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ObjectiveTo date, there are no predictive biomarkers to guide selection of patients with gastric cancer (GC) who benefit from paclitaxel. Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) was a 2×2 factorial randomised phase III study in which patients with GC were randomised to Pac-S-1 (paclitaxel +S-1), Pac-UFT (paclitaxel +UFT), S-1 alone or UFT alone after curative surgery.DesignThe primary objective of this study was to identify a gene signature that predicts survival benefit from paclitaxel chemotherapy in GC patients. SAMIT GC samples were profiled using a customised 476 gene NanoString panel. A random forest machine-learning model was applied on the NanoString profiles to develop a gene signature. An independent cohort of metastatic patients with GC treated with paclitaxel and ramucirumab (Pac-Ram) served as an external validation cohort.ResultsFrom the SAMIT trial 499 samples were analysed in this study. From the Pac-S-1 training cohort, the random forest model generated a 19-gene signature assigning patients to two groups: Pac-Sensitive and Pac-Resistant. In the Pac-UFT validation cohort, Pac-Sensitive patients exhibited a significant improvement in disease free survival (DFS): 3-year DFS 66% vs 40% (HR 0.44, p=0.0029). There was no survival difference between Pac-Sensitive and Pac-Resistant in the UFT or S-1 alone arms, test of interaction pConclusionUsing machine-learning techniques on one of the largest GC trials (SAMIT), we identify a gene signature representing the first predictive biomarker for paclitaxel benefit.Trial registration numberUMIN Clinical Trials Registry: C000000082 (SAMIT); ClinicalTrials.gov identifier, 02628951 (South Korean trial)

Purpose The efficacy of fluorouracil + oxaliplatin + irinotecan with bevacizumab (FOLFOXIRI + BV) has been verified for metastatic colorectal cancer (mCRC). In clinical practice, the original (O-FOLFOXIRI + BV) and modified dose settings (M-FOLFOXIRI + BV) are adopted for Asian patients. We aimed to compare the real-world efficacy and safety of these two regimens. Methods This retrospective cohort study reviewed clinical data of all consecutive mCRC patients treated with FOLFOXIRI + BV at a cancer centre in Japan. One hundred patients were divided into two groups: one that received O-FOLFOXIRI + BV (group O, n = 30) and another that received M-FOLFOXIRI + BV (group M, n = 70). Progression-free survival (PFS) was set as the primary endpoint, with overall survival (OS), overall response rate (ORR), and safety as secondary endpoints. Results PFS was superior in group M (median PFS; 8.7 vs. 11.5 months, P = 0.098). The use of O-FOLFOXIRI + BV emerged as an independent risk factor of poor PFS (hazard ratio = 2.155, P = 0.012). Both ORR (43.3 vs. 65.7%, P = 0.047) and OS (median OS; 17.9 vs. 27.0 months, P = 0.127) were more favourable in group M. Grade ≥ 3 adverse events were more frequently observed in group O (90 vs. 74.3%, P = 0.108), whereas dose intensity was higher in group M because a shorter duration was required for cytotoxic drug administration (2.9 vs. 2.6 weeks/course, P = 0.051) in the induction term. Conclusion We found that M-FOLFOXIRI + BV had more favourable efficacy and safety than O-FOLFOXIRI + BV, which may be a better fit for Asian patients and can be potentially used as an alternative for upfront chemotherapy for mCRC.

Background: Analytical information obtained from clinical tissue samples has recently become more important due to recent advancements in the clinical practice of medicine, for example, gene panel testing. However, acquiring and managing the sample quality, which greatly influences the analyses, are not sufficient and hence requires immediate attention. We introduced time stamp (TS) recording and documentation using the Standard PREanalytical Code (SPREC) for breast cancer surgery samples to monitor and control their quality. Materials and Methods: The TS recording used SPREC for quality control of each sample by recording seven factors: type of sample, type of collection, warm ischemia time (WIT), cold ischemia time (CIT), fixation type, fixation time (FT), and long-term storage. The responsibilities to record each factor were assigned among group members (breast surgeons, anesthesiologists, pathologists, operating room nurses, and medical technologists in pathology). Results: Records based on SPREC were recorded for 393 surgical cases of first-time breast cancer patients performed at the Kanagawa Cancer Center from May 2018 to April 2019. The vascular clamp time was defined as when skin flap formation was completed, regardless of the surgical procedure. An anesthesiologist recorded the vascular clamp time and sample collection time, and the pathologist recorded the fixation start time and fixation end time. WIT was 23 (3-116) minutes (breast-conserving surgery, 11 [3-38] minutes; mastectomy, 26 [5-116] minutes; and nipple-sparing mastectomy, 39 [31-43] minutes), CIT was 37 (3-1052) minutes, and FT was 43 (17-115) hours. The median CIT and FT were significantly shortened after introducing the TS system, and the variabilities were reduced. Conclusion: A TS system for quality control of breast cancer surgical sample functions well due to the establishment of highly versatile WIT and a working group consisting of multiple members of different occupations who shared roles.

