[Chemotherapy and Conversion Surgery for Advanced Gastric Cancer Patient with a Liver Metastasis in 81 Years Old Woman].

Eighty-one year-old woman was pointed out pulmonary tumor by health check and transferred to our hospital. Her performance status was fine. In imaging study, she had advanced gastric cancer with a solitary liver metastasis and highly suspected left lung cancer. She received chemotherapy combined with oxaliplatin and S-1 as first-line. However, the tumor enlarged and then received second-line chemotherapy combined with paclitaxel and ramucirumab. The tumor shrank and a solitary liver metastasis remained. She underwent gastrectomy and partial hepatectomy. After conversion surgery, she had no chemotherapy and had survived over 5 years. Even in old person over 80 years old, chemotherapy and surgery are considerable in patients with well performance status.

Randomized controlled phase III trial to investigate superiority of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer patients (JCOG1907, MONA LISA study): a study protocol.

BACKGROUND: Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. METHODS: We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien-Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. DISCUSSION: This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. TRIAL REGISTRATION: The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

[Three Cases of Solitary Brain Metastasis in Advanced Gastric Cancer].

We have experienced 3 cases of solitary brain metastasis after radical surgery in advanced gastric cancer. All of them have similar characteristics such as, upper third location, solitary metastasis to the cerebellum, and no other organ metastasis. As there is a risk of brain hernia, resection have been underwent first, and radiotherapy administered after surgery. One case has been provided over 2-year survival.

The Risk of Developing Multiple Primary Cancers among Long-Term Survivors Five Years or More after Stomach Carcinoma Resection.

Recently, the number of long-term survivors of ≥ 5 years after stomach carcinoma resection is increasing in Japan. The clinical courses of 4,883 patients who underwent stomach carcinoma resection were retrospectively reviewed to investigate the cause of death including multiple primary cancers (MPC) and delayed stomach carcinoma recurrence among long-term survivors of ≥ 5 years. Of 3,061 patients who survived for ≥ 5 years, 1,203 patients (39.3%) were dead after 5 years survival, including 299 patients (24.9%) who died of MPC. Of 84 patients (7.0%) who died of recurrent stomach carcinoma, 25 patients were newly diagnosed ≥ 5 years postoperative. The most common site of MPC was lung in 124 patients, and 347 patients (44.7%) had a smoking-related MPC, including 124 lung, 63 esophagus, 62 head and neck, and 98 other cancers. We examined the prognostic differences in 527 patients with MPC according to the diagnosis time. In 325 patients of long-term survivors in whom MPC was diagnosed ≥ 5 years postoperative, 5-year survival rate and the median survival time after diagnosis were 35.1% and 17.7 months, respectively. This outcome was significantly poorer than that of 160 patients in whom MPC was diagnosed within 5 years postoperative (58.5% and 62.7 months, P < 0.0001). In conclusion, MPC accounted for approximately a quarter of the cause of death in long-term survivors. Lifestyle instructions including smoking cessation are important. Periodical cancer screening allows the early asymptomatic diagnosis and may contribute to a decrease in cancer mortality of MPC in long-term cancer survivors.

Clinical advantages of robotic gastrectomy for clinical stage I/II gastric cancer: a multi-institutional prospective single-arm study.

BACKGROUND: Robotic gastrectomy (RG) for gastric cancer (GC) has been increasingly performed for a decade; however, evidence for its use as a standard treatment has not yet been established. The present study aimed to determine the safety, feasibility, and effectiveness of RG for GC. METHODS: This multi-institutional, single-arm prospective study, which included 330 patients from 15 institutions, was designed to compare morbidity rate of RG with that of a historical control (conventional laparoscopic gastrectomy, LG). This trial was approved for Advanced Medical Technology ("Senshiniryo") B. The included patients were operable patients with cStage I/II GC. The primary endpoint was morbidity (Clavien-Dindo Grade ≥ IIIa). The specific hypothesis was that RG could reduce the morbidity rate to less than half of that with LG (6.4%). A sample size of 330 was considered sufficient (one-sided alpha 0.05, power 80%). RESULTS: Among the 330 study patients, the protocol treatment was suspended in 4 patients. Thus, 326 patients fully enrolled and completed the study. The median patient age and BMI were 66 years and 22.4 kg/m2, respectively. Distal gastrectomy was performed in 253 (77.6%) patients. The median operative time and estimated blood loss were 313 min and 20 mL, respectively. No 30-day mortality was seen, and morbidity showed a significant reduction to 2.45% with RG (p = 0.0018). CONCLUSIONS: RG for cStage I/II GC is safe and feasible. It may be effective in reducing morbidity with LG.

