Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Predictive value of the Naples prognostic score on postoperative outcomes in patients with rectal cancer.

PURPOSE: The Naples prognostic score (NPS) is a prognostic index based on the nutritional and inflammatory status. However, its utility in predicting postoperative complications (POCs) has not been examined in rectal cancer (RC). We evaluated the predictive value of the preoperative NPS for POCs in RC. METHODS: We retrospectively analyzed 235 patients who underwent surgery for RC. The NPS was calculated based on serum albumin, serum total cholesterol, the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR). Severe POCs were defined as Clavien-Dindo classification grade ≥ III. The optimal cut-off value of the NPS was determined by a receiver operator characteristic (ROC) curve analysis. The NPS, NLR, LMR, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR), Glasgow prognostic score (GPS), Onodera prognostic nutritional index (PNI) and controlling nutritional status score (CONUT) were investigated as inflammation-based and/or nutritional markers. Predictors of severe POCs were analyzed by logistic regression modeling. RESULTS: Severe POCs were observed in 64 patients (27.2%). Male sex, operation time (> 257 min), blood loss (≥ 30 mL), albumin (< 4.0 g/dL), CRP (≥ 1.0 mg/dL), total cholesterol (≤ 180 mg/dL), NPS (≥ 2), LMR (≥ 3.48), PLR (≥ 103.6), CAR (> 0.025), GPS (≥ 1), PNI (< 48.1) and CONUT (≥ 2) were significantly associated with severe POCs. The multivariate analysis revealed that male sex, operation time (> 257 min), and a high NPS (≥ 2) were independent predictors of severe POCs. The ROC curve analysis revealed that the NPS had the greatest predictive value among the inflammation-based and/or nutritional markers. CONCLUSION: The NPS is a valuable predictor of severe POCs in RC.

The impact of the surgical Apgar score on oncological outcomes in patients with colorectal cancer: a propensity score-matched study.

BACKGROUND: The surgical Apgar score (SAS) predicts postoperative complications (POCs) following gastrointestinal surgery. Recently, the SAS was reported to be a predictor of not only POCs but also prognosis. However, the impact of the SAS on oncological outcomes in patients with colorectal cancer (CRC) has not been fully examined. The present study therefore explored the oncological significance of the SAS in patients with CRC, using a propensity score matching (PSM) method. METHODS: We retrospectively analyzed 639 patients who underwent radical surgery for CRC. The SAS was calculated based on three intraoperative parameters: estimated blood loss, lowest mean arterial pressure, and lowest heart rate. All patients were classified into 2 groups based on the SAS (≤6 and >6). The association of the SAS with the recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) was analyzed. RESULTS: After PSM, each group included 156 patients. Univariate analyses revealed that a lower SAS (≤6) was significantly associated with a worse OS and CSS. A multivariate analysis revealed that the age ≥75 years old, ASA-Physical Status ≥3, SAS ≤6, histologically undifferentiated tumor type, and an advanced pStage were independent factors for the OS, and open surgery, a SAS ≤6, histologically undifferentiated tumor type and advanced pStage were independent factors for the CSS. CONCLUSIONS: A lower SAS (≤6) was an independent prognostic factor for not only the OS but also the CSS in patients with CRC, suggesting that the SAS might be a useful biomarker predicting oncological outcomes in patients with CRC.

Long-term follow up in two cases of pelvic reconstruction using a combined VRAM flap-sacrocolpopexy for severe perineal hernia after abdominoperineal resection.

Perineal hernia is an infrequent complication of abdominoperineal resection (APR) and, currently, there is no consensus as to the optimal operative technique. Surgical repair can be achieved by either cerclage or the use of mesh or autologous tissue, and it has been reported that the recurrence rate after repair using autologous tissue is 33%. We present two post-APR cases of severe perineal hernia with pelvic organ prolapse (POP) which did not improve after repair using mesh. We regenerated the pelvic floor using a vertical rectus abdominis myocutaneous (VRAM) flap and performed a concomitant sacrocolpopexy to fix the POP. Drooping of the perineum and pelvic floor was greatly improved, and the patients have not experienced any recurrence for 6 years. This dual procedure has not been previously mentioned in the literature, and we consider this the first report of its kind.

