Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

PURPOSE: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). METHODS: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. RESULTS: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. CONCLUSION: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

[A Case of Neuroendocrine Carcinoma of the Extrahepatic Bile Duct].

A 77-year-old man visited a clinic because of nausea and chest discomfort. On blood test, hepatobiliary enzymes were elevated, and he referred to our hospital. Contrast-enhanced CT revealed stenosis of the extrahepatic bile duct and brush cytology of the bile duct showed adenocarcinoma. We therefore performed pancreatoduodenectomy for extrahepatic bile duct cancer. Pathological diagnosis was small cell neuroendocrine carcinoma, pT3N2M0, Stage ⅢA. The patient did not receive adjuvant chemotherapy and 3 months later contrast-enhanced CT and MRI showed multiple liver metastases. The patient was treated with cisplatin plus irinotecan in the first-line, cisplatin plus etoposide in the second-line, and amrubicin in the third-line and accordingly he died 1 year and 3 months after the surgery. Chemotherapy for neuroendocrine carcinoma of the bile duct is recommended as in small cell lung cancer, but the prognosis is extremely poor. We report this case with a review of some of the literature.

[A Case of T-Cell Lymphoma Treated by Emergency Surgery Due to Bleeding of Jejunal Lesion].

A 78-year-old man was aware of lightheadedness and darkness at a routine outpatient visit, and his blood pressure was declined at 87/51 mmHg. Contrast-enhanced CT scan showed an extravascular leakage image at jejunum. We diagnosed as small intestinal hemorrhage. Because he was in hemorrhagic shock, emergency surgery was performed. A tumor was found coincident with the bleeding site, and partial resection of the small intestine including enlarged lymph nodes was performed. Based on the pathological findings of T-cell origin and positive for serum anti-HTLV-1 antibody, he was suspected as adult T-cell leukemia/lymphoma(ATLL). Endoscopic examination of the upper and lower gastrointestinal tracts, bone marrow examination, and PET-CT scan were performed, but no other lesions were found. We report a case of the T-cell lymphoma with suspected solitary ATLL of the jejunum.

Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).

BACKGROUND AND OBJECTIVES: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

[A Case of Curative Surgery for Locally Advanced Small Bowel GIST after Imatinib Therapy].

According to the risk classification of recurrence, the standard treatment for gastrointestinal stromal tumor(GIST)is complete surgical resection and postoperative adjuvant therapy with imatinib; however, the usefulness of neoadjuvant therapy is unclear. We report a case of giant GIST in the pelvis suspectedly having bladder infiltration that was radically resected and underwent preoperative imatinib therapy. A 52-year-old man visited a clinic because of abdominal pain, fever, and frequent urination. An abdominal mass was determined, and the patient was referred to our hospital for detailed examination and treatment. Contrast-enhanced CT revealed a 17 cm diameter irregular mass from the lower navel to the pelvis, and the bladder boundary was partially unclear. Transrectal biopsy was performed using endoscopic ultrasonography, and according to the Fletcher classification, a high-risk GIST was diagnosed. After preoperative imatinib therapy of 400 mg/day was administered for 3 months, surgery was performed. The tumor was strongly adhered to the bladder, but no invasion was observed, and partial small intestine resection was performed. The surgical margin was negative without capsule damage. On day 34 postoperatively, imatinib therapy was resumed, and as of 1 year postoperatively, the course is well without recurrence.

Short-term results of a phase II study of preoperative docetaxel/cisplatin/S-1 therapy for locally advanced gastric cancer.

BACKGROUND: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer. METHODS: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%. RESULTS: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively. CONCLUSIONS: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.

Does the Endoscopic Surgical Skill Qualification System improve patients' outcome following laparoscopic surgery for colon cancer? A multicentre, retrospective analysis with propensity score matching.

BACKGROUND: This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer. METHODS: This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed. RESULTS: Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966). CONCLUSION: Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon's qualifications.

Lateral lymph node dissection for mid-to-low rectal cancer: is it safe and effective in a practice-based cohort?

