# Editorial Review — Critical-Reader Pass

**Manuscript:** Axillary Management After NAC in cN+ Breast Cancer: Umbrella Review of 23 SRs/MAs (2006-2026)
**Reviewer persona:** Demanding journal editor + senior breast surgical oncologist (30 yrs editorial experience, BJS / EJSO / Ann Surg Oncol calibre)
**Date:** 2026-05-14
**Verdict (one-sentence):** Strong manuscript that passes the substance bar but is currently **NOT submission-ready** because of multiple high-impact internal-consistency failures (reference numbering, abstract-table mismatches, supplementary-file numbering collisions, GRADE/AMSTAR-2 narrative drift) that any competent BJS reviewer will weaponise against acceptance.

---

## 1. Substantive issues — flagged for Sergio + David's review (NOT auto-fixed)

### S1 [CRITICAL] Reference numbering in manuscript body is misaligned with references.md after Vancouver renumber
The body of the manuscript cites e.g. **Samiei²¹**, but Samiei is reference **24** in `references.md`. Likewise **Tee³¹** = ref 21; **Simons 2019³²** = ref 22; **Cao²³** is actually Cao=ref 23 in refs but body uses ²³ for Abdulla; **de Wild²⁵** = ref 33; **Wang 2025⁴⁰** = ref 39; **Vasigh²⁸** = ref 34. The body superscripts appear to be derived from an earlier draft ordering or a parallel numbering scheme. Every superscript citation in §3.3, §3.4, §3.5, §3.6, §3.7, §3.8, §4.2 needs to be reconciled against the final references.md. **Recommended fix:** Sergio re-walks references.md and applies a single Vancouver renumber pass; alternatively, re-order references.md to match body. This is the #1 reason the paper would currently be desk-rejected.

### S2 [CRITICAL] Phantom citation — "Yang 2023" appears in §3.5 but is not in references.md
Section 3.5 line: *"...FNR 1.4-4.2% (Caudle 2016⁵ and confirmatory SR estimates from Yang 2023, Wang 2025⁴⁰)..."* — there is no Yang 2023 in `references.md`. Either (a) the citation should be replaced (likely Yang & Caudle is shorthand for Caudle 2016 / co-author Yang WT, but that conflates author names), or (b) Sergio must add a Yang 2023 reference. Reviewers who check refs always catch this.

### S3 [MAJOR] Supplementary-file numbering collision (S4 used for both excluded SRs and search strings)
- §2.2 says: "*per-SR rationale in Supplementary File S4*" (excluded SRs documented in S4)
- §2.3 says: "*The complete search strings... are reproduced in Supplementary Material S4*" (search strings in S4)
- §2.6 says: "*Supplementary Files S3 (per-rater scores) and S8 (κ + consensus)*" — but no S5, S6 are described.
- §2.7 references S7 for GRADE.
- §3.1 says PRISMA flow data in `prisma_flow_data.md` (project repo) — but PRISMA checklist is S2 (line 40) — internally consistent here.

**Recommendation:** Sergio must build a single Supplementary Material index (S1 protocol; S2 PRISMA checklist; S3 per-rater AMSTAR-2 scores; S4 PRIOR-O checklist OR excluded-SRs rationale OR search strings — pick one and re-letter the others S5/S6 etc; S7 GRADE; S8 κ + consensus). The current text mentions S1, S2, S3, S4, S7, S8 but skips S5 and S6, and S4 is overloaded.

### S4 [MAJOR] AMSTAR-2 narrative drift between Abstract, §3.3, Discussion and Table 2
- Abstract (revised) now says ELIGIBLE consensus = 3 Mod / 4 Low / 6 Crit Low.
- §3.3 reports the same: "**3 Moderate (23.1%), 4 Low (30.8%), 6 Critically Low (46.2%); 0 High**".
- §3.3 also names Tee 2018 BJS, Wang 2025 Oncology, Cao 2021 Breast as the Moderate trio.
- **But Table 2 (anchor SR scoring) shows Tee 2018 = "Critically Low" and Simons 2019 = "Low"** — contradicting §3.3's claim that Tee is Moderate.
- Table 2 anchor narrative says Simons 2019 = "highest overall confidence (Low)" in anchor set; §3.3 lists Simons in neither stratum's named Moderate trio.
- Discussion §4.3 still says "predominantly Low / Critically Low confidence ratings across the 23 retained reviews" — softer than §3.3's specific consensus distribution.

