Prognostic Relevance of Primary Tumor Sidedness in Early-stage Colorectal Cancer: An Integrated Analysis of 4 Randomized Controlled Trials (JCOG2003A).

OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.

[Laparoscopic Gastro-Jejunostomy Using the Overlap Method after Subtotal Gastrectomy for Upper Gastric Cancer].

BACKGROUND: Due to an aging society, patients with gastric cancer are also getting older. Although total gastrectomy should be avoided for elderly patients, laparoscopic subtotal gastrectomy(LSTG)is a technically demanding procedure. Here, we present a safe procedure of gastro-jejunostomy using the overlap method. METHODS: After transection of the stomach using gastroscopy, an entry hole was created at the center of the staple line of the remnant stomach. The jejunum was anastomosed to the dorsal wall of the gastric remnant with a linear stapler, and the entry hole was closed by hand-sewn sutures. Nineteen patients with gastric cancer in the upper third of the stomach underwent LSTG using this technique, and the short-term clinical outcomes were analyzed retrospectively. RESULTS: The median operative time was 221 minutes(143-318), and the median blood loss was 10 mL(3-100). The median postoperative hospital stay was 7 days(6-13), and there were no complications related to anastomosis. CONCLUSIONS: The short-term clinical outcomes of the laparoscopic gastro-jejunostomy using the overlap method after LSTG reveal that this technique is safe and feasible to use for improving patient outcomes.

[Clinicopathological Examination of Differentiated Gastric Cancer].

OBJECTIVE: The common type carcinoma of gastric cancer is divided into 3 groups, papillary adenocarcinoma(pap), well differentiated tubular adenocarcinoma(tub1)and moderately tubular adenocarcinoma(tub2). In this study, we tried to individualize treatments of them by evaluating their clinicopathological features. METHODS: Examined resected specimens were collected from 2000 to 2016. We compared among pap, tub1, and tub2 as the clincopathological features retrospectively. RESULTS: Histological diagnosis was confirmed to 55 cases with pap, 639 cases with tub1 and 718 cases with tub2. Comparing the ratio of lymph node metastasis(LNM)according to the depth of invasion, tub2 and pap show higher incidence of LNM than tub1 in T1b, T2, and T4(a+b). Tub2 and pap patients have larger number of LNM and worse 5 year survival rates than tub1 patients. CONCLUSION: We demonstrated that tub2 and pap may have higher malignancy and show earlier LNM than tub1. When we consider of endoscopic treatment, individualizataing tub1, tub2 and pap is important.

Cancer-type OATP1B3 mRNA has the potential to become a detection and prognostic biomarker for human colorectal cancer.

AIM: We aimed to clarify diagnostic and prognostic biomarker potentials of cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3) mRNA in colorectal cancer (CRC) patients. PATIENTS & METHODS: Ct-OATP1B3 mRNA levels in 97 CRC and adjacent normal colon tissues were measured by real-time PCR. The receiver operating characteristic curve analysis and the Kaplan-Meier curve analysis were performed to characterize its biomarker potentials. RESULTS: Ct-OATP1B3 mRNA showed noticeable diagnostic power (the area under the receiver operating characteristic = 0.91) in the CRC patients. Additionally, the higher/lower mRNA expression was clearly associated with better/poorer overall survival in the CRC patients (p < 0.05). CONCLUSION: Ct-OATP1B3 mRNA has the potential to be a tissue-based biomarker for definitive diagnosis and prognostic stratification in CRC.

Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5-fluorouracil after mesorectal excision with lateral pelvic lymph node dissection for stage iii lower rectal cancer.

BACKGROUND/AIM: Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. PATIENTS AND METHODS: This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. RESULTS: The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. CONCLUSION: Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD.

[The Different Indications and Treatment Effect between Preoperative Chemotherapy and Preoperative Radiotherapy for Advanced Rectal Cancer].

We evaluated the difference in effectiveness between preoperative radiotherapy (RT) and chemotherapy (C) as part of multimodal therapy for locally advanced rectal cancer. In the RT group, 43 patients were enrolled and preoperative radiotherapy was performed with 42.6 Gy for 4 weeks. In the C group, 16 patients were treated with preoperative chemotherapy consisting of mFOLFOX6/XELOX plus bevacizumab for 3 months. All 43 tumors in the RT group were located in the lower rectum. The C group was composed of 9 in the lower rectum and 7 in the middle or upper rectum. The C group was more advanced than the RT group in terms of depth of invasion, lymph node metastasis, and tumor diameter. The histological treatment response was better after RT (7 with little, 10 with a minor, 24 with a major, and 2 with a complete response) than after C (10 with little, 4 with a minor, 1 with a major, and 1 with a complete response). The tumor reduction ratio by colonography showed 36.5% after RT and 28.7% after C. CEA was reduced by 47.2% after RT and 45.2% after C. Though RT is more effective for local lesions than C, C is expected to be preferred as the local and systemic therapy for locally advanced rectal cancer with pelvic organ involvement or lateral lymph node metastases.

