A case of superficial spreading type of poorly differentiated adenocarcinoma of the stomach with invasion to the esophagus.

BACKGROUND: Invasion is more likely to occur in gastric cancer affecting larger areas. Poorly differentiated adenocarcinoma tends to invade deep. The cardiac region prefers submucosal invasion because the submucosa is coarser than the other regions. CASE PRESENTATION: A 75-year-old man presented with a chief complaint of abdominal discomfort and weight loss. Esophagogastroduodenoscopy revealed an irregular ulcerative lesion with partial redness of the upper body and lesser curve of the stomach. A continuous shallow depressed lesion invaded the abdominal esophagus by approximately 40 mm. Poorly differentiated adenocarcinomas (por, sig) were observed on biopsy. Grossly, the cancer appeared to extend into the muscle layer; however, we could not confirm invasion into the muscle layer in our biopsy tissue. We diagnosed the lesion as a superficial spreading type of advanced gastric cancer and performed a total gastrectomy, D2-lymph node dissection (spleen preservation), Roux-en-Y reconstruction, and cholecystectomy. Postoperative histopathological examination revealed extensive infiltration of poorly differentiated adenocarcinoma (90 mm × 55 mm), and all were intramucosal lesions. The final pathological diagnosis was T1a, N0, M0, and Stage IA. The postoperative course was uneventful and the patient was discharged on postoperative day (POD) 11. Five years have passed since the operation, and the patient is alive without recurrence. CONCLUSION: We encountered a case of gastric carcinoma in which poorly differentiated adenocarcinomas expanded extensively. All lesions were intramucosal.

Thoracoscopic subtotal esophagectomy via a right thoracic cavity approach to treat an intractable fistula after 20 months from onset of an idiopathic esophageal rupture: A case report.

An intractable fistula caused by idiopathic esophageal rupture is a rare but severe condition. In the present case, a 69-year-old man had been treated conservatively at another hospital for esophageal rupture but had developed an abscess in the left thoracic cavity due to an intractable fistula at the rupture site. He was referred to our hospital for treatment 19 months after the esophageal rupture. On admission, the intractable fistula was found to be continuous with an abscess in the left thoracic cavity. Preoperative continuous enteral nutrition was administered to improve the patient's nutritional status, and drainage was performed to reduce the size of the abscess. Then, to minimize the invasion of the intractable fistula, thoracoscopic subtotal esophagectomy was performed via a right thoracic cavity approach 20 months after the esophageal rupture. Preoperative management and thoracoscopic surgery via an opposite chest cavity approach was found to be safe and feasible for the intractable fistula caused by idiopathic esophageal rupture.

[A Case of Malignant Lymphoma of the Breast after Treatment of the Contralateral Breast Cancer].

A 57-year-old female was referred to our hospital due to a palpable tumor of the left breast; she was diagnosed with cancer in the left breast 3 years prior, in 201X. After the administration of FEC and docetaxel plus trastuzumab as preoperative chemotherapy, left mastectomy with axillary lymph node dissection was performed, and irradiation and trastuzumab were administered postoperatively for 1 year. During the observation, there was skin thickening around the right nipple. A skin biopsy was then performed in 201X, and the patient was diagnosed with diffuse large B-cell lymphoma(DLBCL). PET-CT revealed a slight accumulation in the peripheries of the right nipple and mammary glands. Core needle biopsy of the tumor in the mammary gland showed DLBCL similar to that observed in the skin biopsy. Imaging revealed complete response after chemotherapy, whole-body irradiation, and intrathecal administration. Currently, both breast cancer and DLBCL of the breast have not relapsed.

Endoscopic duodenal stent versus surgical gastrojejunostomy for gastric outlet obstruction in patients with advanced pancreatic cancer.

