Clinical practice guidelines for molecular tumor markers, 2nd edition review part 1.

With advances in gene and protein analysis technologies, many target molecules that may be useful in cancer diagnosis have been reported. Therefore, the "Tumor Marker Study Group" was established in 1981 with the aim of "discovering clinically" useful molecules. Later, the name was changed to "Japanese Society for Molecular Tumor Marker Research" in 2000 in response to the remarkable progress in gene-related research. Currently, the world of cancer treatment is shifting from the era of representative tumor markers of each cancer type used for tumor diagnosis and treatment evaluation to the study of companion markers for molecular-targeted therapeutics that target cancer cells. Therefore, the first edition of the Molecular Tumor Marker Guidelines, which summarizes tumor markers and companion markers in each cancer type, was published in 2016. After publication of the first edition, the gene panel testing using next-generation sequencing became available in Japan in June 2019 for insured patients. In addition, immune checkpoint inhibitors have been indicated for a wide range of cancer types. Therefore, the 2nd edition of the Molecular Tumor Marker Guidelines was published in September 2021 to address the need to revise the guidelines. Here, we present an English version of the review (Part 1) of the Molecular Tumor Marker Guidelines, Second Edition.

Low skeletal muscle radiodensity is a risk factor for adjuvant chemotherapy discontinuation in colorectal cancer.

BACKGROUND: Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. METHODS: In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. RESULTS: The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). CONCLUSION: The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.

Remnant gastritis in gastric cancer patients causes loss of muscle mass 6 months after gastrectomy: a retrospective cohort study of Helicobacter pylori infection.

PURPOSE: In this study, we assessed the relationship between remnant gastritis and muscle mass loss and then investigated the potential relationship between Helicobacter pylori (HP) infection and remnant gastritis and muscle loss. METHODS: We reviewed the medical records of 463 patients who underwent distal gastrectomy between January 2017 and March 2020. Of these patients, 100 with pStage I after laparoscopic surgery were included in this analysis. RESULTS: A multivariate analysis showed that the total Residue, Gastritis, Bile (RGB) classification score, which indicates the degree of gastritis, was significantly associated with the rate of change (rate of decrease) in the psoas muscle area (PMA) during the first 6 months after surgery (p = 0.014). Propensity score matching was performed according to HP infection, and the rate of change in the PMA and the degree of remnant gastritis in 56 patients were compared. Neither was significantly associated with HP infection. CONCLUSIONS: Remnant gastritis did contribute to psoas muscle mass loss during the initial 6 months after gastrectomy, and HP infection was not significantly associated with either remnant gastritis or psoas muscle mass loss. Nevertheless, the potential for HP eradication to prevent muscle loss and improve the survival prognosis for gastrectomy patients merits further research.

Mapping the Japanese orthopedic association national registry (JOANR) to the international classification of health interventions (ICHI).

BACKGROUND: The Japanese Orthopedic Association launched the Japanese Orthopedic Association National Registry (JOANR), Japan's first large-scale nationwide musculoskeletal disease registry, in 2020. The World Health Organization released the International Classification of Health Interventions (ICHI) Beta-3 version in the same year. This concurrence served as an impetus to examine the relationship between domestic and international classification for orthopedic interventions. Our objective was to evaluate the possibility of utilizing JOANR for international comparison and the potential usage of ICHI in the domestic medical fee reimbursement system. This study is a novel attempt at mapping a domestic orthopedic scheme to the ICHI. METHODS: We mapped 149 codes out of 581 orthopedic surgical codes, on JOANR's registration form, to the ICHI, and then classified the nature of JOANR codes' relationship, to both ICHI single stem codes and stem codes accompanied by other additional stem codes, extension codes, and International Classification of Diseases for Mortality and Morbidity Statistics (ICD) codes, into five categories: Equivalent (exact match), Narrower (compared to ICHI; can be smoothly incorporated into ICHI), Broader (compared to ICHI), Slipped (combination of both Narrower and Broader), and None (no appropriate code). Finally, debatable issues that arose during the mapping operation were noted. RESULTS: The domestic codes' relationship to ICHI single stem code by category were Equivalent: 27 (18.1%) and Narrower: 65 (43.6%), respectively. Further, the rate of Equivalent rose to 120 (80.5%) on adding other stem codes, extension codes, and ICD codes. Additionally, certain domestic titles, which were unsuitable for classification as they included diagnostic information, and arthroscopic surgeries without corresponding ICHI codes, were recoded. CONCLUSIONS: JOANR can be converted to an international comparison standard via ICHI to a certain extent, and ICHI accompanied by ICD codes has potential for deployment in the domestic medical fee reimbursement system.