[A Case of the Large Rectal GIST Treated by Laparoscopic Anus Preserving Operation after Neoadjuvant Therapy with Imatinib Mesylate].

A 50s old woman admitted to our hospital with anal pain, who was diagnosed as rectal gastrointestinal stromal tumor (GIST). After neoadjuvant therapy with imatinib mesylate for 6 months, the tumor reduced by 75% from its original size and anus preserving operation(low anterior resection)was performed. After operation adjuvant therapy with imatinib mesylate was performed for 2 years and 6 months. The patient is alive without recurrence 5 years after surgery. It is suggested that neoadjuvant therapy with imatinib mesylate is useful and safety for large rectal GIST, from the standpoint of anal preservation.

[A Case of Hyperammonemic Encephalopathy following mFOLFOX6 plus Panitumumab Therapy for Rectal Cancer].

An 80-year-old man underwent laparoscopic rectal high anterior resection with perineal dissemination for the management of RS rectal cancer. Following the diagnosis of RS rectal cancer with muc, pT4a, N3(14/15), M1c, P1, pStage Ⅳc, RAS/BRAF: wild type, treatment was initiated with mFOLFOX6 plus panitumumab(Pmab). Laboratory examination on admission revealed mild renal dysfunction(Cr 1.45 mg/dL). The patient became confused on day 3 of chemotherapy(JCS Ⅲ-200). Furthermore, laboratory findings revealed a serum ammonia level of 338µg/dL. He was diagnosed with 5-FU- induced hyperammonemic encephalopathy. Discontinuation of high-dose 5-FU and branched-chain amino acid solutions improved his mental status and decreased serum ammonia levels. We switched his chemotherapy regime to CPT-11 plus Pmab, but it was discontinued after 1 course on his request.

[A Case of Submucosal-Like Tumor at Cecum That Was Diagnosed as Colon Metastasis from Gastric Cancer].

The patient was a 70-year-old woman who had received distal gastrectomy for the gastric cancer which histology was poorly differentiated adenocarcinoma, pT4a(SE), ly2, v0, pNX, H0, P1, cy0 and pStage Ⅳ. She was treated with SOX after the operation. However, 4 years after gastrectomy, contrast enhanced abdominal CT showed a mass in the cecum and colonoscopy revealed submucosal-like tumor in the cecum, but the pathological diagnosis was unclear. We diagnosed the malignant tumor in the cecum and performed laparoscopic ileocolic resection. Histology of the tumor showed a poorly differentiated adenocarcinoma and immunohistochemical staining showed CK7+, CK20± and CDX2±, therefore, the colon tumor was diagnosed as a metastasis from the gastric cancer. After the ileocolic resection, she was treated with SOX. It was suggested that we need to consider colon metastasis from gastric cancer in mind, when we find submucosal-like tumor in colon after gastric cancer resection.

[A Case of Advanced Rectal Cancer with Metastasis Successfully Treated with an Anti-Vascular Endothelial Growth Factor (VEGF) Drug].

A 63-year-old asymptomatic woman was diagnosed with multiple liver tumors and a left pulmonary tumor by CT. Colonoscopy( CS)showed a Type 2, quarter circular tumor on Rb. The diagnosis was cT3N1aM1b(H3, PUL1), cStage Ⅳb rectal cancer. She was administered 8 courses of induction-adjuvant chemotherapy with CAPOX and bevacizumab(BEV). After the chemotherapy, CT and CS revealed shrinkage(up to 50%)of the metastatic liver tumor and primary tumor, and decreasing tumor marker levels. Laparoscopic abdominoperineal resection and partial hepatectomy(S5/6, S8)were performed. After the operation, she was administered 2 courses of chemotherapy with UFT and LV, after which thoracoscopy-assisted upper lobectomy of the left lung was performed. Currently, at 1 and a half years after treatment, no recurrence has been observed, and she is being followed up as an outpatient.

