Theoretical therapeutic impact of lymph node dissection on adenocarcinoma and squamous cell carcinoma of the esophagogastric junction.

BACKGROUNDS: The aim of this study was to evaluate the theoretical therapeutic impact of dissecting each lymph node station for adenocarcinoma and squamous cell carcinoma of the esophagogastric junction. METHODS: This multicenter study included 431 junctional cancer patients (381 adenocarcinomas and 50 squamous cell carcinomas) who fulfilled the following criteria: (1) the center of the tumor was located between 1 cm above and 2 cm below the esophagogastric junction, and (2) the tumor invaded the junction. The theoretical therapeutic impact of dissecting each lymph node station was evaluated based on the therapeutic value index calculated by multiplying the frequency of metastasis to each station and the 5-year survival rate of patients with metastasis to that station. RESULTS: The 5-year overall survival rates (95% confidence interval) were 60.4% (55.1-65.7) in the adenocarcinoma cases and 52.3% (35.6-69.0) in the squamous cell carcinoma cases. The nodal stations showing the first to fifth highest index were the paracardial and lesser curvature nodes (nos. 1, 2 and 3), nodes at the root of the left gastric artery (no. 7) and lower mediastinal lymph nodes, regardless of the histology. CONCLUSIONS: Nodal dissection achieved by proximal gastrectomy and lower esophagectomy should be the minimal requirement for junctional cancer regardless of the histology, considering the therapeutic value indices for the relevant lymph node stations.

Primary diffuse large B cell lymphoma of the common bile duct causing obstructive jaundice.

We report a rare case of a diffuse large B-cell lymphoma (DLBCL) arising from the common bile duct (CBD). A 77-year old man presented with general fatigue and obstructive jaundice. Abdominal computed tomography revealed a well-circumscribed enhancing mass in the midportion of the CBD with proximal bile duct dilatation. Endoscopic retrograde cholangiopancreatography (ERCP) also showed a midportion of the CBD stricture. Direct peroral cholangioscopy revealed smooth mass in the midportion of the CBD, and narrow-band imaging (NBI) showed irregular tortuous microvessels. The brushing cytology of the CBD was performed, and it was diagnosed as suspicious for poorly differentiated adenocarcinoma or malignant lymphoma. We performed extrahepatic bile duct resection for accurate diagnosis. Histological and immunohistochemical examination of the resected specimen revealed DLBCL. Although systemic chemotherapy is the mainstay of treatment for DLBCL, he refused scheduled subsequent chemotherapy, and died of multiple liver metastases 6 months after surgery.

Management of granulomatous mastitis: a series of 13 patients who were evaluated for treatment without corticosteroids.

Granulomatous mastitis (GM) is a rare chronic inflammatory breast condition with unknown etiology. There is still no generally accepted optimal treatment for GM. Corticosteroid treatment and/or wide excision is most commonly reported in the literature. Incision and drainage or limited excision alone has little benefit because of a strong tendency of recurrence. Corticosteroids also have a high failure rate and possible side effects. In the current series, we treated GM patients without corticosteroids, except for one patient. We also devised multidirectional deep drainage for advanced and complicated abscesses, which are characteristic of GM. This retrospective study included 13 women who met the required histologic criteria of GM. The mean age of the patients was 41 years. All of the patients were premenopausal. Six patients had breast-fed in the last 5 years. Five patients were under medication with antidepressants. A total of 11 patients developed abscesses during the clinical course, and the abscesses penetrated the retromammary space in 4 patients. We treated 2 of these 4 patients with multidirectional deep drainage and obtained complete remission in 5 and 6.5 months, respectively. These times were much shorter than those in the other 2 patients. The time to resolution in 11 patients was 4 to 28 months. This overall outcome was comparable with that of corticosteroid treatment reported in the literature. Because the natural history of GM is thought to be self-limiting, close observation and minimally required drainage of abscesses without corticosteroid administration remain the treatment modality of choice.

Comparison of gastric cancer surgery between patients aged >80 years and <79 years: complications and multivariate analysis of prognostic factors.