CAFs-Associated Genes (CAFGs) in Pancreatic Ductal Adenocarcinoma (PDAC) and Novel Therapeutic Strategy.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer with striking fibrosis, and its mortality rate is ranked second across human cancers. Cancer-associated fibroblasts (CAFs) play a critical role in PDAC progression, and we reviewed the molecular understanding of PDAC CAFs and novel therapeutic potential at present. CAFs-associated genes (CAFGs) were tentatively classified into three categories by stroma specificity representing stroma/epithelia expression ratios (SE ratios). The recent classification using single cell transcriptome technology clarified that CAFs were composed of myofibroblasts (myCAFs), inflammatory CAFs (iCAFs), and other minor ones (e.g., POSTN-CAFs and antigen presenting CAFs, apCAFs). LRRC15 is a myCAFs marker, and myCAFs depletion by diphtheria toxin induces the rapid accumulation of cytotoxic T lymphocytes (CTLs) and therefore augment PDL1 antibody treatments. This finding proposes that myCAFs may be a critical regulator of tumor immunity in terms of PDAC progression. myCAFs are located in CAFs adjacent to tumor cells, while iCAFs marked by PDPN and/or COL14A1 are distant from tumor cells, where hypoxic and acidic environments being located in iCAFs putatively due to poor blood supply is consistent with HIF1A and GPR68 expressions. iCAFs may be shared with SASP (secretion-associated phenotypes) in senescent CAFs. myCAFs are classically characterized by CAFGs induced by TGFB1, while chemoresistant CAFs with SASP may dependent on IL6 expression and accompanied by STAT3 activation. Recently, it was found that the unique metabolism of CAFs can be targeted to prevent PDAC progression, where PDAC cells utilize glucose, whereas CAFs in turn utilize lactate, which may be epigenetically regulated, mediated by its target genes including CXCR4. In summary, CAFs have unique molecular characteristics, which have been rigorously clarified as novel therapeutic targets of PDAC progression.

Efficacy and safety of patient-controlled thoracic epidural analgesia alone versus patient-controlled intravenous analgesia with acetaminophen after laparoscopic distal gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control. METHODS: We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration. RESULTS: Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups. CONCLUSIONS: PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG.

Early administration of postoperative BCAA-enriched PPN may improve lean body mass loss in gastric cancer patients undergoing gastrectomy.

BACKGROUND: It has been reported that weight loss or lean body mass (LBM) loss after gastrectomy for gastric cancer is associated with prognosis and nutritional support alone is insufficient to prevent LBM loss. Branched-chain amino acids (BCAA) play an important role in muscle catabolism, however their clinical effects on suppression of LBM loss in gastric cancer patients undergoing gastrectomy remains elusive. In this current study, we investigated the effect of our original PPN regimen including BCAA (designated to BCAA-regimen) on LBM loss. METHODS: We conducted a randomized controlled trial (RCT) at a single institution where patients undergoing gastrectomy were assigned to either receive a five-day early postoperative course of the BCAA-regimen (BCAA group) or conventional nutrition. The primary endpoint was the % reduction in LBM at postoperative day 7. The secondary endpoints included the % reduction in LBM at 1 and 3 months postsurgery. RESULTS: At postoperative day 7, LBM loss in the BCAA group tended to be lower than in the control group (0.16% vs. 1.7%, respectively; P = 0.21), while at 1 month postsurgery, LBM loss in the BCAA group was significantly different to that of the control group (- 0.3% vs. 4.5%, respectively; P = 0.04). At 3 months postgastrectomy, however, LBM loss was similar between the BCAA and the control groups. CONCLUSION: Our RCT clinical trial clarified that early administration of the postoperative BCAA regimen improved LBM loss at 1 month after surgery in gastric cancer patients undergoing gastrectomy.

