Possibilities for and limits of upfront surgical strategy with lateral pelvic node dissection for low rectal cancer.

BACKGROUND: Metastatic lateral pelvic nodes represent an important cause of pelvic recurrence in low rectal cancer patients even after preoperative chemoradiotherapy. This study aimed to evaluate the prognostic benefit of an upfront lateral pelvic nodes dissection strategy. METHODS: A total of 175 consecutive patients with stage II/III low rectal adenocarcinoma who underwent mesorectal excision with lateral pelvic nodes dissection between 1998 and 2013 were identified. Regional lateral pelvic nodes were categorized as LD2 nodes (internal iliac, hypogastric and obturator) and LD3 nodes (external iliac, common iliac, lateral sacral, presacral and sacral promontory) according to the current Japanese Society for Cancer of the Colon and Rectum classification. RESULTS: Five-year cumulative risks of local recurrence and recurrence-free survival were 4.8% and 78.1% for stage II patients, and 11.8% and 61.7% for stage III patients, respectively. Among stage III patients, no differences were observed in cumulative risks of local recurrence (5 years: 9.3% vs 14.7%, P= 0.463) and recurrence-free survival (5 years: 65.1 vs 61.2%, P = 0.890) between lateral pelvic nodes (-) and LD2 (+) patients. In multivariate analyses, metastatic lateral pelvic nodes had no impact on cumulative risks of local recurrence (hazard ratioadj: 1.389; 95% confidence interval: 0.409-4.716) and recurrence-free survival (hazard ratioadj: 0.884; 95% confidence interval: 0.425-1.837). CONCLUSIONS: Metastatic lateral pelvic nodes had no impact on cumulative risks of local recurrence and recurrence-free survival based on an upfront lateral pelvic nodes strategy. Lateral pelvic nodes can improve recurrence and survival outcomes in locally advanced low rectal cancer patients with metastatic lateral pelvic nodes.

Aggressive and frequent resection of recurrences in retroperitoneal sarcoma contributes to long-term survival.

PURPOSE: Retroperitoneal sarcoma (RPS) is a rare tumor with a poor prognosis and is often undetected until it is significantly enlarged. While surgical resection remains the primary treatment, there is little research on its benefits, especially that concerning the reoperation of recurrent disease. This study investigated the impact of surgical procedures, especially reoperation of recurrent RPS, on prognosis. METHODS: This retrospective study included 51 patients who underwent radical resection surgery (R0 status) for primary or recurrent RPS without distant metastasis. Patient outcomes and prognosis were defined in terms of the clinicopathologic factors and surgical techniques performed. RESULTS: In all cases, the 5-year disease-free survival (DFS) rate was 28.2%, 5-year overall survival rate was 89.9%, and 5-year no residual liposarcoma rate was 54.3% after operation and re-reoperation. There was a statistically significant difference between the 5-year DFS rate and 5-year no residual liposarcoma rate due to frequent re-reoperation (p = 0.011). On univariate analysis of primary and recurrent lesions, the histological type and the number of organs involved were identified as statistically significant prognostic factors. Patients with well-differentiated liposarcomas had a statistically better prognosis than those with other cancer types (primary RPS, p = 0.028; recurrence, p = 0.024). CONCLUSIONS: Aggressive and frequent resection of recurrent RPS with combined resection of adjacent organs contributes to long-term survival. The establishment of a surgical strategy for RPS will require a prospective study.

Risk factors for peristomal skin disorders associated with temporary ileostomy construction.

PURPOSE: Skin disorders are the most common stoma-related complications after temporary diverting loop ileostomy with proctectomy. The aim of the present study was to investigate risk factors for skin disorders associated with temporary ileostomy construction. METHODS: A total of 185 consecutive patients who underwent curative proctectomy with temporary diverting loop ileostomy for rectal malignancies at a single comprehensive cancer center between 2013 and 2018 were collected and analyzed. RESULTS: The most frequent stoma-related complications were skin disorders (n = 62, 33.5%), followed by mucocutaneous separation (n = 38, 20.5%) and high-output stoma (n = 34, 18.4%). Patients with skin disorders had a higher median body mass index (BMI; 22.4 vs. 21.3 kg/m2, P = 0.002) and lower stoma height (16 vs. 20 mm, P < 0.001) than those without skin disorders. According to a multivariable logistic regression analysis, independent predictors of skin disorders included overweight (median BMI ≥ 25 kg/m2 [odds ratio = 3.6, 95% confidence interval: 1.5-8.6], P = 0.004) and lower stomal height (median stoma height < 20 mm [odds ratio = 3.2, 95% confidence interval: 1.6-6.3], P < 0.001). CONCLUSION: Overweight and lower stoma height are correlated with the presence of skin disorders. Construction of a well-elevated stoma can reduce skin disorders associated with temporary ileostomy construction.