Background/aim Population aging results in increasing numbers of elderly persons undergoing surgery for colorectal cancer. We sought to identify objective preoperative indicators of outcomes, with a view toward development of safe, effective treatments for such patients. Patients and methods The study included 99 patients aged 80 years or more, who were treated surgically for stage I- III colorectal cancer. Preoperative nutritional status was compared retrospectively between those who suffered postoperative complications (n=40) and those who did not (n=59). Results Univariate analysis revealed low prealbumin (PreAlb) concentration (p=0.032) and low platelet-to-lymphocyte ratio (p=0.116) as risk factors for postoperative complications. Multivariate analysis showed preoperative PreAlb concentration to be an independent risk factor (OR=0.884; 95% confidence interval=0.791-0.989; p=0.024) associated with postoperative length of hospital stay (coef.=-0.336, p=0.002). Conclusion PreAlb, a rapid turnover protein, shows promise as a simple predictor of postoperative complications in elderly patients treated for colorectal surgery.

Background/aim The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). Patients and methods We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. Results High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. Conclusion Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.

Background/aim This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). Patients and methods PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. Results No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). Conclusion PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

The lymph node (LN) ratio (LNR) has been proposed as a sensitive prognosticator in patients with esophageal squamous cell carcinoma (ESCC), especially when the number of LNs harvested is insufficient. We investigated the association between the LNR and survival in patients with locally advanced ESCC who received neoadjuvant chemotherapy (NAC) and explored whether the LNR is a prognosticator in these patients when stratified by their response to NAC. We retrospectively reviewed 199 locally advanced ESCC patients who received curative resection after NAC between January 2011 and December 2019. The predictive accuracy of the adjusted X-tile cut-off values for LNR of 0 and 0.13 was compared with that in the Union for International Cancer Control pathological N (UICC pN) categories. The association between survival rate and clinicopathological features was examined. Multivariate analysis identified that the LNR was an independent risk factor for recurrence-free survival [RFS; hazard ratio (HR) 6.917, p

There are few reports of conversion surgery (CS) after nivolumab monotherapy because it is considered as a third-line standard chemotherapy for unresectable or recurrent gastric cancer. Here, we report a rare case of stage IV gastric cancer effectively treated with CS after nivolumab monotherapy as a third-line chemotherapy. A 73-year-old man was referred to our hospital with loss of appetite and abdominal discomfort. Stage IV gastric cancer with liver metastasis was diagnosed via upper gastrointestinal endoscopy and CT. Twelve courses of capecitabine, cisplatin, and trastuzumab were administered as the first-line treatment, 25 courses of paclitaxel plus ramucirumab as the second-line treatment, and 31 courses of nivolumab monotherapy as the third-line treatment. After 31 courses of nivolumab monotherapy, CT showed that the primary tumor shrank with no liver metastasis or ascites. Diagnostic laparoscopy was performed with no peritoneal dissemination (P0), and the peritoneal lavage cytology was negative (CY0). CS was performed with total gastrectomy and D2 lymph node dissection (R0 resection). The pathological diagnosis was U, Ant-Less, Type 2, 70 × 63 mm, poorly differentiated adenocarcinoma (ypT3N0M0 ypStage IIA). R0 resection was performed, and the histological response was grade 1a. The patient did not show recurrence for 9 months after CS.

Objectives Molecular profiling of marker mutations has become an essential aspect in the treatment planning for colorectal cancer (CRC). Anaplastic lymphoma kinase (ALK) mutations could be used as markers in CRC molecular profiling. However, the extremely low frequency of these mutations makes their confirmation in all patients inefficient. Thus, to determine whether ALK positivity could be indicated by morphological features, we have analyzed ALK positivity in CRC tissues with a signet-ring cell carcinoma (SRCC) component. Methods We screened cases of patients who underwent CRC surgical resection at the Department of Gastrointestinal Surgery of the Kanagawa Cancer Center between January 2015 and December 2019. The selected samples were then assessed immunohistochemically using an antibody against p80 ALK. Results In total, we were able to retrieve 29 cases of CRC with the SRCC component from the database; however, 5 cases were excluded owing to the absence of formalin-fixed paraffin-embedded tissue sections or the absence of the SRCC component when the tissues were observed. In the immunohistochemical analysis, two cases showed diffused positive immunoreactivity for ALK and were defined as ALK-positive CRC. Thus, the ALK positivity rate in CRC with SRCC was determined to be 8.3%. Conclusions This present study sheds light on the morphological features of ALK-positive CRC. Our findings could contribute to the effective screening and improvement of front-line therapy for CRC.

Background/aim Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC). Patients and methods Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction. Results Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival. Conclusion High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.