Relative dose intensity and 1-year psoas muscle index reduction rate as prognostic factors in gastric cancer patients with postoperative adjuvant chemotherapy.

BACKGROUND: Higher relative dose intensity (RDI) of chemotherapy improves the clinical outcomes of various cancers. The psoas muscle index (PMI) is related to sarcopenia, and patients with low PMI have worse prognoses. However, few studies have demonstrated its clinical relevance in gastric cancer. METHODS: This retrospective study included 188 stage II/III gastric cancer patients who had undergone curative gastrectomy between January 2013 and March 2017, 124 of whom had received postoperative S-1 adjuvant chemotherapy. RESULTS: Per receiver operating characteristic analysis, patients were divided into high and low RDI groups, between which relapse-free survival differed marginally significantly and disease-specific survival differed significantly. In patients who received adjuvant chemotherapy, multivariate analysis found that high RDI and low PMI reduction rate 1 year after surgery were significantly associated with better relapse-free survival. Low RDI can be predicted by a combination of low preoperative PMI and non-distal gastrectomy, whereas high PMI reduction rate at 1 year can be affected by non-distal gastrectomy. CONCLUSION: High RDI with preserved psoas muscle up to 1 year after gastrectomy may be associated with prognoses in gastric cancer requiring postoperative adjuvant chemotherapy. Since RDI and PMI reduction rate can be predicted preoperatively, respectively, interventional consideration is possible for optimal adjuvant therapy in gastric cancer.

Deaths caused by osteoporotic fractures in Japan: An epidemiological study.

BACKGROUND: Osteoporosis is a global issue with a worldwide prevalence of 18.3%, and the presence of coexisting fragility fractures can reduce the survival rate by approximately 20%. In Japan, the prevalence of osteoporosis is estimated to be 12.8 million, and the annual occurrence of hip fractures is approximately 193,400. Remarkably, coexisting hip or spinal fragility fractures caused by slight external force meet the Japanese diagnostic criterion for osteoporosis regardless of bone mineral density. However, only 191 deaths due to osteoporosis were published in 2021 in Japan. With the concern that some cases of hip and spinal fragility fractures were assigned an underlying cause of death of traumatic fracture instead of osteoporosis, this study aimed to elucidate the actual number of deaths due to osteoporosis in Japan. METHODS: We used the data from Japan in 2018. First, the number of deaths due to osteoporosis and hip or spinal fractures was reviewed using published vital statistics. Second, we calculated the number of elderly deaths (age ≥80 years) resulting from hip or spinal fractures caused by falls on the same level using data from approximately 1.4 million annual individual death certificates. Combining the above data, the actual number of deaths due to osteoporosis was estimated. RESULTS: Only 190 deaths due to osteoporosis were reported in the published data. The individual certificate data revealed 3437 elderly deaths due to hip or spinal fractures caused by falls on the same level, which could meet the criteria of osteoporotic fragility fractures. Accordingly, the estimated number of deaths caused by osteoporosis was calculated as 3,627, approximately 19 times the published value. CONCLUSIONS: After researching the individual death certificate data focusing on the coexisting hip or spinal fragility fracture, it was implied that osteoporosis may have a higher mortality rate in Japan than what is published.

Risk Factors for Para-Aortic Lymph Node Metastasis in Esophagogastric Junction Cancer: Results from a Prospective Nationwide Multicenter Study.