Assessment of the Safety of the New Hybrid Pencil Type Energy (NP) Device Used Close to the Recurrent Laryngeal Nerve in a Porcine Model: Comparison With a Conventional Electrosurgical Knife.

BACKGROUND: Recurrent laryngeal nerve (RLN) paralysis is mainly associated with esophagectomy, and it may result in not only other morbidities, such as aspiration pneumonia, but also in long-term issues. Therefore, an approach to prevent RLN paralysis is necessary. The present study was designed to determine the technical usability of the new hybrid pencil type energy (NP) device developed by Olympus Corporation (Tokyo, Japan) and compare it with a conventional electrosurgical knife (EK) for resection around the RLN lymph nodes. METHODS: This nonsurvival (acute) study included 10 pigs (20 RLNs) and investigated the threshold for thermal RLN damage with the NP device and a conventional EK. To obtain basic information for our study, a preliminary experiment for heat spread was performed. RESULTS: When using the EK device, the amplitude value disappeared at a distance of 1 mm from the RLN, but when using the NP device, the amplitude value was maintained up to a distance of 0.5 mm. There were significant differences at distances of 0 mm, 0.5 mm, and 1 mm between the NP and EK devices. Furthermore, heat spread was lower with the NP device than with the EK device. CONCLUSIONS: The new energy device developed by Olympus Corporation was found to be technically safe for resection of the RLN lymph nodes in a porcine model. To the best of our knowledge, this is the first study to demonstrate the potential advantages of using this new energy device in a clinical aspect.

Feasibility Study of a Newly Developed Hybrid Energy Device Used During Laparoscopic Liver Resection in a Porcine Model.

BACKGROUND: Although various devices have been clinically used for laparoscopic liver resection (LLR), the best device for liver parenchymal transection remains unknown. Olympus Corp (Tokyo, Japan) developed a laparoscopic hybrid pencil (LHP) device, which is the first electric knife to combine ultrasound and electric energy with a monopolar output. We aimed to evaluate the feasibility of using the LHP device and to compare it with the laparoscopic monopolar pencil (LMP) and laparoscopic ultrasonic shears (LUS) devices for LLR in a porcine model. METHODS: Nine male piglets underwent laparoscopic liver lobe transections using each device. The operative parameters were evaluated in the 3 groups (n = 24 lobes) during the acute study period. The imaging findings from contrast-enhanced computed tomography and histopathological findings of autopsy on postoperative day 7 were compared among groups (n = 6 piglets) during the long-term study. RESULTS: The transection time was shorter ( P = .001); there was less blood loss ( P = .018); and tip cleaning ( P < .001) and instrument changes were less often required ( P < .001) in the LHP group than in the LMP group. The LHP group had fewer instances of bleeding ( P < .001) and coagulator usage ( P < .001) than did the LUS group. In the long-term study, no postoperative adverse events occurred in the 3 groups. The thermal spread and depth of the LHP device were equivalent to those of the LMP and LUS devices (vs LMP: P = .226 and .159; vs LUS: P = 1.000 and .574). CONCLUSIONS: The LHP device may be an efficient device for LLR if it can be applied to human surgery.

Three-dimensional computed tomography analysis of the vascular anatomy of the splenic hilum for gastric cancer surgery.