We investigated the impact of the neutrophil to lymphocyte ratio on esophageal cancer survival and recurrence after curative treatment. This study included 120 patients who underwent curative surgery followed by adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival and recurrence-free survival (RFS) were identified. Neutrophil to lymphocyte ratio of 2.38 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rate. The overall survival rates at 3 and 5 years after surgery were 70.5% and 63.0% in the neutrophil to lymphocyte ratio low group, respectively, and 41.0% and 29.7% in neutrophil to lymphocyte ratio high group, which amounted to a statistically significant difference (p=0.001). The recurrence-free survival rates at 3 and 5 years after surgery were 48.6% and 40.7% in the neutrophil to lymphocyte ratio low group, respectively, and 33.6% and 26.9% in neutrophil to lymphocyte ratio high group, which amounted to a statistically significant difference (p=0.046). A multivariate analysis demonstrated that the neutrophil to lymphocyte ratio was a significant independent risk factor for both the overall survival and recurrence-free survival. Neutrophil to lymphocyte ratio was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the neutrophil to lymphocyte ratio.

We present the case of a 35-year-old man with intractable nausea, vomiting, and severe anemia. A computed tomography (CT) scan of the chest, abdomen, and pelvis showed a circumferential lesion thickening of up to 3.5 cm at the level of the third portion of the duodenum. No aortocaval, retroperitoneal lymphadenopathy, nor secondary lesion was observed. Esophagogastroduodenoscopy (EGD) revealed a circumferential mass within the third portion of the duodenum. Histopathology of biopsy materials from the duodenal mass showed it most likely to be a poorly differentiated adenocarcinoma. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. Histologically, tumor cells with basophilic cytoplasm and pleomorphic nuclei showed a solid pattern, and expressed CD30 and SALL4 immunohistochemically, leading to a diagnosis of embryonal carcinoma-like tumor. No other primary tumor could be identified, and the location of the tumor, mainly on the mucosal surface, suggested a duodenal origin. The UICC TNM staging was T3N2M0, stage IIB. This is a rare case of primary duodenal carcinoma with features of embryonal carcinoma.

Some authors have suggested that a relationship exists between gastrectomy for gastric cancer and metabolic bone disorders. However, few studies have investigated metabolic bone disorders after gastrectomy for gastric cancer in detail. Thus, we reviewed the findings of our recent prospective study and those of other reports on this subject. Osteoporosis and osteomalacia have been observed after gastrectomy and appear to be caused by reduced food intake and absorption, and steatorrhea. Moreover, the incidence of fracture is high after gastrectomy, although subtotal or total gastrectomy and reconstruction for gastric cancer have not been identified as significant risk factors for decreased bone mineral density (BMD). Recently, we reported that the BMD decreased significantly within 12 months after gastrectomy for gastric cancer in both male and female patients, but there was no significant gender-related difference in the rate of change in BMD. More than 1 year after gastrectomy, the steep decrease in the BMD stabilized and normal levels of 1,25(OH)2 vitamin D3 were maintained, despite the lack of precursor for 1,25(OH)2 vitamin D3 synthesis after gastrectomy. Alendronate therapy might be effective and prevent postgastrectomy metabolic bone disorders; however, the optimal treatment and prevention strategy for this bone disorder has not been delineated.

Complete mesocolic excision with central vessel ligation may be important for accurate staging and improving the prognosis of right-sided colon cancer. Although the procedure is often performed laparoscopically, approaching the middle colic artery (MCA) is technically demanding, especially when complete ligation of arteries at their roots is desired. We standardized our laparoscopic approach by establishing the dissection boundary along the superior mesenteric artery to achieve D3 lymphadenectomy in the region of the MCA. The aim of the present study was to evaluate, on the basis of perioperative and short-term oncologic outcomes, the feasibility and safety of our technique We conducted a retrospective study on consecutive patients with cancer located at the ascending colon and transverse colon who had laparoscopic right hemicolectomy requiring ligation of the MCA. There were 41 patients (22 males, median age 71 years [range 49–86] years). The median operation time was 285 min, and blood loss volume was 40 mL. Conversion to open surgery was required in 1 case. Complications that were Clavien–Dindo grade III or above occurred in 3 patients (7.3%). There was no anastomotic leakage. The median number of lymph nodes harvested was 46. Our technique was shown to be a safe, feasible, and useful strategy for performance of right hemicolectomy requiring ligation of the MCA in cases of colon cancer. The technique facilitates maximal lymph node dissection. Having obtained favorable outcomes, we look forward to investigation into long-term outcomes.

Naples prognostic score (NPS) is a scoring system based on albumin, cholesterol concentration, lymphocyte-to-monocyte ratio, and neutrophil-to-lymphocyte ratio reflecting host systemic inflammation, malnutrition, and survival for several malignancies. This study was designed to assess the prognostic significance of NPS in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to compare its prognostic accuracy with that of other systemic inflammatory and nutritional index. We retrospectively examined 165 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by curative resection between January 2011 and September 2019. Patients were divided into three groups based on their NPS before neoadjuvant therapy (Group 0: NPS = 0; Group 1: NPS = 1–2; Group 2: NPS = 3–4). We compared the clinicopathological characteristics and survival rates among the groups. The 5-year recurrence-free survival (RFS) and overall survival (OS) rates were significantly different between the groups (P

The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs.The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor.Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p 0.05).LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs.

