Impact of surgical proximal and distal margins on the recurrence of resectable colon cancer: a single-center observational cohort study.

PURPOSE: Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. METHODS: We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. RESULTS: Patients who had pT4 colon cancer with margins of more than 7 cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20-0.89). Multivariate analysis identified a margin of < 7 cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013-6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. CONCLUSION: A resection margin of at least 7 cm should be maintained for patients with pT4 colon cancer.

Neoadjuvant Chemotherapy in Patients With T4b or Obstructive Colon Cancer: A Single Center Retrospective Cohort Study.

BACKGROUND/AIM: The efficacy of neoadjuvant chemotherapy (NAC) for colon cancer remains unestablished. This study aimed to investigate the outcomes of NAC in patients with locally advanced T4b or obstructive T4a colon cancers (LACC). PATIENTS AND METHODS: Data of patients with LACC who underwent colon surgery between 2010 and 2022 after NAC at our institution were retrospectively reviewed. Patient characteristics, surgical outcomes, tumor features, and prognosis were analyzed. RESULTS: Among 800 patients with LACC who underwent radical resection, 11 received NAC because of cT4b or cT4a with mechanical obstruction. NAC, administered as a doublet regimen, had a median duration of three months, without grade ≥3 adverse events. R0 resection was achieved in all patients and downstaging was observed in eight patients. One patient developed a postoperative abdominal abscess, and adjuvant chemotherapy was administered to eight patients. Four patients experienced recurrence: liver metastasis in two, and local recurrence in two. Among these, three patients underwent resection of recurrent tumors. Median follow-up was 30 months. CONCLUSION: NAC is feasible for T4b or obstructive T4a colon cancer and may be a treatment option for LACC. Further large-scale studies are required to confirm the efficacy of NAC in these patients.

Sarcopenia discriminates poor prognosis in elderly patients following emergency surgery for perforation panperitonitis.

AIM: Sarcopenia has been reported as a prognostic predictor in various conditions; however, it has not been examined in patients with perforation panperitonitis. METHODS: A total of 103 consecutive patients with perforation panperitonitis who underwent emergency surgery from 2008 to 2016 were retrospectively evaluated. Skeletal muscle index (SMI) was measured as the cross-sectional area (cm2) of skeletal muscle in the L3 region on computed tomography images normalized for height (cm2/m2). Sarcopenia was defined as an SMI of ≤43.75 and ≤41.10 cm2/m2 in men and women, respectively. The impact of sarcopenia on postoperative outcomes was investigated. RESULTS: Sarcopenia was present in 50 (48.5%) patients. Severe complications (Clavien-Dindo grade ≥IIIb) and in-hospital mortality were more frequently observed in patients with than without sarcopenia (28.0% vs 9.4%, P = .015) (20.0% vs 5.7%, P = .029) respectively. Multivariate analysis showed that age, sarcopenia, and renal dysfunction were independent risk factors for severe complications and in-hospital mortality. The optimal cut-off levels of age and SMI for predicting these were ≥79 years and SMI <38 cm2/m2, respectively. Among the patients aged ≥79 years, those with SMI <38 cm2/m2 had a severe complication rate of 71% and an in-hospital mortality rate of 57%, whereas the rate of those with SMI ≥38 cm2/m2 was 22% (P = .011) and 11% (P = .008), respectively. CONCLUSION: Sarcopenia is a predictive factor of severe complications and in-hospital mortality following emergency surgery for perforation panperitonitis, especially in elderly patients. Estimation of sarcopenia may identify patients eligible or not eligible for emergency surgery among elderly patients.

Therapeutic Strategy for Incarcerated Obturator Hernia Using Preoperative Manual Reduction and Laparoscopic Repair.