PURPOSE: Splenic infarction may occur if the splenic branches are injured or ligated accidentally during gastrectomy. We used three-dimensional computed tomography (3D-CT) imaging to distinguish the vascular anatomy of the splenic hilum in individual patients, focusing on the splenic polar branches and the gastric branches. METHODS: The subjects of this study were 104 patients who underwent computed tomography (CT) with intravenous contrast before gastrectomy. SYNAPSE 3D® (Fujifilm Medical, Tokyo, Japan) was used to generate the 3D-CT images. The total spleen volume and the area supplied by the superior polar artery (SPA) in each patient were estimated using the "liver analysis" function. RESULTS: The SPA without the gastric branch (supplying only the spleen), the SPA with the gastric branch (supplying both the stomach and the spleen), and the posterior gastric artery (supplying only the stomach) were present in 14, 45, and 18% of the patients, respectively. The SPA supplied 12% of the total spleen volume on average; however, it supplied over 30% in two patients. CONCLUSION: We identified the vascular anatomy around the splenic hilum in over 100 patients. Based on our findings, we recommend preservation of the SPA when it is supplying a large area of the spleen. Preoperative 3D-CT analysis provides useful information to optimize safe gastrectomy.

[Laparoscopic Total Gastrectomy(LTG)in Patient with Multiple Gastric Neuroendocrine Tumor Related to Multiple Endocrine Neoplasia Type 1 - Two Case Reports].

We herein report 2 cases of laparoscopic total gastrectomy(LTG)in patient with multiple gastric neuroendocrine tumor (NET)related to multiple endocrine neoplasia type 1(MEN1). Case 1: A 66-year-old female was diagnosed with multiple gastric NET. There was no finding of any other tumor, and parathyroid function was normal. She underwent LTG. Case 2: A 58-year-old female was diagnosed with multiple gastric NET. The patient had a previous history of surgery for pituitary gland tumor. There was no finding of any other tumor, and parathyroid function was normal. She underwent LTG. In our cases, we could perform complete resection of gastric NET by laparoscopic surgery. Multiple gastric NET is a good indication of laparoscopic gastrectomy.

Accurate, safe, and rapid method of intraoperative tumor identification for totally laparoscopic distal gastrectomy: injection of mixed fluid of sodium hyaluronate and patent blue.

BACKGROUND: In totally laparoscopic distal gastrectomy, determining the resection line with safe proximal margins is often difficult, particularly for tumors located in a relatively upper area. This is because, in contrast to open surgery, identifying lesions by palpating or opening the stomach is essentially impossible. This study introduces a useful method of tumor identification that is accurate, safe, and rapid. METHODS: On the operation day, after inducing general anesthesia, a mixture of sodium hyaluronate and patent blue is injected into the submucosal layer of the proximal margin. When resecting stomach, all marker spots should be on the resected side. In all cases, the proximal margin is examined histologically by using frozen sections during the operation. RESULTS: From October 2009 to September 2011, a prospective study that evaluated this method was performed. A total of 34 patients who underwent totally laparoscopic distal gastrectomy were enrolled in this study. Approximately 5 min was required to complete the procedure. Proximal margins were negative in all cases, and the mean ± standard deviation length of the proximal margin was 23.5 ± 12.8 mm. No side effects, such as allergy, were encountered. CONCLUSIONS: As a method of tumor identification for totally laparoscopic distal gastrectomy, this procedure appears accurate, safe, and rapid.

[Useful device for hepatectomy in patients with a surgical history of bile duct-GI tract anastomosis at the porta hepatis].

We experienced three hepatectomies in patients with a history of bile duct-gastrointestinal (GI) tract anastomosis at the porta hepatis. Patient 1 had a history of pancreaticoduodenectomy for bile duct cancer. Because the third liver metastasis of cecal cancer postoperatively invaded the right kidney, after 5 courses of FOLFOX we performed partial resection of the liver (S6) and the right kidney using microwave pre-coagulation and a cavitron ultrasonic surgical aspirator (CUSA) without the Pringle method. Patient 2 had a history of splenectomy for congenital spherocytosis, cholecystectomy, choledocholithotomy, and bile duct duodenal anastomosis for hepatolithiasis. Partial (S5) liver resection was performed to treat hepatocellular carcinoma. Patient 3 had a history of bile duct resection and choledochojejunostomy for congenital cystic dilatation of the common bile duct. She had repeated episodes of cholangitis in the year following surgery. Extended liver segmental (S4) resection was performed to treat intrahepatic bile duct carcinoma. Bile duct jejunum anastomosis was performed, and the portal vein and the hepatic artery in the porta hepatis were exfoliated. Hepatectomy was performed using the Pringle method and a CUSA. Surgical procedures using various devices are necessary for hepatectomy in patients with a history of bile duct-GI tract anastomosis at the porta hepatis.