The prognostic relevance of primary tumor sidedness to surgical treatment for recurrent colon cancer.

PURPOSE: The aim of this study was to investigate the predictive relevance of tumor sidedness on surgical resection after recurrence by evaluating the treatment outcomes after primary resection and recurrence in patients with localized colon cancer (CC). METHODS: A total of 735 consecutive patients who underwent curative resection for Stage I-III CC from 1997 to 2013 were categorized as having either right- or left-sided CC, and survival after primary surgery and after recurrence were analyzed. RESULTS: A total of 104 patients (14.1%) developed recurrence, 94 of which were in a single organ, and 59 patients underwent curative resection. For recurrence from both sides of the colon, a significantly better 5-year overall survival (OS) was experienced by patients who underwent curative resection compared to those who received palliative treatment (right: 42.2% vs not reached, respectively; P < 0.001; left: 71 vs 15.9%, respectively; P < 0.001). Meanwhile, a still worse OS was observed in patients with curative resection for recurrent right-sided CC compared to those with resection for recurrent left-sided CC (5-year: 42.2 vs 71%; P = 0.03). CONCLUSION: Surgical resection undoubtedly improved survival after recurrence, however, patients with surgical resection for recurrent right-sided CC tended to have a worse prognosis.

Prognostic predictions based on pathological findings of peritoneal dissemination in patients with stage IV colorectal cancer without residual disease (R0 status).

PURPOSE: This study aimed to clarify the prognosis of patients after resection of stage IV colorectal cancer and synchronous peritoneal metastasis (no residual disease: R0 status) based on histopathologic findings. METHODS: The subjects of this study were 26 patients who underwent radical resection of synchronous peritoneal metastases of stage IV colorectal cancer. Only patients with one synchronous peritoneal metastasis were included in this study. The peritoneal lesions were initially classified into two categories based on the presence or absence of adenocarcinoma on their surface: RM-negative or RM-positive. The lesions were subsequently classified as being of massive or diffuse type and of small (< 6 mm) or large (≥ 6 mm) type according to the maximum metastatic tumor dimension. RESULTS: Multivariate analysis revealed that massive type metastatic tumors were associated with a better disease-free survival (DFS; p = 0.047) and overall survival (OS; p = 0.033), than diffuse type tumors. CONCLUSION: A detailed stratification of pathological findings could contribute remarkably to prognostic predictions for patients with synchronous peritoneal metastases.

Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy.

PURPOSE: Our sincere hope is to establish the predictive factors of neoadjuvant chemotherapy (NAC) response and provide patients with greater certainty regarding treatment outcomes. The aim of this study was to assess the response to NAC and survival in patients with locally advanced rectal cancer (LARC) according to their RAS/BRAF mutation status. METHODS: Data on 57 patients with LARC who received NAC between 2009 and 2016 were analyzed retrospectively. The patients were classified into two groups based on their mutation status: wild-type in both RAS and BRAF (WT) or mutant-type in either RAS or BRAF (MT). RESULTS: Twenty-three patients were classified as WT, and the remaining 34 patients were MT. Histological response to NAC was similar in both groups. In responders, the 3-year relapse-free survival (RFS) was better compared with the non-responders (92 and 66%, respectively). In the WT group, the 3-year RFS was 95% which was significantly better than that in the MT group (59%, p = 0.011). The MT group was further subdivided into the following 2 groups by the pathological response; the MT responders (n = 10) and MT non-responders (n = 24). The 3-year RFS was 50% in the MT non-responders, which was significantly worse compared to that in the remaining patients (92%, p = 0.001). CONCLUSION: RAS/BRAF mutations did not affect the response to NAC. However, the RFS was likely to be poor for those in the MT group who did not achieve favorable pathological response. In contrast, the RFS was favorable in the WT group regardless of the pathological response.

