High frequency of bone recurrence as an initial recurrence site after radical surgery in T1N3 gastric cancer: a propensity score matching analysis.

PURPOSE: T1 gastric cancer (GC) with seven or more metastatic lymph nodes is extremely rare, and very few clinical studies have been conducted to evaluate the clinicopathological features of their recurrence. METHODS: We retrospectively analyzed the outcomes of T1 GC and T2-4 GC patients who had multiple nodal metastases after radical surgery from 2006 to 2020. Propensity score matching was performed to compare the two groups of patients. RESULTS: After propensity score matching, 18 of 22 patients in the T1 group and 36 of 144 patients in the T2-4 group were selected. Recurrence occurred in six patients (33.3%) in the T1 group. In the T1 group, the most common site of initial recurrence was bone (15.0%). The prevalence of bone recurrence was significantly higher in the T1 group than in the T2-4 group (P = 0.02). The median interval time between radical surgery and bone recurrence was 24 months, and the median survival time after bone recurrence was 14 months. CONCLUSION: Bone recurrence was more frequently identified as an initial recurrence site in T1 GC cases with multiple metastases after radical surgery compared with that in T2-4 GC cases. Careful attention should be paid to postoperative bone recurrence in the long-term postoperative course of these patients.

Functional Outcomes of Delta-Shaped Anastomosis After Laparoscopic Distal Gastrectomy.

BACKGROUND: We invented a simple and secure method of intracorporeal gastroduodenostomy, the delta-shaped anastomosis (DA), using endoscopic linear stapler only and standardized the DA procedure by resecting two-thirds of the stomach based on the anatomical landmarks. This study aimed to evaluate the feasibility of the standardized DA as the standard reconstruction procedure after a laparoscopic distal gastrectomy assessing functional outcomes including postoperative complications, body weight loss, nutritional status, and endoscopic findings. METHODS: The medical records of 349 patients with gastric cancer who underwent laparoscopic distal gastrectomy from April 2011 to December 2017 at our hospital were retrospectively reviewed. Functional outcomes were assessed according to nutritional status and endoscopic findings. RESULTS: The operation time was shorter and complication rate was lower in the standardized DA than those in Billroth-II (BII) and Roux-en-Y (RY). The body weight loss in DA was 10% 1 year postoperatively and remained stable during the follow-up period, which showed no significant difference. The endoscopic findings showed the ratio of residual food in DA was lower than that in RY (DA:RY = 13.3%:13.6% and 8.4%:33.3% at 1 and 3 years postoperatively, respectively). Severe gastritis was extremely rare in DA (6.7% at 1 year and 15.6% at 3 years postoperatively). Bile reflux was more often found in DA than RY (DA:RY = 19.9%:4.8% and 26.6%:0% at 1 and 3 years postoperatively, respectively). Reflux esophagitis was found 10% of DA only. CONCLUSIONS: Functional outcomes of the standardized DA were satisfactory and feasible. Our intracorporeal Billroth-I reconstruction, by resecting two-thirds of the stomach, can be one of the standard reconstruction methods after a laparoscopic distal gastrectomy.

Upper mediastinal lymph node dissection based on mesenteric excision in esophageal cancer surgery: confirmation by near-infrared image-guided lymphatic mapping and the impact on locoregional control.

BACKGROUND: We previously reported a novel method of mesenteric excision for esophageal cancer surgery. The esophagus, trachea, recurrent laryngeal nerves (RLNs), and surrounding lymph nodes (LNs) are contained in a common mesenterium, which we termed the "mesotracheoesophagus". In addition, near-infrared (NIR) image-guided lymphatic mapping has recently been used. The purpose of this study was to confirm the feasibility of NIR image-guided lymphatic mapping for upper mediastinal LN dissection, and to confirm the oncological feasibility of our surgical approach. METHODS: Fifteen patients with resectable esophageal cancer underwent submucosal injection of indocyanine green (ICG), and underwent robot-assisted esophagectomy. The frequency of ICG positivity in the LN basins along the RLNs, and metastatic frequency were assessed. Regarding the oncological feasibility of our thoracoscopic esophagectomy, the recurrence patterns and survival of 72 consecutive patients who underwent curative resection from 2011 to 2016 were analyzed. RESULTS: ICG-positive LN basins along the right and left RLNs were found in 12 (80% of 15) patients (3 patients positive for metastatic LNs) and 11 (73% of 15) patients (2 positive for metastatic LNs and 1 false-negative), respectively. All ICG-positive LN basins were found within the mesotracheoesophagus. The sensitivity was 5/6 (83%), and the negative predictive value was 6/7 (86%). Among the 72 patients, with a median follow-up period of 1644 days, only 3 (4.2%) patients developed locoregional recurrence. CONCLUSIONS: The NIR image-guided lymphatic mapping was feasible. Our results with no ICG-positive basins outside of the '"mesotracheoesophagus", supported our surgical approach. It might become standard, with acceptable locoregional control.

