5-year follow-up results of a JCOG1104 (OPAS-1) phase III non-inferiority trial to compare 4 courses and 8 courses of S-1 adjuvant chemotherapy for pathological stage II gastric cancer.

BACKGROUND: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is the standard treatment for pathological stage II gastric cancer. The phase III trial (JCOG1104) investigating the non-inferiority of four courses of S-1 to eight courses was terminated due to futility at the first interim analysis. To confirm the primary results, we reported the results after a 5-years follow-up in JCOG1104. METHODS: Patients histologically diagnosed with stage II gastric cancer after radical gastrectomy were randomly assigned to receive S-1 for eight or four courses. In detail, 80 mg/m2/day S-1 was administered for 4 weeks followed by a 2-week rest as a single course. RESULTS: Between February 16, 2012, and March 19, 2017, 590 patients were enrolled and randomly assigned to 8-course (295 patients) and 4-course (295 patients) regimens. After a 5-years follow-up, the relapse-free survival at 3 years was 92.2% for the 8-course arm and 90.1% for the 4-course arm, and that at 5 years was 87.7% for the 8-course arm and 85.6% for the 4-course arm (hazard ratio 1.265, 95% CI 0.846-1.892). The overall survival at 3 years was 94.9% for the 8-course arm, 93.2% for the 4-course arm, and that at 5 years was 89.7% for the 8-course arm, and 88.6% for the 4-course arm (HR 1.121, 95% CI 0.719-1.749). CONCLUSIONS: The survival of the four-course arm was slightly but consistently inferior to that of the eight-course arm. Eight-course S-1 should thus remain the standard adjuvant chemotherapy for pathological stage II gastric cancer.

Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors.

BACKGROUND: Initial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the efficacy of chemotherapy in GC. METHODS: One hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The influence of initial treatment on overall survival (OS) in each group was evaluated. RESULTS: In the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% confidence interval, 0.375-0.933: P = 0.023). CONCLUSIONS: Initial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC.

Evaluating the efficacy of post-operative chemotherapy after curative resection of stage IV gastric cancer with synchronous oligo metastasis: a multicenter retrospective study.

BACKGROUND: Surgical resection of oligo-metastasis in gastric cancer (GC) is weakly recommended for patients without other incurable factors in the Japanese GC Treatment Guidelines. While post-operative chemotherapy is the standard treatment in patients with stage II or III GC, its efficacy for resected stage IV GC is unclear. This study aimed to evaluate the efficacy of post-operative chemotherapy after curative resection of GC with oligo-metastasis. METHODS: We retrospectively reviewed the medical records of patients with GC who were diagnosed with synchronous oligo-metastasis at 20 institutions in Japan between 2007 and 2012. The selection criteria were: adenocarcinoma, stage IV with oligo-metastasis at liver or lymph node without other distant metastasis, curative resection including synchronous oligo-metastasis, and no prior treatment of GC before surgery. RESULTS: A total of 110 patients were collected. Of the 94 eligible patients, 84 underwent gastrectomy with surgical resection of oligo-metastasis (39 [41%] liver metastasis and 55, [59%] distant lymph node metastasis), followed by post-operative chemotherapy with S-1 (S1: n = 55), S1 plus cisplatin (CS: n = 22), or Others (n = 7). Moreover, 10 patients did not receive post-operative chemotherapy (Non-Cx). The median overall survival (OS) was 35.2 and 11.1 months in the post-operative chemotherapy and Non-Cx groups (hazard ratio, 3.56; 95% confidence interval, 1.74-7.30; p < 0.001), respectively. In multivariable analysis, Non-Cx and age over 70 years were identified as poor prognostic factors for OS (p < 0.05). CONCLUSIONS: Curative resection followed by post-operative chemotherapy in patients with GC with synchronous oligo-metastasis showed favorable survival.

Impact of tumor-related factors and inter-institutional heterogeneity on preoperative T staging for gastric cancer.