BACKGROUND: Several studies have reported a high incidence of metastasis to para-aortic station 16a2lat (no. 16a2lat) among patients with esophagogastric junction (EGJ) cancer. However, the risk factors for no. 16a2lat metastasis are unclear. This study aimed to clarify the risk factors for no. 16a2lat metastasis in patients with EGJ cancer. METHODS: Among 371 prospectively enrolled patients with EGJ cancer, 344 patients who underwent no. 16a2lat lymph node dissection were analyzed. Background factors were compared between the patients with and those without no. 16a2lat metastasis. The association between the histologic status of 10 regional lymph node stations and that of no. 16a2lat metastasis was evaluated. RESULTS: Among the background factors, clinical N2-3 was the only independent risk factor for no. 16a2lat metastasis (odds ratio [OR], 5.90; p = 0.003). The metastasis rate of no. 16a2lat was 11.8% (11/93) for the patients with cN2-3 disease and 2.0% (5/251) for those with cN0-1 disease. The multivariate analysis showed that nos. 2 and 7 metastases were independent risk factors for no. 16a2lat metastasis, with respective ORs of 5.53 (p = 0.018) and 4.00 (p = 0.041). The patients with neither station no. 2 nor no. 7 metastasis did not exhibit no. 16a2lat metastasis, whereas the rate of no. 16a2lat metastasis was 23.7% for the patients with metastases of both stations. CONCLUSIONS: Clinical N2-3 and histologic positivity of station nos. 2 and 7 were independent risk factors for no. 16a2lat metastasis. These findings could potentially assist in determining the indication for no. 16a2lat dissection for patients with EGJ cancer.

Pancreas-contactless gastrectomy for gastric cancer prevents postoperative inflammation.

BACKGROUND: Pancreas-related complications after laparoscopic gastrectomy (LG) for gastric cancer can be fatal. We developed a gastrectomy procedure with no pancreas contact to prevent such complications and herein report the surgical outcomes. METHODS: We retrospectively reviewed 182 consecutive patients with gastric cancer who underwent LG at Kitasato University Hospital from January 2017 to January 2020. These patients were divided into a pancreas-contact group (C group) and pancreas-contactless group (CL group) for comparison of postoperative complications, and inflammatory parameters such as body temperature (BT) and C-reactive protein (CRP). RESULTS: Postoperative complications of CDc grade ≧ IIIa were significantly fewer in the CL group than in the C group [0/76 (0%) vs. 6/106 (5.7%), P = 0.035]. The median drain amylase (drain-AMY) on postoperative day 1 (POD1) was significantly lower in the CL group than in the C group (641 vs. 1162 IU/L, P = 0.02), as was BT at POD1 (37.4 °C vs. 37.7 °C, P = 0.04), the patient group with a BT above 37.5 °C at POD3 [5/76 (6.5%) vs. 18/106 (17%), P = 0.037], and those showing a CRP above 20.0 mg/dL at POD3 [5/76 (6.5%) vs. 20/106 (19%), P = 0.018]. CONCLUSIONS: Our technique to prevent pancreas contact during supra-pancreatic lymph node dissection during LG could minimize the inflammatory response and prevent further postoperative complications. Further large-scale, prospective studies are now required.

Improved anastomotic technique for esophagojejunal anastomosis using circular stapler.

PURPOSE: In total gastrectomy, Roux-en-Y reconstruction with esophagojejunal anastomosis has been widely used in gastrointestinal reconstruction. In the case of anastomotic leakage of RY reconstruction, esophagojejunal anastomosis should be paid attention, and esophageal fragility is considered the reason for the leakage. Here, we introduce an atraumatic and innovative technique for esophagojejunostomy. METHODS: We prospectively performed routine novel esophagojejunal anastomosis using circular stapler device and reviewed the records of 14 consecutive patients with gastric cancer who underwent open total gastrectomy at Kitasato University Hospital from April 2019 to March 2020. By placing about 10 stay sutures around the entire esophageal stump, the esophageal stump can be opened to the maximum diameter. The forceps grasping the tissue was not necessary for these procedures, consequently preventing either tears the esophageal stump tissue or narrowing the esophageal lumen. RESULTS: These 14 cases were far advanced cases of gastric cancer, 6 cases of splenectomy and 3 cases of distal pancreatectomy. No technical problems such as esophageal tear were observed in all cases. Postoperative complications were observed in 6 patients (42.9%), and their contents varied. However, they all improved conservatively. Regarding anastomotic complications, anastomotic leakage of Clavien-Dindo-II was observed in one case, but it improved conservatively. CONCLUSION: Our new atraumatic anastomosis technique could abolish problems such as tear of esophagus wall due to introduce a larger-sized anvil, trauma of esophageal wall by grasping with forceps such as Alice or Babcock. Consequently, the atraumatic and innovative technique might make the esophagojejunostomy safe. This method might prevent anastomotic leakage and other complications effectively.