BACKGROUND/AIMS: To evaluate the clinicopathological features and results of surgery for gastric cancer in elderly patients aged ˃80 years relative to those aged ˂79 years, and to recommend the appropriate surgical treatment for elderly patients. METHODOLOGY: A total of 332 patients with gastric cancer who underwent gastrectomy in our department between 2002 and 2012 were evaluated. Of these, 81 were aged ˃80 years (Group A) and 251 were aged ˂79 years (Group B). We compared surgical outcomes and survival in these two groups. RESULTS; Postopeartive complications were associated with preoperative cormorbid disease(p<0.01). D2 and R0 resection was common in GroupB (p<0.01). Respiratory complications and hospital deaths were higher in Group A than in Group B. Overall survival (OS) was significantly lower in Group A than in Group B. Regarding Stage I disease, OS was significantly lower in Group A; however, cause-specific survival was similar between the two groups. Multivariate analysis showed that radicality and postoperative complications were independent prognostic factors for OS in elderly gastric cancer patients. CONCLUSIONS: These results indicate that postoperative respiratory complications and other causes of death worsened the prognosis of elderly. Preoperative accurate judgment of co-morbid disease, meticulous postoperative management and follow up might be improved survival of gastric cancer in elderly.

Mesenchymal phenotype after chemotherapy is associated with chemoresistance and poor clinical outcome in esophageal cancer.

The relationship between the epithelial-mesenchymal transition (EMT) and resistance to anticancer treatment has attracted attention in recent years. However, to date, there is no direct clinical evidence for a link between the mesenchymal phenotype and chemoresistance in human malignancies. The expression of EMT-related markers, including E-cadherin, Snail, vimentin, ZEB1, ß-catenin and N-cadherin was examined immunohistochemically in 185 tissue samples from patients with esophageal cancer (including 93 patients who received preoperative chemotherapy followed by surgery and 92 patients who underwent surgery without preoperative therapy). The relationship between the expression of the above markers and clinical outcome including prognosis and response to chemotherapy was also examined. The expression of E-cadherin, a marker of epithelial cells, was significantly lower in residual tumors than chemo-naive tumors (P=0.003). The expression of Snail (P=0.028), ZEB1 (P<0.001) and N-cadherin (P=0.001), markers of mesenchymal cells, was higher in residual tumors than in chemonaive tumors. The expression of E-cadherin correlated inversely with that of Snail (P<0.001). Reduced expression of E-cadherin and increased expression of Snail in residual tumors from patients who received chemotherapy correlated significantly with poor response to chemotherapy and short survival time. Multivariate analysis identified Snail expression as an independent prognostic factor, along with tumor depth, in patients who received preoperative chemotherapy for esophageal cancer. The results suggest transition of residual esophageal cancer cells to mesenchymal phenotype after chemotherapy and this contributes to resistance to chemotherapy and poor prognosis in patients with esophageal cancer.

Neoadjuvant chemoradiotherapy followed by esophagectomy vs. surgery alone in the treatment of resectable esophageal squamous cell carcinoma.

In order to improve the survival of esophageal cancer patients, a trimodality therapy consisting of esophagectomy in combination with neoadjuvant chemoradiotherapy (CRT) has been developed. In this study, we evaluated whether neoadjuvant CRT improved the outcomes of patients with resectable esophageal squamous cell carcinoma (ESCC) compared to surgery alone. Eighty-eight patients with resectable ESCC were treated with either neoadjuvant CRT followed by surgical resection (Group A, n=52), or surgery alone (Group B, n=36). CRT consisted of 5-fluorouracil (5-FU, 500 mg/m2 on days 1-5) and cisplatin (CDDP, 10-20 mg/kg body weight on days 1-5), repeated after 3 weeks. Survival analysis was performed using the log-rank test with the Kaplan-Meier method. The clinical response of the primary tumor and metastatic nodes was 80.8%. The postoperative complications profile was similar between the two groups, except for anastomotic leakage. The median survival time (MST) was not reached in Group A and was 27.4 months in Group B. The estimated 5-year overall survival (OS) rate was 50.3% in Group A and 39.9% in Group B (P=0.134). As regards stage II/III disease, Group A exhibited a better disease-free survival (DFS) compared to Group B (5-year DFS: 57.2% in Group A vs. 31.4% in Group B; P=0.025). Simultaneous locoregional and distant recurrences were more common in the surgery alone group (Group B, P=0.047). Neoadjuvant CRT with 5-FU and CDDP did not contribute to a better prognosis in patients with resectable ESCC. However, it may be beneficial for patients with stage II/III disease.

[Four cases of double bypass surgery involving choledochojejunostomy and gastrojejunostomy for inoperable peripancreatic head cancer].