Background: To improve the diagnostic accuracy of preoperative T staging in gastric cancer, the authors evaluated tumor-related factors that might affect the diagnosis. Materials & methods: The authors analyzed the data of cT2-4b gastric cancer patients enrolled in the prospective, multicenter JCOG1302A study. They used contrast-enhanced computed tomography to analyze the association between tumor-related factors and the diagnostic accuracy of T3-4b staging for gastric cancer. Results: Among 876 cT3-4b tumors, the diagnostic accuracy was relatively low in the lower third of the stomach compared with those in the upper or middle. A multivariable analysis revealed that accuracy was higher in the lesser curvature or entire circumference region than in other areas (p < 0.001), in macroscopic types 3/5 than in types 0/1/2 (p = 0.003) and in the undifferentiated histological type than in the differentiated type (p = 0.011). Conclusion: The authors found tumor-related factors affecting preoperative T staging by enhanced computed tomography.

Additional chemotherapy before surgery is expected to have potentially beneficial effects on prognosis compared with chemotherapy only after surgery for advanced gastric cancer. The consideration of chemotherapy before surgery depends on preoperative diagnosis of the depth of tumor invasion in the stomach wall. Overdiagnosis of the depth of tumor invasion may lead to unnecessary administration of chemotherapy that is harmful to the patient. Tumor-related factors such as tumor location, macroscopic type and histological type may affect the diagnosis. Therefore, these factors should be considered with special care for the diagnosis, which may lead to higher accuracy in diagnosing the depth of tumor invasion in gastric cancer.

Impact of COVID-19 on gastric cancer treatment in Japanese high-volume centers: a JCOG stomach cancer study group survey.

PURPOSES: The spread of coronavirus disease 2019 (COVID-19) has affected socioeconomic and healthcare systems in many countries. Accordingly, many individuals may have canceled their annual health-check programs, including esophagogastroduodenoscopy, which would have resulted in lower numbers of newly diagnosed patients with gastric cancer in comparison to other times. METHODS: Questionnaires were distributed to 62 hospitals every week from May 2020 to August 2020 (total 744) through mailing lists of the Stomach Cancer Study Group of the Japan Clinical Oncology Group. The number of patients with gastric cancer and hospital systems during the COVID-19 pandemic were surveyed. RESULTS: In total, 74% (551 out of 744) of the questionnaires were answered and analyzed. In early May, approximately 50% of hospitals had to restrict surgical slots due to the COVID-19 pandemic. However, they gradually loosened the restrictions thereafter. The number of gastrectomies was < 80% that of the same period in the previous year, and hospitals in Tokyo were seriously affected by a 50% decrease in the number of gastrectomies. CONCLUSIONS: The number of gastrectomies was lower than that in the previous year. Further multi-center follow-up studies are required to evaluate the long-term effects of COVID-19 on the clinical outcomes of patients with gastric cancer.

Conversion surgery for stage IV gastric cancer: a multicenter retrospective study.

BACKGROUND: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC. METHODS: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis. RESULTS: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011). CONCLUSIONS: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.

Prognosis of intrahepatic cholangiocarcinoma stratified by albumin-bilirubin grade.

AIM: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy. However, the characteristics and prognosis of ICC is not well known. This study aims to reveal the relationship between liver function and prognosis of ICC. METHODS: A total of 83 ICC patients were recruited retrospectively from March 2009 to August 2020. Child-Pugh (CP) and albumin-bilirubin (ALBI) scores were used to assess liver function. The extent of portal vein tumor thrombosis (PVTT) was classified from Vp0 to Vp4. The end-point for this analysis was overall survival (OS). RESULTS: The median age was 72 (44-88) years, 48 patients were male (57.8%), and 70 patients were classified as CP grade A (84.3%). At baseline, chronic liver disease (hepatitis B, 9.6%; hepatitis C, 15.7%; alcoholic liver disease, 9.6%; and nonalcoholic fatty liver disease, 4.8%) were diagnosed. The median OS of all ICC patients was 21.2 months. A total of 27 patients underwent surgical resection; these patients showed a longer median OS compared to those who did not undergo surgery (50.8 months vs. 5.5 months, p < 0.001). The prognosis of patients with ICC can be stratified by ALBI grade (grade 1, 54.3 months; grade 2a, 8.4 months; grade 2b, 3.9 months; and grade 3, 1.4 months; p < 0.001) and the extent of PVTT (Vp0, 54.3 months; Vp1/2, 8.4 months; and Vp3/4, 3.9 months; p = 0.0039). CONCLUSION: In this study, viral hepatitis (25.3%) was identified as the most prevalent background liver disease of ICC. Assessing liver function using ALBI grade is useful for stratifying the prognosis of patients with ICC.