BACKGROUND: Obturator hernia (OH) is a rare but serious disease associated with high morbidity and mortality due to advanced patient age and comorbidities. This study evaluated the feasibility of a laparoscopic approach to OH. STUDY DESIGN: We retrospectively reviewed the records of 32 patients (median age 84 years; 31 women) with OH treated between 2003 and 2016. RESULTS: Five patients with incidental OH underwent total extraperitoneal (TEP) repair. Of 27 patients with incarcerated OH, 18 patients underwent laparotomy, 13 of which required bowel resection, and the remaining 9 patients underwent preoperative ultrasound-guided manual OH reduction. Of 6 patients with successful OH release, 3 and 2 patients underwent TEP and transabdominal preperitoneal repair, respectively, and 1 patient declined the operation. Three patients with failure underwent laparoscopic exploration and conversion to open operation for bowel resection. Comparing the open and laparoscopic groups, the median operation times were 67.5 minutes vs 124 minutes, respectively (p = 0.004); median postoperative stay was 19 vs 11 days, respectively (p = 0.028); and Clavien-Dindo grade II or higher complications tended to be lower (28% vs 8%, respectively; p = 0.359). Even in patients without bowel resection, the median postoperative stay was significantly shorter in the laparoscopic group compared with the open group (7.5 vs 15 days, respectively; p = 0.032). During a mean follow-up of 24.5 months, the 3-year recurrence rate for OH was 25% for non-mesh repair and 0% for mesh repair (p = 0.335). Three- and 5-year cumulative survival rates were 83% and 71%, respectively. CONCLUSIONS: Laparoscopic operations after ultrasound-guided manual reduction can be an alternative to emergent laparotomy in select OH patients.

DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation.

Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1P29S, has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1P29S remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1P29S. Enforced expression of Rac1P29S induced matrix invasion and macropinocytosis in wild-type (WT) mouse embryonic fibroblasts (MEFs), but not in DOCK1-deficient MEFs. Consistently, a selective inhibitor of DOCK1 that blocks its GEF function suppressed the invasion and macropinocytosis in WT MEFs expressing Rac1P29S. Human melanoma IGR-1 and breast cancer MDA-MB-157 cells harbor Rac1P29S mutation and express DOCK1 endogenously. Genetic inactivation and pharmacological inhibition of DOCK1 suppressed their invasion and macropinocytosis. Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1P29S, and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1P29S mutation.

Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1.

Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells. By screening chemical libraries, we have identified 1-(2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl-2(1H)-pyridone (TBOPP) as a selective inhibitor of DOCK1. TBOPP dampened DOCK1-mediated invasion, macropinocytosis, and survival under the condition of glutamine deprivation without impairing the biological functions of the closely related DOCK2 and DOCK5 proteins. Furthermore, TBOPP treatment suppressed cancer metastasis and growth in vivo in mice. Our results demonstrate that selective pharmacological inhibition of DOCK1 could be a therapeutic approach to target cancer cell survival and invasion.

Prognostic Significance of Sarcopenia in Patients with Esophagogastric Junction Cancer or Upper Gastric Cancer.

BACKGROUND: The association between sarcopenia and postoperative outcomes for patients with gastrointestinal malignancies remains controversial. This study aimed to assess the impact of sarcopenia on short- and long-term outcomes after surgery for esophagogastric junction cancer (EGJC) or upper gastric cancer (UGC). METHODS: The study reviewed 148 patients with EGJC or UGC who underwent surgical resection. The patients were categorized into the sarcopenia group or the non-sarcopenia group according to their skeletal muscle index calculated using abdominal computed tomography images. The study compared clinicopathologic factors, postoperative complications, and prognosis between the two groups. RESULTS: Sarcopenia was present in 19 patients (32.2%) with EGJC and 23 patients (25.8%) with UGC. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were significantly poorer in the sarcopenia group than in the non-sarcopenia group (OS 85.5 vs 54.8%, P = 0.0010; RFS 78.7 vs 51.7%, P = 0.0054). The development of postoperative complications did not differ significantly between the two groups. Both the uni- and multivariate analyses showed that N stage (P < 0.0001) and sarcopenia (P = 0.0024 and 0.0293, respectively) were independent poor prognostic factors for OS. CONCLUSIONS: Sarcopenia was strongly associated with a poor long-term prognosis for patients with EGJC or UGC who underwent surgery. The results suggest that special attention might be needed during the development of treatment strategies for patients with sarcopenia who intend to undergo operations for EGJC and UGC.