A case of local recurrence of T1 rectal cancer 10 years after transanal excision.

We report a case of a patient with T1 rectal cancer, which recurred locally after 10 years from the primary operation. A 78-year-old woman was diagnosed with rectal cancer. Transanal excision (TAE) was performed in December 2006. The pathological findings revealed stage I rectal cancer [tub2>muc, pSM (2,510 µm), ly0, v0, pHM0, pVM0]. Because she did not opt for additional treatment, she received follow-up examination. After approximately 10 years from the primary operation, she presented to her physician, complaining of melena, and she was referred to our hospital again in November 2016. She was diagnosed with recurrent rectal cancer. Laparoscopic abdominoperineal resection was performed in December 2016. Pathological findings revealed stage IIIB rectal cancer (tub2>muc, pA, pN1). The reported postoperative local recurrence rate for T1 rectal cancer after TAE is high, but local recurrence after years from the primary operation is rare. In high-risk cases, local recurrence may be observed even after 10 years from the primary operation. Long-term and close postoperative follow-up is important to detect local recurrence early.

[The Case of a Patient with Gastric Cancer Who Showed No Neutropenia Only When Using the Generic S-1 Adjuvant Chemotherapy Formulation].

We report the case of a 72-year-old female who underwent laparoscopic total gastrectomy for gastric cancer. The pathological diagnosis was pT3, N1, M0, pStage II B. She received adjuvant chemotherapy with the TS-1®combination OD tablet, beginning 48 days after gastrectomy. The first course was stopped at day 7 because of neutropenia. The dose was decreased, a second course was started, and the patient completed her second course without neutropenia. After completion of the second course, we discovered that she had taken generic drugs(NKS-1®combination OD tablet)during the second course. She was enrolled in a clinical trial in which the administration of generic drugs was not permitted, as per the protocol. Beginning with the third course, we once again treated her with TS-1, and we observed a return of neutropenia in every subsequent course. We decreased the dose of TS-1 and changed the administration schedule each time. She exhibited no neutropenia only when using the generic S-1 formulation. It is possible that the anti-tumor effect of the generic S-1 formulation, and its associated adverse events, are not identical to the innovator formulation.

A case of metachronous left ovarian metastasis 8 years after surgery for cecal cancer and right ovarian metastasis: Report of a case.

Metachronous ovarian metastasis of colorectal adenocarcinoma is mostly identified within 3 years. Here we present a case of a 64-year-old woman with cecal cancer who underwent right oophorectomy for ovarian metastasis. Imaging was performed because of abdominal bloating; it detected a swollen right ovary with ascites. On laparotomy, a right ovarian tumor and cecal cancer were identified. After right oophorectomy, a diagnosis of unilateral ovarian metastasis from colon cancer was made. One month later, right hemicolectomy was performed. Eight years after initial surgery, the patient presented with vaginal bleeding. A computed tomography (CT) scan revealed a pelvic mass approximately 10 cm in diameter, but no mass was evident on a CT image taken 6 months before. The patient was diagnosed with left ovarian metastasis from colon cancer. A third laparotomy revealed a left ovarian tumor, but there was no evidence of other metastases or peritoneal dissemination. Left oophorectomy was performed. Oophorectomy is considered to be associated with a survival benefit in ovarian metastasis without other extensive metastasis. However, ovarian metastasis is often bilateral. Although complete resection was achieved in the present case, the findings support performing prophylactic bilateral oophorectomy if metastasis is identified in a unilateral ovary.

Histopathologic risk stratification of stage IIB colorectal cancer.

