Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study.

BACKGROUND: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer. METHODS: A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively. RESULTS: Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P < 0.03) and 12 months (P < 0.001) were independent prognostic factors for a shorter recurrence-free interval. CONCLUSIONS: Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer. CLINICAL TRIAL REGISTRATION: UMIN000007925.

[A Case of Single Hole Ileal Resection for Ascendiry Colon Cancer with Ureterocutaneous Fistula in the Right Lower Abdomen].

The patient is a 70s woman. She underwent cystectomy for bladder cancer 6 years ago and had a ureterocutaneous fistula in the right lower abdomen. After colonoscopy for positive fecal occult blood, a type 1 elevated lesion was found in the ascending colon, which was diagnosed as a well-differentiated adenocarcinoma on biopsy. Surgery was performed with a single hole. The approach from the right lower abdomen, where the ureterocutaneous fistula and ureter are located, was avoided, and the approach from the hepatic flexure of the transverse colon was used first. After the right colon was mobilized, the large mesh adhesions around the ureter were carefully dissected, and the right ureter was identified and preserved, extending from the lateral ascending colon to the abdominal wall. The ileal artery was dissected at the root and after dissection of the D3 lymph node, the intestine was dissected and anastomosed extracorporeally. The operative time was 246 minutes with small amount of blood loss. The patient was discharged on the 6th postoperative day without any postoperative complications. The pathology result was pT3N0M0, pStage Ⅱa, and radical resection had been performed. The patient is currently undergoing recurrence-free follow-up.

[A Case of Pathological Complete Response for MSI-High Locally Advanced Unresectable Transverse Colon Cancer Treated with Nivolumab plus Ipilimumab Combination Therapy].

74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.

[A Case of Conversion Surgery after Chemotherapy for Locally Advanced Unresectable Rectal Cancer].

We report a case of locally advanced rectal cancer that could not be curatively resected, in which the patient underwent conversion surgery after chemotherapy. The patient is a 70-year-old woman. She came to our hospital with a chief complaint of lower abdominal pain, and a close examination revealed rectal cancer with invasion of the external iliac artery and pelvic wall. She was treated with mFOLFOX6 plus cetuximab for locally advanced rectal cancer that was not amenable to surgical resection. After 11 courses of chemotherapy, significant shrinkage of the tumor was observed, and robot assisted laparoscopic high-anterior resection was performed. The patient didn't relapse at 12 months after surgery without adjuvant chemotherapy.

Surgical plume from tissue infected with human hepatitis B virus can contain viral substances.

INTRODUCTION: Evidence on the biological danger associated with surgical plume is lacking. We examined whether surgical plume, generated by the energy devices ultrasonically activated scalpel (US) or electrocautery (EC) contains virus-related substances. MATERIAL AND METHODS: Experiment 1, ex-vivo model: Tumor mass of a hepatocellular carcinoma line was prepared in a Nod/SCID mouse. Surgical plume generated on the mass by US or EC was collected and detection of HBs gene fragment and antigens (HBsAg or AFP) was conducted. Experiment 2, clinical specimen: Detection of HBV-DNA and HBsAg was conducted following the collection of surgical plume generated from clinically obtained liver specimens from six HBV-associated hepatocellular carcinoma patients. RESULTS: Experiment 1: HBs gene fragment was detected in the solutions regardless of the device used. HBsAg was detected in US and EC solutions and AFP was also detected in a US solution. Experiment 2: HBV-DNA was detected in both devices, in all three cases whose preoperative serum HBV-DNA was positive. In the other serum-negative cases, HBV-DNA was not detected. While serum HBsAg was positive in five of six cases, it was not detected in any solution. CONCLUSIONS: DNA fragments or antigens of virus can exist in the surgical plume generated by EC or US.

A phase II study of S-1 therapy for patients with advanced and recurrent esophageal cancer resistant or intolerable to fluorouracil, platinum, and taxane therapy (OGSG 1404).

