Introduction

Gastrectomy for gastric cancer causes long term complications. However, cancer treatment-induced bone loss remains unclear¹. We have previously evaluated osteoporosis in several disease by using Dual-energy X-ray Absorptiometry(DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT)^2-4.

Aims & Methods

The aim of this study was to evaluate osteoporosis by using DXA and HR-pQCT more than 5 years after gastrectomy.
This observational study included 42 male patients (21 distal gastrectomy (DG), 21 total gastrectomy (TG)) more than 5 years after gastrectomy due to gastric cancer (GC group) and age-matched 63 male healthy volunteer donors (control group). We excluded women to avoid the effects of menopause.
In osteoporosis markers, such as 25-OH Vitamin D (25OHVD), tartrate-resistant acid phosphatase-5b (TRACP-5b), and procollagen type-I N-terminal propeptide (Total P1NP), were measured in both groups
Areal bone mineral density (aBMD) of the lumbar spine and proximal femur were analyzed by DXA.
Total, cortical, and trabecular volumetric bone mineral density (Tt.vBMD, Ct.vBMD, and Tb.vBMD) of the radius and distal tibia were analyzed by HR-pQCT. Cortical and trabecular thickness (Ct.Th and Tb.Th) of the radius and distal tibia were analyzed by HR-pQCT.
The primary endpoint was the difference of bone mineral density, bone microstructure and bone metabolism markers between the control and the GC groups.
The secondary endpoint was the difference of bone mineral density, bone microstructure and bone metabolism markers between the DG and TG groups.

Results

1. Gastrectomy on bone mineral density and microstructure
In DXA, lumbar and femoral aBMD were significantly lower in the GC group (control vs GC; 1.24 ± 0.23 vs 1.08 ± 0.30, P < 0.01, control vs GC; 0.88 ± 0.13 vs 0.78 ± 0.15, P < 0.01, respectively).
In HR-pQCT, Tt.vBMD of the radius and tibia was also significantly lower in the GC group. Radial and tibial Ct.vBMD were significantly lower in the GC group .Radial and tibial Ct.Th were significantly lower in the GC group.

Radius	Control	GC	P value		Tibia	Control	GC	P value
Tot.vBMD	271.5 ± 58.5	240.8 ± 70.7	P = 0.02		Tot.vBMD	276.9 ± 46.4	243.4± 70.7	P = 0.02
Tb.vBMD	145.1 ± 34.4	130.1 ± 41.8	P < 0.05		Tb.vBMD	159.4 ± 31.2	146.4 ± 39.5	n.s.
Ct. vBMD	847.3 ± 57.5	811.0 ± 83.9	P < 0.01		Ct. vBMD	852.5 ± 52.4	798.3 ± 72.4	P < 0.01
Tb.Th	0.24 ± 0.02	0.23 ± 0.02	n.s.		Tb.Th	0.26 ± 0.02	0.25 ± 0.02	n.s.
Ct.Th	1.01 ± 0.21	0.90 ± 0.24	P = 0.02		Ct.Th	1.49 ± 0.26	1.30 ± 0.33	P < 0.01

The serum intact PTH, TRACP-5b, and Total P1NP levels in the GC group were significantly higher than in control group (control vs GC; med 44.6 vs 55.3, P < 0.01, control vs GC; med 325 vs 474.5, P < 0.01, and control vs GC; med 40.6 vs 46.9, P < 0.01, respectively). The serum 25OHVD and albumin level in the GC group were significantly lower than in control group (control vs GC; med 20.2 vs 16.3, P = 0.05, control vs GC; 4.3 vs 4.1, P < 0.01, respectively).
2. Total and distal gastrectomy on bone mineral density and microstructure
In DXA, lumbar and femoral aBMD was significantly lower in the TG group (DG vs TG; 1.17 ± 0.28 vs 1.00 ± 0.30, P < 0.01, DG vs TG; 0.83 ± 0.13 vs 0.73 ± 0.15, P < 0.01, respectively). In HR-pQCT, radial and tibial Ct.vBMD were significantly lower in the GC group (DG vs TG; 834.1 ± 71.6mg/cm3 vs 787.8 ± 90.5mg/cm3, P = 0.03, DG vs TG; 811.4 ± 72.1mg/cm3 vs 785.3 ± 72.0 mg/cm3, P < 0.01, respectively). There were no differences in osteoporosis markers between the DG and TG groups.