BACKGROUND: Malignant gastric outlet obstruction (GOO) often develops in patients with advanced pancreatic cancer (APC). It is not clear whether endoscopic duodenal stenting (DS) or surgical gastrojejunostomy (GJJ) is preferable as palliative treatment. AIMS: To compare the efficacy and safety of GJJ and DS for GOO with APC. METHODS: Consecutive 99 patients who underwent DS or GJJ for GOO with APC were evaluated. We compared the technical and clinical success rates, the incidence of adverse event (AE), the time to start chemotherapy and discharge and survival durations between DS and GJJ. Prognostic factors for overall survival (OS) were investigated on the multivariate analysis. RESULTS: GOO was managed with GJJ in 35 and DS in 64. The technical and clinical success rates were comparable. DS was associated with shorter time to start oral intake and earlier chemotherapy start and discharge. No difference was seen in the early and late AE rates. Multivariate analyses of prognostic factors for OS showed that performance status ≧2, administration of chemotherapy, and presence of obstructive jaundice to be significant factors. There were no significant differences in survival durations between the groups, regardless of the PS. CONCLUSIONS: There were no significant differences in the technical and clinical success and AE rates and survival duration between DS and GJJ in management of GOO by APC. DS may be a preferable option over GJJ given that it will lead to an earlier return to oral intake, a shortened length of hospital stay, and finally an earlier referral for chemotherapy.

Intrahepatic Biliary Metastasis of Colonic Adenocarcinoma: A Case Report With Immunohistochemical Analysis.

Although intrabiliary metastasis of carcinoma in the liver is unusual, intraductal and/or intraepithelial spread of cancer cells along intrahepatic bile ducts is now well recognized as hepatic metastasis. However, several clinical and laboratory findings, including images, lead us to differentially diagnose from primary intrahepatic cholangiocarcinoma. We report here on a case of colonic adenocarcinoma that metastasized to the liver with spread along with the intrahepatic bile duct of S5/6 area. The patient was a 51-year-old man and clinically diagnosed liver metastasis of sigmoid colon cancer (tub2, pMP, ly1, v0, n0), which was diagnosed and treated by sigmoidectomy 7 years ago. The right hepatic lobectomy was performed in March 2016 and histopathological examination revealed that moderately differentiated adenocarcinoma proliferated along the epithelium of intrahepatic bile ducts. Immunohistochemistry (IHC) showed that cancer cells in the intrahepatic bile ducts were positive for CK20, CDX2, CK17 and CK19, but negative for CK7, MUC-5AC, MUC-2 and CA19-9. The findings were almost the same as those of the sigmoid colon cancer removed in July 2009. We finally diagnosed the liver tumor as intrahepatic biliary metastasis of sigmoid colon cancer. Patients with liver metastasis of cancer are hard to be detected biliary invasion and spread on diagnostic image examination. Knowledge of distinctive morphological and IHC features can help to accurately diagnose this rare intrahepatic biliary metastasis of colonic cancer in routine pathological diagnostic procedures.

[Strategy of treatment for gastric cancer with peritoneal metastasis].

In advanced gastric cancer with peritoneal metastasis, adjuvant chemotherapy after primary tumor resection showed considerably poor prognosis with a median survival time of only 232 days. So, we changed the strategy that we start systemic chemotherapy at the earliest opportunity without resecting the primary tumor for gastric cancer patients who were diagnosed peritoneal metastasis by laparotomy or staging laparoscopy. Eleven cases of gastric cancer with peritoneal metastasis were administered systemic chemotherapy first including S-1+paclitaxel (PTX). The regimen of chemotherapy of two weeks administration of S-1 (80 mg/m2/day)followed by one week rest and injections of PTX (50mg/m2) at day 1 and 8 for 21 days as one course. Five of eleven cases were performed S-1+PTX as the first-line, the other six cases as the second-line. In some cases, this therapy led to transient responses. Ultimately, most of them showed progressive disease. However, two of eleven cases showed a complete response in the peritoneal metastasis and could receive radical operation for gastric cancer. Both patients were still alive without any relapse at the time of this report. The median survival time of eleven cases of gastric cancer with peritoneal metastasis performed the systemic chemotherapy first with this regimen was 464 days. The survival was considerably prolonged (p=0. 0500), compared to 232 days in postoperative cases.

[Therapeutic outcome and prognosis in S-1+CDDP chemotherapy for advanced gastric cancer--postoperative histopathological assessment].

UNLABELLED: The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (< or =75 y.o.) having type 4/large type 3 (diameter> or = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414). CONCLUSION: These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).

[Neoadjuvant chemotherapy using TS-1 and CDDP against large type 3/Type 4/Bulky N 2 advanced gastric cancer].