Appropriate traction can help identify the optimal dissectable layer for infrapyloric lymph node dissection in laparoscopic gastrectomy.

INTRODUCTION: Appropriate dissection of the infrapyloric lymph nodes (no. 6 LNs) is important in gastric cancer surgery. In laparoscopic surgery, dissection of the no. 6 LNs along the inner dissectable layer from the left side of patient has been reported. However, it is difficult for surgeons to provide appropriate traction with their left hand from the left side. To resolve this difficulty, we dissected the no. 6 LNs from the patient's right side to identify the optimal layer. We then evaluated the oncologic reliability of the layer and the safety of this procedure. METHODS: From the patient's right side, the surgeon used their left hand to provide appropriate traction when pulling the adipose tissue, including the no. 6 LNs. This exposed the optimal layer between the adipose tissue and the pancreas. To assess this maneuver, the surgical outcomes of patients who underwent laparoscopic distal gastrectomy from April 2011 to March 2013 were retrospectively analyzed. The surgical outcomes included the number of the no. 6 LNs resected, time to dissect the no. 6 LNs, incidence of pancreatic complications, and recurrence in the no. 6 LNs. RESULTS: There were 112 patients identified. The median number of the no. 6 LNs resected was five. The median time to dissect the no. 6 LNs was 14 minutes. Four patients developed pancreatic fistula, and another four patients developed intra-abdominal abscess. There was no recurrence in the no. 6 LNs. CONCLUSION: The optimal layer was oncologically reliable, and these procedures were safe.

Laparoscopic gastrectomy with and without prophylactic drains in gastric cancer: a propensity score-matched analysis.

BACKGROUND: The number of patients who are undergoing laparoscopic gastrectomy for treating gastric cancer is increasing. Although prophylactic drains have been widely employed following the procedure, there are few studies reporting the efficacy of prophylactic drainage. Therefore, this study assessed the efficacy of prophylactic drains following laparoscopic gastrectomy for gastric cancer. METHODS: Data of patients who received laparoscopic gastrectomy for treating gastric cancer in our institution between April 2011 and March 2017 were reviewed, and the outcomes of patients with and without a prophylactic drainage were compared. Propensity score matching was used to minimize potential selection bias. RESULTS: A total of 779 patients who underwent surgery for gastric cancer were reviewed; of these, 628 patients who received elective laparoscopic gastrectomy were included in this study. After propensity score matching, data of 145 pairs of patients were extracted. No significant differences were noted in the incidence of postoperative complications between the drain and no-drain groups (19.3% vs 11.0%, P = 0.071). The days after the surgery until the initiation of soft diet (6.3 ± 7.4 vs 4.9 ± 2.9 days, P = 0.036) and the length of postoperative hospital stay (15.7 ± 12.9 vs 13.0 ± 6.3 days, P = 0.023) were greater in the drain group than those in the no-drain group. CONCLUSIONS: This study suggests that routinely using prophylactic drainage following laparoscopic gastrectomy for treating gastric cancer is not obligatory.

Is complete right cervical paraesophageal lymph node dissection possible in the prone position during thoracoscopic esophagectomy?