Background: We investigated the impact of the pre-surgical C-reactive protein-to-albumin ratio (CAR) on survival and recurrence after curative treatment for gastric cancer. Patients and Methods: This study included 481 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. Results: A CAR of 0.05 was regarded as the optimal critical point of classification considering the 3- and 5-year survival rates and patients were divided according to their CAR. The OS rates at 3 and 5 years after surgery were significantly higher at 92.5% and 87.9%, respectively, in the low-CAR group compared with 84.9% and 71.9%, respectively, in the high-CAR group. The corresponding RFS rates were 89.1% and 85.5%, and 81.0% and 72.2%, respectively, also a significant difference. A multivariate analysis demonstrated that the CAR was a significant independent risk factor for the OS and marginally significant independent risk factor for the RFS. In addition, the incidences of pancreatic fistula and abdominal abscess were significantly higher and the rate of introduction of adjuvant chemotherapy significantly lower in the high-CAR group. Conclusion: The CAR was a risk factor influencing survival in patients who underwent curative treatment for gastric cancer. An effective perioperative care plan and surgical strategy need to be developed according to the CAR.

Aim: Recent studies have reported that the albumin-to-globulin ratio (AGR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis in various types of patients with cancer. However, its prognostic value in patients with esophageal cancer is still unclear. We aimed to examine the utility of the AGR for predicting the short- and long-term outcomes in patients with esophageal cancer who underwent curative resection. Patients and Methods: This was a retrospective cohort analysis reviewing the medical records of consecutive patients who underwent esophagectomy for clinical stage I to III esophageal cancer at Yokohama City University. A total of 105 patients were identified between 2005 and 2018. The overall survival (OS), recurrence-free survival (RFS), and postoperative complication rates were compared between patients with high AGR (>1.48) and those with low AGR (≤1.48) group. Results: A total of 57 and 48 patients were classified into the high and low AGR groups, respectively. There was no significant difference between the two groups in the rate of overall postoperative complications of more than Clavien-Dindo grade 3 (50.9% vs. 54.2%, p=0.85). The long-term findings showed that 5-year OS and RFS rates were significantly better for the group with a high AGR (67.2% vs. 33.8%, p

Background/Aim: We hypothesised that the prognostic nutrition index (PNI) is useful for evaluating host immunity and response to immune checkpoint inhibitors. We investigated the effect of PNI on nivolumab monotherapy efficacy in advanced or recurrent gastric cancer (GC) or gastro-oesophageal junction cancer (GOC) patients. Patients and Methods: We retrospectively examined 110 patients, divided them into a high-PNI group and a low-PNI group, and compared treatment efficacy, adverse events (AEs), and survival between the groups. Results: Median overall survival (OS) was significantly longer in the high-PNI group than in the low-PNI group (205 vs. 109 days; p < 0.001). Multivariate analysis revealed that low PNI was an independent risk factor for OS (hazard ratio=2.398; 95% confidence interval=1.384-4.154; p=0.002). The overall response rate and frequency of AEs were not significantly different between the groups. Conclusion: PNI could be a useful prognostic factor in GC or GOC patients undergoing nivolumab monotherapy.

INTRODUCTION Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe. PATIENTS AND METHODS We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019. RESULTS The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P

Guidelines advocate minimal ileal resection when right hemicolectomy is performed for right-sided colon cancer. The practice, thought to prevent malabsorption syndrome, does not appear to foster local recurrence. Little evidence based on rigorous study exists, however. To understand the pattern of lymphatic spread of right-sided colon cancer toward the small bowel and thus determine the appropriate margin size, we prospectively investigated anatomical distribution of lymph nodes (LNs) in the small bowel mesentery and of metastasis to these nodes in patients with right-sided colon cancer treated by such surgery. In each case, the mesenteric specimen, which had been dissected along the ileocolic vessels and included intermediate LNs, was divided into 2 areas: that 0–3 cm from the vessel pedicle (area 1) and that 3–5 cm from the pedicle (area 2). The peri-intestinal mesentery was cut into 9 segments. Ninety-one patients were included in the study. Overall, 3366 LNs were dissected. Four hundred fifty-three of these LNs were located in area 1 (90 cases), and 15 (3.3%) were metastatic. Only 63 LNs were located in area 2 (34 cases; average of 0.69 per patient); none was metastatic. Overall, 269 LNs were found in the small bowel mesentery (in 56 of the 91 patients). Only 4 were positive (3 cases), and all were within 5 cm of the ileocecal valve. Our data indicate that a surgical margin 3 cm from the ileocecal pedicle and a short (5 cm) ileal margin are oncologically reasonable for effective right hemicolectomy.