Dismal prognosis of elderly gastric cancer patients who underwent gastrectomy with American Society of Anesthesiologists (ASA) 3.

BACKGROUND: Although the American Society of Anesthesiologists (ASA) score of 3 is relatively common in elderly patients, there have been few debates on the indications for gastrectomy in elderly gastric cancer (GC) patients with ASA3. Therefore, this study aimed to investigate gastrectomy's clinical relevance in elderly patients with GC and ASA3. METHODS: We retrospectively analyzed 228 consecutive elderly GC patients (aged ≥ 75 years) without prior treatments who underwent curative gastrectomy between 2013 and 2017. RESULTS: Thirty-three patients with ASA3 showed significantly poorer prognosis than those with ASA1 and 2 (p = 0.004). The multivariate Cox proportional hazards model showed that ASA3 (p = 0.021) and pStage (p = 0.007) were independent prognostic factors, respectively. Elderly GC patients with pStage III and ASA3 exhibited uniquely dismal prognosis (p < 0.001); however, several survivors were still confirmed. Postoperative complications (PCs) were only the final remnant independent prognostic factor (p = 0.020) among the 33 elderly GC patients with ASA3, where dead patients included cancer-specific and other deaths, especially pneumonia. PCs were independently associated with prognostic nutritional index (PNI) (< 42.7) in elderly GC patients, and the most frequent complication was pneumonia, which was significantly associated with ASA3 and marginally associated with PNI in a multivariate analysis. CONCLUSIONS: ASA3 has a dismal prognosis after curative gastrectomy in the elderly GC patients, but the number of survivors was confirmed. Curative gastrectomy is not considered contraindicated even in elderly GC with ASA3. Preoperative malnutrition is associated with PCs, which proposing preoperative nutritional intervention in the context of treatment strategy for the elderly GC patients with ASA3.

Impact of the first era of the coronavirus disease 2019 pandemic on gastric cancer patients: a single-institutional analysis in Japan.

BACKGROUND: Little is known about the disadvantages of the coronavirus disease 2019 (COVID-19) pandemic in patients with gastric cancer. This study aimed to examine the negative impact of the COVID-19 pandemic on patients with gastric cancer in the first era in Japan. METHODS: This retrospective study included 725 patients diagnosed with gastric cancer who visited our hospital between April 2019 and March 2021. The number of patients and their characteristics before and during the COVID-19 pandemic were compared. RESULTS: The number of patients diagnosed with gastric cancer during the COVID-19 pandemic decreased by 26.2% (from 417 to 308; p = 0.013) compared to that before the COVID-19 pandemic. There was a significant decrease in cStage I cancer and an increase in cStage III cancer (p = 0.004). Patients were often symptomatic (p = 0.029), especially those with stenosis-related symptoms (p < 0.001) and longer symptom duration (p < 0.001). The number of endoscopic resections was decreased by 34.8% (p = 0.005). The number of total gastrectomy was higher than that of partial gastrectomy (p = 0.021). The median time to treatment was significantly shorter (p < 0.001). CONCLUSIONS: In Japan, delays diagnosing patients with gastric cancer, probably due to refraining from consultation, may have resulted in an increase in the diagnosis of advanced-stage cancer. Moreover, an increasing proportion of patients required more invasive gastrectomy. Therefore, it may be necessary to educate patients not to refrain from consultation, even during the COVID-19 pandemic, as it can have a negative impact on treatment, policy decision, and prognosis of gastric cancer.