**Recommendation:** Sergio must reconcile (a) the AMSTAR-2 consensus distribution per stratum, (b) the named Moderate-confidence SRs in §3.3, and (c) the anchor scoring in Table 2. Given the Table 2 LLM-full-text scoring of Tee 2018 = Crit Low, the §3.3 sentence "Moderate-confidence reviews including Tee 2018 BJS, Wang 2025 Oncology and Cao 2021 Breast" is internally inconsistent.

### S5 [MAJOR] GRADE Table 6 references "Table 6" but no Table 6 .md file exists in tables/ directory
The tables/ directory contains: table1, 1A, 1B, 2, 3, 4, 5. There is `grade_table_for_results.md` but it is not named `table6_*.md`. §2.7 and §3.9 both reference "Table 6". Either rename `grade_table_for_results.md` → `table6_grade_summary_of_findings.md` or update manuscript text to reference the actual filename. **Recommended fix:** rename the file (preferred for journal submission convention).

### S6 [MAJOR] GRADE assessment full document (`grade_assessment.md`) is structurally broken
- Outcome 9 (or Outcome on lymphedema) is missing its **header** at line 175 — the section starts with "**Effect estimate:**" but no `### Outcome 9 — ...` precedes it. The summary table at line 192 lists 8 outcomes (so Outcome 9 may have been intentionally collapsed), but `grade_table_for_results.md` (Table 6) only shows 8 rows — implying lymphedema was deliberately removed but the grade_assessment.md fragment was not cleaned up. The orphan paragraph at line 176-188 with its own "Final certainty: Moderate ⊕⊕⊕○ — Important" rating cannot be matched to any outcome.
- §3 of grade_assessment.md is also missing item "2." — it jumps from `1. AMSTAR-2 anchoring is conservative` to `3. Two outcomes are Very Low`.
- Manuscript §2.7 cites references **⁹¹⁻⁹²** for GRADE (Guyatt 2008 + 2024 Handbook) but the references.md lists Guyatt as ref **71**, not 91, and there is no ref 92 (refs only go to 90).

**Recommendation:** Sergio cleans up grade_assessment.md (remove orphan outcome, restore numbering), and updates §2.7 superscripts from ⁹¹⁻⁹² to the correct ref number (likely 71 + a new entry for the GRADE Handbook if needed, or simply 71).

### S7 [MAJOR] Methods §2.6 mentions "(n = 14/33; remaining 19 abstract-only)" — this strands a "33" outside the audit-trail context and a hostile reviewer will flag it as inconsistent with the 23-SR primary corpus
The sentence reads: *"...one independent agent applied the 16-item rubric to each SR with full-text content appended where the open-access PDF was available (n = 14/33; remaining 19 abstract-only)."*

This is technically correct (the AMSTAR-2 pipeline was originally run on 33 SRs before triage, and that historical audit trail is preserved per §2.6 line 64). But mid-paragraph it abruptly refers to "33" without flagging the audit-trail context. **Recommendation:** Sergio rewords to *"(n = 14 of the 33 originally screened SRs had full-text PDFs available; the remaining 19 were scored abstract-only; the post-PICOS-triage 23-SR corpus inherits these scorings — see §2.2)"*.

### S8 [MAJOR] Discussion §4.4 Strengths claims "20-year temporal span" — but title says (2006-2026) which is 20 years; abstract calls it "two decades" — internally consistent, but §4.5 Limitations does not address the 36-month median follow-up issue raised in GRADE Outcome 8. Hostile BJS reviewer will press on this.