The aim of this study is to reveal the vascular branching variation in SFC (splenic flexure cancer) patients using the preoperative three-dimensional computed tomography angiography with colonography (3D-CTAC). We retrospectively analyzed patients with SFC who underwent preoperative 3D-CTAC between January 2014 and December 2019. Among 1256 colorectal cancer (CRC) patients, 96 (7.6%) manifested SFC. The arterial branching from the superior mesenteric artery (SMA) was classified into five patterns, as follows: (type 1A) the left branch of middle colic artery (LMCA) diverged from middle colic artery (MCA) (N = 47, 49.0%); (2A) the LMCA diverged from the MCA and the accessory middle colic artery (AMCA) (N = 26, 27.1%); (3A) the LMCA independently diverged from the SMA (N = 16, 16.7%); (4A) the LMCA independently diverged from the SMA and AMCA (N = 3, 3.1%); (5A) only the AMCA and the LMCA was absent (N = 4, 4.1%). Venous drainage was classified into four patterns, as follows: (type 1V) the SFV flows into the inferior mesenteric vein (IMV) then back to the splenic vein (N = 50, 52.1%); (2V) the SFV flows into the IMV then back to the superior mesenteric vein (SMV) (N = 19, 19.8%); (type 3V) the SFV independently flows into the splenic vein (N = 3, 3.1%); (type 4V) the SFV is absent (N = 24, 25.0%). 3D-CTAC could reveal accurate preoperative tumor localization and vascular branching. These classifications should be helpful in performing accurate complete mesocolic excision and central vessel ligation for SFC.

Background/aim Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). Patients and methods GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. Results Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. Conclusion GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

BACKGROUND The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer. PATIENTS AND METHODS Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses. RESULTS A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p

Background Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD). Methods Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients. Results A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors. Conclusions The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy in patients with gastric or gastroesophageal junction cancer. The long-term outcomes and treatment responses to nivolumab monotherapy were assessed in patients with gastric or gastroesophageal junction cancer. We compared patients with a NLR > 2.5 and those with a NLR ≤ 2.5 at the time of starting nivolumab monotherapy. The proportion of patients who have received three or more regimens was higher in the NLR > 2.5 group than in the NLR ≤ 2.5 group. The disease control rate was significantly worse in the NLR > 2.5 group than in the NLR ≤ 2.5 group (23% and 46%, respectively; p = 0.044). Overall survival was significantly better in the NLR ≤ 2.5 group than in the NLR > 2.5 group. Multivariate analysis showed that the macroscopic type, primary site resection, and the NLR were independent prognostic factors for overall survival (hazard ratio [95% confidence interval], 2.586 [1.286–5.203], 0.473 [0.260–0.861], and 1.736 [1.007–2.992], respectively). This study demonstrates that the NLR is an independent prognostic factor in patients with gastric or gastroesophageal junction cancer treated with nivolumab monotherapy. Careful attention must be paid when nivolumab monotherapy is used to treat patients with gastric cancer with a NLR > 2.5.

Background Several immune-inflammatory markers are associated with cancer progression. The purpose of the present study was to clarify the influence of the preoperative C-reactive protein-to-albumin ratio (CRP/ALB ratio) on survival of patients with esophageal cancer and recurrence after curative resection. Patients and methods The preoperative CRP/ALB ratio was evaluated in 122 patients who underwent radical resection for esophageal cancer from 2005 to 2018. The correlations between the CRP/ALB ratio and cancer-specific overall (OS), recurrence-free (RFS) survival and the clinicopathological status were analyzed. Results The optimal cut-off value of the CRP/ALB ratio determined using receiver operating characteristic curve analysis was 0.04. Patients were divided into two groups based on this cut-off value: the low CRP/ALB group (n=59) and the high CRP/ALB group (n=50). The OS rate at 5 years after surgery was significantly lower in the group with high CRP/ALB at 40.5% whilst it was 63.5% in the low CRP/ALB group (p=0.005). The corresponding RFS rates at 5 years after surgery were 32.5% and 48.3%, respectively, which was a statistically significant difference (p=0.007). A multivariate analysis showed that a high CRP/ALB ratio was a significant independent risk factor for poorer cancer-specific OS and RFS. Conclusion The preoperative CRP/ALB ratio was a strong prognostic marker for patients with esophageal cancer. The surgical strategy, including procedure and perioperative care should be carefully planned for patients with a high CRP/ALB ratio.

AIM To clarify the benefits of robotic-assisted laparoscopic surgery (RALS) regarding short-term outcomes in patients with technically demanding rectal cancer (TDRC). PATIENTS AND METHODS Between April 2015 and September 2019, 88 TDRC cases were identified from our database, and divided into the RALS (n=32) and conventional laparoscopic surgery (CLS) (n=56) groups. TDRC was defined as mid-rectal tumors presenting at least one of the following risk factors: Male sex, high body mass index, T4 stage, bulky tumor, or low rectal tumor. RESULTS Patient baseline characteristics were similar in both groups. One and 15 patients developed anastomotic leakage in the RALS and CLS groups (3% vs. 27%, p

Background/aim Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets. Materials and methods We retrospectively studied surgical specimens from 15 patients who underwent surgery for MBC at Kanagawa Cancer Center between 2005 and 2016, and similarly from 14 patients with TNDC. The frequencies of high methylation/demethylation enzyme expression were compared among them. Results The frequencies of high enhancer of zeste homolog 2 (EZH2) and multiple myeloma SET domain (MMSET) expression were significantly higher in both MBC and TNDC than in normal tissue. Conclusion EZH2 and MMSET may be useful therapeutic targets in MBC.