BACKGROUND: Effective treatment of esophageal cancer requires dissection of the regional lymph nodes (LNs) from the cervical to the abdominal area. In this study, we hypothesized that adequate no. 101R dissection is achieved through a thoracoscopic approach in the prone position. METHODS: The study cohort was limited to 42 patients who underwent thoracoscopic subtotal esophagectomy with bilateral cervical lymphadenectomy for thoracic esophageal cancer between January 2015 and March 2017. The number of LNs and the incidence of metastasis were analyzed. During the proposed thoracoscopic procedure, cervical paraesophageal LNs were dissected continuously, with the LNs surrounding the recurrent laryngeal nerve (RLN; no. 106rec) as an en bloc resection. In this study, LNs that required further picking up via a cervical incision were defined as no. 101. The recurrent sites among the consecutive patients during the 3-year follow-up, for whom bilateral cervical lymphadenectomy was omitted for lower and middle thoracic tumors between 2012 and 2014, were analyzed further. RESULTS: The data of 42 patients were analyzed. The lymphatic tissues dorsal to the right cervical RLN were almost completely dissected via thoracoscopy. A median of 0 (0-6) LNs were ventral to the right RLN (no. 101R) and no LN metastasis was observed. There were no lymph nodes in 27 patients (64%). By contrast, there was a median of 1(0-10) no. 101L nodes, and LN metastasis was observed in two patients (4.7%). The numbers of LNs at no. 106recR and no. 106recL were 3 (0-9) and 2(0-13), respectively, and the corresponding numbers of patients with metastases at these sites were 11(26%) and 5(12%), respectively. Among the 33 patients who completed the 3-year follow-up, 9 patients developed recurrence, but none involved 101R LNs. CONCLUSIONS: There were no residual LNs in the area ventral to the right cervical RLN in 64% of the patients who underwent additional cervical lymphadenectomy after the right thoracoscopic approach in the prone position. Further studies with larger patient cohort or randomization are required to confirm our results.

Strategy for treatment of stage IV human epidermal growth factor 2-positive gastric cancer: a case report.

BACKGROUND: The prognosis of stage IV gastric cancer and human epidermal growth factor 2 (HER2)-positive gastric cancer is poor, although new drugs and regimens have been developed. We report a case of a patient with stage IV HER2-positive gastric cancer treated successfully by conversion therapy and trastuzumab. CASE PRESENTATION: The patient was a 73-year-old Japanese man diagnosed as L, type 3, circ, T4aNxCy1P1M1, stage IV (the Japanese classification of gastric carcinoma). The patient was treated with docetaxel, cisplatin, and TS-1 (DCS regimen). After two courses of the regimen, peritoneal dissemination disappeared, and peritoneal lavage cytology revealed no tumor cells in the abdominal cavity. Subsequently, he underwent laparoscopic distal gastrectomy with D1+. Pathological findings were ypT2(MP), ypN2(3/15), ypP0, ypCY0, M0, ypstage II. He received TS-1 as an adjuvant chemotherapy, but he had peritoneal recurrence. The original gastric cancer was HER2-positive. We therefore treated him with TS-1 with trastuzumab. This regimen was quite effective and achieved a complete response. After complete response, we switched the patient to trastuzumab monotherapy. He had no evidence of recurrence for 6 years, 3 months after surgery. CONCLUSION: DCS regimen, R0 resection, and adjuvant chemotherapy with trastuzumab can be a powerful strategy for stage IV HER2-positive gastric cancer.

Mesenteric excision for esophageal cancer surgery: based on the concept of mesotracheoesophagus.

The fundamental principle of surgery for intestinal cancer is mesenteric excision. It has been widely accepted as radical surgery for colorectal cancer, and it comprises procedures such as complete mesocolic excision for colon cancer and total mesorectal excision for rectal cancer. So far, the concept of mesenteric excision of the esophagus has not been well documented, but our surgical experience with a magnified view using a thoracoscope and understanding of the surgical anatomy based on embryologic foregut development has led us to introduce the concept of mesotracheoesophagus. Using this concept, our technique is reproducible, effective, and safe for lymph node dissection along the left recurrent laryngeal nerve. Here we report our concept, procedure, and results of thoracoscopic esophageal cancer surgery.

Esophagojejunostomy With Linear Staplers in Laparoscopic Total Gastrectomy: Experience With 168 Cases in 5 Consecutive Years.