Short- and long-term outcomes of laparoscopic distal gastrectomy versus open distal gastrectomy for gastric cancer in overweight patients.

PURPOSE AND BACKGROUND: Gastrectomy for gastric cancer in overweight patients is associated with a high incidence of postoperative complications and difficulties in achieving adequate lymph node dissection. We conducted this study to compare the outcomes of laparoscopic and open distal gastrectomy (ODG) for gastric cancer in overweight Japanese patients. METHODS: This retrospective study analyzed data from 180 patients with a body mass index ≥ 25 who underwent distal gastrectomy for pStage I-III gastric cancer. Postoperative complications, the number of harvested lymph nodes, and long-term survival were compared between ODG and laparoscopic distal gastrectomy (LDG). RESULTS: Postoperative complications of Clavien-Dindo (CD) grade ≥ 2 and ≥ 3 were significantly higher after ODG than after LDG (p < 0.001 and p = 0.004). Multivariate analysis identified age and ODG as factors related to complications of CD ≥ 2 (p = 0.014 and 0.002). The number of harvested lymph nodes at region 4sb was significantly higher in LDG for patients with pStage III disease. The 5-year lymph node recurrence-free survival tended to be better in LDG; however, no difference was found between ODG and LDG at any pathological stage. There were no significant differences in the 5-year overall and recurrence-free survival rates after ODG vs. LDG. CONCLUSIONS: LDG for gastric cancer appears to be associated with a lower incidence of postoperative complications than ODG, without compromising long-term survival, even for overweight patients.

Impact of loss of skeletal muscle mass within 6-12 months after gastrectomy and S1 adjuvant chemotherapy on the survival prognosis of elderly patients with gastric cancer.

BACKGROUND AND PURPOSE: We investigated the impact of postoperative changes in the psoas muscle mass index (PMI) after gastrectomy and S1 adjuvant chemotherapy (AC) on the long-term outcomes of elderly patients with gastric cancer. METHODS: We reviewed the medical records of 228 patients aged over 75 years, who underwent distal, proximal, or total gastrectomy between January, 2013 and March 2017. Among these patients, 78 with pStage IIA-IIIC who survived for at least 1 year without recurrence after gastrectomy were the subjects of this analysis. RESULTS: The log-rank test using the cut-off value from the rate of change in PMI from 6 to 12 months after gastrectomy (late rate of decrease) showed significantly poorer prognosis for the group above the cut-off value for both overall survival (OS) and recurrence-free survival (RFS) (RFS: PMI decrease ≥ 1.55%, p < 0.001; OS: PMI decrease ≥ 1.55%, p < 0.001). Patients with a relative dose intensity of S1 below 68.7% and a late rate of decrease in PMI above 1.55% were found to have a poor prognosis. CONCLUSION: It is necessary to prevent decline in the PMI of elderly patients from 6 months after gastrectomy and to administer adjuvant chemotherapy with about two-thirds or more RDI of S1 to improve their survival prognosis.

Prospective study to validate the clinical utility of DNA diagnosis of peritoneal fluid cytology test in gastric cancer.

The clinical efficacy of DNA cytology test (CY) in gastric cancer (GC) has been retrospectively proposed using cancer-specific methylation of cysteine dioxygenase type 1 (CDO1). We confirmed the clinical utility of DNA CY in a prospective cohort. Four hundred GC samples were prospectively collected for washing cytology (UMIN000026191), and detection of the DNA methylation of CDO1 was assessed by quantitative methylation-specific PCR in the sediments. Endpoint was defined as the match rate between conventional CY1 and DNA CY1 (diagnostic sensitivity), and the DNA CY0 rate (diagnostic specificity) in pStage IA. DNA CY1 was detected in 45 cases (12.5%), while CY1 was seen in 31 cases (8.6%) of 361 chemotherapy-naïve samples, where the sensitivity and specificity of the DNA CY in the peritoneal solutions were 74.2% and 96.5%, respectively. The DNA CY was positive for 3.5/0/4.9/11.4/58.8% in pStage IA/IB/II/III/IV, respectively (P < .01). In the multivariate analysis, DNA CY1 was independently correlated with pathological tumor depth (pT) (P = .0012), female gender (P = .0099), CY1 (P = .0135), P1 (P = .019), and carcinoembryonic antigen (CEA) (P = .036). The combination of DNA CY1 and P factor nearly all covered the potential peritoneal dissemination (P1 and/or CY1 and/or DNA CY1) (58/61:95.1%). DNA CY1 had a significantly poorer prognosis than DNA CY0 in GC patients (P < .0001). DNA CY1 detected by CDO1 promoter DNA methylation has a great value to detect minimal residual disease of the peritoneum in GC clinics, representing poor prognosis as a novel single DNA marker.

