Risk stratification of oesophageal squamous cell carcinoma using change in total lesion glycolysis and number of PET-positive lymph nodes.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NACT) correlates with patient survival in oesophageal squamous cell carcinoma (OSCC), but optimal evaluation of the treatment response based on PET-CT parameters has not been established. METHODS: We analysed 226 OSCC patients who underwent PET-CT before and after NACT followed by surgery. We assessed SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for the primary tumour and the number of PET-positive lymph nodes before and after NACT to predict patient survival. RESULTS: In a stepwise analysis, we defined 60%, 80%, and 80% as the optimal cut-off values for SUVmax, MTV, and TLG reduction, respectively, to distinguish responders and non-responders to NACT. In the ROC analysis, the TLG reduction rate was the best predictor of recurrence among PET-CT parameters. The TLG responders achieved significantly more favourable prognoses than non-responders (2-year progression-free survival [PFS] rate: 64.1% vs. 38.5%; P = 0.0001). TLG reduction rate (HR 2.58; 95% CI 1.16-5.73) and the number of PET-positive lymph nodes after NACT (HR 1.79; 95% CI 1.04-3.08) were significant independent prognostic factors. CONCLUSIONS: TLG reduction is the best predictor of prognosis. Preoperative PET-CT evaluation of both the primary tumour and lymph nodes could accurately stratify risk in OSCC patients.

The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell death protein 1 (PD-1) antibody (nivolumab) in patients with gastric cancer. METHODS: We collected peripheral blood samples from gastric cancer patients (n = 29) before and after treatment with nivolumab and investigated the relationship between the frequency of surface or intracellular markers among nivolumab-binding PD-1+CD8+ T cells and treatment responses using multicolor flow cytometry. The tumors, lymph nodes, and peripheral blood of gastric cancer patients who underwent gastrectomy following nivolumab treatment were collected, and nivolumab-binding PD-1+CD8+ T cells in these tissue samples were characterized. RESULTS: Patients with a high frequency of CD103 among PD-1+CD8+ T cells in peripheral blood 2 weeks after the start of treatment had significantly better progression-free survival than the low group (P = 0.032). This CD103+PD-1+CD8+ T cell population mainly consisted of central memory T cells, showing the high expression of Ki-67 and few cytotoxic granules. In contrast, effector memory T cells were more frequently observed among CD103+PD-1+CD8+ T cells in tumors, which implied a change in the differentiated status of central memory T cells in lymph nodes and peripheral blood to effector memory T cells in tumors during the treatment with ICIs. CONCLUSIONS: A high frequency of CD103 among PD-1+CD8+ T cells 2 weeks after nivolumab treatment in patients with advanced gastric cancer may be a useful biomarker for predicting the efficacy of anti-PD-1 therapy.

Perioperative Ghrelin Administration Attenuates Postoperative Skeletal Muscle Loss in Patients Undergoing Esophagectomy for Esophageal Cancer: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Ghrelin has been reported to reduce postoperative weight loss by improving appetite and food intake in patients undergoing upper gastrointestinal surgery. OBJECTIVE: We aimed to investigate whether growth hormone induction, another essential effect of ghrelin, may attenuate skeletal muscle loss in patients during postoperative starvation. METHODS: Esophageal cancer patients were randomized to receive a continuous intravenous infusion of high-dose ghrelin (HD; 0.5 µg/kg/h), low-dose ghrelin (LD; 0.25 µg/kg/h), or placebo for 7 days after surgery. During this period, oral feeding was not introduced but the patients received the same parenteral and enteral nutrition. We investigated the effects of ghrelin on body weight, skeletal muscle mass, nutritional status, and hormone levels. RESULTS: Overall, 73 patients were enrolled in this study. The rate of weight loss on postoperative day (POD) 7 relative to that before surgery was significantly lower in the HD group than in the placebo group (HD vs. placebo: -0.61% vs. 1.8%, p = 0.030). The rate of muscle loss in the erector spinae muscle on POD 7 in the HD and LD groups was significantly lower than that in the placebo group (HD vs. placebo: 2.8% vs. 8.5%, p < 0.001; LD vs. placebo: 4.9% vs. 8.5%, p = 0.028). The levels of growth hormone on PODs 1, 3, and 7, and insulin-like growth factor 1 on PODs 3, 7, and 14 were significantly higher in patients who received ghrelin. CONCLUSION: Continuous ghrelin administration could attenuate skeletal muscle loss in esophageal cancer patients during postoperative starvation.

