Reducing anastomotic leakage in TaTME by mucosal coverage of staple lines: a pilot study with preliminary results.

PURPOSE: We have performed a single stapled anastomosis with double purse-string sutures as a Trans anal Total Mesorectal Excision (TaTME) reconstruction for low rectal cancer. We report an attempt to control local infection and reduce anastomotic leakage (AL) at this anastomotic site. PATIENTS AND METHODS: Fifty-one patients who underwent TaTME for low rectal cancer from April 2021 to October 2022 were included. TaTME was performed by two teams, and reconstruction was performed by anastomosis with a single stapling technique (SST). After the anastomosis was thoroughly cleaned, Z sutures were placed parallel to the staple line to suture the mucosa on the oral and anal side of the staple line and to cover the staple line circumferentially. Data on operative time, Distal Margin (DM), recurrence and postoperative complications including AL were prospectively collected. RESULTS: The mean age of patients was 67 years. There were 36 males and 15 females. The overall mean operative time was 283.1 min, and the mean Distal Margin was 2.2 cm. Postoperative complications were observed in 5.9% of the patients, but no AL was observed, nor any serious complications with Clavien-Dindo ≥ 3 grade. Of the 49 cases excluding Stage 4, postoperative recurrence was observed in 2 cases (4.9%). CONCLUSION: In patients with lower rectal cancer who underwent TaTME, additional mucosal coverage of the anastomotic staple line by transanal manipulation after reconstruction may be associated with a reduction in the incidence of postoperative AL. Further studies including late anastomotic complications are needed.

Does Pathological T-Factor Affect Long-term Prognosis of Locally Advanced Colorectal Cancer Treated With Laparoscopic Multivisceral Resection?

BACKGROUND/AIM: Locally advanced colorectal cancer (LACC) has poor long-term outcomes. Our hypothesis was that the pathological tumor depth would affect postoperative outcomes in patients who underwent multivisceral resection with clear margins (R0). The aim of this study was to analyze short- and long-term outcomes in patients who underwent multivisceral resection for LACC, comparing between T3 and T4 stages. PATIENTS AND METHODS: This was a propensity score-matched, retrospective study. All 8,764 consecutive patients who underwent surgery for colorectal cancer between April 2007 and January 2021 at the Saitama Medical University International Medical Center were screened; 572 underwent multivisceral resection for LACC. We compared the T3 and T4 groups to evaluate outcomes. RESULTS: The 5-year disease-free survival (DFS) rates did not significantly differ between the two groups (hazard ratio=1.344, 95% confidence interval=0.638-2.907, p=0.33). The 5-year overall survival (OS) rates were significantly worse for the T4 group than for the T3 group (hazard ratio=3.162, 95% confidence interval=1.077-11.44), p=0.037). To determine the association between American Society of Anesthesiologists (ASA) score, transfusion, pathological T and OS, we performed univariate and multivariate analyses. ASA, transfusion, and pathological T-stage were associated with worse OS in univariate analysis (T4 vs. T3, respectively). CONCLUSION: Our study showed that postoperative complications and DFS of the T4 group were similar to those of the T3 group of locally advanced colorectal cancer treated with laparoscopic multivisceral resection. However, OS was worse in the T4 group compared with the T3 group. Multivariate risk factors for poor OS were ASA>2, transfusion, and T4 stage.

Small bowel fistula with colorectal cancer and mesenteric lymph node metastasis: a report of two cases.

A 65-year-old man presented to our hospital with complaints of diarrhea. Computed tomography showed a fistula with the small intestine, and a single incision laparoscopic low anterior resection for rectum with D3 dissection and partial resection of the small intestine were performed. Lymph node dissection, including a part of the inflow vessel area, was also performed because lymph node swelling was observed in the mesentery of the small intestine around the fistula. Histopathological analysis revealed that the lymph nodes in the small intestine were positive for metastasis. The patient was a 61-year-old woman who presented to our hospital with a chief complaint of diarrhea. A partial resection of the small intestine, including resection of the left hemicolectomy and lymph node dissection around the fistula, was performed at laparotomy. Histopathological examination revealed numerous lymph node metastases in the small intestinal mesentery.

Risk Factors for Lymph Node Metastasis and Recurrence in T1 Colorectal Cancer: Analysis of 801 Patients in a Single Institute.