PURPOSE: To stratify stage IIB (pT4a PN0) colorectal cancer in terms of histopathologic findings. METHODS: We reviewed the medical records of 80 patients who underwent surgery for stage IIB colorectal cancer. The disease-free survival (DFS) and overall survival (OS) rates were evaluated and correlated with the presence or absence of "Tumor Necrosis", "Crohn's-like lymphoid reaction", and "Perineural Invasion". RESULTS: Patients with "Tumor Necrosis" had significantly lower DFS rates (p < 0.0001), those with "Crohn's-like lymphoid reaction" had significantly higher DFS rates (p = 0.037), and those with "Perineural Invasion" had significantly lower DFS rates (p < 0.0001). Patients with "Tumor Necrosis" had significantly lower OS rates (p = 0.016), those with "Crohn's-like lymphoid reaction" had significantly higher OS rates (p = 0.022), and those with "Perineural Invasion" had significantly lower OS rates (p = 0.003). CONCLUSIONS: Since stage IIB colorectal cancers accompanied by the pathological findings of "Tumor Necrosis" and "Perineural Invasion", but with the absence of "Crohn's-like lymphoid reaction" carried a poor prognosis, the efficacy of adjuvant chemoradiation must be considered for these patients.

Aggressive multimodality treatment for advanced rectal cancer.

A case of advanced rectal cancer treated by aggressive local and systemic treatment who has survived more than 7 years from initial recurrence is presented. A 55-year-old woman was diagnosed with advanced lower rectal cancer and underwent a low anterior resection with complete removal of all regional lymph nodes and total mesorectal excision. The tumor was diagnosed as a moderately differentiated adenocarcinoma, pStage IIIB (T3, N2a, M0). Twenty-six months after the initial surgery, local recurrence in the pelvis was detected by computed tomography, and total pelvic exenteration with distal sacrectomy (TPES) was performed after systemic chemotherapy with a molecular-targeted drug. Six months after the TPES, multiple lung metastases were detected. Consequently, the patient underwent radiofrequency ablation (RFA) and chemotherapy. The disease has since been controlled for 38 months. As volume control is essential for cancer treatment, it may be important to combine appropriate local therapy with systemic therapy to metastatic or recurrent sites in order to achieve much longer disease control.

Frequent lack of GNAS mutations in colorectal adenocarcinoma associated with GNAS-mutated villous adenoma.

Colorectal villous adenoma is thought to be associated with a high risk of progression to adenocarcinoma. To better characterize the genetic alterations involved in colorectal carcinogenesis related to villous adenoma, we analyzed mutations in APC, BRAF, KRAS, TP53, and GNAS in 12 colorectal adenocarcinomas associated with villous adenomas. APC, KRAS, and BRAF mutations were identified in five, 11, and one lesion, respectively, and most of these mutations were shared between the villous adenoma and the adenocarcinoma components in the respective lesions, except in one lesion with APC mutations and in two lesions with KRAS mutations. TP53 mutations were observed exclusively in four adenocarcinoma components, consistent with their role in the progression from adenoma to adenocarcinoma. Activating GNAS mutations were found in nine villous adenomas; however, unexpectedly, these mutations were shared only in three associated adenocarcinomas. Notably, all six adenocarcinomas with discordant GNAS mutation statuses were nonmucinous type, whereas all the other adenocarcinomas, including three adenocarcinomas associated with GNAS wild-type villous adenomas, were mucinous type. The current study suggests that GNAS-mutated villous adenomas may not necessarily be direct precursors of associated adenocarcinomas. At the same time, our observations support the role of activating GNAS mutations in increased mucin production in colorectal neoplasms.

Case-matched comparison of the short-term outcomes between laparoscopic and open abdominoperineal resection for rectal cancer.

PURPOSE: The aim of this study was to evaluate the short-term surgical outcomes of laparoscopic abdominoperineal resection (APR) for rectal cancer, by comparing it with a case-control series of open APR. METHODS: Fourteen patients with rectal cancer who underwent laparoscopic APR between August 2004 and November 2011 were compared with the open APR group of 14 patients matched for age, gender, and surgical procedure. RESULTS: There were no cases of conversion to laparotomy in the laparoscopic APR group and no mortality in either of the groups. The median operation was longer (P = 0.002), but the median amount of blood loss was smaller (P = 0.019), in the laparoscopic APR group. The median length of hospital stay of the laparoscopic APR group was 8 days, shorter than that of the open APR group (16 days, P < 0.001). The changes of the WBC count and serum CRP level after operations were significantly smaller in the laparoscopic APR group (P < 0.05). There were no significant differences between the groups in terms of the perioperative morbidity and readmission rates within 30 days. CONCLUSION: Patients undergoing laparoscopic APR had superior perioperative outcomes to those undergoing open APR, except for the longer operation.

Safety and Feasibility of Temporary Ileostomy in Older Patients: A Retrospective Study.