The GRADE assessment (Outcome 8 OS) anchors a Very Low certainty on "Median follow-up of 36 months in the only two SRs reporting it falls short of the optimal information size for a favourable-prognosis ypN0 cohort". Manuscript §3.6 and §3.9 mention this. But §4.5 Limitations does not surface "immature OS follow-up" as an explicit limitation — only mentions Montagna 2024 has "limited Latin-American representation and immature follow-up beyond 5 years" in §3.9. Recommend adding a sentence to §4.5: *"Eighth, OS comparisons between TAD and ALND remain very-low certainty because the median follow-up across the two SRs reporting OS is only ~36 months, well short of the optimal information size for a favourable-prognosis ypN0 cohort."*

### S9 [SUBSTANTIVE] §3.10 cites NCCN/ESMO/ASCO/St Gallen/AGO/EUSOMA/EUBREAST as superscripts ¹²⁻¹⁸ but references.md lists them as 56-62
Same numbering-drift as S1. The Introduction also uses ¹²⁻¹⁸ for these guidelines (line 32).

### S10 [SUBSTANTIVE] Conclusion does not mention GRADE certainty — Editor will ask why
The paper added GRADE assessment as a major methodological strength (§2.7, §3.9, Table 6). The Conclusion (line 174) says nothing about certainty grading. A senior breast oncology reviewer at BJS will ask: *"You added GRADE; what does it tell us about how confident we should be in the recommendations? Why is it absent from the Conclusion?"* — Recommend adding one sentence: *"The certainty of the underlying evidence ranges from Moderate (nodal pCR estimates; FNR comparison TAD vs SLNB) to Low (5-year axillary recurrence; HR+/HER2- pCR; TNBC chemo-IO) with one Very Low outcome (long-term OS), implying that the convergent recommendations should be re-assessed as longer-follow-up data accumulate."*

### S11 [SUBSTANTIVE] Author contributions paragraph promises "Biostatistician conducted the corrected-covered-area and overlap analyses" — but the manuscript does not present a quantitative CCA value
§3.2 says only "the CCA across the 23 reviews indicates 'high overlap' in the categorisation of Pieper and colleagues²⁰". The earlier abstract draft said CCA = 12.4% (now removed in the edited Version A). Either restore an explicit CCA number in §3.2, or remove the "biostatistician CCA" promise from Author contributions to avoid raising reviewer expectations the body does not satisfy.

### S12 [SUBSTANTIVE] Methods §2.2 PICOS ages "18 years or older" — fine, but the manuscript never reports patient-age distribution in Results §3.2. A demanding reviewer will note that the eligibility criterion is operationally orphaned.

### S13 [SUBSTANTIVE] Limitations §4.5 contains a logical sequence numbering collision
The paragraph numbers limitations First → Second → Third → Fourth → Fifth → Sixth → Seventh, but the opening sentence (after my edit) now says "Seven limitations should be acknowledged." That is internally consistent. However, the original "Sixth — an explicit equity limitation" was followed by "Seventh, **strict PICOS triage applied post hoc reduced our included corpus from 33 to 23 SRs..."** — this is in fact the most defensible limitation and arguably should be Limitation #1, not #7, since reviewers will see post-hoc PICOS triage as the single biggest methodological vulnerability. **Recommend reordering limitations** to put the post-hoc PICOS triage first.

### S14 [SUBSTANTIVE] Methods §2.7 says "Two reviewers (S.C., D.D.) independently rated each outcome [GRADE]; discrepancies resolved by discussion" — but grade_assessment.md headers list "SCB" and "DD" as raters (consistent), and shows no κ or per-outcome agreement metric. A BJS reviewer will ask: *"How many discrepancies, on which outcomes, and what fraction were upheld at consensus?"* — Recommend Sergio adds at least a sentence (e.g., "Across the 8 outcomes × 5 GRADE domains = 40 cells, 6 cells (15%) had initial discrepancy and all were resolved by discussion within one round").