OBJECTIVE: To identify risk factors for lymph node metastasis and postoperative recurrence of pT1 colorectal cancer by clinicopathological study of surgically resected cases. METHODS: In 801 patients with pT1 colorectal cancer who underwent surgical resection with lymph node dissection between April 2007 and January 2021, we evaluated clinicopathological factors (age, gender, BMI, serum CEA level, tumor localization, additional resection after endoscopic treatment, operation time, blood loss, histological type, tumor size, vascular invasion, and central lymph node dissection). We performed univariate and multivariate analyses to examine risk factors for lymph node metastasis. We also examined risk factors for recurrence in 583 patients up to December 2017. RESULTS: Lymph node metastasis was observed in 100/801 patients (12.5%). Multivariate analysis of lymph node metastasis showed that patients with positive lymphatic invasion (odds ratio 2.57, 95% CI 1.62-4.04, P < .0001), positive venous invasion (odds ratio 2.31, 95% CI 1.48-3.61, P = .0002), and histologically poorly differentiated type (odds ratio 4.54, 95% CI 1.35-15.2, P = .014) were identified as risk factors. Postoperative recurrence was observed in 18/580 patients (3.1%). Risk factors for postoperative recurrence were also examined, including preoperative endoscopic treatment (odds ratio 3.59, 95% CI 1.18-10.9, P = .024), positive venous invasion (odds ratio 3.63, 95% CI 1.22-10.8, P = .021), positive lymph node metastasis (odds ratio 4.91, 95% CI 1.10-21.8, P = .037) were extracted as risk factors. DISCUSSION: In this study, venous invasion, lymphatic invasion, and histologically poorly differentiated type were identified as risk factors for lymph node metastasis in T1 colorectal cancer, and positive venous invasion, positive lymph node metastasis, and preoperative endoscopic treatment were identified as risk factors for recurrence. We hope that large prospective study will lead to the development of a more specific treatment strategy, including endoscopic treatment and additional surgical resection.

Short-term results of robot-assisted colorectal cancer surgery using Senhance Digital Laparoscopy System.

BACKGROUND: The Senhance Digital Laparoscopy System (Asensus Surgical Inc, Morrisville, NC, United States), which was introduced for the first time in Japan by our hospital, is a new surgical assistive robot following the da Vinci Surgical System. We herein report the short-term outcomes of 55 colorectal cancer surgery cases using this system at our hospital to assess the feasibility and safety of our procedures. MATERIALS AND METHODS: We retrospectively reviewed the patient backgrounds and surgical outcomes of 55 patients who underwent Senhance-assisted laparoscopic colorectal cancer surgery. RESULTS: The median age was 71 years. There were 31 males and 24 females, and the median body mass index was 23.1 kg/m2 . Fifteen patients had a history of abdominal surgery. The most common surgical technique was ileocecal resection (18 cases, 32.7%), followed by high anterior resection (11 cases, 20.0%). D2 or D3 dissection was performed in each operation, and D3 dissection was performed in 41 cases (74.5%). The median operative time was 240 minutes, the median blood loss was 5 mL, there were no intraoperative complications, and there were no cases of intraoperative blood transfusion. The median postoperative hospital stay was 7 days, which was comparable to conventional laparoscopic surgery. Postoperative complications of grade 2 or higher in the Clavien-Dindo classification were observed in two cases. CONCLUSION: The short-term results of 55 colorectal cancer surgery cases using the Senhance Digital Laparoscopy System were excellent and the system was introduced and surgery was safely performed.

The primary tumor location in colorectal cancer: A focused review on its impact on surgical management.

The primary tumor location (PTL) has attracted increasing attention in recent years for colorectal cancer (CRC) patients. Although the underlying mechanisms for differences caused by PTL remain still unclear, right-sided colon (RCC) and left-sided colon (LCC) are now considered as distinct entities because of their different molecular profile and clinical response to surgery and chemotherapy. In this article, we review the influence of PTL particularly on surgical management of primary and metastatic CRC settings. For nonmetastatic CRC, RCC could be a slightly superior prognostic factor after curative resection in stage I-II CRC, while RCC could be an inferior prognostic factor in stage III CRC with worse survival after recurrence, suggesting the oncological aggressiveness of recurrent RCC. For metastatic CRC, RCC could be a predictor of worse survival after hepatectomy of liver metastases from CRC with aggressive recurrence pattern and lower chance of re-resection. In lung metastases from CRC, the role of PTL still remains uncertain because of the limited number of studies. As to the impact of PTL on survival outcome after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal metastases from CRC, a discrepancy exists among studies and further investigation will be needed. The very simple clinical factor of PTL could provide important information for the prediction of the survival outcome after surgery in CRC. Further clinical and basic research will facilitate the clinical application of PTL in a more specified and personalized manner.