BACKGROUND: Most evidence regarding lateral lymph node dissection for rectal cancer is from expert settings. This study aimed to evaluate the safety and efficacy of this procedure in a practice-based cohort. METHODS: A total of 383 patients who were diagnosed with stage II-III mid-to-low rectal cancer between 2010 and 2019 and underwent primary resection with curative intent at a general surgery unit were retrospectively reviewed. After propensity matching, 144 patients were divided into the following groups for short- and long-term outcome evaluation: mesorectal excision with lateral lymph node dissection (n = 72) and mesorectal excision (n = 72). RESULTS: This practice-based cohort was characterized by a high pT4 (41.6%) and R1 resection (10.4%) rate. Although the operative time was longer in the lateral dissection group (349 min vs. 237 min, p < 0.001), postoperative complications (19.4% vs. 16.7%, p = 0.829), and hospital stay (18 days vs. 22 days, p = 0.059) did not significantly differ; 5-year relapse-free survival (62.5% vs. 66.4%, p = 0.378), and cumulative local recurrence (9.7% vs. 15.3%, p = 0.451) were also in the same range in both groups. In the seven locally recurrent cases in the lateral dissection group, four had undergone R1 resection. CONCLUSIONS: Lateral lymph node dissection was found to be safe in this practice-based cohort; however, the local control effect was not obvious. To maximize the potential merits of lateral lymph node dissection, strategies need to be urgently established to avoid R1 resection in clinical practice.

[A Case of Right Kidney Metastasis of Gastric Cancer].

We experienced a case of kidney metastasis of a gastric tumor. An 81-year-old man underwent distal gastrectomy with D2 lymph node dissection and partial hepatic resection for antral gastric tumor with hepatic infiltration in July 2019. A histological examination showed undifferentiated tubular adenocarcinoma. The final stage was pT4bN1P0H0M0, Stage ⅢB. He rejected the recommended adjuvant chemotherapy. Seven months after surgery, abdominal enhanced CT showed a hypovascular mass, 20 mm in diameter, on the right upper pole of kidney. Eleven months after surgery, CT showed that the mass had enlarged to 35 mm, infiltrated the renal pelvis, and advanced to para-aortic lymph node metastasis. We performed a retroperitoneoscopic partial right nephrectomy and diagnosed kidney metastasis of the gastric tumor. His right flank pain worsened, and radiotherapy(50 Gy)was performed for the mass and para-aortic lymph node metastasis. His right flank pain resolved. Kidney metastasis of the gastric tumor is very rare. Radiotherapy effectively relieves pain.

[A Case of Perforation of the Diverticulum of the Appendix during Chemotherapy with Ramucirumab plus Nab-Paclitaxel for Gastric Cancer].

A 65-year-old woman underwent distal gastrectomy with D2 lymph node dissection for advanced gastric cancer in November 2016. The histopathological diagnosis was pT3N0M0, pStage ⅡA, HER2-negative. In August 2019, transverse colon stenosis due to peritoneal dissemination was detected, and an ileum-transverse colon anastomosis was performed. Postoperatively, she received chemotherapy with S-1 plus oxaliplatin. After 6 courses, CT revealed an increase in ascites and dissemination nodules. We diagnosed her with progressive disease and initiated second-line chemotherapy, a ramucirumab plus nab-paclitaxel regimen. On the 20th day during the 5th course of treatment, she visited our hospital with acute abdominal pain. CT revealed free air, and we diagnosed acute panperitonitis with a gastrointestinal perforation. Emergency surgery was performed, and perforation of the appendix end and mild cloudy ascites were observed. We performed an appendectomy and intraperitoneal drainage. Histopathological examination revealed perforation of the appendix, possibly as an adverse effect of the ramucirumab. It should be noted that angiogenesis inhibitors may cause the fatal adverse effect of gastrointestinal perforation.

[A Case of Refractory Chylothorax after Surgery for Esophageal Cancer in Which Lymphangiography and Thoracic Duct Ligation Was Useful].

Chylothorax after esophagectomy is a relatively rare complication that can be difficult to manage. Here, we report a case of refractory chylothorax after surgery for esophageal cancer treated with lymphatic duct lipiodol imaging by inguinal lymph node puncture to confirm patency of the thoracic duct and thoracic duct ligation. A 71-year-old female with esophageal cancer(cT3N0M0)underwent video-assisted thoracoscopic esophagectomy with 2-field lymph node dissection, intrathoracic gastric tube reconstruction, and an enterostomy. A chylothorax appeared when we started enteral nutrition on the day after surgery. She became markedly dehydrated due to over 2,000 mL/day of drainage from the chest drain, and we managed her general condition in the ICU. We started octreotide acetate on postoperative day(POD)6 and etilefrine on POD 8, but neither was effective. Lymphatic duct lipiodol imaging by bilateral inguinal lymph node puncture was performed, and we confirmed leakage from the main thoracic duct. On POD 11, a thoracic duct ligation performed via a thoracotomy revealed that the volume of the chylothorax was remarkably decreased. The chest tube was removed on re-POD 12.

D3 lymph node dissection reduces recurrence after primary resection for elderly patients with colon cancer.