This study was conducted to assess therapeutic results following neoadjuvant chemotherapy (NAC) for large type 3/type 4/Bulky N 2 advanced gastric cancer having a poor prognosis following resection. The subjects consisted of cases (< or = 75 y.o.) having large type 3 (diameter > or = 8 cm), type 4 or Bulky N 2 gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of TS-1 at 80-120 mg/body on days 1-21 p. o. and CDDP at 60 mg/m2 on day 8 divided. Upon completion of two courses of 4 weeks per course, gastrectomy with > or = D2 lymph node dissection was carried out on days 21-34. The average age of the subjects was 60.7 years, and the therapy completion rate was 80% (8/10 cases). Five of ten cases were responders diagnosed as grade 2 by histopathological examination of excised specimens (response rate 50%). Two of five responders were histopathologically evaluated as down-staging as a result of NAC (Stage III A--> f Stage I A, Stage IV--> f Stage I A). Three of the five non-responders have relapsed, and the relapse-free interval was an average 238 days. In the five responders,one has relapsed at 331 days,while the other 4 responders have shown no relapse yet. Although NAC consisting of TS-1 and CDDP is considered to be effective against advanced gastric cancer, a phase III study with surgical treatment only will be necessary to confirm its true value.

Transient and sustained ERK phosphorylation and nuclear translocation in growth control.

Growth stimulation and inhibition are both associated with tyrosine phosphorylation. We examined the effects of epidermal growth factor (EGF), a growth stimulant, and compound 5 (Cpd 5), a protein-tyrosine phosphatase (PTPase) inhibitor, which inhibits the growth of the same Hep3B hepatoma cells. We found that both EGF and Cpd 5 induced tyrosine phosphorylation of EGF receptor (EGFR) and ERK. However, the phosphorylation caused by EGF was transient and that caused by Cpd 5 was prolonged. Furthermore, Cpd 5 action caused a strong nuclear phospho-ERK signal and induced phospho-Elk-1, a nuclear target of ERK activation, in contrast to the weak effects of EGF. An ERK kinase assay demonstrated that ERK activated by Cpd 5 could phosphorylate its physiological substrate, Elk-1. The MEK inhibitors PD098056 and U0126 abrogated both the induction by Cpd 5 of phospho-ERK, its nuclear translocation and phospho-Elk-1 and also antagonized its growth inhibitory effects. Furthermore, phospho-ERK phosphatase and phospho-Elk-1 activities were lost from nuclear extracts from Cpd 5 treated, but not EGF treated cells. In conclusion, the data show that Cpd 5 causes growth inhibition as a consequence of prolonged ERK and Elk-1 phosphorylation, likely a result of inhibition of multiple PTPases, including those acting on phospho-EGFR, on phospho-ERK, and on phospho-Elk-1, in contrast to the kinase driven transient activation resulting from EGF.

EGFR-independent activation of ERK1/2 mediates growth inhibition by a PTPase antagonizing K-vitamin analog.

The K-vitamin analog Cpd 5 or [2-(2-mercaptoethanol)-3-methyl-1,4-napthoquinone] is a potent cell growth inhibitor in vitro and in vivo, likely due to arylation of enzymes containing a catalytic cysteine. This results in inhibition of protein tyrosine phosphatase (PTPase) activity with resultant hyperphosphorylation of EGF receptors (EGFR) and ERK1/2 protein kinases, which are downstream to EGFR in the MAPK pathway. We used NR6 fibroblast cells, which lack endogenous EGFR and its variant cells transfected with different EGFR mutants to assess the contribution of the EGFR-mediated signaling pathway to Cpd 5-mediated ERK activation and cell growth inhibition. Cpd 5 treatment resulted in enhanced phosphorylation of EGFR at carboxyl-terminal tyrosines. This phosphorylation and activation of EGFR were found to be necessary neither for growth inhibition nor for the activation of the downstream kinases ERK1/2, since both occurred in EGFR-devoid mutant cells. U0126 and PD 098059, specific inhibitors of MEK1/2, the ERK1/2 kinases, antagonized both cell growth inhibition and ERK1/2 phosphorylation mediated by Cpd5. Cpd 5 was also found to inhibit ERK1/2 phosphatase(s) activity in lysates from all the cells tested, irrespective of their EGFR status. These results show that EGFR-independent ERK1/2 phosphorylation was involved in the mechanism of Cpd5 mediated growth inhibition. This is likely due to the observed antagonism of ERK phosphatase activity. A candidate PTPase was found to be Cdc25A, a recently identified ERK phosphatase.