BACKGROUND/AIM The purpose of this study was to evaluate the usefulness of minimally invasive esophagectomy (MIE) for stage II/III esophageal cancer (EC). PATIENTS AND METHODS We compared surgical outcomes between MIE and open esohagectomy in EC patients with pStage II/III using the propensity scoring system. RESULTS Fifty-seven patients were classified into the MIE group and 57 patients into the open esophagectomy (OE) group. The incidence of major complications was similar between the two groups. The 5-year OS was significantly better in the MIE group (69.0% vs. 35.5%; p=0.004) and no significant difference was observed in the 5-year recurrence-free survival (RFS, 52.2% vs. 29.2%; p=0.064). Multivariate analysis showed MIE was a prognostic factor of OS (p

Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). We investigated FGFR4 expression in patients with ATC and analyzed their clinical responses to lenvatinib. Primary tumor samples were obtained from 12 patients with ATC who underwent surgery or core needle biopsy. FGFR4 protein expression in all ATC samples was analyzed via immunohistochemistry, and the treatment efficacy of lenvatinib was evaluated. The proportion of FGFR4-positive cells in the samples ranged from 0 to 50%. Four patients had partial responses, and three patients had stable diseases as a best clinical response to lenvatinib. The median PFS durations of patients with none, weak, and moderate intensity were 0.5, 3.2 (95% CI 1.1–not estimable [NE]), and 4.6 (95% CI 1.1–NE) months, respectively (p = 0.003). Because FGFR4 was expressed in ATC tissues, the FGFR4 expression might be associated with the treatment efficacy of lenvatinib in a part of ATC patients. To clarify whether FGFR4 can serve as a prognostic or predictive factor for lenvatinib therapy, more cases must be accumulated.

BACKGROUND The short- and long-term outcomes of esophagectomy for esophageal cancer were fully evaluated in patients older than 75 years of age. PATIENTS AND METHODS The present study selected patients who received esophagectomy for esophageal cancer. Patients were divided into non-elderly patients [age

Few studies have investigated the risk factors for postoperative pneumonia after esophageal cancer surgery. The aim of the present study was to identify risk factors of postoperative pneumonia after esophagectomy for esophageal cancer. This study included 122 patients who underwent curative surgery for esophageal cancer between January 2005 and September 2018. The rate of postoperative pneumonia was measured by the revised Uniform Pneumonia Score. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for postoperative pneumonia. Postoperative pneumonia was found in 34 of the 122 patients (27.9%). Among the factors examined (age, gender, preoperative chemotherapy status, operative type, operative duration, blood loss, lymph node dissection, smoking habit, and alcohol habit), the age (p = 0.038) and operative duration (p = 0.035) were identified as significant independent risk factors for postoperative pneumonia in the univariate and multivariate analyses. The incidence of postoperative pneumonia was 40% (22 of 55) in patients ≥ 70 years old and 17.9% (12 of 67) in those

Background/Aim: We investigated the clinical impact of the lymph node ratio (LNR) on overall survival (OS) and recurrence-free survival (RFS) in esophageal cancer patients who underwent curative surgery. Patients and Methods: One hundred twenty patients who underwent curative surgery for esophageal cancer between 2005 and 2017 were included in this study. The LNR was defined as the ratio of the number of metastatic lymph nodes (LNs) to the total number of harvested LNs. Results: A lymph node ratio of 10% was regarded as the optimal critical point for classification based on the overall survival rate. The 3-year and 5-year OS rates were 65.5% and 57.0%, respectively, in the LNR10% group; the difference was also statistically significant (p10% group was significantly higher than that in the LNR

Background/Aim: The present study aimed to identify risk factors for anastomosis leak (AL) after esophagectomy for esophageal cancer. Patients and Methods: One-hundred twenty-two patients who underwent esophagectomy for esophageal cancer between 2008 and 2018 were included. The rate of AL was measured based on the definition of leak as adapted from the Surgical Infection Study Group. To identify the risk factors for AL, logistic regression analysis was used. Results: AL was found in 44 of the 122 patients (36.1%). Among the factors examined, the lymph node dissection status (p=0.007) and preoperative serum albumin level (p=0.022) were significant independent risk factors for AL. The incidence of AL was 26.7% (20 of 75) among patients who received 2-field lymph node dissection and 51.1% (24 of 47) among those who received 3-field lymph node dissection. The incidence of AL was 29.9% (23 of 77) in the preoperative serum albumin levels ≥4.0 g/dl group and 46.7% (21 of 45) in the serum albumin levels

Aim To compare long- and short-term outcomes of laparoscopic surgery with those of open surgery for patients with colorectal cancer and body mass index over 25 kg/m2 Patients and Methods: This multicentre, retrospective study analysed clinical records and identified 178 patients with body mass index over 25 kg/m2 who underwent surgery for colon and rectosigmoid cancer between 2000 and 2016. After applying propensity score matching, 96 patients were finally included. The primary outcome was the 3-year recurrence-free survival rate, and the secondary outcomes were short-term results during and after surgery. Results The 3-year recurrence-free survival rates were similar for the laparoscopic and open surgery groups. The laparoscopic surgery group had longer operative times but less blood loss and shorter periods of hospital stay. There were no differences in incidence of postoperative complications. Conclusion Laparoscopic and open surgeries had similar long-term outcomes for obese patients. Laparoscopic surgery is an effective option for this population.