BACKGROUND: Fluorouracil (FU), platinum (PT), and taxane (TAX) therapy was the standard chemotherapy for esophageal squamous cell carcinoma (ESCC) before the era of anti-programmed death-1 antibodies. The aim of this phase II trial was to evaluate the efficacy and safety of S-1 monotherapy for patients with recurrent or metastatic (R/M) ESCC resistant or intolerable to FU, PT, and TAX therapy. METHODS: Eligible patients had R/M ESCC; no prior S-1 use; were intolerant or refractory to prior FU, PT, and TAX therapy; aged ≧ 20 years; and Eastern Cooperative Oncology Group performance status 0 or 1. S-1 was administered orally from days 1 to 28, every 6 weeks until disease progression. The primary endpoint was the disease control rate (DCR) for each patient, assessed by Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints were overall survival, progression-free survival, time to treatment failure, response rate, and toxicity. RESULTS: Between October 2015 and December 2017, 17 patients were recruited, and the trial was terminated because of slow accrual. The DCR was 46.7%. The response rate was 13.3%. The median progression-free survival was 2.0 months. The median time to treatment failure was 1.9 months. The median overall survival was 8.4 months, and the 1 year overall survival rate was 30.5%. CONCLUSIONS: Although this trial closed early because of slow accrual, we observed modest clinical activity with S-1 in patients with R/M ESCC who could not tolerate or whose tumors were refractory to FU, PT, and TAX therapy.

[A Case of Locally Advanced Rectal Cancer with Multiple Liver Metastases Could Be Resected after Triplet Chemotherapy].

The patient was a 60's man, whose chief complaints were melena and weight loss. He visited our hospital, and further evaluation revealed rectal cancer(Ra)invading the abdominal wall with multiple liver metastases. The clinical diagnosis was cT4b(abdominal wall)N2bM1a(H1), cStage Ⅳ. We performed a transverse colostomy on the day prior to chemotherapy administration. He was administered 8 courses of FOLFOXIRI plus bevacizumab. After the chemotherapy, the primary tumor and liver metastases showed PR, with a diagnosis of ycT3N1bM1a(H1), Stage Ⅳ. We performed a robot-assisted laparoscopic low anterior resection for the primary tumor. Two months later, the partial resection of liver S6 and S8 was performed. The patient has been cancer-free for 6 months now.

[A Case of Anastomotic Recurrent Descending Colon Cancer Successfully Treated with Single-Incision Laparoscopic Partial Colectomy with Intracorporeal Anastomosis].

A 60s-year-old male, who had laparoscopic partial colectomy with resection of left colic artery for descending colon cancer 8 years ago and completed 5-year-follow-up without the evidence of recurrence, was diagnosed as anastomotic recurrence of descending colon cancer, and referred to our hospital. We planned and safely performed single-incision laparoscopic colectomy(SILC)with intracorporeal anastomosis(ICA)(operation time of 390 min and estimated blood loss of 60 g). Following the adhesiolysis, the intracorporeal resection of the lesion was performed with automatic stapling device preserving middle colic and inferior mesenteric arteries and veins. Then, after the recovery of the specimen, ICA was performed as follows; after making a small hole just below the staple line at the opposite side of mesenteric attachment, the oral and the anal stump of colon was pulled-up and placed side-by-side with temporary strings and automatic suturing device was inserted into the holes and fired to form a side-to-side anastomosis, then the common stab incision was pulled- up with 3 temporary strings and closed with a stapler. The postoperative course was smooth and discharged on postoperative day 8. The ICA can be a good option for SILC when colonic and vascular tension would be the limiting factor of anastomosis.

A phase II trial of dose-reduced nab-paclitaxel for patients with previously treated, advanced or recurrent gastric cancer (OGSG 1302).

BACKGROUND: For unresectable or recurrent advanced gastric adenocarcinoma (AGC), tri-weekly administration of nanoparticle albumin-bound paclitaxel (nab-PTX) at 260 mg/m2 achieved a response rate of 27.8% in a phase II trial in Japan. However, frequent neutropenia and peripheral neuropathy limit its use in clinical settings. We, thus, conducted a single-arm phase II trial to investigate the efficacy and safety of a reduced dose (220 mg/m2) of tri-weekly nab-PTX. METHODS: Eligible patients included those with AGC and ECOG performance status of 0-2 who had received one or more prior chemotherapy containing fluoropyrimidine regimens. A reduced dose of nab-PTX (220 mg/m2) was administered tri-weekly. The primary endpoint was response rate (RR). Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity (RDI) and proportion of patients receiving subsequent chemotherapy. RESULTS: Among 33 patients enrolled, 32 were treated with protocol therapy. RR was 3.1% [95% confidence interval (CI), 0-16.2%], which did not reach the protocol-specified threshold (p = 0.966). DCR was 37.5% (95% CI, 21.1-56.3%). Median OS and PFS were 6.3 (95% CI, 4.4-14.2) and 2.2 (95% CI, 1.8-3.1) months, respectively. RDI was 97.8%. Twenty (62.5%) patients received subsequent chemotherapy. Toxicity was relatively mild with the most common grade ≥ 3 adverse events being neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). CONCLUSION: Tri-weekly nab-PTX with a reduced dose (220 mg/m2) is not recommended for AGC in a second-line or later setting, despite demonstrating less toxicity than at 260 mg/m2. Clinical trial registration The OGSG1302 trial was registered with UMIN-CTR as UMIN000000714.