[A Case of Robot-Assisted Abdominoperineal Resection for Local Control for Lower Rectal Cancer with Synchronous Liver and Lung Metastases].

The patient was a 70s woman who was referred to our hospital with a complaint of bloody stool. Colonoscopy revealed type 2 tumor at a distance of 1 cm from the dentate line, without obstruction. The pathological diagnosis was adenocarcinoma. Enhanced CT revealed a tumor at the rectum below peritoneal reflection as well as swelling of the mesorectal lymph nodes. Multiple liver and lung metastases were also observed. The diagnosis was lower rectal cancer cT4aN2M1b(H2, PUL2), cStage Ⅳ. Chemotherapy was performed for disease control because of unresectable metastases. She received 7 courses of mFOLFOX plus bevacizumab. Further, as the metastatic lesion was inhibited, the primary lesion was excised for the purpose of symptom control. We judged that sphincter preservation was impossible because it was 1 cm away from the dentate line. She underwent robot-assisted abdominoperineal resection with D3 lymphadenectomy and sigmoid colostomy.

[A Resected Case of Hepatocellular Carcinoma Recurrence with Bile Duct Tumor Thrombus after RFA].

Hepatocellular carcinoma with bile duct invasion is rare, with a reported incidence of 3.4%. A 71-year-old man with hepatocellular carcinoma underwent radiofrequency ablation(RFA)(S6, S7, S8)and required readmission 22 months after the RFA for hepatocellular carcinoma recurrence detected by gadoxetic acid-enhanced magnetic resonance imaging. Enhanced abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a tumor thrombus in a biliary branch and left adrenal gland metastases. We performed a right lobectomy and left adrenalectomy. The biliary thrombus was easily removed. Postoperative histopathological examination of the resected specimen showed a moderately differentiated hepatocellular carcinoma invading the biliary tract and the absence of viable cells in the liver tumor. The patient has shown no recurrence 6 months after the hepatectomy.

[Long-Term Survival in a Patient with Stage â £ Gastric Cancer Successfully Treated with Multidisplinary Treatment].

A man in his 60s who had epigastric pain was referred to our hospital and diagnosed with advanced type 3 gastric cancer with multiple liver metastases, cT4acN2cN1(H1), cStage Ⅳ(HER2 3+). He underwent chemotherapy using capecitabine, cisplatin(CDDP), and trastuzumab(T-mab)(XPT). After 7 courses of XPT and 23 courses of XT, liver metastases disappeared, and we decided to perform open distal gastrectomy, D2+ #18 lymphadenectomy, and Billroth Ⅰ reconstruction as a conversion surgery. Despite adjuvant chemotherapy with S-1 plus T-mab, multiple lymph nodes recurrence occurred 3 months after the surgery. He was found to be in complete remission as assessed by CT after 5 courses of second-line CPT-11 treatment, which was discontinued after 17 courses. The patient is alive without recurrence at 57 months after the initial treatment and 22 months after the last treatment.

[Sustained Complete Response of Hepatocellular Carcinoma with Multiple Intrahepatic Metastases following the Discontinuation of Sorafenib].