The prognostic significance of the advanced lung cancer inflammation index in patients with unresectable metastatic colorectal cancer: a retrospective study.

BACKGROUND: Growing evidence indicates that inflammation contributes to cancer progression, and several inflammatory markers have been reported to be associated with the clinical outcomes in patients with various types of cancer. Recently, the advanced lung cancer inflammation index (ALI) has been developed as a prognostic marker in patients with lung cancer. The difference between the ALI and the inflammatory markers reported in the previous studies is that the ALI contains not only indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. The aim of this study was to evaluate the prognostic significance of the ALI in patients with unresectable metastatic colorectal cancer. METHODS: We retrospectively reviewed a database of 159 patients who underwent combination chemotherapy for unresectable metastatic colorectal cancer between 2008 and 2016. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated from a blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI × serum albumin concentration/NLR. RESULTS: The overall survival rate was significantly worse in the low-ALI group than in the high-ALI group (p < 0.0001). Furthermore, the ALI was an independent prognostic factor for the overall survival (hazard ratio: 2.773, 95% confidence interval: 1.773-4.335, p < 0.001). CONCLUSIONS: A newly developed prognostic marker, the ALI, was found to be a novel prognostic marker in patients with unresectable metastatic colorectal cancer as well as in patients with lung cancer.

A review of reports on single-incision laparoscopic surgery for Crohn's disease.

The aim of this review was to analyze the currently available literature on single-incision laparoscopic surgery (SILS) for Crohn's disease (CD) with respect to surgical indications, surgical techniques, feasibility, and possible benefits of SILS for CD. A systematic query of articles published from January 2010 to July 2018 was performed. The studies were assessed for patient's age, gender, body mass index, disease type, SILS procedure, surgical procedure, incision length, operation time, rates of conversion to open surgery, postoperative complications, mortality, length of hospital stay, and rates of reoperation. After an initial review, 11 reports were selected. The surgical techniques and instruments showed wide variation. The mean operation time for SILS tended to be shorter than that for multiport laparoscopic surgery (MLS). The reported rates of conversion to open surgery and postoperative complications were not very different from those reported for MLS. In conclusion, the present review suggests that the SILS technique may be feasible and safe for select patients with CD. However, because we reviewed only a few studies with small sample sizes, prospectively designed trials with a large number of patients are required to clarify the true benefits of SILS for CD.

[A Case of a Patient with Type â £ Adachi Classification Treated with Laparoscopic Ileocecal Resection].

A 72-year-old woman was diagnosed with cecal cancer. Preoperative enhanced abdominal computed tomography(CT) and three-dimensional(3D)-CT angiographyrevealed a celiacomesenteric trunk(CMT). We performed a laparoscopic ileocecal resection without anyproblems owing to the obtained preoperative 3D-CT images. The postoperative course was uneventful. The celiac arteryhas manyanomalies, and 6 categories have been defined. Patients can be divided into 28 groups bycombining these anomalies with mutations in the hepatic artery, as explained byAdachi. Our case was a Type Ⅳ anomaly according to the Adachi classification, which accounts for 2.4% of all cases. We herein report this extremelyrare case.

[A Case of Laparoscopic Abdominoperineal Resection for Rectal Cancer with Left-Sided Inferior Vena Cava].

A 66-year-old-man was hospitalizedfor the treatment of rectal cancer. Preoperative contrast-enhancedcomputedtomography revealedrectal cancer, left-sided inferior vena cava, and distant metastasis. He was diagnosed with cStage Ⅳb rectal cancer. Laparoscopic abdominoperineal resection with standard lymph node dissection was performed. There have been a few reports on laparoscopic colorectal resection for patients with left-sided inferior vena cava. We report a case of laparoscopic abdominoperineal resection for a patient with left-sided inferior vena cava.

[Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer].