[A Case of Sigmoid Colon Cancer with Metastasis to the Uterus].

A 65-year-old woman complaining of fetor ex vagina was diagnosed with endometrial adenocarcinoma of the uterus based on the pathological findings of an endometrial biopsy. Sigmoid colon cancer was found on a pre-operative CT scan. Diagnosis of double cancer was made and we performed sigmoidectomy and panhysterectomy with associated resection of both adnexa. Histopathological examination found that the tumor accounted for almost all of the uterine mucosa and over half of the muscular layer. Immunostaining showed CK7 (-), CK20 (+), CDX2 (+), ER (-), and PgR (-), and we diagnosed it as a metastasis to the uterus of the sigmoid colon cancer. The pathological diagnosis was a moderately differentiated adenocarcinoma, pT4b (SI: urinary bladder), pN0 (0/12), H0, P1,M1a (uterus), pStage Ⅳ. As adjuvant chemotherapy, she was administered XELOX for 6 months. Although colorectal cancer rarely metastasizes to the uterus, due to the increase in the prevalence of colorectal cancer, it may be also increase. To choose the best treatment course, it is necessary to diagnose whether it is a primary uterine cancer or a metastatic uterine cancer.

[A Case of Double Cancers of the Stomach and Endometrium with Peritoneal Metastasis].

The patient was a 59-year-old woman with advanced double cancers of the stomach and endometrium with peritoneal metastasis. Abdominal computed tomography revealed that the endometrial cancer was more advanced than the gastric cancer; therefore, the peritoneal metastasis was diagnosed as arising from the endometrial cancer. Treatment of the endometrial cancer with cytoreductive surgery followed by adjuvant chemotherapy was performed first. She underwent total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Disseminated nodules were found throughout her abdomen. The histopathological findings indicated carcinosarcoma of the uterus, pT3bNXM1, Stage Ⅳb. One month after surgery, she received 6 courses of adjuvant chemotherapy with paclitaxel plus carboplatin. After the adjuvant chemotherapy, abdominal computed tomography revealed that both the ascites and the disseminated nodules had disappeared. Therefore, a second-look surgery for the endometrial cancer and definitive surgery for the gastric cancer were planned. At the laparotomy, no disseminated nodules were found, so distal gastrectomy and D2 lymphadenectomy were performed. The histopathological findings were pT4aN1M0P0Cy0, Stage ⅢA. She received adjuvant chemotherapy with S-1 for 1 year, and has been alive with no evidence of recurrence for 2 years and 7 months after the initial surgery.

[Treatment Strategy for Gastric Carcinoma with Lymphoid Stroma].

Gastric carcinoma with lymphoid stroma (GCLS) is a histological type with severe lymphocytic infiltration. GCLS is very rare and few cases have been reported. We examined the clinical features, problems of preoperative diagnosis, and treatment of 14 cases (1.8%) that were diagnosed as GCLS out of 790 gastric cancers surgically resected in our hospital. The mean age was 69 years. Six, 8, and 0 cases were located in the upper, middle, and lower fields of the stomach, respectively, and 8, 1, 4, and 1 cases were macroscopically 0-Ⅱc, 0-Ⅰ, type 2, and type 3, respectively. The depth of invasion was M, SM1, SM2, MP, and SS in 0, 0, 9, 3, and 2 cases, respectively. There were 12 cases(86%)with infection by Epstein-Barr virus, and just 1 case with lymph node metastasis. All cases have had no evidence of recurrence. There were no cases that were diagnosed as GCLS before surgery. GCLS is recognized as having a more favorable prognosis compared with other types of gastric carcinoma, so an aggressive surgery might achieve good outcomes. However, preoperative diagnosis is very difficult and there is a compelling need for new techniques or criteria for diagnosis of GCLS.

Performing simple and safe dunking pancreaticojejunostomy using mattress sutures in pure laparoscopic pancreaticoduodenectomy.