PURPOSE: The favorable oncological impact of D3 lymph node dissection after colon cancer surgery has been described previously. However, D3 lymph node dissection is potentially more invasive than conventional D2 lymph node dissection. The oncological merit of D3 lymph node dissection in elderly patients with colon cancer remains unclear. This study aimed to clarify the oncological outcome after D3 lymph node dissection in patients with colon cancer aged > 75 years. METHODS: This is a retrospective cohort analysis using propensity matching method. The study was conducted at a university hospital and two community teaching hospitals in a large urban city. A total of 378 consecutive patients with pathological stage II and stage III colon cancer who underwent primary resection with either D2 or D3 lymph node dissection were retrospectively identified on a prospective database between 2000 and 2015. The primary and secondary outcomes of interests were recurrence-free survival and postoperative complication rate, respectively. RESULTS: After propensity matching, 232 patients were analyzed. The long-term findings showed that the elderly who underwent D3 lymph node dissection had significantly better recurrence-free survival than those who underwent D2 lymph node dissection (p = 0.01). The incidence of postoperative complication was almost similar between the two groups. CONCLUSIONS: D3 lymph node dissection provides better recurrence-free survival than D2 lymph node dissection after primary resection for elderly patients with pathological stage II and stage III colon cancer.

Laparoscopic surgery in patients diagnosed with clinical N2 colon cancer.

PURPOSE: The benefits of laparoscopic surgery for colorectal cancer have been well established. Several randomized controlled trials have demonstrated similar oncological outcomes between laparoscopic and open surgery for colon cancer. However, whether or not laparoscopic surgery is acceptable in patients with clinical N2 colon cancer is unclear. Therefore, the present study aimed to evaluate the safety and oncological outcomes of laparoscopic surgery for clinical N2 colon cancer. METHODS: This retrospective study assessed a prospective database and identified 262 consecutive patients with clinical N2 colon cancer who underwent either laparoscopic or open primary resection between 2000 and 2016. After propensity-score matching, 162 patients were analyzed. The primary outcome of interest was the 3-year recurrence-free survival rate, and the secondary outcome of interest was the postoperative complication rate. RESULTS: The 3-year recurrence-free survival rate did not differ markedly between the laparoscopic and open surgery groups (77.4% vs. 76.5%, p = 0.620). In addition, the incidence of postoperative complications did not differ markedly between the laparoscopic and open surgery groups (16.6% vs. 24.0%, p = 0.317). CONCLUSIONS: Our findings suggest that laparoscopic surgery is safe and effective for clinical N2 colon cancer. Laparoscopic resection can be considered in patients diagnosed with clinical N2 colon cancer.

[The Strategy for the Treatment of Perforated Gastric Cancer].

Perforated gastric cancer reported to be relatively rare and to have a poor prognosis. This study examined 9 patients with perforated gastric cancer. Two-thirds of the patients were male and the median age was 69 years. The timing of the diagnosis of gastric cancer was preoperative clinical findings in 4 cases, intraoperative surgical findings in 3 cases, and postoperative examination in 2 cases. The depths of tumor invasion were T3 in 3 cases, T4a in 4 cases, and T4b in 2 cases and 5 patients were Stage Ⅳ. Four patients underwent palliative gastrectomy and only 1 patient underwent curative(R0)gastrectomy. Four patients underwent repair surgery, 2 of which underwent omental patch repair during the initial surgery. One of patients with omental patch repair received 2-stage curative gastrectomy; the other patient received chemotherapy after recovering from acute peritonitis. The median overall survival was 17.9 months and the prognosis was favorable in cases with curative resection or chemotherapy. For patients with perforated gastric cancer, if curative resection cannot be expected, the initial surgery should be directed toward the treatment of peritonitis and radical oncological surgery or systemic chemotherapy should be planned following patient recovery.

[Clinical Outcomes of Palliative Radiation Therapy for Gastric Cancer Bleeding].

Only a few studies have been conducted regarding the palliative radiation therapy(RT)for gastric cancer(GC)bleeding. Data of 9 patients with gastric cancer requiring blood transfusions due to gastric bleeding who were treated with RT were reviewed. All patients were men with a median age of 83(range, 70-91)years. The clinical stage was ⅡB in 2 patients, Ⅲin 1, ⅣA in 1, and ⅣB in 5. Performing gastrectomy was difficult in 4 patients with distant metastasis or tumor invasion to adjacent organ, 3 with poor performance status, and 2 with advanced age. The median hemoglobin levels before RT was 6.0 (range, 3.3-7.7)g/dL, and all patients received blood transfusions before RT. Seven patients received 30 Gy RT and 2 patients received 50 Gy. Two patients received concurrent chemotherapy. A total of 2 hematological and 4 non-hematological treatment-related adverse events occurred. All patients improved conservatively. Hemorrhage occurred in 8 patients, except for 1. Of the 8 patients who responded to RT, 1 had rebleeding on day 81. The median rebleeding-free survival time from the beginning of RT was 125(range, 21-421)days. Palliative radiation therapy was useful for bleeding control in nonresectable gastric cancer.