Efficacy of Postoperative Chemotherapy After Resection that Leaves No Macroscopically Visible Disease of Gastric Cancer with Positive Peritoneal Lavage Cytology (CY1) or Localized Peritoneum Metastasis (P1a): A Multicenter Retrospective Study.

BACKGROUND: Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. PATIENTS AND METHODS: Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. RESULTS: Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18). CONCLUSIONS: Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

A prospective multi-institutional validity study to evaluate the accuracy of clinical diagnosis of pathological stage III gastric cancer (JCOG1302A).

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy. METHODS: We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less. RESULTS: Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of "cT3/T4 with cN1/N2/N3," by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%. CONCLUSION: Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion "cT3/T4 and cN1/N2/N3" instead.

[A Case of Radical Resection after CapeOX Therapy for Locally Advanced Sigmoid Colon Cancer with Anemia and Abscess Formation in a Jehovah's Witness].

The patient-a Jehovah's Witness-was a woman in her 60s, with locally advanced sigmoid colon cancer. She had severe anemia, and a computed tomography scan of her abdomen showed a tumor with abscess formation and perforation that had invaded into the left urinary duct and the left ovary, without distant metastasis. It was difficult to perform curative resections without transfusion; therefore, CapeOX therapy was plannedas the neoadjuvant treatment. After 3 courses of CapeOX therapy, the patient's anemia improved, and the tumor and abscess had shrunk. Subsequently, a sigmoidectomy with D3 lymph node dissection, partial resection of the small intestine, and the left adnexectomy, as a radical surgery, were performed without blood transfusion. In cases of concomitant colon cancer with anemia that are treated with highly invasive surgery, it might be necessary to conduct systematic treatment in order to complete non-transfusion therapy.

Prognostic Impact of Post-operative Infectious Complications in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: Post Hoc Analysis of a Randomized Controlled Trial, JCOG0501.

PURPOSE: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer. METHODS: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses. RESULTS: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456)). CONCLUSION: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected.

Laser microdissection and two-dimensional difference gel electrophoresis reveal the role of a novel macrophage-capping protein in lymph node metastasis in gastric cancer.

To reveal the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed a proteomic study of tumor and matched nontumor tissues obtained from surgically resected specimens of 22 patients with or without LNM. Using laser microdissection, we recovered specific populations of tumor and nontumor cells. We used two-dimensional difference gel electrophoresis with a large format electrophoresis apparatus to obtain protein expression profiles consisting of 3228 protein spots, and we classified them according to their expression pattern. We found that macrophage-capping protein (CapG) was up-regulated in the tumor tissues of patients with LNM, whereas it showed an equivalent expression level between nontumor and tumor tissues of patients without LNM. It was reported that CapG associated with invasion and metastasis in various malignancies. However, CapG was not investigated in gastric cancer until our study. Western blotting of the laser microdissected tissue samples confirmed up-regulation of CapG in the tumor tissues of patients with LNM. Functional assays demonstrated that CapG promoted tumor cell invasion, but not cell proliferation. The association between CapG expression and LNM is a novel finding in gastric cancer. Further investigation for a prognostic utility of CapG may lead to a risk stratification therapy for gastric cancer.

Totally laparoscopic anterior resection with transvaginal assistance and transvaginal specimen extraction: a technique for natural orifice surgery combined with reduced-port surgery.