### S15 [SUBSTANTIVE] §3.10 mentions Figure 6 ("Mapping to clinical-practice guidelines") but the manuscript references Figures 1-6 in the closing section (line 190). The tables/ directory contains no figure files; figures are likely in `01_figuras/` or generated separately. **Recommend** Sergio confirms each figure (1 PRISMA, 2 AMSTAR-2 heatmap, 3 pCR by subtype, 4 FNR forest, 5 [unspecified], 6 guideline mapping) exists and is referenced in the correct section.

---

## 2. Minor issues (typos, redundancy, citation gaps, Vancouver-style)

### M1. Line 66 (§2.7) opens with "The certainty of evidence for each prespecified outcome was assessed..." but uses superscripts ⁹¹⁻⁹² for Guyatt 2008 and the GRADE Handbook. Refs only go to 90 — superscripts must be 71 (Guyatt) plus a new entry if Handbook needed.

### M2. Line 70 has "### 2.8 Synthesis" and Line 74 has (was) "### 2.8 Patient and public involvement" — DUPLICATE section number. **FIXED** to §2.9.

### M3. Line 160 (§4.5 Limitations) opened with "Six limitations should be acknowledged" but listed seven. **FIXED** to "Seven".

### M4. §4.7 Implications for future research opened with "Five priorities" but only listed four (First, Second, Third, Fourth). **FIXED** to "Four priorities".

### M5. §4.6 says "six implications follow" then numbers First→Sixth — verified, correct.

### M6. §3.2 line 88: "with a median publication year of 2021 reflecting the acceleration of the field after the introduction of TAD in 2016." — *Median of 23 reviews from 2006-2026; the median is fine but worth verifying it matches the actual publication-year list.* Counted from Table 1: 2006, 2009, 2009, 2014, 2015, 2015, 2016, 2018, 2018, 2019, 2021, 2021, 2021, 2022, 2022, 2022, 2024, 2024, 2025, 2025, 2025, 2025, 2026 — median position (12th of 23) = 2021. **Confirmed.**

### M7. Line 50 "Reference lists of recent guideline documents and of all included reviews were hand-searched (~15 additional records)" — fine. But line 84 says "complemented by approximately 15 records from hand-searching" — consistent. Good.

### M8. Line 84 says "146 unique records" deduplicated, then "9 were excluded at title/abstract for evident off-topic content (e.g. Parkinson disease, irritable-bowel syndrome, robotic nephrectomy, fetal anaemia, valproate, mitapivat, tirzepatide, phyllodes tumour, pneumococcal vaccine)" — 9 named off-topic items, count matches.

### M9. §3.2 line 88: "approximate cumulative N across reviews with reported denominators is ~95,000 patients". Earlier abstract draft said "n>120,000" and table 1 footer says "~120,000". The 95,000 vs 120,000 vs 92,200 (Table 1A footer) discrepancy is unresolved. After post-PICOS triage to 23 SRs (Tables 1A+1B sum), the cumulative N is dominated by Samiei 57,531 + Vasigh 18,037 + Lin 10,680 + Mocellin 7,451 + Wang 5,249 + de Wild 4,512 + Man 4,268 + Cao 3,578 + El Hage Chehade 3,398 + Abdulla 2,849 + van Deurzen 2,148 + Simons 2019 2,217 + Tee 1,921 + Song 1,920 + Kelly 1,799 + Xing 1,273 + Boland 374 + Schipper 572 + Swarnkar 366+521 = ~130,200. Even allowing for "see SR text" entries that lack a denominator (van Nijnatten 2015, Vázquez 2022, Krug 2018, Ding 2025) the 95,000 figure looks low. **Recommend** Sergio recompute and harmonise across §3.2, abstract Version A, and Table 1A footer (currently 92,200 in Table 1A footer for ELIGIBLE only — that figure is plausible).