[Short-Term Outcomes of Laparoscopic-Assisted Total Gastrectomy Using the Endoscopic Purse-String Suture Instrument ENDO-PSI].

Laparoscopic-assisted total gastrectomy(LATG)has several complications early during the introduction of the procedure, so a careful approach is necessary. In this study, we evaluated short-term outcomes after LATG at our hospital. From 2014 to 2017, 21 patients underwent LATG using ENDO-PSI. A 6-cm midline incision was made at the epigastrium, and the abdominal esophagus was transected using ENDO-PSI. The anvil head was fixed with extracorporeal ligation, and an end loop was added to the proximal side of the first suture. Reconstruction was performed with the Roux-en-Y method. The jejunojejunal anastomosis was performed extracorporeally, and esophagojejunostomy was performed using a circular stapler through the small incision. There were 15 men and 6 women, with a mean age of 74 years. The mean operation time was 296 min, and volume of blood loss was 75 mL. The median fasting period was 3(3-10)days, and the postoperative hospitalization period was 12(8-28)days. The postoperative complications were Grade Ⅱ in 4 patients and Grade Ⅲ in 1 patient. The complication due to esophagojejunostomy was anastomotic leakage in 1 patient, while no anastomotic stenosis was found. LATG using ENDO-PSI can be safely performed.

[Short-Term Comparison between Trans-Anal Ileus Tube and Self-Expandable Metallic Stent for Obstructive Colorectal Cancer].

The aim of this study was to compare the outcome of using trans-anal ileus tube and self-expandable metallic stent(SEMS) for obstructive colorectal cancer. METHODS: Between 2014 and 2018, 14 patients received trans-anal ileus tube placement (group I)and 34 received SEMS insertion as bridge to surgery(BTS)and underwent primary resection. RESULTS: The technical success rate was 100%in both groups, and the clinical success rate was 85.7%(12/14 cases)in group I and 91.2%(31/34 cases)in group S. In group S, the CROSS score significantly improved, the rates of stoma construction and postoperative complications were significantly lower, and the period until oral intake and hospital discharge was significantly short. CONCLUSION: SEMS insertion is more effective than trans-anal ileus tube placement in terms of short-term outcome.

[Clinical Assessment of 33 Patients with Perforated Colorectal Cancer Who Underwent Surgery].

The aim of this study was to clarify the risk factors of severe postoperative complications and prognostic factors in patients who underwent emergent surgery for colorectal cancer perforation. ASA-PSB3 and Mannheim Prognostic Index(MPI)B27 were selected as the independent risk factors for postoperative severe complications on multivariate analysis. Moreover, severe postoperative complications and non-curative surgery were selected as the independent factors of poor prognosis.

Statistical inference for noninferiority of difference in proportions of clustered matched-pair data from multiple raters.

In clinical investigations of diagnostic procedures to indicate noninferiority, efficacy is generally evaluated on the basis of results from independent multiple raters. For each subject, if two diagnostic procedures are performed and some units are evaluated, the difference in proportions for matched-pair data is correlated between the two diagnostic procedures and within the subject, i.e. the data are clustered. In this article, we propose a noninferiority test to infer the difference in the correlated proportions of clustered data between the two diagnostic procedures. The proposed noninferiority test was validated in a Monte Carlo simulation study. Empirical sizes of the noninferiority test were close to the nominal level. The proposed test is illustrated on data of aneurysm diagnostic procedures for patients with acute subarachnoid hemorrhage.

[Appropriate Range of Lymph Node Dissection in Elderly Patients with Colorectal Cancer].

In elderly patients, surgical procesure is decided considering the general condition and surgical invasion. The aim of this study was to clarify the appropriate rage of lymph node dissection for elderly colorectal cancer patients. One hundred forty one colorectal cancer patients aged 75 years or more, who underwent R0 colorectal resection with D2 or D3 lymph node dissection in clinical T3/T4 or clinical N+, were enrolled in this study. The patients whose tumor located in the rectum below the peritoneal reflection(Rb)were excluded. Five-year overall survival(OS)rate and disease specific survival(DSS)rate were 79.1% and 89.4%, respectively. More than 2 preoperative co-morbidities and macroscopic type 3-5 were independent prognostic factors in OS, whereas the rage of lymph node dissection was not risk factor. When comparing the outcomes of D2 and D3 dissections by age, D3 dissection was better tendency in DSS in patients aged under 80, however, D2 dissection was better tendency in patients aged 80 or more. In elderly colorectal cancer patients, there was no difference in prognosis between D2 and D3 dissection, and especially in patients aged 80 years or more, D2 might be sufficient if R0 resection was possible.