Background We investigated the clinical influence of the prealbumin level on the gastric cancer survival and recurrence after curative treatment. Methods This study included 447 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. Results A prealbumin level of 20 mg/dl was regarded as the optimal point of classification, considering the 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 80.7% and 65.0% in the low-prealbumin group, respectively, and 93.1% and 87.9% in the high-prealbumin group, respectively, a statistically significant difference (p p = 0.031). A multivariate analysis demonstrated that the prealbumin level was a significant independent risk factor for the OS and RFS. In addition, the rate of introduction of adjuvant chemotherapy was significantly lower and the frequency of peritoneal recurrence and lymph node recurrence significantly higher in the low-prealbumin group than in the high-prealbumin group. Conclusion Prealbumin is a risk factor for the survival in patients who undergo curative treatment for gastric cancer. It is necessary to develop an effective plan of perioperative care and surgical strategy according to the prealbumin level.

Background: The aim of the present study was to determine the utility of the C-reactive protein-to-albumin ratio (CAR) for predicting the overall survival (OS) in locally advanced colorectal cancer (CRC) patients. Patients and Methods: This retrospective multicenter study was performed using data from a prospectively maintained database of pathological Stage II or III patients undergoing CRC surgery at the Yokohama City University, Department of Surgery, and its affiliated institutions between April 2000 and March 2016. The risk factors for the OS were identified. Results: A CAR of 0.03 was considered to be the optimal cutoff point for classification based on the 1-, 3-, and 5-year survival rates and receiver operating characteristic curve. The OS rates at 3 and 5 years after surgery were 92.4% and 85.7% in the CAR-low group, respectively, and 86.7% and 81.1% in the CAR-high group. A multivariate analysis showed that the CAR was a significant independent risk factor for the OS. When comparing the patients' demographic and clinical characteristics between the CAR ≤0.03 and >0.03 groups, the incidence of patients who received adjuvant chemotherapy and the incidence of postoperative complications were significantly different between the two groups. Conclusion: The present study showed that the preoperative CAR was a risk factor for the OS in patients who underwent surgery for CRC. To improve the patients' survival, CAR might be a useful tool for devising treatment strategies.

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

Background/aim The number of patients who have cardiovascular-morbidities and use antiplatelet and/or anticoagulation therapy is rapidly growing worldwide. The present study evaluated the safety and feasibility of gastrectomy for gastric cancer in patients who received antiplatelet and/or anticoagulation therapy in the perioperative period. Patients and methods Cases were selected from the medical records of consecutive patients who were diagnosed with gastric cancer and underwent complete resection at the Kanagawa Cancer Center from 2013 to 2017. The patients were divided into the antiplatelet and/or anticoagulation treatment group and the non-antiplatelet and/or anticoagulation treatment group. Results Five hundred and six patients underwent gastrectomy for gastric cancer and were analyzed in the present study. Among them, 62 patients (12.3%) received anticoagulation therapy (anticoagulation group). When the anticoagulation and non-anticoagulation groups were compared, although there were some differences in patient background factors, the surgical findings, perioperative clinical course, and details of postoperative complications were similar. The incidence of postoperative bleeding was 0.8% (4/506) in all patients. The incidence of postoperative bleeding was 1.6% (1/62) in the anticoagulation group and 0.7% (3/446) in the non-anticoagulation group. Preoperative anticoagulation therapy was not identified as a significant independent risk factor for postoperative bleeding. Conclusion These results suggest that curative gastrectomy for gastric cancer is safe and feasible, regardless of the perioperative use of antiplatelet and/or anticoagulation treatment. In addition, the perioperative use of antiplatelet and/or anticoagulation treatment was not a significant risk factor for postoperative bleeding after gastrectomy for gastric cancer.

Background/aim Cancer stem cells (CSCs) are reported to associated with cancer metastasis, relapse, and chemoresistance. This study examined the clinical significance of the expression of two CSC markers, the transporter associated with antigen processing 1 (TAP1) and the Delta-like 4 (DLL4) protein, in patients with locally advanced GC. Patients and methods This study was performed using samples obtained from 413 pathological stage II/III GC patients after curative gastrectomy. We examined TAP1 and DLL4 expression using immunohistochemical analysis with tissue microarray and examined the association between TAP1 or DLL4 expression, clinicopathological factors and survival. Results High TAP1 expression was associated with better overall survival compared to low TAP1 expression (p=0.004). Furthermore, in multivariate analysis, high TAP1 expression was defined as a predictive factor for good survival. There was no significant difference between DLL4 expression and clinicopathological features and overall survival. Conclusion TAP1 expression may be a useful prognostic marker in patients with locally advanced GC.