### M10. Vancouver style — references.md is broadly Vancouver-compliant. Minor flags:
- Ref 30 (Banys-Paluchowski 2021) has parenthetical "(Listed in Scand J Surg 2023 issue as commissioned review)" — non-standard Vancouver; remove or move to a separate footnote.
- Ref 6 (Simons 2022 RISAS) cites JAMA Surg 2022;157(11):991-9 — checked, correct.
- Ref 7 (NSABP B-51 Mamounas 2025) has placeholders "Vol/Issue/Pages TBD" and "PMID: [TBD]" — must be completed before submission.
- Refs 41, 42, 44, 45, 54, 58, 60, 61, 62, 82 also have "[TBD]" placeholders — completion mandatory.
- Ref 16 (Mocellin 2015): published 2016 but year in citation says "Int J Cancer. 2016;138(2)..." — original PubMed entry was 2015 e-pub; verify.
- Ref 6 (Simons 2022) is double-cited as both ref 6 (RISAS trial in Intro) and ref 22 (Simons 2019 SR/MA in Ann Surg). These are two different papers by overlapping authors but on the same topic — visually confusing for readers. **Recommend** explicit author/year disambiguation in the body (e.g., "Simons RISAS 2022⁶" vs "Simons SR/MA 2019³²").

### M11. Spelling/diacritic consistency: "Vázquez" (with accent) in Table 1A and Table 1; "Vazquez" (without accent) in §3.2 line 88. Standardise to "Vázquez".

### M12. §3.5 Section bullet list line 113: "(Caudle 2016⁵ and confirmatory SR estimates from Yang 2023, Wang 2025⁴⁰)" — Yang 2023 is unreferenced (S2 above). Caudle 2016 superscript ⁵ matches references.md ref 5. Wang 2025 ⁴⁰ should be ref 39, not 40 (S1 above).

### M13. Title line 1: "Umbrella Review of 23 Systematic Reviews and Meta-Analyses" — matches §1, §3.1, §3.2, §4.1, §5. Internally consistent.

### M14. Figure 2, 3, 4, 6 explicitly cited in body — Figure 1 (PRISMA) cited in §2.4 and §3.1 — but **Figure 5 is never explicitly referenced in the body**. Either remove "Figures 1-6" claim from line 190 or add an explicit Figure 5 reference (perhaps in §3.10 alongside Figure 6, or a recurrence-rate forest plot in §3.6).

### M15. Footer line 12 (word count): I updated the estimate to ~6,330 to reflect actual count after edits (originally ~6,500 placeholder). For BJS the cap is typically 4,500-5,000 words; for EJSO 5,000; for Ann Surg Oncol 4,500. **The manuscript at 6,330 words exceeds typical BJS limits by ~30%**. Sergio must either trim or pre-clear with the editor.

### M16. References 56-72 are listed as "Clinical-practice guidelines" + methodological standards but include refs 65-70 which are methodological (PRISMA, AMSTAR-2, JBI, PRIOR, Pieper CCA, GRADE). The header on line 130 should split into two: "Clinical-practice guidelines (refs 56-64)" and "Methodological standards (refs 65-71)". Minor.

### M17. Ref 72 (the companion ypN0 prediction tool — Cervera & Duque) is "manuscript in preparation 2026" — for BJS submission, Sergio must either upgrade this to a preprint with DOI (e.g., medRxiv) or remove the citation pending companion-paper publication. Currently it is cited in §4.4 Strengths via "(https://ganglio.cicatra.com)" — fine for the URL, but a citation to a manuscript-in-preparation will be flagged by reviewers as self-citation that cannot be verified.

### M18. Acknowledgements (line 186) says "We thank the patient advocates from [Spanish patient organisation TBD]" — must be filled in pre-submission.

### M19. Authors (line 3) contains [Biostatistician TBD] and [Senior Breast Surgeon TBD] — must be filled in pre-submission.

### M20. Abstract "Conflicts of interest: None declared. Full ICMJE forms will be uploaded with the submitted manuscript" — if Sergio declares any honoraria, advisory boards or research funding, this must be updated; "None" is rare in modern breast-oncology authorship.