[Gastric Gastrointestinal Stromal Tumor Appearing Nine Years after Resection of a Duodenal Gastrointestinal Stromal Tumor-A Case Report].

Multiple sporadic gastrointestinal stromal tumor(GIST)are rare, except for those restricted to von Recklinghausen disease or hereditary conditions.We reported a case of a gastric GIST resected 9 years after the resection of a duodenal GIST.The patient was a 58-year-old male who had been followed-up with computed tomography scans after pancreatoduodenectomy for a duodenal GIST when he was 49-years-old.The patient was admitted to our hospital for anemia examination.A CT scan detected a tumor in the stomach, with a diameter of over 10 cm, and necrosis.Esophagogastroduodenoscopy revealed the presence of a delle on the gastric SMT.Due to suspected invasion of the spleen and left diaphragm by the tumor, we performed subtotal gastrectomy with splenectomy and left diaphragm segmental resection.In the pathological diagnosis, the tumor was diagnosed as a gastric GIST, because the cell type of the tumor was spindle and tested positive for c-kit.Based on the tumor size and mitotic count, the patient was diagnosed with high-risk GIST by the modified-Fletcher classification, and imatinib 400mg/day was administered.There have been no signs of recurrence for 2 years since the operation.

[A Case of Resection of a Metastatic Tumor Combined with the Spleen, Preserving the Remnant Stomach, for Recurrent Gastric Cancer of the Splenic Hilar Region after Distal Gastrectomy].

We describe a case of residual stomach preserving surgery performed under evaluation of residual gastric blood flow with indocyanine green(ICG)fluorography, for gastric cancer with recurrence of splenic lymph node metastasis after distal gastrectomy( DG)in a 65-year-old man. After 4 courses of S-1 plus CDDP(SP)therapy for advanced gastric cancer with ascites, DG, D2 dissection, and Billroth Ⅰ reconstruction were performed and radical resection was obtained(L, Type 3, pap/tub, ypT3N1H0P0CY0M0, ypStage ⅡB). Three years and 6 months after the surgery, a mass 4 cm in diameter was found in the splenic hilum, and a pancreatosplenial resection was performed to remove the tumor for diagnosis and treatment purposes. We confirmed that there was no problem with blood flow, and we were able to preserve the stomach. Intraoperative ICG fluorescence imaging was considered a promising method for evaluating residual gastric blood flow.

[A Resected Case of Hemorrhagic Hepatic Cyst Difficult to Differentiate from Mucinous Cystic Neoplasm of the Liver].

CASE: A 77-year-old woman was referred to our hospital for detailed examination of a cystic liver tumor. Contrast-enhanced CT and MRIshowed a cystic liver tumor with an enhanced mural nodule in S6 of the liver. Under a preoperative diagnosis of hemorrhagic hepatic cyst and mucinous cystic neoplasm(MCN)of the liver, extended posterior segmentectomy was performed. Histological examination of the tumor revealed no neoplastic cells, and the tumor was finally diagnosed as a hemorrhagic hepatic cyst of the liver. CONCLUSION: Similar to previous reports of hemorrhagic hepatic cysts, preoperative differential diagnosis from MCN of the liver was difficult in this case. Hemorrhagic hepatic cysts are rare and are sometimes confused with MCN of the liver, especially when an enhanced mural nodule is found in the cyst. The possibility of hemorrhagic hepatic cysts should be considered during diagnosis of liver cystic tumors.

[Long-Term Survival in a Case of Colon Cancer with Peritoneal Dissemination and Ovarian Metastasis after Multimodality Therapy].