Conclusion

Osteoporosis after gastrectomy was more progressive than healthy volunteers over a long period. Bone deterioration after total gastrectomy was more progressive in the cortical bone than distal gastrectomy.

References

1: Atsumi Y, Rino Y, Wada H, et al. Changes in bone metabolism after gastric cancer surgery in male patients: a prospective observational study. Gastric Cancer. 2019
2: Shiraishi K, Chiba K, Okazaki N et al. In vivo analysis of subchondral trabecular bone in patients with osteoarthritis of the knee using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT). Bone. 2020
3: Kuba S, Watanabe K, Chiba K et al. Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer. J Bone Miner Metab. 2021
4: Doi M, Chiba K, Okazaki N et al. Bone microstructure in healthy men measured by HR-pQCT: Age-related changes and their relationships with DXA parameters and biochemical markers. Bone. 2022

Disclosure

There was no disclosure.

Introduction

It is unknown if gastric bypass surgery for obesity increases the risk and delays the diagnosis of adenocarcinoma in the excluded stomach. This study aimed to help clarify this question.

Aims & Methods

This multinational and population-based cohort study included patients who underwent bariatric surgery in Denmark (between 1996-2019), Finland (1997-2019), or Sweden (1980-2019). Data came from complete nationwide registers for diagnoses and surgery, cancer and death. The risk of developing gastric non-cardia adenocarcinoma was analyzed in two ways: (1) comparing gastric bypass with other bariatric procedures using Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, comorbidity, smoking, alcohol abuse, country, and calendar year, and (2) comparing gastric bypass with the background population of the corresponding age, sex, calendar year, and country by calculating standardized incidence ratios (SIR) with 95% CI. Differences in gastrectomy rates among those who developed gastric non-cardia adenocarcinoma (indicating early and curable tumor stage) between gastric bypass and other bariatric procedures were analyzed using logistic regression, providing odds ratios (OR) with 95% CI, adjusted for confounders.

Results

Among 98,881 patients who underwent bariatric surgery (mean age 42 years, 76% women) 31 (0.03%) developed gastric non-cardia adenocarcinoma during up to 40 years of follow-up. Gastric bypass (n=76,446; 77.3%) was associated with an increased risk of gastric non-cardia adenocarcinoma between 10-40 years after surgery (HR 5.5, 95% CI 1.5-19.8; SIR 2.5, 95% CI 0.8-5.4), but not within the first 1-9 years (HR 0.8, 95% CI 0.1-4.2; SIR 0.9, 95% CI 0.5-1.6). The gastrectomy rate was seemingly decreased after gastric bypass (OR 0.2, 95% CI <0.1-1.0).

Bariatric procedure	Cohort	Observed cases	Expected cases	SIR* (95% CI)	Adjusted HR** (95% CI)
Follow-up year 1-40
Other bariatric surgery	22,435	13	12.3	1.1 (0.6-1.8)	1.0 (reference)
Gastric bypass surgery	76,446	18	15.3	1.2 (0.7-1.9)	2.3 (0.6-9.7)
Follow-up year 1-9
Other bariatric surgery	22,435	6	4.6	1.3 (0.5-2.8)	1.0 (reference)
Gastric bypass surgery	76,446	12	12.9	0.9 (0.5-1.6)	0.8 (0.1-4.2)
Follow-up year 10-40
Other bariatric surgery	9,705	7	7.7	0.9 (0.4-1.9)	1.0 (reference)
Gastric bypass surgery	19,233	6	2.4	2.5 (0.9-5.4)	5.5 (1.5-19.8)

* Adjusted for age, sex, calendar year, and country.
** Adjusted for age, sex, comorbidity, tobacco-related diseases, alcohol-related diseases, country, and calendar year.

Conclusion

Gastric bypass may be associated with an increased risk and a delayed diagnosis of gastric non-cardia adenocarcinoma in the excluded stomach. Yet, this cancer is rare after bariatric surgery.