BACKGROUND: Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. However, NOSE performed using a conventional multiport technique has been reported previously. The current authors performed totally laparoscopic anterior resection with transvaginal specimen extraction (TVSE) using the reduced-port surgery (RPS) technique. The Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) and Free Access (Top Corporation, Tokyo, Japan) were attached to the transvaginal route for transvaginal assistance and smooth specimen extraction. The authors documented this simple and safe technique and its short-term results. METHODS: Data were prospectively collected for five patients who underwent totally laparoscopic anterior resection with TVSE for colorectal cancer between June 2012 and December 2012. A multiport access device (GelPOINT advanced-access platform; Applied Medical) was inserted into the navel, and a 5-mm port was inserted into the right lower quadrant to be used as a drain site. Transverse transvaginal posterior colpotomy then was performed. One ring of an Alexis ring pair was inserted into the peritoneal cavity through the vagina. The other white ring was placed outside of the vagina and then covered with a Free Access to maintain the pneumoperitoneum for insertion of a 12-mm port. Lymph node dissection and transection of the distal colon were performed with transvaginal assistance. The specimen then was extracted transvaginally. After the Alexis had been removed, the vaginal incision was closed transvaginally. End-to-end colorectal anastomosis was performed using the double-stapling technique. RESULTS: Transvaginal extraction was completed in all five cases. The median operation time was 235 min. One case was complicated by chyloperitoneum. The median hospital stay was 6 days. Only one patient required intravenous analgesics once on postoperative day 1. All the patients remained disease free. CONCLUSION: Totally laparoscopic anterior resection using TVSE with RPS appears to be feasible, safe, and oncologically acceptable for selected cases.

Portal vein infusion chemotherapy with gemcitabine after surgery for pancreatic cancer.

PURPOSES: Pancreatic cancer still has a poor prognosis even after curative resection because of the high incidence of postoperative liver metastasis. This study prospectively evaluated the feasibility and tolerability of portal vein infusion chemotherapy of gemcitabine (PVIG) as an adjuvant setting after pancreatic resection. METHODS: Thirteen patients enrolled in this study received postoperative chemotherapy with PVIG. The patients received intermittent administration of gemcitabine (800 mg/m(2)) via the portal vein on days 1, 8, and 15 after surgery. The tolerability and the toxicity of PVIG were closely monitored. RESULTS: The PVIG was started on an average of 3.1 days after surgery. Complete doses of chemotherapy (three sessions of portal infusion) were accomplished in 11 of the 13 patients. Grade 3 or 4 leukocytopenia was observed in three patients (23 %), and liver dysfunction was found in one patient (7.7 %). Grade 2 sepsis developed in two cases due to bloodstream infection. Liver metastasis was the first site of recurrence in only two patients. CONCLUSIONS: PVIG can be administered to the liver with acceptable toxicity, but myelosuppression is similar to the systemic use of gemcitabine. Careful observation is required even for locoregional chemotherapy.

[A case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy].

We report a case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy. An 80-year-old man underwent right hemicolectomy for cecal cancer. After 10 months, surgical resection was performed for its local recurrence. He was then treated with FOLFIRI therapy, and during the fifth course, he presented with a sudden onset of congestive disturbances. Through radiographic examination and laboratory data, only hyperammonemia was found; he was therefore diagnosed with hyperammonemic encephalopathy. By starting branchedamino acid solutions for its treatment, his consciousness and serum ammonia were promptly improved. Hyperammonemic encephalopathy related 5-FU is caused by increasing ammonia production and its metabolic inhibition, and is worsened by renal dysfunction, dehydration, constipation, infections, or body weight loss. On account of the potential decrease of metabolic function of liver and kidney, an aged person tends to have hyperammonnemia more than a youth. Clinicians should be aware of the adverse events associated with hyperammonemia when then administer a large amount of 5-FU to elderly patients.

[A case of pathologically complete response of local recurrence in the mesorectum after multidisciplinary therapy].

The patient was a 68-year-old man who had undergone sigmoidectomy 1 year previously. Adjuvant therapy with tegafur- uraci(l UFT) and Leucovorin( UZEL) was administered. Seven months later, the carcinoembryonic antigen( CEA) level increased to 7.5 ng/mL. Enhanced computed tomography (CT) revealed a 4-cm mass in the mesorectum, and the patient was diagnosed as having local recurrence. Chemotherapy with oxaliplatin, 5-fluorouracil, and Leucovorin( mFOLFOX6) and radiation therapy( 60 Gy) were administered. As the tumor could not be detected after chemoradiotherapy, abdominoperineal resection was performed. Pathological examination showed no cancer and indicated a complete response. The patients CEA level has not increased and no recurrence has been detected on enhanced CT for 3.5 years. The tumor could be decreased in size by chemoradiotherapy and the operation could be safely performed without resecting other organs. Although surgery is generally performed for local recurrence, multidisciplinary therapy could be useful in performing such surgery safely.