BACKGROUND: Temporary ileostomy reduces the incidence of severe anastomotic leakage and postoperative mortality. However, little is known about ileostomy-related complications in older adults. PURPOSE: To clarify the safety and feasibility of temporary ileostomy for rectal cancer in older patients. METHODS: Data were collected from a prospectively created database and complemented by secondary chart review for consecutive patients with rectal malignancy who underwent curative proctectomy with diverting loop ileostomy between 2013 and 2018. Ileostomy construction and closure were compared between two groups (defined as elderly and non-elderly patients). Data for 22 patients who were 75 years of age and older (elderly group) and 160 patients who were younger than 75 years (non-elderly group) were analyzed. RESULTS: The median maximum fecal output was significantly higher in the non-elderly group compared with the elderly group. No significant differences were observed between the two groups in postoperative intravenous hydration, creatinine ratio, and ileostomy-related complication rate. Although the elderly group had a higher rate of early stoma closure, the causes were not related to those complications. CONCLUSION: Temporary ileostomy was a safe and feasible procedure in this population of older patients with rectal malignancies.

PCR-based quantitative detection of intraperitoneal free cancer cells for predicting locoregional recurrence after rectal cancer resection.

INTRODUCTION: Locoregional recurrence after curative resection remains an important issue in the treatment of colorectal cancer (CRC). The aim of the present study was to investigate the clinical significance of quantitative detection of intraperitoneal free cancer cells by a PCR-based method for predicting locoregional recurrence after CRC resection. METHOD: A total of 114 patients with CRC were enrolled between March 2017 and December 2018, and 95 patients with Stage I-III CRC were analyzed. Peritoneal lavage fluid was collected before and after tumour resection and subjected to cytology and quantitative reverse transcription-PCR (qRT-PCR) with carcinoembryonic antigen (CEA) as a genetic marker. RESULTS: 2.1% of patients had positive cytology after resection, whereas 9.5% had positive CEA qRT-PCR (PCR+) after resection. Eight of nine PCR+ patients after resection had tumours in the rectum. Fifteen (15.8%) patients developed recurrence during the follow-up period, including three with locoregional recurrence. One of 86 (1.2%) PCR- patients and 2 of 9 (22.2%) PCR+ patients after resection developed locoregional recurrence. Overall and in rectal cancer patients, the 3-year cumulative risk of locoregional recurrence was 25.0% and 28.6% for PCR+ patients, which is significantly higher than PCR- patients (1.3% and 0%, P < 0.001 and P = 0.001, respectively). CONCLUSION: Intraperitoneal free cancer cells can serve as a sensitive predictor of locoregional recurrence after rectal cancer resection. qRT-PCR for CEA can be a suitable method for detecting intraperitoneal free cancer cells in peritoneal lavage fluid.

Gastroduodenal artery pseudoaneurysm hemorrhage 1 year after laparoscopic distal gastrectomy: a case report.

BACKGROUND: Postoperative bleeding originating from pseudoaneurysms after radical gastrectomy is not common, but it can be fatal. In particular, delayed bleeding that occurs after the seventh postoperative day is rare. CASE PRESENTATION: A 54-year-old man underwent laparoscopic distal gastrectomy, D2 lymph node dissection, and Roux en-Y reconstruction for duodenal neuroendocrine tumors. Drainage was performed for a postoperative pancreatic fistula and abdominal abscess. On the 28th postoperative day, he passed a large amount of bloody stool; therefore, emergency esophagogastroduodenoscopy (EGD) and angiography were performed. However, neither examination demonstrated any bleeding foci or pseudoaneurysm. He was conservatively observed and discharged on the 50th postoperative day. Approximately 1 year after the surgery, he passed a bloody stool and experienced hemorrhagic shock. An EGD revealed exposed blood vessels at the duodenal blind end. His condition was diagnosed as a pseudoaneurysm arising from gastroduodenal artery, which ruptured into the duodenum, based on abdominal contrast-enhanced computed tomography findings. Emergency angiography was performed, and the pseudoaneurysm and artery were successfully embolized. CONCLUSIONS: This case illustrates that there is a possibility of delayed bleeding even 1 year after gastrectomy. Such cases may be serious and require immediate and careful management.