Introduction

Gastric Cancer has been a heavy burden in far East Asian countries. Although there are national programs in South Korea and Japan, their evidence has been suggested as insufficient. We aimed to synthesize currently available comparative data on gastric cancer mortality in healthy, asymptomatic adults by explicitly classifying the screening effects through study designs and types of intervention effects.

Aims & Methods

We searched multiple databases through October 31, 2022, for this systematic review　and meta-analysis. Studies of any design that compared gastric cancer mortality among radiographic or endoscopic screening and no screening in a community-dwelling adult population was included. The method included a duplicate assessment of eligibility, double extraction of summary data, and validity assessment using the Risk Of Bias In Non-randomized Studies of Interventions tool. Bayesian three-level hierarchical random-effects meta-analysis synthesized data corrected for self-selection bias on the relative risk (RR) for per-protocol (PP) and intention-to-screening (ITS) effects. The study registration number at PROSPERO is CRD42021277126.

Results

We included seven studies in which a screening program was newly introduced (median attendance rate, 31%; at a moderate-to-critical risk of bias) and seven cohort and eight case-control studies with ongoing screening programs (median attendance rate, 21%; all at critical risk of bias); thus, data of 1,667,117 subjects were included. For the PP effect, the average risk reduction was significant for endoscopy (RR 0.58; 95% credible interval: 0.39–0.90) but non-significant for radiography (RR 0.80; 95%CI 0.60–1.06). The ITS effect was not significant for both radiography (0.98; 95%CI 0.86–1.21) and endoscopy (RR 0.94; 95%CI 0.74–1.44). The effects' magnitude depended on the self-selection bias correction assumptions. Restricting the scope of East Asian studies only did not change the results.

Conclusion

In limited-quality observational evidence from high-prevalence regions, screening reduced gastric cancer mortality; however, the effects diminished at a program level.

Disclosure

I have no conflict of interest.

Introduction

Gastric cancer continues to be one of the main challenges worldwide, with a predictable increase in the number of new cases in the coming decades. Staging systems for gastric precancerous lesions: Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia (OLGIM) are considered to be the best predictors for gastric cancer development. Only OLGA/OLGIM stages III-IV are considered high-risk lesions with a significant potential of progressing towards gastric cancer.

Aims & Methods

The purpose of this study was to evaluate the predictive role of OLGA and OLGIM staging in gastric cancer development.
We conducted a retrospective cohort study by matching gastric adenocarcinoma cases registered in the Latvian Cancer Registry between 2005 and 2022 to the pathology reports in the database of Academic Histology Laboratory from upper endoscopies performed in the Digestive Diseases Centre GASTRO, Jurmala hospital and Riga 1^st hospital. Only cases with antral and corpus biopsies (as the minimum) available from the index endoscopy allowing OLGA / OLGIM staging were included in the study. If data from several endoscopies were available for the same patient, the case with the highest OLGA/OLGIM stage was used as the index endoscopy; if OLGA/OLGIM staging was identical across several endoscopies, the first endoscopy was used as the index case. The presence of dysplasia in any of the previous pathology reports was also considered. Patients with suspected cancer at the enrolment or having been recorded in the cancer registry less than 6 months after the index endoscopy were excluded from the study.

Results

Altogether 54 patients were available for the analysis; 38.9% were male. The mean age at the time gastric cancer detection 69.2 years, range 40-90. The median time between the index endoscopy and gastric cancer diagnosis was 1403.5 days (IQR: 826.5-2793.3). Forty-one patients (75.9%) had one endoscopy, eleven (20.4%) had two, one (1.9%) had four and one (1.85%) – 8 endoscopies. Biopsies from incisura angularis of the stomach were available for 43 patients (79.6%).
Altogether 16 patients (29.6%) had dysplasia reported at one of the preceding endoscopies, of those 14 were low grade, 2 – high grade. Patient distribution per OLGA and OLGIM stages at the index endoscopy is shown in Table 1. Among patients ultimately diagnosed with gastric cancer, only 11 (20.4%) had OLGA III-IV stages and 10 (18.6%) had OLGIM III-IV stages at the time of the index endoscopy. Excluding cases with dysplasia reported during any of the preceding endoscopies did not make a substantial change in the OLGA and OLGIM stage distribution at the index endoscopy.