[Surgical management for more than 10 liver metastases from colorectal cancer].

We examined the clinical course of patients with multiple liver metastases (≥10) from colorectal cancer after hepatectomy. Of 455 patients, 336 patients had 1-4 metastases, 71 had 5-9 metastases, and 48 had ≥10 metastases (31 patients had undergone chemotherapy along with hepatectomy and 17 had not undergone chemotherapy). Chemotherapy was effective in improving the 5-year survival rate of patients with 5 or more metastases. The 5-year survival rate in patients who underwent hepatectomy along with chemotherapy (52.7%[1-4 metastases], 49.9%[5-9 metastases], and 42.3% [≥10; n=5]) was better than that in patients who did not undergo chemotherapy( 56.1%[not significant: ns], 13.1% [p=0.0003], and 0%[p<0.0001], respectively). Five patients with ≥10 liver metastases survived for 5 years after hepatectomy, of which, 1 received FOLFOX (Leucovorin plus 5-FU plus oxaliplatin) adjuvant chemotherapy, 2 received preoperative FOLFOX, and 2 received LV5FU2 (5-FU plus Leucovorin) hepatic arterial infusion chemotherapy. Our results suggest that long-term improvement in prognosis could be possible with aggressive repeat hepatectomy along with effective chemotherapy.

[A case of laparoscopic partial hepatectomy and splenectomy for hepatocellular carcinoma and pancytopenia].

A 69-year-old woman with chronic hepatitis B and esophageal varices was admitted to our hospital because of a hepatocellular carcinoma( HCC) measuring 3 cm in segment S3. Computed tomography( CT) scan revealed splenomegaly, and the platelet count was 6.0×104/µL. Partial hepatectomy and splenectomy were performed sequentially under laparoscopic guidance in a right half-lateral decubitus position, using 7 working ports. The operation time was 237 min, and the amount of bleeding was 26 mL. Her postoperative course was uneventful, and she was discharged on the 10th day after the operation.

[A case of superficial carcinoma in a diverticulum of the thoracic esophagus].

An upper gastrointestina(l GI) series revealed a diverticulum in the anterior wall of the middle thoracic esophagus of a 72-year-old man. Endoscopy revealed a type 0-IIc lesion in the esophageal diverticulum. The margin of the lesion was unclear. Biopsy proved that it was squamous cell carcinoma. Endoscopic ultrasonography showed that the deepest layer of the tumor was the lamina propria mucosae (cT1a-LPM) and that the underlying muscularis propria was thinning. No distant metastasis or regional lymph node metastasis was detected. Diverticulectomy or endoscopic submucosal dissection (ESD) was out of indication due to the unclear margin and thin muscularis propria. We conducted mediastinoscopy-assisted esophagectomy. The pathological diagnosis of the resected specimen was moderately differentiated squamous cell carcinoma with invasion to the lamina propria mucosae (pT1a-LPM). Pathological examination proved the thinning of the underlying muscularis propria in the diverticulum. The patient is alive without recurrence at 6 months after surgery.

Simultaneous presence of the hepato-spleno-mesenteric trunk, a common trunk for both inferior phrenic arteries, the left gastric artery, and a common hepatic artery that ran behind the portal vein in a patient with gastric cancer.

The celiac artery usually trifurcates into the common hepatic artery, splenic artery, and left gastric artery, but it is known to present several anatomical variations. In such cases, detailed knowledge of the variation is needed preoperatively to safely perform surgery. A 77-year-old woman was referred to our hospital for the treatment of gastric cancer. She had a triple anatomical variation: simultaneous presence of the hepato-spleno-mesenteric trunk, a common trunk for both inferior phrenic arteries and the left gastric artery, and a common hepatic artery that ran behind the portal vein. We detected this variation on routine preoperative multidetector computed tomography angiography, and safely and adequately performed laparoscopic distal gastrectomy.

[Evaluation of efficacy and safety of first-line docetaxel/cisplatin/5-FU combined therapy for advanced esophageal cancer].