Prognostic Significance of Postoperative Complications After Curative Resection for Patients With Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The objective of this study was to elucidate the impact of postoperative complications on long-term survival after curative resection for esophageal squamous cell carcinoma. BACKGROUND: The relation between postoperative complications and long-term survival after curative surgery for esophageal squamous cell carcinoma is controversial; thus, this issue should be resolved with a large-scale, well-designed study. METHODS: Clinicopathological features and survival of 580 consecutive patients who received curative resection for esophageal squamous cell carcinoma were investigated according to the development of postoperative pulmonary complications and anastomotic leakage. RESULTS: The 5-year survival rates of patients with pStage 0, I, and II disease with postoperative complications (n = 116) were significantly poorer than those of patients without postoperative complications (n = 288) (overall 69.6% vs 46.9%, P < 0.0001; disease-specific; 76.7% vs 58.9%, P < 0.0022), whereas no differences were found in patients with pStage III and IV disease (n = 176). In the univariate and multivariate analyses for disease-specific survival, pT3, pT4, pN positivity, and development of postoperative complications were significant prognostic factors in all patients. Also, when the analysis was limited to the pStage 0, I, and II patients, development of postoperative complications, and pT3, pT4, and pN positivity, were found to be independent poor prognostic factors in multivariate analyses (hazard ratio: 1.56, 95% confidence interval, 1.01-2.41, P = 0.0476). CONCLUSIONS: The development of postoperative complications is an independent disease-specific poor prognostic factor after curative resection for patients with less-advanced esophageal squamous cell carcinoma.

Clinicopathological Features of Cervical Esophageal Cancer: Retrospective Analysis of 63 Consecutive Patients Who Underwent Surgical Resection.

OBJECTIVE: The objectives of this retrospective study were to elucidate the clinicopathological features and recent surgical results of cervical esophageal cancer. SUMMARY BACKGROUND DATA: Cervical esophageal cancer has been reported to have a dismal prognosis. Accurate knowledge of the clinical characteristics of cervical esophageal cancer is warranted to establish appropriate therapeutic strategies. METHODS: The clinicopathological features and treatment results of 63 consecutive patients with cervical esophageal cancer (Ce group) who underwent surgical resection from 1980 to 2013 were analyzed and compared with 977 patients with thoracic or abdominal esophageal cancer (T/A group) who underwent surgical resection during that time. RESULTS: Among the patients who received curative resection, the 5-year overall and disease-specific survival rates of the Ce patients were significantly better than those of the T/A patients (overall: 77.3% vs 46.5%, respectively, P = 0.0067; disease-specific: 81.9% vs 55.8%, respectively, P = 0.0135). Although total pharyngo-laryngo-esophagectomy procedures were less frequently performed in the recent period, the rate of curative surgical procedures was markedly higher in the recent period (2000-1013) than that in the early period (1980-1999) (44.4% vs 88.9%, P = 0.0001). The 5-year overall survival rate in the recent period (71.5%) was significantly better than that in the early period (40.7%, P = 0.0342). CONCLUSIONS: Curative resection for cervical esophageal cancer contributes to favorable outcomes compared with other esophageal cancers. Recent surgical results for cervical esophageal cancer have improved, and include an increased rate of curative resection and decreased rate of extensive surgery.

Distant lymph node metastases caused by esophageal cancer invasion to the lamina propria: a case report.

BACKGROUND: Pathological examination after endoscopic submucosal dissection revealed that a 62-year-old male had esophageal squamous cell carcinoma with lamina propria mucosal invasion and lymphatic permeation. CASE PRESENTATION: The patient underwent subtotal esophagectomy and reconstruction as an additional therapy. At 3 years and 4 months after esophagectomy, enlargement of abdominal para-aortic lymph nodes metastases was detected by computed tomography scanning. A total of 50.4 Gy of radiation and two cycles of 5-fluorouracil plus cisplatin were administered. The lymph node metastases were markedly reduced by chemoradiotherapy; however, at 1 year and 1 month later (4 years and 5 months after esophagectomy), left adrenal gland recurrence was found. Although resection was performed, the patient died from cancer progression at 5 years and 4 months after esophagectomy. CONCLUSIONS: This case demonstrates that esophageal squamous cell carcinoma with invasion to the lamina propria and lymphatic permeation has the potential to cause distant metastases.