Table 1. OLGA and OLGIM stages at the time of the index upper endoscopy in patients having developed gastric cancer thereafter.

	Stage 0	Stage I	Stage II	Stage III	Stage IV
OLGA (all cases)	7 (13.0%)	17 (31.5%)	19 (35.2%)	6 (11.1%)	5 (9.3%)
OLGIM (all cases)	12 (22.2%)	15 (27.8%)	17 (31.5%)	5 (9.3%)	5 (9.3%)
OLGA (excluding cases with previously reported dysplasia)	7 (18.4%)	15 (39.5%)	10 (26.3%)	4 (10.5%)	2 (5.3%)
OLGIM (excluding cases with previously reported dysplasia)	12 (31.6%)	12 (31.6%)	9 (23.7%)	3 (7.9%)	2 (5.3%)

Conclusion

The majority of patients having undergone upper endoscopy before the diagnosis of gastric cancer were in low-risk OLGA and OLGIM stages. Continued research is warranted to identify the best approach for risk stratification of gastric precancerous lesions. Yet, the current study demonstrates that the assessment should not be solely based on OLGA or OLGIM staging.

Introduction

In the eighth edition of the TNM classification, clinical stage (cStage) and pathological stage after neoadjuvant chemotherapy (ypStage) were newly defined for gastric cancer. However, cStage after prior chemotherapy (ycStage) has not yet been defined.

Aims & Methods

This study aimed to validate ypStage and construct ycStage after preoperative chemotherapy in gastric cancer from the viewpoint of survival outcomes. One hundred-eighty-seven patients who planned to undergo gastrectomy with curative intention after preoperative chemotherapy were enrolled. Survival outcomes stratified by ypStage and ycStage was evaluated. ycStage was evaluated by extrapolating TNM cStage. In addition, macroscopic type, tumor size, histological type, and tumor marker (CEA/CA19-9) after chemotherapy were selected as other prognostic factors. These staging system and variables were evaluated by univariate and multivariable analysis. Harrell’s concordance index (C-index: time dependent area under the curve) was used to evaluate predictive ability.

Results

Gastrectomy was not performed in 14 patients (7.5%) due to incurable factors during operation. Remaining 173 patients underwent surgery. Residual tumor was R0: 148 cases (85.5%), R1: 17 cases (9.8%), R2: 19 cases (4.6%), respectively. ypStage: The survival distribution of ypStage was assessed in 173 patients who underwent gastrectomy. The 5-year survival rates (ysr) for ypStage I (n = 36), II (n = 55), III (n = 60), and IV (n = 22) were 82.3%, 76.5%, 42.7%, and 14.1%, respectively. There were significant differences between II/III (P=0.001) and between III/IV (P=0.009), respectively. There was a tendency for there to be a difference in survival between I/II (P=0.087). The C-index of ypStage was 0.713 (standard error: se=0.027). ycStage constructed by ordinal TNM factor: The survival distribution of ycStage, ycT, and ycN was assessed in all 187 patients. The 5-ysr for ycStage I (n = 12), II (n = 39), III (n = 90), and IV (n = 46) were 54.7%, 57.5%, 61.0%, and 40.6%, respectively. The predictive ability was poor with C-index of 0.533 (se=0.031). The 5-ysr for ycT1 (N=9): 66.7%, ycT2 (N=16): 64.2%, ycT3 (N=27): 60.6%, ycT4 (N=135): 52.0%, respectively. There were no significant differences between ycT1/2 (P=0.734) and between ycT2/3 (P=0.872). The 5-ysr for ycN0 (N=55): 45.9%, ycN1 (N=55): 59.3%, ycN2 (N=54): 68.2%, ycN3 (N=23): 36.4%, respectively. The survival outcomes among cN0, cN1 and N2 are completely reversed. Other preoperative prognostic factors: In univariate analysis histological type (P=0.703), macroscopic type (P=0.125), and CA19-9 (P=0.296) were not significant prognostic factors, but tumor size [<80mm (n=117): 5-ysr; 64.6% vs. >80mm (n=70): 34.2%, P<0.001] and CEA [(negative (n=152): 5-ysr; 59.2% vs. positive (n=35): 33.0%, P<0.001)] were significant prognostic factors. Multivariate Cox proportional hazard model selected tumor size (P<0.001) and CEA (P=0.007) as independent prognostic variables. Construction of proposal ycStage: A new proposal stage was constructed from the results of multivariate analysis. ycStageI: size<80mm and CEA-negative, ycStageII: size<80mm and CEA-positive, ycStageIII: size>80mm and CEA-negative, ycStageIV: size>80mm and CEA-positive. The 5-ysr for new proposal ycStage I (n = 94), II (n = 26), III (n = 52), and IV (n = 15) were 71.3%, 54.0%, 37.0%, and 20.0%, respectively. The C-index of new proposal ycStage was 0.662 (se=0.029). It is significant higher value than that of ycStage constructed by ordinal TNM factor.