Sorafenib is an oral multi-targeted tyrosine kinase inhibitor used in cases of unresectable advanced HCC that significantly improves progression-free and overall survival. Complete response(CR)is uncommon; however, if major or complete radiological response are obtained, the issue of the discontinuation of sorafenib remains unresolved. The present study reported a case of a 75-year-old man with non-hepatitis B and C virus-related cirrhosis and multiple recurrent HCCs followingresection. In December 2010, a CT scan revealed multiple intrahepatic recurrence after TACE. Laboratory testingshowed Child-Pugh class A cirrhosis and an alpha-fetoprotein level of over 20,000 ng/mL. Sorafenib(800mg/day)was started in December 2010. The subsequent dynamic CT performed at the 6th month of therapy showed a partial response accordingto RECIST criteria and a complete response accordingto mRECIST. The AFP had decreased to within normal levels. In May 2012, the sorafenib dose was reduced(200 mgtwice daily)due to side effects(skin reaction). In December 2013, treatment was stopped after confirmation of a CR associated with shrinkage of the HCC. The patient maintained this remission until June 2018, more than 54 months after the discontinuation of sorafenib therapy. The adverse events of sorafenib were reversible. Further reportingof similar cases should help in the design of treatment strategies after CR to sorafenib therapy.

[A Resected Case of Tumorigenic Pancreatic Endocrine Cell Hyperplasia].

A 51-year-old man with a gallstone was found to have a tumor in the tail of the pancreas during preoperative examination. We performed EUS-FNA and a pancreatic neuroendocrine tumor was suspected.Therefore, laparoscopic distal pancreatectomy and cholecystectomy were performed.Pathological examination and immunohistochemistry showed that the pancreatic endocrine cells were uniformly increased and were composed of normal Langerhans islets.Therefore, the patient was diagnosed with pancreatic endocrine cell hyperplasia.Typical pancreatic endocrine cell hyperplasia does not form a tumor and is asymptomatic.However, some cases are symptomatic; therefore, when hypoglycemia or pancreatic hormone elevation are found without a clear cause, it should be distinguished.Because pancreatic tumors are difficult to diagnose definitely by imaging inspection alone, needle biopsy is necessary.However, neuroendocrine tumor and neuroendocrine cell hyperplasia are difficult to differentiate by biopsy.

[A Case of Strangulating Intestinal Obstruction Caused by Coiling of Low-Grade Appendiceal Mucinous Neoplasm to Terminal Ileum].

The patient was a 67-year-old female without a history of surgery. She presented with an abdominal pain and vomiting, and was rushed to our hospital. The abdominal pain was severe, but no peritoneal irritation sign was observed. Abdominal CT scan revealed a strangulating intestinal obstruction and accumulation of ascitic fluid. Emergency surgery was performed for diagnosis and treatment. The intraoperative finding showed serous ascitic fluid and strangulating intestinal obstruction caused by appendiceal tumor coiling around the terminal ileum, which had become ischemic with thinning of its wall. Ileocecal resection with removal of lymph nodes(D3)was performed. The postoperative course was uneventful, and the patient was discharged 13 days after the surgery. Pathological examination of the appendiceal tumor revealed a low-grade appendiceal mucinous neoplasm(LAMN)with no metastasis to the lymph nodes. We had a rare case of strangulating intestinal obstruction caused by coiling of LAMN to the terminal ileum.

[A Case of Leiomyosarcoma of the Sigmoidal Mesocolon].

Leiomyosarcoma of the mesocolon is a very rare disease. Previously, there was no recommendation for chemotherapy or radiotherapy for leiomyosarcoma of the mesocolon, and only surgical resection reportedly offers a chance for cure. However, the reported cases of leiomyosarcoma of the mesocolon were not distinguished from those of gastrointestinal stromal tumor (GIST), which is the same mesenchymal tumor; thus, there is a possibility that they include cases that should be diagnosed as GIST. We report a case of leiomyosarcoma of the sigmoidal mesocolon.

[A Case of Rectal Cancer with Multiple Endocrine Neoplasia Type 2].