We retrospectively evaluated the efficacy and safety of a first-line combination chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil (DCF therapy) in nine patients with advanced esophageal cancer. Dose administrated were 75 mg/m² of Docetaxel on day 1, 75 mg/m² of CDDP on day 1, and 750 mg/m² of 5-FU on day 1-5. Complete response (CR) in two patients (22. 2%), partial response (PR)in three patients ( 33. 3%), and no change (NC) in four patients (55. 6%) were shown for main lesions, while CR in one (11. 1%), PR in five (55. 6%), and NC in three (33. 3%) were shown for lymph node metastases. Response rates of the DCF therapy were 55. 6% for main lesions and 66. 7% for lymph node metastases. Five patients who achieved PR or CR underwent esophagectomy with lymph node dissection. Toxicity from DCF therapy was grade 3 or 4 emergent adverse events (77. 8% of neutropenia, 55. 6% of febrile neutropenia, and 55. 6% of anorexia). DCF therapy improved the response rate in esophageal cancer patients, but resulted in some increase in toxicity. Prospective study with prevention of toxicity should be planned in order to evaluate first-line DCF therapy for advanced esophageal cancer.

Laparoscopic treatment in a patient with median arcuate ligament syndrome identified at the onset of superior mesenteric artery dissection: a case report.

BACKGROUND: Median arcuate ligament syndrome (MALS) is a rare clinical entity caused mainly by extrinsic compression of the celiac axis by the median arcuate ligament (MAL). Severe celiac artery stenosis can lead to the development of collateral circulation, aneurysms, and, rarely, superior mesenteric artery (SMA) dissection. The treatment of MALS involves the surgical release of the MAL. However, a standard procedure with the use of laparoscopy has not been established, and intraoperative complications can lead to severe vascular injury. CASE PRESENTATION: The patient was a 43-year-old man with MALS identified at the onset of SMA dissection. After treatment for the SMA dissection, he underwent laparoscopic MAL release. Using the technique of laparoscopic gastrectomy within the surgical field, we performed laparoscopic MAL release and ganglionectomy safely with a good view. Immediate symptomatic improvement was acquired, and no recurrence was observed at the 20-month follow-up. CONCLUSION: We reported a rare case of MALS and SMA dissection. A horizontal 3D laparoscopic approach of the celiac axis allows for safe, meticulous, and radical MAL release and ganglionectomy.

[A case of advanced esophageal cancer with liver metastases: efficacy of combination therapy of docetaxel/cisplatin/5-FU].

The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is potentially very effective for advanced esophageal SCC.

[Modified FOLFOX6 in a patient on hemodialysis with metastatic colorectal cancer].

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, chemotherapy for a hemodialysis patient should be considered with due care. We administered chemotherapy of modified FOLFOX6 to a patient on hemodialysis with inoperable metastatic colorectal cancer, and measured his plasma concentration of total platinum and non-protein-bound platinum. Since there is no reported case of oxaliplatin use in patients on hemodialysis so far, we evaluated whether it could be safely used for such patients. We made a dose escalation study with 40, 50, 60, 70 and 85 mg of oxaliplatin, and evaluated the pharmacokinetics at each dose. AUC was 5.67-10.21 mg/L x h. The dialysis removal rate was 84.0%. Although this patient could accept it relatively safely without any severe side effect, the optimal dosage and the timing of hemodialysis for inoperable metastatic colorectal cancer patients should be determined by a further study using more cases.

[Value of postoperative surveillance of tumor recurrence after curative esophageactomy].

A study of 256 patients whose dates and patterns of first mode of recurrence after curative esophagectomy from 1984 to 2004 revealed the recent improvement in survival after the detection of tumor recurrence. This tendency was evident in lymphatic recurrence, particularly in the cervical area. Lung metastasis was another mode of recurrence that has shown recent improvement. In this series, 20 patients with lymph node metastases underwent reoperation for local or regional tumor control. The addition of systemic chemotherapy or chemoradiotherapy was our general rule. The 5-year survival rate after the detection of tumor recurrence in these 20 patients was 47.4%. Six with lung metastases in the group of patients whose esophagectomies were performed in the last 7 years underwent video-assisted pulmonary tumor resection. Five patients in this group are alive without signs of further recurrence for 92 to 1,437 days. The early detection of recurrent tumor, vigorous attempts to achieve locoregional control, and the addition of systemic chemotherapy are all important in achieving better results. We routinely perform conventional cervical and abdominal ultrasonography and computed tomography every 6 months until 6 years after surgery is performed.