Conclusion

The predictive ability of the ypStage, on the basis of TNM factors, considered favorable. However, survival separation was poor for both ycT and ycN. Thus, ycStage based on ordinal TNM did not have the perspective of survival outcome prediction. Proposal ycStage constructed by tumor diameter and CEA may be recommended.

Disclosure

The first author (Etsuro Bando) received honorarium from Johnson & Johnson, Medtronic plc, Intuitive Surgical G.K., KAKEN PHARMACEUTICAL CO., LTD, and
DAIICHI SANKYO COMPANY, LIMITED.

Introduction

It is unclear whether post-operative complications reduce the long-term survival following gastrectomy for gastric cancer, despite research on the subject. We aimed to help fill this knowledge gap in a study that took the main methodological concerns of the existing literature into account.

Aims & Methods

This population-based cohort study included patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2020, with follow-up until 2024. Data came from medical records and national health data registries. The exposure was in-hospital complications defined by the Clavien-Dindo classification, categorised into three groups: no complications, mild complications (grade I-II), and severe complications (grade IIIa-IVb). The outcomes were all-cause and disease-specific mortality between 91 days and 5 years following gastrectomy. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, comorbidity, neoadjuvant therapy, extent of the gastrectomy (total or subtotal), microscopically radical surgery, and pathological tumour stage.

Results

The study included 2102 patients. Compared to patients without complications (n=1219), those with severe complications (n=383, 18%) had an adjusted HR of 1.10 (95% CI 0.94-1.29) for all-cause mortality and HR of 1.15 (95% CI 0.97-1.36) for disease-specific mortality. The corresponding unadjusted HRs were statistically significant (HR 1.22 [95% CI 1.04-1.42] for all-cause mortality and HR 1.24 [95% CI 1.04-1.46] for disease-specific mortality). Patients with mild complications (n=500, 24%) had no increased risk of mortality outcomes.

Table 2. In-hospital complications (according to the Clavien-Dindo classification) and risk of mortality within 91 days to 5 years of gastrectomy for gastric adenocarcinoma, presented as hazard ratios (HR) with 95% confidence intervals.

Complication status	Number (%)	All-cause mortality
		Unadjusted HR (95% CI)	Adjusted HR (95% CI)a
No complications	1219 (58)	1.00 (reference)	1.00 (reference)
Mild complicationsb	500 (24)	1.07 (0.93-1.23)	1.00 (0.86-1.15)
Severe complicationsc	383 (18)	1.22 (1.04-1.42)	1.10 (0.94-1.29)
		Disease-specific mortality
		Unadjusted HR (95% CI)	Adjusted HR (95% CI)a
No complications	1219 (58)	1.00 (reference)	1.00 (reference)
Mild complicationsb	500 (24)	1.13 (0.97-1.31)	1.06 (0.91-1.23)
Severe complicationsc	383 (18)	1.25 (1.06-1.47)	1.15 (0.97-1.36)

^a Adjusted for age, sex, education, comorbidity, pathological tumor stage, preoperative chemotherapy, microscopically radical resection, and extent of the gastrectomy
^b Clavien-Dindo grade I-II
^c Clavien-Dindo grade IIIa-IVb

Conclusion

Severe in-hospital complications might increase the 5-year mortality following gastric cancer surgery also after excluding the initial 90 days of surgery.