PURPOSE: We evaluate surgical outcomes of intracorporeal esophagojejunostomy in laparoscopic total gastrectomy using 2 linear stapler methods. MATERIALS AND METHODS: The functional end-to-end anastomosis (FEEA) method was chosen as a first choice. The overlap method was chosen in cases with esophageal invasion. We retrospectively analyzed the early and late surgical outcomes of consecutive 168 laparoscopic total gastrectomy cases from April 2011 to December 2016. RESULTS AND CONCLUSIONS: The FEEA method was selected in 120 cases, and the overlap method was selected in 48 cases. The mean time of esophagojejunostomy for the FEEA and overlap method was 13.2 and 36.5 minutes, respectively. Two cases with FEEA method and 3 cases with overlap method experienced complications due to esophagojejunostomy leakage. These cases were treated without performing a reoperation. One case with FEEA method was complicated due to esophagojejunostomy stenosis. This case was endoscopically treated. Our procedures are safe and feasible.

Our experience with laparoscopic partial gastrectomy by the 'lift-and-cut method' for gastric gastrointestinal stromal tumor with maximal preservation of the remnant stomach.

BACKGROUND: Wedge resection is the most commonly used method in laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST). However, this method can involve inadvertent resection of additional gastric tissue and cause gastric deformation. To minimize the volume of resected gastric tissue, we have developed a laparoscopic partial gastrectomy with seromyotomy which we call the 'lift-and-cut method' for gastric GIST. Here, we report a case series of this surgery. METHOD: First, the seromuscular layer around the tumor is cut. Because the mucosa and submucosa are extensible, the tumor is lifted toward the abdominal cavity. After sufficient lifting, the gastric tissue under the tumor is cut at the submucosal layer with a linear stapler (thus 'lift-and-cut method'). Finally, the defect in the seromuscular layer is closed with a hand-sewn suture. RESULTS: From April 2011 to December 2015, 28 patients underwent laparoscopic partial gastrectomy by this method at Osaka Red Cross Hospital. Average operation time was 126 min (range 65-302 min) and average blood loss was 10 ml (range 0-200 ml). No intraoperative complications including tumor rupture or postoperative complications regarded as Clavien-Dindo Grade II or higher occurred. All patients took sufficient solid diet at discharge. Median postoperative hospital stay was 7 days (range 5-21 days). On median follow-up of 26.6 months (range 6-54 months), no recurrence was reported. CONCLUSION: Laparoscopic partial gastrectomy by the lift-and-cut method is safe and simple, and widely applicable for gastric GIST.

Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer.

Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.

Tissue tablet method: an efficient tissue banking procedure applicable to both molecular analysis and frozen tissue microarray.

Frozen human tissues are necessary for research purposes, but tissue banking methods have not changed for more than a decade. Many institutions use cryovial tubes or plastic molds with an optimal cutting temperature compound. However, these methods are associated with several problems, such as samples sticking to one another and the need for a larger storing space. We established an efficient tissue freezing and storing procedure ("tissue tablet method") applicable to both molecular analysis and frozen tissue microarray. Tissue samples were chopped into tiny fragments and embedded into tablet-shaped frozen optimal cutting temperature compound using our original tissue-freezing plate. These tablets can be sectioned and stored in cryovial tubes. We compared the tissue quality of tablet-shaped samples with that of conventional optimal cutting temperature blocks and found no significant difference between them. Tissue microarray is a key method to utilize tissue-banking specimens. However, most tissue microarrays require the coring out of cylindrically shaped tissues from formalin-fixed, paraffin-embedded tissue blocks. Antigenic changes and mRNA degradation are frequently observed with formalin-fixed, paraffin-embedded samples. Therefore, we have applied tablet-shaped samples to construct frozen tissue microarrays with our original mounting base. Constructed tissue microarray sections showed good morphology without obvious artifact and good immunohistochemistry and in situ hybridization results. These results suggest that the quality of arrayed samples was sufficiently appropriate for research purposes. In conclusion, the tissue tablet method and frozen tissue microarray procedure can save time, provides easy tissue handling and processing, and satisfies the demands of research methodologies and tissue banking.

MAL2 expression predicts distant metastasis and short survival in pancreatic cancer.