A 63-year-old man with multiple endocrine neoplasia type 2(MEN2)was admitted to the hospital because of positive fecal occult blood tests. Colonoscopy revealed a 50mm type 2 tumor at the rectum, which was diagnosed as an adenocarcinoma based on histology. Since there was no apparent distant metastasis, laparoscopy-assisted low anterior resection with regional lymph node dissection was performed. The final diagnosis was pT3, pN0, pM0, pStage II . Almost all patients with MEN2 have RET mutations, and they are resistant to EGFR inhibitors. Those who have thyroid cancer with RET mutations are often given a RET kinase inhibitor. In this case, if the patient develops recurrent rectal cancer, it warrants checking for RET mutations and using a multi-kinase inhibitor.

[A Case of Laparoscopic Rectal Amputation Performed for Anal Gland Mucinous Carcinoma with Pagetoid Spread].

A 69-year-old man was admitted for the growing anal tumor and referred to our hospital. The tumor was about 40mm in size, and by biopsy, he was diagnosed the adenocarcinoma. Based on this diagnosis, abdominoperinealresection and edge resection were performed. Histopathologicalfindings showed mucinous carcinoma originating from analgl and with pagetoid spread. Postoperative chemotherapy was not performed, but 1 year 6 months after the surgery, inguinall ymph node recurrence was found, and lymph node dissection was performed. One year after the operation, recurrence was not found.

[A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

[A Case of Gastric Schwannoma with Regional Lymphadenopathy].

Schwannomas are rarely observed in the gastrointestinal tract. A 63-year-old man was referred to our hospital with gastric submucosal tumor with central ulceration by upper gastrointestinal endoscopy. Biopsy was performed, but pathological diagnosis was not obtained. A contrast-enhanced computed tomography scan of the abdomen revealed a round mass in the lower part of the stomach and regional lymphadenopathies. A distal gastrectomy with dissection of the regional lymph nodes (D2)was performed. The submucosal tumor measuring 67×49mm was resected. Histopathological examination revealed spindle-shaped cells arranged in palisades. The specimen was positive for S-100 protein, but negative for desmin, SMA, c-kit, and CD34. No tumor cells were found in the resected enlarged lymph nodes, indicating reactive lymphadenopathies. Based on these findings, the tumor was identified as a benign gastric schwannoma. Our patient shows no recurrence at 6 month follow-up.

[Treatment Outcomes of Gemcitabine and Cisplatin Combination Therapy for Unresectable and Recurrent Biliary Tract Cancer].

Gemcitabine and cisplatin combination therapy(GC therapy)is now considered a highly effective regimen for patients with unresectable and metastatic biliary tract cancer. We performed GC therapy for 18 patients between January 2014 and April 2018. The median age of the patients was 67.5 years, and 13 patients were men. Fifteen patients had a performance status (PS)score of 0, and 3 patients had a PS score of 1. Nine patients had distal cholangiocarcinoma, 3 had intrahepatic cholangiocarcinoma, 3 had duodenum papilla cancer, and 3 had gallbladder cancer. Fourteen patients showed recurrence after the radical resection, and 9 had liver metastasis. Sixteen patients had over Grade 3 hematological or non-hematological toxicities. The most-common adverse event was neutropenia. None of the patients had Grade 5 adverse events. The response rate was 11.1%, and the disease-control ratio was 66.7%. GC therapy was effective for patients with unresectable and recurrent biliary tract cancer. However, it is necessary to examine the eligibility of patients before treatment.

[Laparoscopic Pancreatectomy for Pancreatic Neuroendocrine Tumor - A Single Institution Experience].