Peripancreatic head cancer often causes obstructive jaundice and duodenal obstruction, which reduces the quality of life and hinders the administration of anti-cancer drugs. Here, we report 4 cases of double bypass surgery( biliary and gastric) for the treatment of inoperable peripancreatic head cancer. The patients' ages ranged from 64 to 72 years. Two patients had pancreatic head cancer and 2 had ampullary cancer. No postoperative morbidity was observed and all 4 patients resumed oral intake within 5 days after surgery and began receiving chemotherapy within 1 month after surgery. There was immediate relief of biliary obstruction in all 3 patients with obstructive jaundice. None of the patients experienced recurrence of obstructive jaundice requiring biliary drainage. Two patients who died of cancer were able to consume food orally just before they died. Although bypass surgery is more invasive than endoscopic stenting, it may be safe and useful not only for palliation, but also for induction or continuation of chemotherapy.

Pattern of abdominal nodal spread and optimal abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma of the cardia: results of a multicenter study.

BACKGROUND: It remains uncertain whether radical lymphadenectomy combined with total gastrectomy actually contributes to long-term survival for Siewert type II adenocarcinoma of the cardia. We identified the pattern of abdominal nodal spread in advanced type II adenocarcinoma and defined the optimal extent of abdominal lymphadenectomy. METHODS: Eighty-six patients undergoing R0 total gastrectomy for advanced type II adenocarcinoma were identified from the gastric cancer database of 4,884 patients. Prognostic factors were investigated by multivariate analysis. The therapeutic value of lymph node dissection for each station was estimated by multiplying the incidence of metastasis by the 5-year survival rate of patients with positive nodes in each station. RESULTS: The overall 5-year survival rate was 37.1%. Age less than 65 years [hazard ratio, 0.455 (95% confidence interval (CI), 0.261-0.793)] and nodal involvement with pN3 as referent [hazard ratio for pN0, 0.129 (95% CI, 0.048-0.344); for pN1, 0.209 (95% CI, 0.097-0.448); and for pN2, 0.376 (95% CI, 0.189-0.746)] were identified as significant prognosticators for longer survival. Perigastric nodes of the lower half of the stomach in positions 4d-6 were considered not beneficial to dissect, whereas there were substantial therapeutic benefits to dissecting the perigastric nodes of the upper half of the stomach in positions 1-3 and the second-tier nodes in positions 7 and 11. CONCLUSIONS: Limited lymphadenectomy attained by proximal gastrectomy might suffice as an alternative to extended lymphadenectomy with total gastrectomy for obtaining potential therapeutic benefit in abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma.

A case of simultaneous transvaginal NOTES gastrectomy and vaginal hysterectomy in a patient with gastric submucosal tumor and uterine prolapse.

A 5-cm gastric submucosal tumor was incidentally found through abdominal CT as a preoperative work-up for hysterectomy in a 62-year-old woman with uterine prolapse. NOTES using a flexible gastrointestinal endoscope via the transvaginal route was indicated to accomplish concomitant partial gastrectomy and hysterectomy. Perigastric dissection was performed, followed by stapled partial gastrectomy using transvaginal NOTES technique with two transabdominal ports. The specimen was delivered transvaginally by enlarging the initial vaginal entry site. Vaginal hysterectomy was then accomplished by utilizing the enlarged vaginal wound. The patient showed rapid and uneventful postoperative recovery without any narcotic need. No complication was noted, her cosmetic result was satisfactory, and there was complete resolution of preoperative gynecological symptoms. Female patients with concomitant gastrointestinal and gynecological conditions requiring large specimen retrieval would potentially be suitable candidates for the transvaginal NOTES approach.

Laparoscopic intragastric surgery revisited: its role for submucosal tumors adjacent to the esophagogastric junction.

PURPOSE: When the gastric submucosal tumor (SMT) locates adjacent to the esophagogastric junction (EGJ), it is difficult to preserve EGJ technically and oncologically. In this study, we describe our clinical experience with laparoscopic intragastric surgery (LIGS) and discuss its role for gastric SMTs adjacent to EGJ. METHODS: A retrospective review was performed on patients who underwent surgical treatment of gastric SMTs adjacent to EGJ (April 1994 to May 2010). They were divided into 3 groups: laparoscopic partial gastrectomy (LAP, n=10), LIGS (n=10), and open laparotomy (OPEN, n=7), respectively. RESULTS: The completion rates were 50% in LAP and 90% in LIGS. Overall preservation rate of EGJ was 80% (LAP), 100% (LIGS), and 29% (OPEN), respectively. The patients who underwent total/proximal mastectomy showed significantly higher incidence of postoperative gastrointestinal symptoms, which required long-term medication. CONCLUSIONS: LIGS stays as a valuable alternative and would be an attractive option for gastric SMTs adjacent to EGJ.

Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway.

PURPOSE: To determine the relationship between resistance to chemotherapy and microRNA (miRNA) expression in esophageal cancer, we focused on miRNAs known to be associated with maintenance of stem cell function. EXPERIMENTAL DESIGN: Using 98 formalin-fixed, paraffin-embedded samples obtained from patients with esophageal cancer who had received preoperative chemotherapy followed by surgery, we measured expression levels of several miRNAs that are considered to be involved in the regulation of stem cell function (e.g., let-7a, let-7g, miR-21, miR-134, miR-145, miR-155, miR-200c, miR-203, and miR-296) by real-time reverse transcriptase PCR. Then, we examined the relationship between miRNA expression and prognosis or response to chemotherapy. To investigate the mechanism of miRNA-induced chemoresistance, in vitro assays were carried out using esophageal cancer cells. RESULTS: Analyses of the 9 miRNAs expression showed that overexpression of miR-200c (P = 0.037), underexpression of miR-145 (P = 0.023), and overexpression of miR-21 (P = 0.048) correlated significantly with shortened overall duration of survival. In particular, miR-200c expression correlated significantly with response to chemotherapy (P = 0.009 for clinical response; P = 0.007 for pathologic response). In vitro assay showed significantly increased miR-200c expression in cisplatin-resistant cells compared with their parent cells (∼1.7-fold). In anti-miR-200c-transfected cells, chemosensitivity to cisplatin and apoptosis after exposure to cisplatin was found to increase as compared with the negative control. Western blotting showed that knockdown of miR-200c expression was associated with increased expression of PPP2R1B, a subunit of protein phosphatase 2A, which resulted in reduced expression of phospho-Akt. CONCLUSIONS: Results of this study emphasized the involvement of miR-200c in resistance to chemotherapy among esophageal cancers and that this effect was mediated through the Akt pathway.

Partial gastrectomy using natural orifice translumenal endoscopic surgery (NOTES) for gastric submucosal tumors: early experience in humans.

BACKGROUND: Transvaginal endoscopic gastric surgery is one of the cutting edge procedures in the field of natural orifice translumenal endoscopic surgery (NOTES). Its feasibility has been shown sporadically in bariatric cases but not in oncologic conditions. The authors report their early experience with hybrid transvaginal NOTES gastrectomy for gastric submucosal tumors (SMTs). METHODS: Two female patients with SMTs in the distal stomach participated in this institutional review board (IRB)-approved study. Surgical indication was determined according to the National Comprehensive Cancer Network (NCCN) sarcoma guidelines, and the study adhered to the following oncologic principles: no direct handling of the lesion, full-thickness resection, and reasonable surgical margins. The study protocol required a minimum of two laparoscopic ports to ensure procedural safety and aforementioned oncologic appropriateness. Under laparoscopic guidance, a transvaginal route was created and secured with a 50-cm flexible overtube. A gastrointestinal endoscope was introduced, and the perigastric dissection was performed using an insulation-tipped diathermy knife (IT knife) and needle knife. This process was assisted with two laparoscopic graspers. After perigastric mobilization, the transvaginal endoscope was replaced with a digital stapling device, and partial gastrectomy was accomplished. The resected specimen was isolated and delivered through the vagina, and the vaginal wound was closed under direct vision. Outcomes measurements included surgical results, pain scoring, and clinical outcomes. RESULTS: Both operations were completed successfully in compliance with the aforementioned oncologic principles. The operating time was 365 and 170 min, respectively. The estimated blood loss was negligible. A minilaparotomy for specimen delivery was successfully avoided in both cases. A minimal vaginal incision was added for one patient at retrieval. Postoperatively, both patients reported no pain and recovered rapidly. The final diagnosis was hemorrhagic lipoma and gastrointestinal stromal tumor (GIST), respectively. CONCLUSION: Our initial experience with human transvaginal NOTES gastrectomy showed it to be feasible and safe for gastric SMTs. It is a complex but promising surgical alternative for female oncologic patients undergoing partial gastric resection.