The RAINBOW trial showed that paclitaxel(PTX)plus ramucirumab(RAM)therapy improved the survival of patients with advanced gastric cancer, previously treated with chemotherapy. We retrospectively investigated 33 patients with unresectable or recurrent gastric cancer who underwent PTX plus RAM treatment as second- or third-line chemotherapy between September 2015 and December 2017. The median age was 68(45-84)years with 22 patients(67%)aged 65 years or older. Seventeen patients had unresectable and 16 patients had recurrent gastric cancer. ECOG PS was 2 in 5 patients(16%). PTX plus RAM was administered as second-line therapy for 24 patients, and as third-line therapy for 9 patients. Best overall response was partial response(PR)in 4 patients, stable disease(SD)in 14 patients, and progressive disease(PD)in 9 patients. Response rate(RR)and disease control rate(DCR)were 14.8% and 66.7%, respectively. Grade 3/4 adverse events were observed in 28(85%)of(leucopenia·neutropenia[64%], neuropathy[9%], etc). Median follow-up period was 7.3(0.4- 22.4)months. Median OS and PFS were 9.3(0.4-22.4)months and 4.7(0.4-22.4)months, respectively. We conclude that PTX plus RAM therapy is useful for treating unresectable or recurrent gastric cancer. In clinical practice, we have many opportunities to provide PTX plus RAM therapy for patients of older age and poorer PS; careful attention to adverse events is essential in such cases.

Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer.

Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty-four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post-treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post-treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post-treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte-mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.

A comparison of the local immune status between the primary and metastatic tumor in colorectal cancer: a retrospective study.

BACKGROUND: The anticancer immune response has been reported to correlate with cancer progression. Tumor-infiltrating lymphocytes (TILs), which are one of the indicators of host immunity, affect the tumor growth, metastasis and chemoresistance. Both TILs in the primary tumor and those in the metastatic tumor have been reported to be a useful predictor of the survival and therapeutic outcome. However, the correlation between the density of TILs in the primary and metastatic tumor is unclear. The aim of this study was to elucidate the correlation between the density of TILs in the primary and metastatic tumor. METHODS: A total of 24 patients with stage IV colorectal cancer who underwent concurrent resection of the primary tumor and liver metastasis were enrolled in order to assess the correlation between the density of TILs in the primary tumor and that in the metastatic tumor. Hematoxylin and eosin (HE)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by the measurement of the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. In addition, to evaluate TIL subsets and the activation/suppression status of the lymphocytes, immunohistochemistry for CD4, CD8, Forkhead boxprotein P3 (FOXP3), programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), inducible T-cell co-stimulator (ICOS), Glucocorticoid induced tumor necrosis factor receptor related protein (GITR), Human Leukocyte Antigen - antigen D Related (HLA-DR) and Granzyme B was performed, and the number of immunoreactive lymphocytes was counted. RESULTS: According to the evaluation using the HE-stained sections, the density of tumor-infiltrating mononuclear inflammatory cells in the primary tumor was significantly associated with that in the metastatic tumor. In addition, according to the immunohistochemistry evaluation, the density of CD4+, CD8+ and FOXP3+ TILs in the primary tumor and that in the metastatic tumor were significantly correlated with that in the metastatic tumor. Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B and the PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor. CONCLUSIONS: The local immune status of the primary tumor was revealed to be similar to that of the metastatic tumor. This suggests that the evaluation of the local immunity of the primary tumor may be a substitute for the evaluation of the local immunity of the metastatic lesion. Therefore, information on the primary tumor may be useful when considering treatment strategies for metastatic lesions.

The feasibility and short-term clinical outcomes of single-incision laparoscopic surgery for patients with complex Crohn's disease.

PURPOSE: Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multi-port laparoscopic surgery. Recently, this technique has been applied to Crohn's disease (CD) with primary ileocolic strictures; however, the application of a laparoscopic approach for complex CD, which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the safety and feasibility of SILS for patients with complex disease and to compare its clinical results in patients with complex disease vs. those with simple stricture disease. METHODS: Fifty patients who underwent SILS for CD were divided into two groups: those with complex disease (complex group, n = 25), and those with simple strictures (simple group, n = 25). The preoperative data and clinical outcomes were analyzed and compared between the groups. RESULTS: The operative time, blood loss and length of laparotomy incision were not significantly different between the groups. Although the rate of conversion and need for an additional port tended to be higher in the complex group, the rate of postoperative complications and length of hospital stay did not differ significantly between the groups. CONCLUSION: SILS may be feasible for carefully selected patients with complex CD.