BACKGROUND: Pancreatic neuroendocrine tumor(P-NET)is relatively rare and often has less aggressive biological behavior. P-NET was re-designated by the WHO in 2010 and 2017. Laparoscopic surgery is minimally invasive but has technical difficulties such as limitation of movement and laparoscopic view. The purpose of this study is to evaluate the efficacy of laparoscopic pancreatectomy(LPT)for P-NET. METHODS: Between January 2012 and June 2017, 6 patients underwent LPT for P-NET at Kansai Rosai Hospital. Five patients who received open pancreatectomy(OPT)for P-NET and 41 patients who received laparoscopic distal pancreatectomy(LDP)for cystic tumor(CyT)or invasive ductal carcinoma(IDC)were included for comparison. RESULTS: All patients who underwent LPT for P-NET were NET G1 in WHO Classification 2017 and Stage I in UICC TNM 2016. No significant differences were noted between LPT and OPT groups with respect to patient age or gender. Operation time was 421.5 versus 423.5 minutes(ns), blood loss was 121.7 versus 1,918.3mL(ns), hospital stay was 20.5 versus 58.0 days(ns)for LPT and OPT respectively. In LDP, there were no significant differences between PNEN, CyT, and IDC groups with respect to patient age, gender, operation time, blood loss and hospital stay. All patients who underwent LPT for P-NET alive without recurrence. The average observation period was 58.4 months. CONCLUSIONS: Laparoscopic pancreatectomy is safe and effective approach to the management of pancreatic neuroendocrine neoplasm.

[The Treatment Outcomes of FOLFIRINOX for Unresectable and Recurrent Pancreatic Cancer].

FOLFIRINOX is now considered to be a highly effective regimen for patients with metastatic pancreatic cancer. We administered FOLFIRINOX therapy in 18 patients between October 2014 and April 2017 as follows: 2-hour infusion of L-OHP at a dose of 85mg/m2, 2-hour infusion of LV at a dose of 200 mg/m2, infusion of CPT-11 for over 90 minutes at a dose of 150 mg/m2, followed by continuous infusion of 5-FU over 46 hours at a dose of 2,400mg/m2. The median age of the patients was 66.5 years. There were 15 patients with performance status(PS)0, and 3 with PS 1. Two patients were Stage III and 16 patients were Stage IV . More than half of the patients had over Grade 3 hematological or non-hematological toxicities. The most common adverse event was neutropenia. Two patients had Grade 5 adverse events: severe cholangitis occurred in the patient with a biliary stent and overwhelmingpost -splenectomy infection occurred in the patient who underwent distal pancreatectomy. The response rate was 11.1%, and the disease control rate was 77.8%. FOLFIRINOX was effective in the patients with unresectable and recurrent pancreatic cancer. However, it is necessary to examine the eligibility of the patients.

[A Case of Resection of Obstructive Colon Cancer Associated with Aspiration Pneumonia, Under Combined Epidural-Spinal Anesthesia].

An 89-year-old woman was admitted to our hospital with vomiting, abdominal distension, and anorexia.A CT scan revealed an enhanced thickening lesion on the wall of the ascending colon, and intestinal expansion from the small intestine to the caecum.On colon fibroscopy, a round tumor was observed adjacent to the oral side of the hepatic flexure even though the end of the microscope could not progress toward the deeper regions.As the obstructive colon cancer was complicated by the presence of aspiration pneumonia, surgery could not be performed under general anesthesia.We initiated curative therapy for aspiration pneumonia right at the onset.Subsequently, due to lack of improvement in the patient's general condition, we conducted a right hemicolectomy under combined epidural-spinal anesthesia.

[Multidisciplinary Treatment for High-Risk GIST of the Stomach].

A 59-year-old man underwent total gastrectomy(with D2 dissection)and cholecystectomy for gastric cancer and a submucosal tumor of the stomach. The specimen was immunohistochemically positive for c-kit, the Ki-67 label index was 10%, and the mitotic count was 20/HPF. Finally, the patient was diagnosed with high-risk gastrointestinal stromal cancer with normal type gastric cancer. After discharge from hospital, we started administration of TS-1 as adjuvant therapy for the gastric cancer. As multiple recurrences of the GIST in the abdomen developed, the patient underwent 3 radical local resections. Mutational analysis revealed a PDGFRA mutation in exon 18, which causes resistance to both imatinib and sunitinib. As he was refractory to imatinib, the patient received regorafenib. After a while, it caused liver failure, which required 7 rounds of plasmapheresis. The patient died from multiple organ failure resulting from multiple recurrences 4 years after the first surgery.