[A Case of Cystoid Macular Edema Secondary to Albumin-Bound Paclitaxel Therapy].

A 73-year-old woman diagnosed with unresectable pancreatic cancer received weekly gemcitabine(GEM)plus albuminbound paclitaxel(nab-PTX)therapy. Four months after nab-PTX therapy was initiated, she presented with a rapidly decreasing vision in her left eye at an ophthalmology clinic. On admission, her visual acuity was decreased, and optical coherence tomography(OCT)revealed a cystoid macular edema(CME)only in her left eye. She discontinued the nab-PTX therapy immediately. Her visual acuity improved on follow-up 6 months later. The CME finding on OCT was reduced but not completely resolved. CME is a rare adverse event induced by nab-PTX therapy, with only 14 cases reported since 2008. In most of the reported cases, the patients had breast cancer, and this is the first reported case of CME in a patient with pancreatic cancer. The time to CME onset from starting nab-PTX therapy was reported to range from3 to 30months, but the predilection time has not been clarified. Many reports indicated that symptoms improved in a short period after discontinuation of nab-PTX therapy, but effective treatment was not established, except discontinuation of nab-PTX therapy. In daily medical treatment, the incongruity of the ophthalmologic domain should be confirmed for early detection of CME.

Effect of hospital volume on long-term outcomes of laparoscopic gastrectomy for clinical stage I gastric cancer.

BACKGROUND: This study aimed to examine the effect of hospital volume on long-term outcomes of patients who underwent laparoscopic gastrectomy for clinical stage I gastric cancer. PATIENTS AND METHODS: A total of 420 patients with clinical stage I gastric cancer who underwent laparoscopic gastrectomy at our university hospital (high-volume group) and affiliated hospitals (low-volume group) were included in this study. Overall survival (OS) and cause-specific survival (CSS) rates were analyzed. RESULTS: No significant differences were observed in the number of lymph nodes retrieved (29.9 vs. 27.7, p=0.21) and CSS between the high- and low-volume groups (p=0.92), although the OS rate in the low-volume group was significantly less than that in the high-volume group (p=0.045). CONCLUSION: These results indicate no clinical impact of hospital volume on prognosis of patients who underwent laparoscopic gastrectomy for clinical stage I gastric cancer when performed by surgeons with sufficient experience in open gastrectomy.

Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia.

Cytotoxic lymphodepletion therapies augment antitumor immune responses. The generation and therapeutic efficacy of antitumor effector T cells (T(E)s) are enhanced during recovery from lymphopenia. Although the effects of lymphodepletion on naive T cells (T(N)s) and T(E)s have been studied extensively, the influence of lymphodepletion on suppressor cells remains poorly understood. In this study, we demonstrate a significant increase of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in sublethally irradiated lymphopenic mice. These radio-resistant Tregs inhibited the induction of T(E)s in tumor-draining lymph-nodes (TDLNs) during recovery from lymphopenia. The transfer of T(N)s into lymphopenic tumor-bearing mice resulted in some antitumor effects; however, Treg depletion after whole-body irradiation and reconstitution strongly inhibited tumor progression. Further analyses revealed that tumor-specific T cells were primed from the transferred T(N)s, whereas the Tregs originated from irradiated recipient cells. As in irradiated lymphopenic mice, a high percentage of Tregs was observed in cyclophosphamide-treated lymphopenic mice. The inhibition of Tregs in cyclophosphamide-treated mice significantly reduced tumor growth. These results indicate that the Tregs that survive cytotoxic therapies suppress antitumor immunity during recovery from lymphopenia and suggest that approaches to deplete radio and chemo-resistant Tregs can enhance cancer immunotherapies.

Clinical significance of vascular endothelial growth factors C and D and chemokine receptor CCR7 in gastric cancer.