---

## 3. Numerical consistency check

| Number | Where used (correct) | Where used (incorrect / drift) | Status |
|---|---|---|---|
| **23** (final corpus) | Title, §1, §2.2, §2.4, §3.1, §3.2, §3.3, §3.5, §4.1, §4.5, §5, Highlights | — | OK after edits |
| **13** (ELIGIBLE) | §2.2, §2.4, §3.1, §3.2, §3.3, §3.5, §4.1, §5, Tables 1, 1A | — | OK |
| **10** (BORDERLINE) | §2.2, §2.4, §3.1, §3.2, §3.3, §3.5, §4.1, §5, Tables 1, 1B | — | OK |
| **10** (EXCLUDED) | §2.2 (post-hoc PICOS triage), §2.4, §3.1, §190 (per-SR list), Table 1, Supp S4 | — | OK |
| **33** (legitimate audit-trail uses only) | §2.6 (AMSTAR-2 historical pool, n=14/33 full-text), Table 1 title, Table 2 full-cohort frequency, grade_assessment.md "Bodies of evidence assessed" | §2.6 mid-paragraph reads abruptly; flagged S7 | Each remaining "33" should be qualified as "originally screened" |
| **120,000** (cumulative N — pre-triage abstract-era figure) | Table 1 footer ("~120,000") | Abstract Version A pre-edit ("n>120,000"); B pre-edit ("cumulative >120,000") | Edited abstract now uses ~95,000 — but §3.2 also says ~95,000 while my recount above suggests ~130,200 incl Vasigh 18,037 — needs Sergio recount |
| **95,000** (manuscript §3.2) | §3.2 line 88; abstract Version A revised | Inconsistent with Table 1A footer (~92,200 ELIGIBLE only) and with quick recount (~130k for all 23) | Flagged M9 |
| **57,531** (Samiei N) | §3.2, Table 1, Table 1A, Table 2 narrative | Consistent | OK |
| **5,516** (search hits) | §2.3, §3.1, abstract A & B | Consistent | OK |
| **146** (deduplicated unique) | §3.1, abstract A & B | Consistent | OK |
| **137** (full-text) | §3.1 ("One hundred and thirty-seven") | Implied 146-9=137 | OK |
| **9** (off-topic exclusions) | §3.1 (lists 9 named off-topic items) | Consistent | OK |
| **CCA value** | §3.2 says "high overlap"; abstract pre-edit said 12.4%; abstract post-edit dropped 12.4 | Inconsistency | Flagged S11 |

**Verdict on numerical consistency:** Solid except for cumulative-N (M9) and the few stranded "33" references that lack audit-trail context (S7).

---

## 4. Vancouver reference style check (skim of references.md)

References.md is broadly Vancouver-compliant. Minor issues:
- **Ref 16 (Mocellin)** — listed in chronological position 9 (between Schipper 2014 and van Nijnatten 2015) as "Mocellin S... Int J Cancer. 2016" but the chronological list header says "(chronological order)" and 2016 is later than 2015 (which appears as ref 17, van Nijnatten). **Recommend** swap ref 16/17 to true chronological order, OR the body retains the current numbering and the chronology header is corrected.
- **Refs with "[TBD]"** (3 PMIDs, 1 Vol/Issue, 1 Pages) on refs 7, 41, 42, 44, 45, 54, 58, 60, 61, 62, 82 — must complete before journal upload.
- **Refs 56-64** journal style is consistent (Curigliano, Burstein, Korde, Loibl, Park, Reimer, Rubio, Weber).
- **Ref 30 Banys-Paluchowski 2021** — has odd parenthetical "(Listed in Scand J Surg 2023 issue as commissioned review)". Remove parenthetical and clarify whether the citation is for the *Cancers* 2021 paper or the *Scand J Surg* 2023 commissioned review (the DOI 10.1177/14574969221145892 is the Scand J Surg one, but the journal name in the citation says *Cancers (Basel)*, year 2021). **Major Vancouver inconsistency** — Sergio must verify and correct.
- **Ref 70 (Pieper)** — Vancouver-OK.
- **Ref 28 (Song 2022)** — listed as "Cancer Med. 2022;11(22):4085-103" — checked, correct.
- **Ref 38 (Man 2025)** — listed as "Breast Cancer (Tokyo). 2025;32(3):xxx" — has a "xxx" placeholder for pages. Fix.
- **Ref 39 (Wang 2025)** — same: "Oncology. 2025;103(4):xxx" — fix.
- **Ref 37 (Ding 2025)** — "J Cancer Res Ther. 2025;21(2):xxx" — fix.
- **Ref 58 (Park ASCO 2025)** — "J Clin Oncol. 2025;43(13):xxx" — fix.
- **Ref 60 (Reimer AGO 2025)** — "Geburtshilfe Frauenheilkd. 2025;85(3):xxx" — fix.

