatic veins, and multiple lymph node metastases. Liver biopsy examination revealed intrahepatic cholangiocellular carcinoma (cStage IVB). Therefore, chemotherapy with gemcitabine(GEM)was administered. The hepatic tumor and multiple lymph nodes were reduced in size after eight courses of GEM chemotherapy. In May 2013, we performed an extended left hepatectomy with biliary tract reconstruction and extended lymph node dissection. The histological diagnosis was intrahepatic cholangiocellular carcinoma, pT3N0H0P0M (-), fStage III. The patient's postoperative recovery was good, and 1 month after surgery, the patient received 6 course of postoperative adjuvant GEM chemotherapy. No serious adverse events occurred during the postoperative adjuvant therapy period. The patient is alive without recurrence 14 months after surgery and 23 months after diagnosis.

[A case of curative resected pancreatic cancer coincident with a retroperitoneal abscess].

A 64-year-old man presented with a chief complaint of abdominal pain. An abdominal computed tomography (CT) scan showed a mass 30-mm in diameter at the splenic flexure, and we diagnosed a retroperitoneal abscess. Conservative therapy was successful, and the patient was discharged. However, 1 month later, he again experienced abdominal pain. To reassess the abscess, contrast-enhanced abdominal CT was performed. In addition to the retroperitoneal abscess, the CT scan showed an approximate 30-mm mass in the head of the pancreas with no contrast uptake. The abscess was also detected by endoscopic retrograde pancreatography. We suspected but could not confirm pancreatic cancer. Two months later, the patient developed obstructive jaundice. At this time, we diagnosed pancreatic cancer, and subtotal stomach-preserving pancreaticoduodenectomy was performed. The histopathologic diagnosis was pancreatic cancer, T4, N0, M0, Stage IVa. The postoperative course was favorable, and the patient received postoperative adjuvant chemotherapy. He remains alive without recurrence 15 months after surgery.

[HER2 testing for advanced recurrent gastric cancer in a general hospital].

The Japanese gastric cancer treatment guidelines(published as a web supplement for version 3)recommend the implementation of HER2 testing prior to the selection of chemotherapy. Since we had not yet implemented HER2 immunohistochemistry(IHC)methods for gastric cancer, we tried to compare the HER2 testing results from a reference laboratory(ref lab) and our hospital(in-house). The HER2 concordance rates were calculated between the results from in-house and ref lab using 26 cases(31 samples)which were from patients with advanced, metastatic unresectable, or Stage IV resectable gastric cancer. The HER2 expression(in-house/ref lab)was distributed as follows: negative/negative, 18 cases; negative/equivocal, 2 cases; negative/positive, 1 case;equivocal/equivocal, 2 cases; and positive/positive, 3 cases. The concordance rate was 88. 4%(23/26), and the mismatch rate was 11. 6%(3/26)between in-house and ref lab. Although IHC test results with in-house and ref lab had been generally consistent, it is still necessary to improve and standardize diagnostic accuracy in the near future.

[Efficacy of endoscopic gastroduodenal stenting for gastric outlet obstruction caused by unresectable gastric cancer].

BACKGROUND: In this retrospective study, we investigated the clinical outcomes of endoscopic gastroduodenal stenting (EGDS) for gastric outlet obstruction( GOO) caused by unresectable gastric cancer( UGC). METHODS: A retrospective study was performed on 20 UGC patients with GOO between 2007 and 2012. We compared the clinical outcomes of EGDS using the WallFlex stent( GDS group, n=8) and palliative Roux-en-Y gastrojejunostomy( RYGJ group, n=12). RESULTS: The numbers of patients with a poor performance status and prior use of chemotherapy were higher in the GDS group than in the RYGJ group. No postoperative complications were observed, and the GOO score improved in both groups. The median days taken to resume oral food intake, the median duration of oral food intake, and the median survival time in the RYGJ and GDS groups were 4 and 3 days( p=0.0008), 301 and 151 days( p=0.0698), and 345 and 161 days (p=0.0070), respectively. CONCLUSIONS: EGDS for GOO caused by UGC can be performed safely even after chemotherapy and is beneficial in terms of improvement of oral food intake.