Phase II trial of preoperative chemotherapy with docetaxel, cisplatin and S-1 for T4 locally advanced gastric cancer.

The standard treatment for T4 locally advanced gastric cancer is gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy with S-1 for 12 months; however, prognostic outcome in Stage IIIb has been insufficient. It is expected that survival is improved by preoperative treatment with a triplet regimen of docetaxel, cisplatin and S-1 (divided DCS therapy). A multicenter Phase II study has been conducted to evaluate the safety and efficacy of two courses of preoperative chemotherapy followed by gastrectomy. Fifty-five patients are required for this study. The primary endpoint of the study is pathological response rate of primary lesions. Secondary endpoints are overall survival, disease-free survival, R0 resection rate and adverse events.

[A case of locally advanced rectal cancer had a pathological complete response to XELOX Therapy].

The patient was a 62-year-old man with bowel obstruction in a locally advanced rectal cancer. Computed tomography (CT) scan of the abdomen showed tumor enlargement(11.4 × 9.0 cm)that invaded the urinary bladder, but no distant metastasis. XELOX therapy was planned in order to shrink or eliminate the tumor after a sigmoid colostomy. Four courses of XELOX therapy were perfomed. Consequently, the level of the tumor marker had been restored to a normal range. CT scan revealed marked shrinkage of the tumor (6.1 × 5.2 cm) and a sharply-defined border between the tumor and the urinary bladder. Three weeks after chemotherapy, a low anterior resection as a radical surgery, and a temporary ileostomy were performed. The post-operative course was good. The histological effect was judged to be grade 3. There were no viable cancer cells in the rectal tumor and lymph nodes. The patient is alive and has been disease-free for 10 months after the operation. XELOX therapy as pre-operative chemotherapy might be safe and effective for patients with locally advanced rectal cancer.

Prediction of the peritoneal recurrence via the macroscopic diagnosis of the serosal invasion in patients with gastric cancer: Supplementary analysis of JCOG0110.

BACKGROUND: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence. METHODS: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates. FINDINGS: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively. CONCLUSION: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended.

Totally laparoscopic sigmoid colectomy with transanal specimen extraction.

BACKGROUND: Conventional techniques for laparoscopic-assisted colectomy (LAC) require abdominal minilaparotomy for extraction of the specimen. Abdominal wound complications often increase the invasiveness of LAC. To decrease the incidence of wound complications, natural orifice specimen extraction (NOSE) has been reported. However, only a few devices that allow smooth extraction and reduced intracorporeal contamination have been reported previously. We performed totally laparoscopic sigmoid colectomy using transanal specimen extraction (TASE) and the Alexis(®) wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA). We document this simple and safe technique and its short-term results. METHODS: We prospectively collected data on 18 patients who underwent totally laparoscopic sigmoid colectomy with TASE from April 2009 to July 2010. Lymph node dissection and transection of proximal and distal colon were performed in conventional manner. The transected rectal stump was opened transversely, and a long Babcock grasper was inserted transanally through the opened rectal stump. One of a pair of Alexis rings was held and pulled out of the anus. The other ring was placed in the opened rectal stump. The specimen was then extracted transanally through the Alexis. After the Alexis had been removed, the rectal opening was reclosed with a linear stapler. End-to-end colorectal anastomosis was then performed using the double-stapling technique. RESULTS: Transanal extraction was achieved in 17 cases. We switched to conventional LAC in a case involving a bulky specimen. In 16 cases not including the combined cholecystectomy case, mean operation time was 241 min. One case was complicated by anastomotic leakage and wound infection, while another had enterocolitis. Median hospital stay was 6 days. All patients remained disease free. Mean Wexner score at 12 months after operation was 2.3. CONCLUSION: Totally laparoscopic sigmoid colectomy using TASE and the Alexis appears to be feasible, safe, and oncologically acceptable for selected cases.