BACKGROUND: Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic pancreatic resection, laparoscopic pancreaticoduodenectomy still presents major technical difficulties, such as when performing pancreatic-enteric anastomosis. METHODS: Laparoscopic dunking pancreaticojejunostomy using mattress sutures was performed in 15 consecutive patients with a soft pancreas and a nondilated pancreatic duct between October 2011 and December 2012. RESULTS: According to the International Study Group on Pancreatic Fistula criteria, 3 patients developed PF (grade A), whereas the remaining 12 patients did not. CONCLUSIONS: Dunking pancreaticojejunostomy using mattress sutures is considered to be a feasible and safe method for performing pure laparoscopic pancreaticoduodenectomy.

[A case of rectal gastrointestinal stromal tumor (GIST) locally resected after long-term chemotherapy with imatinib mesylate].

We report a case of gastrointestinal stromal tumor (GIST) locally resected after long-term chemotherapy with imatinib mesylate. A 78-year-old woman was diagnosed with GIST in the lower rectum on screening colonoscopy for anemia. The tumor was 7 cm in diameter, and the anal sphincter was considered to be difficult to preserve due to the extent of the tumor. The patient refused surgery, so she was administered imatinib mesylate chemotherapy. The medication was continued for 5 years without any major adverse events, and the status of the tumor was stable. Five years later, she underwent transanal local resection for anal prolapse and incarceration of the tumor. Pathological findings revealed a 7 cm sized high-risk GIST. The long-term stable status of the tumor was maintained, and the anal function was preserved by the local resection.

Extrahepatic Glissonean approach for laparoscopic major liver resection (with video).

Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic liver resection, laparoscopic major liver resection remains a highly specialized field because there are major technical difficulties, such as hilar dissection and pedicle control. The entire length of the primary branches of the Glissonean pedicle and the origin of the secondary branches are located outside the liver. In contrast, the trunks of the secondary branches and more peripheral branches run inside the liver. The right, left, anterior, or posterior Glissonean pedicle can thus be tied and divided en bloc extrahepatically during open anatomical liver resection. Each Glissonean pedicle can be easily and safely encircled and divided en bloc extrahepatically during laparoscopic anatomical liver resection using an Endo Retract Maxi or Endo Mini-Retract. This report describes a novel technique by which the extrahepatic Glissonean approach appears to be both feasible and safe for the performance of laparoscopic major liver resection.

Arantius' ligament approach for the left extrahepatic Glissonean pedicle in pure laparoscopic left hemihepatectomy.

INTRODUCTION: Laparoscopic hemihepatectomy has not yet become widely accepted because of the technical difficulties in controlling each Glissonean pedicle laparoscopically. MATERIALS AND SURGICAL TECHNIQUE: The subjects in the present study included 12 patients who underwent laparoscopic left hemihepatectomy between August 2007 and June 2011. Arantius' ligament was divided. Retracting the caudal stump of the ligament revealed a space between the left Glissonean pedicle and the liver parenchyma. The left Glissonean pedicle could be easily encircled by using an Endo Retract Maxi. No Glissonean injuries, including bleeding or biliary leakage, occurred in any of the 12 patients. DISCUSSION: Therefore, the Arantius' ligament approach for the left extrahepatic Glissonean pedicle appears to be feasible and safe for successfully performing pure laparoscopic left hemihepatectomy.

Totally laparoscopic pancreas-sparing duodenectomy.

Pancreas-sparing duodenectomy (PSD) is a practical surgical procedure for patients with duodenal adenoma, which is difficult to resect endoscopically. We describe how we performed a totally laparoscopic PSD to resect a duodenal adenoma in a 64-year-old woman, who had been referred for treatment of a 50-mm villous polypoid mass in the second portion of the duodenum. We performed end-to-side anastomosis between the common duct of the bile and pancreatic ducts and the jejunal limb intracorporeally following the duodenal resection. A biliary leak developed, but resolved spontaneously and the patient was discharged on postoperative day (POD) 32. The surgical margin was free of neoplastic change. Although there is limited experience and appropriate indications must await future studies, this case demonstrates that laparoscopic PSD is feasible, safe, and effective for selected patients.

Pure laparoscopic distal pancreatectomy with en bloc celiac axis resection.

BACKGROUND: Recent technological developments and improved endoscopic procedures have greatly enlarged the applications of laparoscopic pancreatic resection. PATIENT AND METHODS: A 77-year-old female with invasive ductal cancer of the pancreatic body touching the common hepatic and splenic arteries underwent a pure laparoscopic distal pancreatectomy with en bloc celiac axis resection (DP-CAR). The celiac axis, the celiac plexus and ganglions, the left gastric artery, the Gerota fascia, the left adrenal gland, and the retroperitoneal fat tissues above the left renal vein were removed en bloc. RESULTS: The procedure took 245 minutes and there was minimal blood loss. The postoperative course was uneventful and the patient was discharged on the seventh postoperative day. The surgical margins were histologically clear (R0 resection). CONCLUSION: Pure laparoscopic DP-CAR is minimally invasive, safe and feasible, and can achieve R0 resection in selected patients with pancreatic invasive ductal adenocarcinoma.