**Verdict on Vancouver style:** Consistent in format, but ~10 entries still carry "xxx", "[TBD]" or "Vol/Issue/Pages TBD" placeholders that block journal submission.

---

## 5. Statement consistency

| Statement | Abstract | Methods | Results | Discussion | Conclusion | Tables |
|---|---|---|---|---|---|---|
| 23 SRs (13 ELIGIBLE + 10 BORDERLINE) | OK (post-edit) | OK | OK | OK | OK | OK |
| TAD as standard for ALND omission | OK | n/a | OK §3.5 | OK §4.6 | OK | Table 4, 5 |
| All 7 guidelines endorse | OK | n/a | OK §3.10 | OK §4.6 | OK | Table 5 |
| Five anchor SRs | n/a | §2.6 (anchors selected) | §3.3 (5 anchors named: Samiei, Tee, de Wild, Simons, Abdulla) | n/a | n/a | Table 2 (5 anchors: Tee, Simons, Samiei, Swarnkar, de Wild) — **MISMATCH** between §3.3 list (includes Abdulla) and Table 2 list (includes Swarnkar) |
| AMSTAR-2 distribution ELIGIBLE | OK (3 Mod / 4 Low / 6 Crit Low) | n/a | OK | softer ("predominantly Low / Crit Low") | n/a | Table 2 anchor scoring shows Tee Crit Low contradicting §3.3's claim Tee=Mod |
| GRADE per outcome | OK (no specific certainty mentioned) | OK §2.7 | OK §3.9 (Table 6) | not mentioned | NOT mentioned (S10) | Table 6 (file misnamed) |

**Anchor SR mismatch (§3.3 vs Table 2):** §3.3 names Samiei, Tee, de Wild, Simons, Abdulla. Table 2 names Tee, Simons, Samiei, Swarnkar, de Wild. **Substantive discrepancy** — Sergio must pick one set and align both.

**AMSTAR-2 Tee 2018 confidence-rating mismatch:** §3.3 calls Tee Moderate; Table 2 scoring shows Tee = Critically Low (2 critical flaws but Item 4 Partial + Item 7 No drives Crit Low per Shea 2017 algorithm). Sergio must reconcile.

---

## 6. Risk-of-rejection analysis — what would a hostile BJS reviewer attack?

**Likely top 5 attacks:**

1. **"Post-hoc PICOS triage from 33 → 23 invalidates the umbrella's claim to systematic-review status."** This is the single biggest vulnerability. The PROSPERO registration (currently TBD per §2.1) must clearly pre-date the triage decision; otherwise reviewer will argue the eligibility criteria were chosen to obtain the desired corpus. **Defence:** Sergio must reorder Limitations to put this first (S13), and the PROSPERO record must precede the decision.

2. **"Abstract-only AMSTAR-2 scoring is conservative junk."** Even with the three-rater pipeline and partial full-text, the AMSTAR-2 ratings are predominantly Crit Low. A BJS reviewer will say: *"You used three raters of which one was an LLM, you scored 19/33 from abstract only, and you call this a methodological assessment of high-impact reviews? Either redo with full text for all 23, or do not bother with AMSTAR-2."* **Defence:** Sergio must complete full-text rescoring before submission, OR reframe §2.6 explicitly as a methodological-mapping exercise rather than a quality-grading exercise.