BACKGROUND: Pancreatic cancer is associated with a devastating prognosis, partially because of its aggressive metastatic ability. Identification of prognostic markers of metastasis would be useful in the clinical management of postoperative patients with pancreatic cancer. Mal, T-cell differentiation protein 2 (MAL2) has been identified as a molecule predictive of metastases; the clinical relevance of MAL2 in pancreatic cancer is unknown. METHODS: Orthotopic human pancreatic cancer xenografts from the pancreatic cancer cell line SUIT-2 were established in nude mice. Only liver metastasis was harvested and cultured. These metastatic cycles were repeated 5 times to establish a highly metastatic cell line, termed metastatic SUIT-2 (MS). We investigated proliferation and motility of MS cells compared with those of the parent SUIT-2. Microarray analysis was performed to investigate differences in gene expression. We also performed immunohistochemical analysis of 89 formalin-fixed, paraffin-embedded human pancreatic cancer tissue samples to investigate the clinical significance of MAL2 expression. RESULTS: MS cells showed a greater metastatic rate after orthotopic implantation than parental SUIT-2. MS cells had increased motility but decreased proliferation compared with parental SUIT-2. Microarray analyses showed that 26 genes were significantly upregulated (>10-fold) in MS cells compared with parental SUIT-2, particularly MAL2 expression. Immunohistochemical analysis showed that high expression of MAL2 was associated with a lesser survival of postoperative patients (P = .03) and a high rate of distant metastasis (P = .008). CONCLUSION: We characterized a newly established pancreatic cancer cell line with highly metastatic potential. MAL2 is a promising predictive marker for distant metastasis and short survival in patients with resected pancreatic cancer.

Pancreatic cancer cells enhance the ability of collagen internalization during epithelial-mesenchymal transition.

BACKGROUND: Extracellular matrix (ECM) remodeling is predominantly mediated by fibroblasts using intracellular and extracellular pathways. Although it is well known that extracellular degradation of the ECM by proteases derived from cancer cells facilitates cellular invasion, the intracellular degradation of ECM components by cancer cells has not been clarified. The aim of this study was to characterize collagen internalization, which is the initial step of the intracellular degradation pathway in pancreatic cancer cells, in light of epithelial-mesenchymal transition (EMT). METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the function of collagen internalization in two pancreatic cancer cell lines, SUIT-2 and KP-2, and pancreatic stellate cells (PSCs) using Oregon Green 488-gelatin. PSCs had a strong ability for collagen uptake, and the pancreatic cancer cells also internalized collagen although less efficiently. The collagen internalization abilities of SUIT-2 and KP-2 cells were promoted by EMT induced by human recombinant transforming growth factor ß1 (P<0.05). Expression of Endo180, a collagen uptake receptor, was high in mesenchymal pancreatic cancer cell lines, as determined by EMT marker expression (P<0.01). Quantitative RT-PCR and western blot analyses showed that Endo180 expression was also increased by EMT induction in SUIT-2 and KP-2 cells. Endo180 knockdown by RNA interference attenuated the collagen uptake (P<0.01) and invasive abilities (P<0.05) of SUIT-2 and KP-2 cells. CONCLUSIONS/SIGNIFICANCE: Pancreatic cancer cells are capable of collagen internalization, which is enhanced by EMT. This ECM clearance system may be a novel mechanism for cellular invasion and a potential therapeutic target in pancreatic cancer.

Single-incision laparoscopic cholecystectomy with needle graspers.

BACKGROUND/AIMS: Single-incision laparoscopic cholecystectomy (SILC) is a promising alternative to standard multi-incision laparoscopic cholecystectomy (LC). However, generalization of SILC is still hampered by technical difficulties mainly associated with the lack of trocars used for retraction of the gallbladder. We therefore developed a modified method of SILC with the use of needle graspers (SILC-N) for optimal retraction and exposure. METHODOLOGY: In addition to two trocars inserted through a single transumbilical incision, two needle ports were placed on the right subcostal and lateral abdominal wall, through which needle graspers were used for retraction of the gallbladder. Since December, 2009, 12 patients with symptomatic cholelithiasis were treated by SILC-N. RESULTS: SILC-N was successfully performed in all but one patient requiring a conversion to the 4-port LC with a mean operative time of 71.5 (48-107) minutes. None of the patients experienced intraoperative or postoperative complications. The transumbilical incision and pinholes for needle graspers were almost invisible on discharge. CONCLUSIONS: Our preliminary results suggest that SILC-N is a simple, safe and feasible technique of cholecystectomy offering similar postoperative recovery and better cosmetic outcome as compared to conventional LC.