[Laparoscopic pancreatic resection of pancreatic cancer].

Laparoscopic pancreatic resection of pancreatic cancer is still not universally accepted as an alternative approach to open surgery because of technical difficulties and a lack of consensus regarding the adequacy of this approach for malignancy. Ten patients with pancreatic cancer underwent laparoscopic pancreatic resection, including pancreaticoduodenectomy and distal pancreatectomy in our institution. Eight of the 10 patients recovered without any complications and were discharged on the 10-29th postoperative day. The remaining 2 patients developed pancreatic fistula and were discharged on the 46 and 60th postoperative day, respectively. All lesions were well clear of surgical margins in 6 patients (R0). In the remaining 4 patients, microscopic neoplastic change was found at the surgical margin (R1). Those 4 patients developed tumor recurrence, including liver metastases or peritoneal dissemination, and 3 of the 4 died of the primary disease. Although experience is limited, laparoscopic pancreatic resection of pancreatic cancer can be feasible, safe, and effective in carefully selected patients. However, the benefit of this procedure has yet to be confirmed. Not only adequate experience in pancreatic surgery but also expertise in laparoscopy is mandatory, and careful selection of patients is essential for successful application of this procedure.

Safe and feasible extrahepatic Glissonean access in laparoscopic anatomical liver resection.

BACKGROUND: Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic liver resection, laparoscopic anatomical liver resection still presents major technical difficulties, such as pedicle control. METHODS: Subjects comprised 27 patients who underwent laparoscopic anatomical liver resection using an extrahepatic Glissonean pedicle transaction between August 2005 and February 2010. RESULTS: A total of 61 Glissonean pedicles could be encircled en bloc extrahepatically, as planned. No serious complications, including major bleeding or injury of the portal triad, were encountered during procedures. CONCLUSIONS: Extrahepatic Glissonean access seems to be feasible and safe for laparoscopic anatomical resection of the liver.

Laparoscopic major hepato-biliary-pancreatic surgery: formidable challenge to standardization.

INTRODUCTION: Although laparoscopic colorectal or gastric surgery has become widely accepted as a superior alternative to conventional open surgery, the surgical management of hepato-biliary-pancreatic disease has traditionally involved open surgery. Recently, many reports have described laparoscopic partial liver resection, lateral segmentectomy, and distal pancreatectomy. However, laparoscopic major hepato-biliary-pancreatic surgery, such as hepatic lobectomy and pancreaticoduodenectomy, has not been widely developed because of technical difficulties. METHODS: We describe our experience with laparoscopic major hepato-biliary-pancreatic surgery, including right hepatectomy using hilar Glissonean pedicle transaction, and pylorus-preserving pancreaticoduodenectomy. CONCLUSION: Although our experience is limited, and randomized study is necessary to elucidate the appropriate indications for and effects of the present procedures, we believe that laparoscopic major hepato-biliary-pancreatic surgery can be feasible, safe, and effective in highly selected patients, and that it will be one of the standard therapeutic options for carefully selected patients with hepato-biliary-pancreatic disease.

Comparison of laparoscopy-assisted and open pylorus-preserving pancreaticoduodenectomy for periampullary disease.

BACKGROUND: Although many reports have described laparoscopic pancreatic surgery, pancreaticoduodenectomy (PD) has not been widely accepted. The present study aimed to compare laparoscopy-assisted and open pylorus-preserving pancreaticoduodenectomy (PPPD) to investigate the feasibility, safety, and tumor clearance. METHODS: Fifteen patients with periampullary disease underwent laparoscopy-assisted PPPD, in which resection was performed laparoscopically and the reconstruction was performed through a small midline incision. These patients were compared with 15 patients who, during the same period, underwent conventional open PPPD. RESULTS: Mean operative time and mean blood loss were similar between groups. No significant differences in the incidence of complications or hospital stay were noted between groups. Surgical margin and number of lymph nodes found in the resected specimen did not differ between groups. CONCLUSIONS: Laparoscopy-assisted PPPD is on the same level with conventional open surgery in terms of perioperative outcomes or treatment efficacy.