A 70-year-old woman underwent treatment for cecal cancer(pT4bN1M0, Stage Ⅲb)in 2010. Four years and 2 months after the first surgery, she underwent ileum resection for stenosis due to perineal dissemination(P3). Two years after this recurrence, during which time she had completed 26 courses of FOLFIRI plus bevacizumab(Bmab), 9 courses of capecitabine plus oxaliplatin(CapeOX)plus Bmab, and 3 courses of Cape, no peritoneal dissemination was detected by computed tomography( CT). Thereafter, an additional 19 courses of Cape plus Bmab were introduced, but CEA continued to increase. Right ovarian metastasis was suspected based on CT and FDG-PET/CT examination. Four years and 1 month after the initial recurrence of perineal dissemination, the patient underwent bilateral ovarian resection, during which the lack of peritoneal dissemination was confirmed. Pathologically, right ovarian metastasis was diagnosed. The patient is still alive 4 years and 6 months after the first operation.

[A Resected Case of Reactive Lymphoid Hyperplasia of the Liver Preoperatively Diagnosed as Hepatocellular Carcinoma].

A60s woman was followed-up regularly for primary biliary cholangitis and a solitary enlarging hepatic mass in the S6 segment of her liver was discovered by ultrasonography. We diagnosed the mass as hepatocellular carcinoma by contrast ultrasonography, contrast computed tomography, and ethoxbenzyl magnetic resonance imaging and laparoscopic partial hepatectomy of S6 segment was performed. The resected specimen was histopathologicaly diagnosed as liver-reactive lymphoid hyperplasia(RLH). The patient is alive without recurrence 17 months after the surgery. Although liver RLH is a rare disease, it should be considered in the differential diagnosis of small liver tumors.

[A Case with Three Resections of the Pulmonary Metastases of a Distal Bile Duct Carcinoma].

A 68-year-old man underwent a subtotal stomach-preserving pancreatoduodenectomy(SSPPD)for a distal bile duct carcinoma(BDC)pT3aN1M0, pStage ⅡB and adjuvant chemotherapy with gemcitabine. One year 7 months after the initial surgery, CT revealed a nodule with an increasing tendency in the left lung. As it was difficult to distinguish primary lung cancer from BDC lung metastasis, we performed a thoracoscopic left wedge resection. The histopathology of the resected specimen was BDC lung metastasis. In the follow-up with adjuvant chemotherapy with S-1 for 10 months, 2 nodules were found in the right lung, and we performed thoracoscopic right S6 segmentectomy. Eight months later, another nodule was found in the left lung, and we performed thoracoscopic left wedge resection. The histopathology was BDC lung metastasis for all the resected specimens. The patient is alive with no evidence of recurrence after 9 months of the latest surgery(4 years 11 months after the initial surgery). Although the standard treatment for metastatic recurrence of BDC is systemic chemotherapy, some cases treated with surgical resection had relatively good prognosis, such as the present case. Surgical resection might be feasible as a treatment option for metastatic recurrence of BDC.

[Surgical Outcomes of Laparoscopic Repeat Hepatectomy at Our Institution].

Laparoscopic hepatectomy has gained popularity owing to its merits, such as low invasiveness and reduced bleeding. However, the efficacy of laparoscopic repeat hepatectomy(LRH)has not been confirmed. The aim of this study was to evaluate the feasibility and efficacy of LRH compared to that of open repeat hepatectomy(ORH). We performed 60 repeat hepatectomies from January 2011 to March 2019, of which 19 were LRH(Lap group)and 41 were ORH(Open group). This study retrospectively compared the patient characteristics and short-term outcomes of repeat hepatectomy between the Lap and Open groups. There were no significant differences in patient characteristics, except for the type of approach in the previous hepatectomy(p<0.01). The Lap group had lesser blood loss(median: 150 mL vs 355 mL, p<0.01)and shorter postoperative hospital stays(median: 8 days vs 11 days, p<0.01). There were no differences in operation time or severe postoperative complications. LRH is feasible and useful, providing good short-term outcomes.

[Pulmonary Metastases of Hepatocellular Carcinoma Treated with Repeated Pulmonary Resection-A Case Report].