3. **"You did not re-pool primary effect estimates — fine — but you also did not present a forest plot of pooled estimates from the contributing SRs (which is allowed in umbrella reviews per Aromataris 2015)."** No Figure 4 forest of FNR-by-technique estimates is described in the manuscript text. **Defence:** Confirm Figure 4 is a forest plot of pooled FNR ranges from the contributing SRs.

4. **"Latin-American equity gap is mentioned but no actionable plan."** §4.7 promises validation but does not name the cohort, the platform, the timeline. **Defence:** Sergio names a partner cohort (e.g., GEICAM in Spain, GBECAM in Brazil) or removes the equity claim.

5. **"6,330 words is too long for BJS."** Manuscript will exceed the journal's word cap. **Defence:** Tighten by ~1,500 words. Recommended cuts: §1 paragraphs 1+3 redundancy with §4.1 Principal findings; §2.6 AMSTAR-2 narrative could lose 200 words; §3.3 has 4 paragraphs, could collapse to 2; §4.5 Limitations has 7 long limitations, could compress each to 2 sentences. See `final_word_count_audit.md` for per-section analysis.

**Less likely but possible attacks:**

6. NSABP B-51 cited as ref 7 with "[TBD]" Vol/Issue — reviewer will check.
7. The "companion ypN0 predictor tool" (https://ganglio.cicatra.com) is mentioned twice (§4.4 + §5) and again in Acknowledgements — may smell of self-promotion. Recommend mention once in §4.4 only.
8. "Three-rater pipeline" — one of the three is an LLM. While this is a defensible methodology (and a paper-worthy contribution), some reviewers will dismiss it. Consider downplaying ("LLM-augmented full-text pre-screen reconciled with two independent breast-surgical-oncologist raters") rather than emphasising LLM as Rater 1 of 3.

---

## 7. Verdict

**Substance:** Strong umbrella review with appropriate scope, methodological rigor (subject to AMSTAR-2 full-text completion), and convergent clinically actionable findings. The cN+→ypN0 question is timely; the synthesis of TAD/RISAS/MARI vs SLNB FNR is well-motivated; the cross-walk against 7 guidelines is a major contribution.

**Submission readiness (today):** **NOT READY.** The reference-numbering misalignment (S1) alone would draw a desk-reject from BJS. Combined with the supplementary-file numbering chaos (S3), the AMSTAR-2 narrative drift between §3.3 and Table 2 (S4), the missing Table 6 file (S5), the broken grade_assessment.md (S6), and the placeholder TBDs in references and acknowledgements, the manuscript needs ~1-2 days of conservative-edit cleanup before it is journal-ready.

**Recommended pathway:**
1. Sergio applies S1 reference-renumber (highest priority).
2. Sergio reconciles §3.3 ↔ Table 2 anchor SR list and AMSTAR-2 Tee 2018 confidence rating (S4).
3. Sergio names the supplementary files and rebuilds S1-S8 index (S3).
4. Sergio renames `grade_table_for_results.md` → `table6_grade_summary_of_findings.md` and cleans `grade_assessment.md` orphan outcome (S5, S6).
5. Sergio fills all "[TBD]" placeholders in references.md, abstract, acknowledgements (M19, M20).
6. Sergio recomputes cumulative N (M9) and reconciles 95,000 vs Table 1A 92,200.
7. Sergio trims to BJS word cap (~5,000) by collapsing §1 + §3.3 + §4.5 (or pre-clears longer limit with editor).
8. Sergio completes AMSTAR-2 full-text rescoring for the 9 ELIGIBLE SRs not yet full-text-scored, OR explicitly relabels §2.6 as a methodological-mapping pilot.

After items 1-5 the manuscript is technically submittable. Items 6-8 are quality-improvement before submission to BJS specifically.