[A Case of Appendiceal Cancer Wherein the Abdominal Abscess Ruptured into the Urinary Bladder Owing to Obstructive Appendicitis].

A 73-year-old woman presented to her doctor because of lower abdominal pain and distension. A neoplastic lesion in the lower abdomen was revealed, and she was referred to our department. Enhanced CT showed wall thickening in the urinary bladder and a 6 cm mass that extended to the appendix. An appendiceal tumor invading the urinary bladder or a urinary bladder tumor invading the appendix was suspected, and we planned surgical treatment. One month later, we repeated enhanced CT scanning on admission. The mass had shrunk, but the thickening of the urinary bladder wall remained, and an enhanced appendiceal tumor was visible. Surgery was performed and we found a 1 cm appendiceal tumor. Intraoperative pathological examination revealed appendiceal cancer. Therefore, we performed ileocecal resection, D2 lymph node dissection, and partial cystectomy. Final histopathological examination revealed appendiceal cancer with pT2N0M0, pStage Ⅰ. Taking into account the patient's clinical course, we diagnosed obstructive appendicitis with an abscess due to appendiceal cancer rupture into the urinary bladder.

The peripheral monocyte count is associated with the density of tumor-associated macrophages in the tumor microenvironment of colorectal cancer: a retrospective study.

BACKGROUND: Inflammation is widely recognized to play an important role in cancer progression, and the peripheral monocyte count has been reported to correlate with the prognosis in patients with colorectal cancer. This is based on the hypothesis that the peripheral monocyte level and the density of tumor-associated macrophages (TAMs) in the cancer microenvironment correlate with each other. However, the influence of TAMs on the prognosis and the correlation between the peripheral monocyte count and the density of TAMs have not yet been elucidated. METHODS: A total of 168 patients with stage II/III colorectal cancer were enrolled in this study. Preoperative blood samples were obtained at the time of the diagnosis before surgery. The expression of TAMs in the cancer microenvironment was assessed by immunohistochemistry. RESULTS: The progression-free and overall survival rate were significantly worse in the high-TAMs group than in the low-TAMs group (p = 0.0012 and p = 0.0207, respectively). The peripheral monocyte count was significantly associated with the number of TAMs (correlation coefficients: 0.202, p = 0.047). CONCLUSIONS: The peripheral monocyte count was associated with the density of the TAMs, which created a microenvironment favorable for cancer development and were correlated with a poor prognosis. Therefore, the peripheral monocyte count is a useful prognostic marker reflecting the status of the tumor microenvironment.

The impact of the preoperative peripheral lymphocyte count and lymphocyte percentage in patients with colorectal cancer.

PURPOSE: We evaluated the prognostic significance of the peripheral lymphocyte count and lymphocyte percentage, which reflect the preoperative immune status, in patients with colorectal cancer (CRC) and then compared their accuracy as predictors of the survival. METHODS: We retrospectively reviewed a database of 362 patients. We classified the patients into high lymphocyte count and low lymphocyte count groups. We also classified the patients into high lymphocyte percentage and low lymphocyte percentage groups. RESULTS: The 5-year relapse-free survival (RFS) rate in the high lymphocyte count group tended to be higher than that in the low lymphocyte count group. The 5-year overall survival (OS) rate in the high lymphocyte count group was significantly higher than that in the low lymphocyte count group. In contrast, the 5-year RFS and OS rates in the high lymphocyte percentage group were both significantly higher than those in the low lymphocyte percentage group. A multivariate analysis showed that the lymphocyte percentage was independently associated with the OS. CONCLUSIONS: These findings suggest that the lymphocyte percentage is a good predictor of the OS and may be a stronger predictor of survival than the lymphocyte count in CRC patients.