Detection of circulating tumor cells in drainage venous blood from colorectal cancer patients using a new filtration and cytology-based automated platform.

Numerous technologies exist to detect circulating tumor cells (CTCs), although reports on cytological detection of CTCs remain limited. We recently developed a cytology-based CTC detection device using glass slides and light microscopy. In this study, we automated this previously manual device to improve its efficiency and cost effectiveness for clinical applications. We conducted a pilot study using this device to compare CTCs in peripheral blood (PB) and draining venous blood (DVB) from patients with colorectal cancer (CRC). The cytology-based automated CTC detection platform consisted of a disposable filtration device with a three-dimensional (3D) metal filter and multichannel automated CTC enrichment device. This platform allowed rapid and gentle filtration of CTCs and their efficient transfer from the filter to glass slides for subsequent Papanicolaou (Pap) and immunocytochemical (ICC) staining. Cytological diagnosis of CTCs was performed by observing permanent glass slide specimens by light microscopy. The current pilot clinical study enrolled CRC patients (n = 26) with stage I-IV tumors, who underwent surgery. PB was collected before surgery, and DVB was obtained from the mesenteric vein immediately after resection. Based on the CTC morphology obtained from PB and DVB samples, we proposed the following cytological criteria for the diagnosis of CTCs: pan-cytokeratin-positive, atypical cells with malignant morphological features identified by Pap staining. The numbers of CTCs defined by these criteria were significantly higher in DVB than PB from CRC patients (p<0.01), and the number of CTCs in DVB was increased significantly with stage progression (p<0.05). These results suggest that DVB may be another potential source of CTCs other than PB for liquid biopsies including downstream analysis. This automated cytology-based CTC detection device therefore provides a unique and powerful tool to investigate the significance of CTCs in CRC patients in a clinical setting.

Surgical Strategy for Rectovaginal Fistula After Colorectal Anastomosis at a High-volume Cancer Center According to Image Type and Colonoscopy Findings.

BACKGROUND/AIM: The reported incidence of rectovaginal fistula is very low. Although some case reports have described surgical procedures, no systematic approach to the treatment of rectovaginal fistula according to diagnostic image and colonoscopy findings has been proposed. We present a comprehensive surgical strategy for rectovaginal fistula after colorectal anastomosis according to diagnostic image and colonoscopy findings. PATIENTS AND METHODS: This retrospective study included 11 patients who developed rectovaginal fistula after colorectal anastomosis. Rectovaginal fistula was classified into 4 types according to contrast enema images and colonoscopy findings, i.e., "Alone type", "Dead space type", "Anastomotic stricture type", and "Dead space and Anastomotic stricture type". The surgical strategies were "Diversion (Stoma)", "Percutaneous drainage", "Anastomotic stricture type", "Endoscopic balloon dilation", "Curettage of foreign bodies", "Simple full-thickness closure", "Split-thickness closure", "Pedicled flaps packing", and "Reanastomosis". The surgical strategy appropriate for each rectovaginal fistula type was investigated. RESULTS: Among "Alone type" cases, 5 (71.4%) healed with "only Diversion (Stoma)". "Alone type" cases (n=11) and all other cases (n=4) healed with "only Diversion (Stoma)" (n=5) or any other method (n=6) (p=0.022). CONCLUSION: For treatment of rectovaginal fistula after colorectal anastomosis, less invasive treatment approaches should be attempted first.

Ileal conduit necrosis after total pelvic exenteration for recurrence of gastrointestinal stromal tumor.

We report a case of ileal conduit necrosis after total pelvic exenteration for recurrence of gastrointestinal stromal tumor. A 47-year-old man was diagnosed with recurrence of gastrointestinal stromal tumor adjacent to the prostate after abdominoperineal resection 10 years prior. With imatinib administration for 18 months, the local recurrence decreased in size but did not separate from the prostate. We performed urinary diversion with conventional total pelvic exenteration. Ileal conduit necrosis was suspected the following day and emergency surgery was performed. The serosa of the ileal conduit showed segmental necrosis extending about 10 cm from the orifice. The ureterointestinal anastomotic site was opposite the orifice and was not necrotic. We resected the necrotic ileum and reconstructed an ileal conduit. The patient was discharged without any symptoms 46 days after surgery for further adjustment to use of a urostomy.