A 65-year-old man visited our hospital for hepatocellular carcinoma(HCC)and underwent extended posterior sectionectomy. Eight months after the hepatic resection, follow-up computed tomography(CT)revealed a solitary, recurrent tumor in S4 of the liver, and transcatheter arterial chemoembolization and radiofrequency ablation were performed for the intrahepatic recurrence. After 12 postoperative months, follow-up CT demonstrated pulmonary metastases in S5 of the right lung and S10 of the left lung. Since there were no other metastases, the 2 metastatic lesions were resected using video-assisted thoracoscopic surgery(VATS). The resected tumors were histologically diagnosed as pulmonary metastases of HCC. Three years after the pulmonary resection, 3 additional pulmonary metastases were detected on CT in S3 and S10 of the right lung and S4 of the left lung. No other metastases were found. Bilateral VATSmetastasectomy was performed for the metastases. The tumors were diagnosed as pulmonary metastases of HCC on histological examination. One year and 8 months after the surgery, he was alive in a good condition, with no recurrences. The present case suggested that some patients with pulmonary metastasis of HCC can have long-term survival with surgical resection of the metastasis. Therefore, while systemic chemotherapy is generally considered the standard treatment for extrahepatic metastasis of HCC, surgical resection might be an option.

[Long-Term Survival after Surgical Treatment of Neuroendocrine Carcinoma of the Ampulla of Vater-A Case Report].

A 60s man underwent upper gastrointestinal endoscopy at a regular medical check-up without symptoms, which showed an ulcerative region in the duodenal ampulla, measuring 3 cm in diameter. He was diagnosed with poorly differentiated adenocarcinoma on biopsy and referred to our hospital. Abdominal contrast-enhanced CT scan revealed an enhanced-ulcerative tumor, measuring 3 cm, at the duodenal ampulla. After the preoperative diagnosis of adenocarcinoma of the duodenal ampulla, subtotal stomach-preserving pancreatoduodenectomy with regional lymph node dissection was performed. The final diagnosis was neuroendocrine carcinoma(NEC)of the duodenal ampulla. He has been alive for 9 years with no recurrences. NEC of the duodenal ampulla is rare, and its prognosis is poor. We report a case of long-term survival after resection of NEC of the duodenal ampulla.

[Intraoperative Assessment of Blood Flow in the Remnant Stomach Using Indocyanine Green and Regional Oxygen Saturation Monitoring at Distal Pancreatectomy Following Gastrectomy].

A92 -year-old man was diagnosed with pancreatic cancer 14 years after undergoing distal gastrectomy for gastric cancer. His remnant stomach was fed by the cardiac branch of the left inferior phrenic artery, short gastric artery, and posterior gastric artery. We planned distal pancreatectomy(DP). Intraoperative indocyanine green(ICG)fluorography showed that the remnant stomach was perfused under the clamp of the splenic artery. We also confirmed that regional oxygen saturation (rSO2)of the remnant stomach was not decreased by the clamp. Based on the findings, we judged that blood flow in the remnant stomach was preserved at the clamp. We then performed DP with preservation of the remnant stomach. Postoperative complications associated with the remnant stomach were not observed. The patient is alive without any postoperative recurrences of pancreatic cancer or trouble associated with the remnant stomach 22 months after the surgery. This case suggested that ICG fluorography and rSO2 monitoring are useful to evaluate blood flow in the remnant stomach.

[A Case of Resected Primary Hepatic Neuroendocrine Tumor].

A 70s man presented with a solitary liver tumor measuring 4.5 cm on CT. On contrast-enhanced CT, the tumor appeared partly well-enhanced in the late phase, and the remaining part was enhanced in the early phase and washed out in the late phase. Contrast-enhanced MRIshowed fused multiple nodules, and the enhancement/washout pattern was clearer than that of the contrast-enhanced CT. The tumor showed a defective image in the hepatobiliary phase and a high signal on diffusionweighted imaging. Then, the tumor was diagnosed as hepatocellular carcinoma, and thus, left liver lobectomy was performed. On histological examination of the resected specimen, the tumor was found to be composed of uniform and small tumor cells with solid or trabecular growth fashion. On immunohistochemical staining, synaptophysin and chromogranin A positivity was noted, and the Ki-67 index was 14%. Finally, the tumor was diagnosed as a NET G2. Postoperatively, somatostatin receptor scintigraphy was performed to identify the primary site; however, no obvious primary site could not be identified, and thus a diagnosis of primary hepatic NET was made. Eighteen months postoperatively, the patient is alive without relapse. Preoperative diagnosis of primary hepatic NETs is difficult because NETs present various imaging findings and are rare. Moreover, no accurate preoperative diagnosis was reached in our case, suggesting the difficulty in the preoperative diagnosis of NETs.