In recent years, surgery without thoracotomy for esophageal cancer has been reported by performing mediastinoscope and laparoscope-assisted esophagectomy. It is reported that this procedure reduces pulmonary complications. Methods Since June 2018, we introduced this surgical operation for esophageal cancer patients using mediastinoscope without thoracotomy. The patient was placed in a supine position and tilts head slightly to the right with bilateral lung ventilation. The upper mediastinal dissection, using a left cervical approach, was performed with a single-port mediastinoscopic technique using LigaSure™ Maryland. But the lymph nodes along the right recurrent laryngeal nerve (RLN) were dissected under direct vision using a right cervical approach. And then, the operation and the course after the operation were examined. Results We experienced 14 cases of surgery by February 2020 and have experienced only one pulmonary complication in the course of the surgery. This case had a left recurrent nerve palsy as a complication after surgery. For this reason, aspiration was combined, but it improved immediately. There were 2 patients that lung cancer and COLD (Chronic Obstructive Pulmonary Disease), but pneumonia did not occur. Suture failure was very high frequent. However, this complication decreased over time. Conclusion We reported that pneumonia after esophageal cancer surgery deteriorates the prognosis. Suppression of pneumonia by this operation formula can be expected to improve the prognosis.

Purpose There is no sufficient data about the clinical course and outcome in thyroid cancer patients who become pregnant after diagnosis of distant metastasis (DM). The current study was conducted to collect information regarding the clinical and reproductive characteristics, and outcomes in thyroid cancer patients who became pregnant after being diagnosed with DM. Methods Records of 125 differentiated thyroid cancer (DTC) patients with age ≤ 45 years at DM diagnosis who had visited Ito Hospital from January 2005 to June 2021 were retrospectively reviewed. Among those 125 patients, 28 who became pregnant after DM diagnosis were classified as pregnant group, and the remained 97 patients were classified as comparator group. Results In pregnant group, the median age at malignancy diagnosis, DM diagnosis, and first pregnancy after DM diagnosis was 25 years (range, 4–41 years), 27 years (range, 11–41 years), and 32 years (range, 25–45 years), respectively. Fifty-five pregnancies and 40 live births were reported. Three patients had live births by embryo transfer. Other pregnancy outcomes were miscarriage (n = 14) and induced abortion (n = 1). No one died during the follow-up period in this study. The 10-year progression free survival (PFS) rates of pregnant and comparator group were 92.1% and 74.4%, respectively. Conclusion DTC patients who became pregnant after DM diagnosis had good survival. Our results add to the information required for counseling thyroid cancer patients who have concerns about their fertility in the future.

Objectives This retrospective study aimed to elucidate the effect of epidermal growth factor receptor (EGFR) gene mutations on the prognosis of patients with pathological stage II–IIIA primary lung cancer after curative surgery. Materials and methods We enrolled 539 patients with p-stage II–IIIA (8th edition tumor–node–metastasis [TNM] classification) lung cancer who underwent curative resection at Kanagawa Cancer Center between January 2010 and December 2020 and whose tumors were tested for EGFR mutations. Relapse-free survival (RFS) and overall survival (OS) of patients with EGFR-mutant lung cancer (Mt, n = 126) including EGFR exon 21 L858R point mutation and EGFR exon 19 deletion mutation and EGFR mutation-wild lung cancer (Wt, n = 413) were analyzed using Kaplan–Meier curves and compared using a log-rank test. Cox regression analysis was performed to evaluate the effects of EGFR gene mutations on RFS and OS at each stage. Results There were 56/256 patients with p-stage II EGFR-Mt/Wt and 70/157 patients with p-stage IIIA EGFR-Mt/Wt. The 5-year RFS rate of patients with EGFR-Mt/Wt was 46.6%/52.0% (p = 0.787) for p-stage II and 17.4%/29.7% (p = 0.929) for p-stage IIIA. The 5-year OS rate was 92.0%/65.7% (p = 0.001) for p-stage II and 56.0%/39.3% (p = 0.016) for p-stage IIIA. EGFR-Mt was not an independent prognostic factor for OS of patients with p-stage IIIA lung cancer (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.51–1.76; p = 0.872); however, EGFR-Mt was an independent favorable prognostic factor for OS of patients with p-stage II lung cancer (HR, 0.59; 95% CI, 0.36–0.96; p = 0.034). Conclusion The OS of lung cancer patients with p-stage II or IIIA, classified according to the 8th edition TNM classification, was remarkably favorable. Incorporating EGFR mutations to the anatomical TNM classification may lead to a more accurate prognosis prediction.

This study aimed to evaluate the short- and long-term outcomes in obese patients with gastric cancer undergoing totally laparoscopic total gastrectomy (TLTG) to clarify its feasibility in this population. We examined 136 consecutive patients who underwent TLTG for gastric cancer (GC) between 2013 and 2018. A total of 45 patients with a body mass index (BMI) ≥ 25 kg/m2 were defined as the obese group (obese and overweight patients by the WHO classification), and 91 patients with a BMI