Preoperative chemotherapy could modify recurrence patterns through postoperative complications in patients with gastric cancer.

PURPOSE: Postoperative infectious complications have a negative impact on survival outcomes in patients with gastric cancer. It is recently reported that preoperative chemotherapy may eliminate this negative impact. This study aimed to confirm whether preoperative chemotherapy can eliminate the negative impact of postoperative infectious complications (IC) on survival outcomes and elucidate the association between postoperative infectious complications and recurrence patterns. METHODS: We retrospectively reviewed data of 86 patients who received preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by R0 gastrectomy at the Kitasato University between 2006 and 2016. Patients who developed grade II or higher infectious complications during hospitalization were grouped into the IC group, while others were grouped into the non-IC (NIC) group. Survival outcomes and recurrence patterns were analyzed between the two groups. RESULTS: Infectious complications with Clavien-Dindo classification of grade II or higher were found in 12 patients (14.0%, IC group). The median observational period was 61 months. Overall survival and progression-free survival were similar in the IC and NIC groups. Recurrence occurred in 39 patients. The proportions of peritoneal and lymph node recurrences were not significantly different between the two groups. However, the proportion of distant metastasis in the IC group was significantly higher than that in NIC group (3/4 [75%] vs. 9/35 [17%], p = 0.04). CONCLUSIONS: Pathological stage after neoadjuvant therapy plays a stronger role in recurrence than postoperative complications. Lymph node and peritoneal metastasis may be suppressed by preoperative chemotherapy.

C-reactive protein adjusted for body mass index as a predictor of postoperative complications following laparoscopic gastrectomy for gastric cancer.

PURPOSE: This study aimed to clarify the relationship between obesity and postoperative C-reactive protein (CRP) and assess the usefulness of obesity status-adjusted CRP levels for predicting early complications following laparoscopic gastrectomy for gastric cancer. METHODS: This study retrospectively analyzed 527 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2013 and March 2019. Patients were classified into three groups according to body mass index (BMI): BMI < 20; BMI ≥ 20 to < 25; and BMI ≥ 25. The correlation between BMI and perioperative CRP was investigated in 447 patients, excluding 80 with postoperative complications. The optimal CRP cutoff value of Clavien-Dindo (CD) grade ≥ 3 for predicting severe complications for each group was determined. RESULTS: BMI was significantly correlated with CRP on postoperative day (POD) 3 (p < 0.001) in 447 patients without complications. According to the receiver operating characteristic curve analysis, CRP cutoff values on POD 3 for predicting severe complications were 92.4, 111.1, and 171.9 in the BMI < 20, BMI ≥ 20 to < 25, and BMI ≥ 25 groups, respectively. In multivariate analysis for CD grade ≥ 3 complications, cardiac history and POD 3 CRP levels higher than the adjusted cutoff were identified as independent factors significantly associated with severe complications (p = 0.021 and 0.015, respectively). CONCLUSION: CRP cutoff values on POD 3 adjusted for BMI were useful for predicting severe complications in gastrectomy for gastric cancer.

Esophageal cancer patients' survival after complete response to definitive chemoradiotherapy: a retrospective analysis.

BACKGROUND: Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow. METHODS: We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking. RESULTS: At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively. CONCLUSIONS: A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.