BACKGROUND/AIM: This study was designed to investigate the clinical significance of lymphangiogenic vascular endothelial growth factors C and D, and chemokine receptor CCR7 in the lymphatic spread of gastric cancer. PATIENTS AND METHODS: The expressions of VEGF-C and -D, and CCR7 were examined in 82 gastric tumors showing a discrepancy between the degree of lymphatic invasion (Ly) and the status of lymph node metastasis (N) (Ly+N-: 72, and Ly-N+: 10 patients). RESULTS: High expression of VEGF-C and -D, and CCR7 was present in 88%, 63% and 67% of cases, respectively. The VEGF-C expression was significantly higher in Ly+N- than Ly-N+ (p<0.05), but VEGF-D and CCR7 were not. CCR7 expression was a prognostic factor in the Ly+N- subgroup (p<0.05), but VEGF-C and -D were not. CONCLUSION: VEGF-C and -D and CCR7 may play critical roles in lymphatic invasion in primary tumors. CCR7 expression should provide prognostic information in node-negative gastric cancer patients showing lymphatic invasion.

Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes.

Suppression of tumor-specific T cell sensitization is a predominant mechanism of tumor escape. To identify tumor-induced suppressor cells, we transferred spleen cells from mice bearing progressive MCA205 sarcoma into sublethally irradiated mice. These mice were then inoculated subdermally with tumor cells to stimulate T cell response in the tumor-draining lymph-node (TDLN). Tumor progression induced splenomegaly with a dramatic increase (22.1%) in CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) compared with 2.6% of that in normal mice. Analyses of therapeutic effects by the adoptive immunotherapy revealed that the transfer of spleen cells from tumor-bearing mice severely inhibited the generation of tumor-immune T cells in the TDLN. We further identified MDSC to be the dominant suppressor cells. However, cells of identical phenotype from normal spleens lacked the suppressive effects. The suppression was independent of CD4(+)CD25(+) regulatory T cells. Intracellular IFN-gamma staining revealed that the transfer of MDSC resulted in a decrease in numbers of tumor-specific CD4(+) and CD8(+) T cells. Transfer of MDSC from MCA207 tumor-bearing mice also suppressed the MCA205 immune response indicating a lack of immunologic specificity. Further analyses demonstrated that MDSC inhibited T cell activation that was triggered either by anti-CD3 mAb or by tumor cells. However, MDSC did not suppress the function of immune T cells in vivo at the effector phase. Our data provide the first evidence that the systemic transfer of MDSC inhibited and interfered with the sensitization of tumor-specific T cell responses in the TDLN.

Effective treatment of spontaneous metastases derived from a poorly immunogenic murine mammary carcinoma by combined dendritic-tumor hybrid vaccination and adoptive transfer of sensitized T cells.

Curative immunotherapy against spontaneous metastases of poorly immunogenic tumors has been difficult to demonstrate, but it is highly relevant to clinical disease conditions. The 4T1 mammary carcinoma shares many characteristics of human mammary cancer. Here, mice with 4T1 spontaneous metastases were treated effectively with a combination of dendritic (DC)-tumor hybrid vaccination and adoptive transfer of tumor-draining lymph node-derived immune T cells. This strategy significantly prolonged survival and cured some mice. In this model, the combined immunotherapy induced a dramatic increase of T cells in the lung where metastases were located and in the spleen where tumor was not present. The mechanism of increasing numbers of T cells is likely attributed to the ability of DC-tumor hybrids to stimulate vigorous proliferation of adoptively transferred T cells rather than to promote their infiltration into tumor-harboring and lymphoid organs. Taken together, the combined approach may be useful for clinical development of cancer immunotherapy.

Successful treatment of intractable esophagothoracic fistula using covered self-expandable stent.

This report concerns the successful treatment with a covered self-expandable stent of an intractable thoracoesophageal fistula after total esophagectomy for esophageal cancer. Total esophagectomy was performed on a 68-year-old man who presented with a huge esophageal cancer in the lower esophagus. Massive leakage was observed on the 5th day postoperatively. Since high fever and coughing continued, he was diagnosed as having esophagothoracic fistula and pyothorax, after which fenestration of the right chest wall was performed. Although the patient's general condition was getting better, stenosis near the anastomosis (esophagogastrostomy) and the esophagothoracic fistula were resistant to treatment with balloon dilatation and repeated endoscopic mucotomy. Further treatment, consisting of glue or fibrin sealant injection was not effective. After a covered self-expandable stent had been placed endoscopically, however, the fistel was completely cured in 2 months. This new endoscopic approach thus represents a promising option for the treatment of intractable esophagothoracic fistula.