Development of fistula between esophagogastric anastomotic site and cartilage portion of trachea after subtotal esophagectomy for cervical esophageal cancer: a case report.

A 65-year-old man with cT3N2M0 stage III cervical esophageal cancer underwent subtotal esophagectomy and gastric tube reconstruction through the retrosternal route after neoadjuvant chemoradiotherapy. The anastomosis was located adjacent to the left side of the trachea, and a circular stapler was used for anastomosis. Postoperative anastomotic leakage occurred, and an esophagotracheal fistula between the esophagogastric anastomotic site and cartilage portion of the trachea was observed on postoperative day 44. The patient underwent division of the fistula, direct suturing of the anastomotic leakage site, left pectoralis major muscle flap placement, and tracheotomy. He was discharged home on postoperative day 120 on an oral diet. All previous reports of tracheobronchial fistula describe the occurrence of the fistula at the membranous portion of the trachea. The formation of a fistula between the esophagogastric anastomotic site and cartilage portion of the trachea is considered a possible complication when a high esophagogastric anastomosis is created.

Treatment results of two-stage operation for the patients with esophageal cancer concomitant with liver dysfunction.

PURPOSE: The aim of this study was to clarify the usefulness of two-stage operation for the patients with esophageal cancer who have liver dysfunction. METHODS: Eight patients with esophageal cancer concomitant with liver dysfunction who underwent two-stage operation were analyzed. The patients initially underwent an esophagectomy, a cervical esophagostomy and a tube jejunostomy, and reconstruction with gastric tube was performed after the recovery of patients' condition. RESULTS: The average time of the 1(st) and 2(nd) stage operation was 410.0 min and 438.9 min, respectively. The average amount of blood loss in the 1(st) and 2(nd) stage operation was 433.5 ml and 1556.8 ml, respectively. The average duration between the operations was 29.8 days. The antesternal route was selected for 5 patients (62.5%) and the retrosternal route was for 3 patients (37.5%). In the 1(st) stage operation, no postoperative complications were observed, while, complications developed in 5 (62.5%) patients, including 4 anastomotic leakages, after the 2(nd) stage operation. Pneumonia was not observed through two-stage operation. No in-hospital death was experienced. CONCLUSION: A two-stage operation might prevent the occurrence of critical postoperative complications for the patients with esophageal cancer concomitant with liver dysfunction.

Repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma associated with chronic hepatitis C: report of a case.

We report a case of repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma (HCC). A 75-year-old man with chronic hepatitis C underwent partial hepatectomy for a 25 mm hepatic tumor in S5. The histological diagnosis was diffuse large B-cell malignant lymphoma and as postoperative (18)F-fluorodeoxyglucose-positron emission tomography showed no hot spots, the mass was presumed to be primary hepatic lymphoma. Thus, adjuvant systemic chemotherapy was given following the hepatectomy. Abdominal ultrasonography, done 12 months after the hepatectomy, showed a hepatic tumor in S6 and repeat partial hepatectomy was performed. This tumor was histologically diagnosed as HCC.

Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: prospective Doppler ultrasound screening.

BACKGROUND: Venous thromboembolism is a relatively rare but serious complication of abdominal surgery. This study evaluated the incidence and risk factors for the development of deep venous thrombosis (DVT) after abdominal oncologic surgery using color Doppler ultrasonography (DUS). METHODS: This study enrolled 132 consecutive patients who underwent elective abdominal surgery for malignant tumors. Patients were investigated for DVT using DUS on postoperative day 7 ± 2. Correlations between the incidence of DVT and clinicopathologic parameters and the postoperative course were evaluated. RESULTS: DVT was found in 15 patients (11.4%) using DUS. Clinically evident venous thromboembolism, including pulmonary embolism, was not found in these patients. The incidence of DVT was significantly higher in females (P=0.002), patients with a lower body mass index (P=0.008), and patients with a higher preoperative D-dimer level (P<0.0001). CONCLUSIONS: DUS is noninvasive and is useful for postoperative DVT screening. Thromboprophylaxis is essential in high-risk patients who have undergone abdominal oncologic surgery.